How does heat intolerance affect fibromyalgia patients. What is the relationship between thermoregulation and pain modulation in fibromyalgia. Why do fibromyalgia symptoms worsen with cold and stress but improve with warmth. How does brown adipose tissue activity potentially relate to fibromyalgia pain.

The Complex Relationship Between Temperature and Fibromyalgia Pain

Fibromyalgia syndrome is a chronic condition characterized by widespread musculoskeletal pain that persists for years and does not respond well to typical anti-inflammatory or analgesic medications. One of the hallmark features of fibromyalgia is that symptoms tend to worsen with exposure to cold temperatures or stress, but improve with warmth. This temperature sensitivity hints at a complex relationship between thermoregulation and pain perception in fibromyalgia patients.

Why does temperature have such a significant impact on fibromyalgia symptoms? The answer likely lies in the overlap between thermal and pain pathways in the body. At multiple points along these neural pathways, temperature changes can influence pain signaling. Understanding these connections may provide valuable insights into the mechanisms underlying fibromyalgia and potential treatment approaches.

The Role of Brown Adipose Tissue in Fibromyalgia

An intriguing hypothesis links brown adipose tissue (BAT) activity to fibromyalgia pain. BAT is a specialized type of fat tissue that generates heat through a process called thermogenesis. Cold exposure initiates thermogenesis in BAT via adrenergic (adrenaline-related) activity, while warmth suspends this heat-generating process.

Several observations support a potential connection between BAT and fibromyalgia:

• The distribution of BAT in the body closely resembles the pattern of tender points used to diagnose fibromyalgia
• Both BAT activity at rest and the incidence of fibromyalgia are higher in females compared to males
• Stress and cold temperatures stimulate BAT thermogenesis and also aggravate fibromyalgia symptoms
• Warmth suspends BAT thermogenesis and provides temporary symptom relief in fibromyalgia

Could dysfunctional BAT activity contribute to the pain and temperature sensitivity experienced by fibromyalgia patients? This is an area that warrants further investigation.

Gender Differences in Thermogenesis and Fibromyalgia

Gender plays a significant role in both thermogenesis and fibromyalgia prevalence. Females have a higher incidence of fibromyalgia and more resting thermogenesis compared to males. However, females are less able to recruit BAT in response to chronic stress than males.

This gender difference in adaptive thermogenesis may help explain why fibromyalgia is more common in women. The reduced ability to activate BAT in response to stress could potentially contribute to pain hypersensitivity and other symptoms.

Key Gender-Related Factors:

1. Higher fibromyalgia prevalence in females
2. Greater resting thermogenesis in females
3. Reduced BAT recruitment in response to stress in females
4. Possible link between impaired stress-induced thermogenesis and fibromyalgia symptoms

Comorbid Conditions and Their Impact on Brown Adipose Tissue Function

Many conditions that frequently occur alongside fibromyalgia can compromise BAT activity, making it less responsive to sympathetic nervous system stimulation. This reduced BAT responsiveness may contribute to several characteristics observed in fibromyalgia patients:

• Lower body temperatures
• Reduced metabolic rates
• Lower circulating cortisol/corticosterone levels in response to stress

These physiological changes could potentially exacerbate pain sensitivity and other fibromyalgia symptoms. Understanding how comorbid conditions affect BAT function may provide new avenues for managing fibromyalgia more effectively.

The Peripheral Nervous System Connection: Sympathetic Nerves and Tender Points

In the periphery of the body, sympathetic nerves that innervate BAT also project to surrounding tissues, including the tender points that characterize fibromyalgia. This anatomical relationship suggests a potential mechanism for referred pain in fibromyalgia.

Is it possible that the musculoskeletal hyperalgesia associated with fibromyalgia results from referred pain in the adjacent muscle and skin tissues? This hypothesis could explain why fibromyalgia patients experience pain in specific tender point locations that correspond to areas of BAT distribution.

Potential Mechanisms of Referred Pain in Fibromyalgia:

1. Sympathetic nerve projections from BAT to surrounding tissues
2. Overlap between BAT distribution and fibromyalgia tender points
3. Possible sensitization of nearby muscle and skin due to BAT activity
4. Referred pain as a contributor to widespread musculoskeletal discomfort

Thermoregulation and Pain Modulation: Shared Brain Regions

The regulation of thermogenesis and pain share several areas in the brain where they may influence each other. This overlap in neural circuitry provides a potential explanation for the close relationship between temperature sensitivity and pain perception in fibromyalgia.

Key brain regions involved in both thermoregulation and pain processing include:

• Hypothalamus
• Periaqueductal gray matter
• Insula
• Anterior cingulate cortex

These shared neural pathways may allow temperature changes to directly modulate pain signaling, and vice versa. Understanding these interactions could lead to novel therapeutic approaches that target both temperature regulation and pain perception simultaneously.

Therapeutic Implications: Targeting Sympathetic Nervous System Activity

The connection between sympathetic nervous system activity, BAT function, and fibromyalgia symptoms suggests potential therapeutic strategies. One intriguing approach involves modulating sympathetic outflow to reduce pain.

For example, injections of local anesthetic into stellate ganglia (sympathetic projections to subclavicular BAT) have been shown to reduce pain in fibromyalgia patients. This intervention may work by interrupting the sympathetic signaling that contributes to both BAT activation and pain sensitization.

Other Potential Therapeutic Approaches:

1. Extended exercise programs: These have been shown to relieve fibromyalgia symptoms, improve thermoregulation, decrease adrenergic activity, and inhibit BAT recruitment.
2. Temperature-based therapies: Applying warmth to specific body regions may help suspend BAT thermogenesis and provide pain relief.
3. Pharmacological interventions: Developing drugs that target the sympathetic nervous system or BAT activity could offer new treatment options.
4. Stress reduction techniques: Since stress activates BAT and exacerbates symptoms, stress management may be crucial for symptom control.

By targeting the complex interplay between thermoregulation, sympathetic nervous system activity, and pain perception, these approaches may offer more effective relief for fibromyalgia patients.

Future Directions in Fibromyalgia Research

The potential link between thermoregulation, BAT activity, and fibromyalgia pain opens up exciting new avenues for research. Future studies should focus on:

• Investigating the precise mechanisms by which temperature changes influence pain signaling in fibromyalgia patients
• Exploring gender differences in BAT function and their relationship to fibromyalgia prevalence
• Developing imaging techniques to visualize BAT activity in relation to pain perception
• Examining the effects of various thermal interventions on fibromyalgia symptoms
• Investigating the role of comorbid conditions in modulating BAT function and pain sensitivity

By delving deeper into these areas, researchers may uncover new insights into the pathophysiology of fibromyalgia and develop more targeted and effective treatments.

Understanding the complex relationship between thermoregulation and pain modulation in fibromyalgia could revolutionize our approach to managing this challenging condition. As we continue to unravel the connections between temperature sensitivity, brown adipose tissue activity, and chronic pain, we move closer to providing better relief and improved quality of life for those living with fibromyalgia.

Review of overlap between thermoregulation and pain modulation in fibromyalgia

Clin J Pain. Author manuscript; available in PMC 2015 Jun 1.

Published in final edited form as:

PMCID: PMC3864605

NIHMSID: NIHMS508071

, Ph.D.,^a,*, M.D., Ph.D.,^b,c and , Ph.D.^d

Alice A. Larson

^aDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul MN, USA

José V. Pardo

^bMental Health Patient Service Line, VA Medical Center, Minneapolis, MN, USA

^cDepartment of Psychiatry, University of Minnesota, Minneapolis, MN, USA

Jeffrey D. Pasley

^dDepartment of Physiology and Pharmacology, University of Minnesota, Duluth, MN, USA

^aDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul MN, USA

^bMental Health Patient Service Line, VA Medical Center, Minneapolis, MN, USA

^cDepartment of Psychiatry, University of Minnesota, Minneapolis, MN, USA

^dDepartment of Physiology and Pharmacology, University of Minnesota, Duluth, MN, USA

^*aCorresponding author, University of Minnesota, Department of Veterinary and Biomedical Sciences, 1988 Fitch Avenue Room 295 Animal Science/Veterinary Medicine Building, St. Paul, Minnesota 55108 U.S.A., *Tel.: 612-624-3650, fax: 612-625-0204, ude.nmu@110osral (A.A. Larson)^bCognitive Neuroimaging Unit (11P), Mental Health PSL, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417 U.S.A., Tel.: 612-725-2000, X3164, fax: 612-725-2249, ude.nmu@odrapvj^dUniversity of Minnesota Medical School-Duluth, Department of Physiology and Pharmacology, 1035 University Drive Rm 329, Duluth, MN 55812, Tel.: 218-726-6657, fax: 218-726-7906, ude.nmu.d@yelsapjThe publisher’s final edited version of this article is available at Clin J PainSee other articles in PMC that cite the published article.

Abstract

Fibromyalgia syndrome is characterized by widespread pain that is exacerbated by cold and stress but relieved by warmth. We review the points along thermal and pain pathways where temperature may influence pain. We also present evidence addressing the possibility that brown adipose tissue activity is linked to the pain of fibromyalgia given that cold initiates thermogenesis in brown adipose tissue via adrenergic activity, while warmth suspends thermogenesis. Although females have a higher incidence of fibromyalgia as well as more resting thermogenesis, they are less able to recruit brown adipose tissue in response to chronic stress than males. In addition, conditions that are frequently comorbid with fibromyalgia compromise brown adipose activity making it less responsive to sympathetic stimulation. This results in lower body temperatures, lower metabolic rates, and lower circulating cortisol/corticosterone in response to stress – characteristics of fibromyalgia. In the periphery, sympathetic nerves to brown adipose also project to surrounding tissues, including tender points characterizing fibromyalgia. As a result, the musculoskeletal hyperalgesia associated with conditions like fibromyalgia may result from referred pain in the adjacent muscle and skin.

Keywords: Thermoregulation, Thermogenesis, Nociception, Adrenergic, Sympathetic, Catecholamine, Positron emission tomography, PET

Introduction

Fibromyalgia syndrome is a chronic condition characterized by musculoskeletal pain that persists for many years and is unresponsive to anti-inflammatory and analgesic compounds. ¹ In addition to decreased body temperature,² several characteristics of fibromyalgia syndrome suggest altered thermoregulatory activity. First, the distribution of brown adipose tissue (BAT) resembles that of tender points, anatomical locations that have been used to diagnose fibromyalgia.¹ This relationship may support referred pain in muscles similar to the referred pain of angina. Secondly, BAT activity at rest and the incidence of fibromyalgia are each relatively greater in females than males, whereas adaptive thermogenesis is greater in males than females.³,⁴ Thirdly, stress and cold each stimulate thermogenesis⁵ and aggravate symptoms of fibromyalgia,⁶ whereas warmth suspends thermogenesis and temporarily relieves the symptoms of fibromyalgia. Fourth, regulation of thermogenesis and pain share several areas in the brain where they may influence each other. Fifth, injections of a local anesthetic into stellate ganglia (sympathetic projections to subclavicular BAT) reduce pain in patients with fibromyalgia. ⁷ Sixth, extended programs of exercise relieve symptoms of fibromyalgia, improve thermoregulation,⁸–¹⁰ decrease adrenergic activity, and inhibit recruitment of BAT. Based on these associations, we examine here the possible overlap between thermoregulation and the modulation of nociception that are consistent with the symptoms of fibromyalgia.

We include information from studies that address the overlap in circuitry of thermoregulatory and pain pathways with a focus on how these topics may relate to our current knowledge of the biological characteristics of fibromyalgia. The result is a literature review that is not intended to be comprehensive as excellent reviews of thermoregulation and of fibromylaglia already exist. Instead, this review highlights multiple areas that warrant additional study to delineate the nature of the relationship between fibromyalgia and thermoregulation.

Fibromyalgia syndrome

After exclusion of other painful disorders, the widespread pain of fibromyalgia is characterized by pain in spite of an absence of gross pathology at these or the surrounding large areas of hyperalgesia. While newer diagnostic criteria are proposed,¹⁰ the sensitivity and number of tender points out of 18 specific anatomical locations () remain a useful investigative tool. These 18 points are distributed symmetrically on the trunk and proximal regions of limbs rather than areas that are usually more sensitive to tactile stimulation in healthy individuals, such as hands, feet, genitals, and mouth.¹¹,¹² Pain is not restricted to tender points; rather, the location of tender points was selected based upon their relative insensitivity to palpation in healthy normal controls. In contrast, only slight pressure at these sites often induces pain in patients with fibromyalgia. Hormones may be important as fibromyalgia is more common in women than in men, and pain sensitivity in healthy women varies over the menstrual cycle.¹³

Comparison between the location of tender points and BAT depots in humans. Panel A shows the location of the 18 tender points, located symmetrically, used to characterize the pain of fibromyalgia (http://www. niams.nih.gov/Health_Info/Fibromyalgia/default.asp). Panel B shows the PET scan of an individual taken during exposure to cold (left panel of ), when BAT tissue is active and visible, compared to when exposed to thermoneutral conditions (right panel of ) (from Lichtenbelt, Vanhommerig, Smulders, Drossaerts, Kemerink, Bouvy, Schrauwen and Teule).⁸⁹

Patients with fibromyalgia often report physical or emotional trauma prior to the onset of their condition,¹⁴ and stress exacerbates their symptoms. Patients are plagued by non-restorative sleep,¹⁵,¹⁶ fatigue,¹ cold intolerance,¹⁷ and neuroendocrine abnormalities¹¹ including abnormally high heart rate, low metabolic rate, low body temperature, and decreased temperature and vasoconstriction in skin over tender points.² There is also a high prevalence of obesity,¹⁸,¹⁹ insulin resistance,²⁰ and hyperlipidemia.²⁰ Their pain appears sensitive to sympatholytic maneuvers and rekindles upon injection with norepinephrine. ²¹ Except in a single study,²²polymorphisms in catechol-O-methyl transferase have been linked to fibromyalgia,²³–²⁷ raising the possibility that faulty degradation of catecholamines increases the risk of developing fibromyalgia.

In healthy individuals, acute stress can either increase or decrease pain perception, depending on how stress affects various secreted proteins and their receptors. In patients with fibromyalgia syndrome, minor daily stresses, particularly cold stress, frequently exacerbate the symptoms of fibromyalgia. Conditioned pain modulation [CPM, previously called diffuse noxious inhibitory controls (DNIC)] can be measured in humans to assess pain sensitivity after immersion of their arms in hot (47°C)²⁸ or cold (12°C)⁶ water. Healthy individuals perceive pain more in ascending trials when progressively greater areas of the arm are dipped into water, than when the whole arm is initially immersed and thereafter incrementally less surface area exposed. This suggests recruitment of inhibitory systems by immersion of the whole arm. That fibromyalgia patients fail to perceive this difference between the two types of exposure suggests a deficit of endogenous pain inhibitory activity.²⁹,³⁰ After the arm is withdrawn, pain induced by the cold water persists longer in fibromyalgia patients than in controls.

In cerebrospinal fluid from patients with fibromyalgia, there is an increased concentration of substance P,³¹,³² dynorphin,³³ and nerve growth factor (NGF).³⁴ In the serum, brain-derived neurotrophic factor (BDNF), the trophic factor that establishes mechanosensitivity of sensory nerves in the adult, is elevated.³⁵ There is no obvious tissue damage in areas of the body that are reported as painful.³⁶ Although peripheral defects have been identified,³⁷ fibromyalgia is primarily attributed to hypersensitized pain pathways in the brain or spinal cord. ³⁸ Yet none of the proposed central or peripheral defects explains the unique distribution of mechanical hypersensitivity, i.e. in and near the trunk, characteristic of fibromyalgia pain.

While stress increases the severity of their symptoms,³⁹–⁴³ patients’ hypothalamic-pituitary-adrenal (HPA) responses to stress are attenuated.⁴⁴ In contrast, their resting adrenergic activity remains high⁴⁵ resulting in a diminished heart rate variability, especially at night.⁴⁵ Corticotropin-releasing factor (CRF) together with enhanced sympathetic tone⁴⁵ may underpin the characteristic sleep disturbances and elevated heart rate in these patients. Others report reduced epinephrine responses to hypoglycemia,⁴⁴ yet an intravenous injection of interleukin-6 in patients with fibromyalgia dramatically increases norepinephrine more than in healthy controls.⁴⁶

There is a high comorbidity between fibromyalgia and other painful or inflammatory disorders. For example, patients with fibromyalgia have a higher incidence of ulcerative colitis (19%),⁴⁷ irritable bowel syndrome (about 70%),⁴⁸–⁵¹ interstitial cystitis,⁵²,⁵³ vulvodynia,⁵⁴ migraines (35.6%),⁵⁵ Sjögren’s syndrome,⁵⁶ and endometriosis⁵⁷ than general female populations. The incidence of fibromyalgia in people with Crohn’s disease is reported to be as high as 49%⁴⁷ or as low as 3%.⁵⁸ These comorbidities may be due to similar etiologies, as previously proposed for migraine and fibromyalgia.⁵⁹ Alternatively, they may result from viscerosomatic convergence on second order dorsal horn neurons in the spinal cord⁶⁰ and thalamic neurons⁶¹,⁶² allowing somatic afferent activity to influence visceral sensations, and vice versa.⁶³ This hypothesis, however, does not explain why patients with inflammatory disorders do not all develop fibromyalgia.

Exercise alleviates fibromyalgia, improving a variety of its symptoms. Even in healthy individuals aerobic exercise decreases blood pressure,⁶⁴ lowers resting heart rate,⁶⁵ increases heart rate variability,⁶⁶ increases vagal tone,⁶⁷ and decreases sympathetic tone.⁶⁸ Individuals who regularly exercise have increased basal metabolic rates,⁶⁹ lower white adipose tissue,⁷⁰ greater baseline cortisol concentrations, and an increased response to stress-induced release of cortisol.⁷¹ Moreover, regular exercise improves sleep patterns,⁷² and lessens physical and mental fatigue.⁷³ It improves circulation to muscles, skin and organs⁶⁷,⁷⁴ and lowers the risk of obesity or diabetes by improving the regulation of insulin and blood glucose.⁷⁵ Exercise not only increases bowel motility in normal individuals,⁷⁶ it improves symptoms associated with irritable bowel syndrome,⁷⁷ a condition frequently diagnosed in patients with fibromyalgia.

Brown adipose tissue (BAT)

BAT is distributed in areas of the body that maintain body temperature in the face of cold exposure by a process referred to as nonexercise thermogenesis.⁷⁸,⁷⁹ In addition to its characteristic distribution, primarily in interscapular (rodents) or supraclavicular (humans) depots, it can also be found in the supra axial and perirenal areas; in striations of skeletal muscle; between the skin and underlying muscle; and on top of sympathetic ganglia (). BAT does not store fat and glucose but uses them to generate heat. Vascular convection carries this heat to adjacent vital organs, such as the thoracocervical regions of the spinal cord, heart, and other thoracic organs. BAT undergoes ‘recruitment’ (increased mass) in response to repeated cold, diets chronically high in calories, or repeated stress. Cross-adaptation between cold and stress (e.g., immobilization of rats) enhances thermogenesis,⁵ whereas increasing age in rats⁸⁰ and corticosteroid administration in mice⁸¹,⁸² reduce thermogenic activity and thermal capacity of BAT.

Although non-shivering thermogenesis induced by cold and stress prevails in many nonhuman primates, it was previously thought inactive in human adults. However, residual BAT remains in most humans.⁸³ When active, BAT takes up ¹⁸F-fluorodeoxyglucose and is visible in and interferes with positron emission tomography (PET), motivating practices that decrease thermogenesis during routine scans. Visualization of BAT on PET scans is decreased by a high fat, very-low-carbohydrate, protein-permitted diet for 5 hr before scans at a normal room temperature⁸⁴ by suppressing glucose metabolism.⁸⁵ Though found primarily in cervical-supraclavicular depots, BAT is widely distributed, but few PET scans taken at 22°C (72°F) reveal BAT when analyzed retrospectively (only 7.5% of women and 3.1% of men),⁸⁶ likely due to fasting prior to scans. Other PET studies report higher percentages, ranging from 25% of patients with visible BAT⁸⁷ to more than 80%⁸⁸ when taken at room temperature. One autopsy series identified BAT in the necks of 84% of patients over the age of 20,⁸³ indicating that this tissue is generally retained into adulthood. Consistent with this, BAT is readily apparent in PET scans in men exposed to 16°C (61°F) cold temperatures prior to their scan.⁸⁹

Thermogenesis is initiated by enhanced sympathetic activity to BAT.⁹⁰ Norepinephrine turnover is higher in cold-acclimated rats than in rats kept at thermoneutrality, reflecting a high sympathetic tone under cold conditions. The released norepinephrine acts at α₂– and β₃-adrenergic receptors, causing production of heat in areas surrounding vasculature leading to vital organs. While β-adrenergic receptors increase thermogenesis and adenosine 3′,5′-cyclic monophosphate (cAMP) production in humans, α_2A-receptors decrease them,⁹¹ such that the balance between α₂– and β₃-receptor activity is key. Cold, stress, or overfeeding initiate sympathetic activity, increasing release of norepinephrine and β-adrenergic activity. Chronically, they increase lipolysis; raise thermogenic activity; induce uncoupling protein (UCP) expression; and recruit BAT. After cold adaptation in hamsters, although the noradrenergic system is tonically activated, the sensitivity of BAT to norepinephrine decreases due to down-regulation of adrenergic receptors,⁹²–⁹⁴ especially β₃-receptors in rats,⁹⁵ and G_s-protein,⁹⁶ limiting adrenergic activity.

Thermogenic activity contributes to metabolic activity, temperature regulation, and regulation of body weight. During thermogenesis, adrenergic stimulation of lipolysis in BAT produces fatty acids that are channeled into the mitochondrial β-oxidation pathway. Lipid oxidation in turn leads to increased NADH and FADH₂ production and electron transport chain-dependent proton pumping producing an increased proton gradient across mitochondrial inner membranes. Such a gradient is dissipated by ATPase or by uncoupling proteins (UCPs) that facilitate proton leak and heat production. Although several UCPs have been identified, only UCP1, found in BAT, takes part in thermogenesis. UCP2 is distributed in many tissues, including the brain and primary afferent fibers,⁹⁷ areas involved in temperature regulation whereas UCP3 is localized in skeletal and cardiac muscle.

The likelihood of having substantial BAT activity at rest is threefold greater in women than in men, indicating a greater resting thermogenesis in females. The greater mass of BAT and greater percent of their body devoted to BAT suggest that women have a high thermogenic capacity as well as activity.⁸⁶ Physiologic concentrations of female sex hormones promote, while testosterone inhibits, thermogenesis. While ovarectomy decreases UCP1 in BAT,⁹⁸ estrogen increases BAT fat pads and oxygen consumption in rats.⁹⁹ Estrogen and progesterone each increase β₃-adrenergic receptors, while there are lower levels of inhibitory α_2A-adrenergic receptors in female than in male rats. ⁴ This higher ratio of β₃– to α₂-receptors may be key to the higher basal thermogenic capacity and resting expression of UCP1 in females.

Gender influences the recruitment of BAT in rats in response to chronic cold¹⁰⁰ and chronic overfeeding.¹⁰¹ There is a greater thermogenic capacity and a lesser body weight gain in males than in females after chronic feeding, chronic cold or chronic stress. This suggests “induced” thermogenic activity is lower in females than in males. High concentrations of estrogen inhibit cold-induced thermogenesis in rats¹⁰² in spite of similar sympathetic activity (norepinephrine turnover) across sexes during cold acclimation.¹⁰³ There is a preferential recruitment of β3-receptors by norepinephrine, resulting in higher levels of β₃-adrenergic receptors in male than in female rats. In chronic situations, the high ratio of β₃– to α_2A-activity in males likely sustains their greater thermogenic capacity in rats³ and recruitment of BAT in mice. ¹⁰⁴

An important therapeutic intervention in patients with fibromyalgia is a sustained pattern of gradually increased daily exercise. Acutely, physical activity generates heat in skeletal muscle and inhibits thermogenesis in BAT. However, the effect of chronic exercise training on BAT is unclear. In mice, BAT activity and mass were unchanged by swim-training,¹⁰⁵ whereas more frequent daily swims increased the mass of BAT in mice.¹⁰⁶ In Wistar-Shizouka Takagi rats, intermittent training produced no change in BAT activity (treadmill),¹⁰⁷ while more continuous training programs decreased BAT mass in Wistar rats (treadmill)¹⁰⁸ and Sprague-Dawley rats (swimming).¹⁰⁹ To resolve these conflicting results, de Castro and Hill¹¹⁰ speculated that exercise can be a stressor, and thereby increase sympathetic activity to BAT. Using voluntary running of rats, their results were consistent with those in humans indicating that as physical activity increases, the metabolic activity of BAT also increases, generally improving thermoregulation. ⁹,¹¹¹ At temperatures that normally induce recruitment in rats, chronic exercise eliminates the recruiting effect of cold.¹¹²–¹¹⁴ In summary, exercise prevents recruitment of BAT.

Association of BAT with fibromyalgia

Basal thermogenic activity and a predisposition to having fibromyalgia are greater in females than in males. Thermogenic activity is increased by the same conditions that exacerbate the symptoms of fibromyalgia, i.e. cold and mild daily stress. In contrast, thermogenic activity and symptoms of fibromyalgia are minimized by warmth and by gradually increasing daily exercise. Yet patients generally have sluggish rather than stimulated rates of metabolism. Lower than anticipated thermogenic responses to cold mimic the tendency for these patients to have relatively low basal concentrations of circulating cortisol and attenuated cortisol responses to stress in spite of excessive activation of the HPA axis.⁴¹ The following summarize thermoregulatory and nociceptive processing () that may overlap, supporting abnormal responses in patients with fibromyalgia to stress and cold.

Table 1

Substrate	Thermoregulation	Nociception
Sympathetic nerve	Activates BAT Dilates blood vessels in muscle	Constricts vessels in skin Sensitizes primary afferents to pain
Primary afferent C-fibers	Detects heat in BAT Inhibits thermogenesis Detects heat in muscle and skin	Detects pain in muscle and skin
TRPV1 receptors	Thermodetectors	Sensitize nociceptors
Substance P	Dilates vesssels in periphery Initiates cooling centrally	Sensitizes C-fibers directly Sensitizes indirectly (mast cells)
Nerve growth factor	Supports sympathetic fibers (BAT)	Supports primary afferent C-fibers Increases substance P, TRPV1, etc
Subcortical areas
Parabrachial nucleus:	Receives temperature input	Receives tactile & visceral input
DMH:	On-cells inhibit BAT activity	On-cells support hyperalgesia
Cortical areas
Insula:	Associated with skin temperature variation	Abnormal somesthesis in FMS Autonomic & visceral pain
VMPFC:	Crossroad for temperature Integrates interoceptive information Activated by self-referential processing e. g., angina activates	Crossroad for pain Reduced gray matter in FMS
Amygdala:	Signatures of emotion/thermal regulation Stress responses (e.g. sweating)	Reduced grey matter in FMS

Innervation of BAT and surrounding tissues

Although the pain of fibromyalgia is widespread, tender points have been traditionally tested in the diagnosis of fibromyalgia. Tender points have greater sensitivity to pain upon palpation in fibromyalgia patients compared to healthy controls. In humans, nerves projecting to BAT are located near regions surrounding tender points, primarily in the supraclavicular region, but also in supra axial, perirenal and subcutaneous areas. This anatomical overlap may provide collateral innervation of tissue adjacent to BAT, e. g., skin and muscle, by sympathetic and primary afferent nerves. Consistent with this, when BAT is activated by injections of adrenaline in rats, muscles surrounding interscapular BAT have greater blood flow than in muscles of the anterior limbs,¹¹⁵ indicating that adjacent tissues operate in synergy with BAT. Consistent with increased adrenergic tone to these areas, the temperature is lower in the skin above tender points,² suggesting that vasoconstriction and local hypoxia in skin coincides with vasodilation in muscle, as shown schematically in . Consistent with a possible simultaneous activation of BAT and skeletal muscle, UCP1 mRNA is detected in progenitor cells in human skeletal muscle and its expression is increased in vivo by PPARγ agonist treatment.¹¹⁶ As a result, sympathetic activity that induces thermogenesis is poised to induce hyperalgesia in tissues surrounding BAT by referred pain. Angina is a good example of referred pain perceived in non-cardiac structures as well as the heart. ¹¹⁷ The pain of angina overlaps unilaterally with some tender points associated with fibromyalgia consistent with their common innervation via stellate ganglia.

Activation of brown adipose tissue may support referred pain in a fashion similar to that during attacks of angina or during the processing of other internal signals (interoception). Schematic diagram of the possible circuitry linking brown adipose tissue to surrounding muscle and skin via collateral projections of sympathetic and primary afferent C-fibers. Visceral afferent information also projects upward in the neuraxis to the nucleus tractus solitarius (NTS) and paraventricular hypothalamus (PVH). In turn, the NTS projects to the PVH, central nucleus of the amygdala, PB, and the bed nucleus of the stria terminalis (BSST). The PVH has reciprocal connections with periaqueducal grey (PAG) and amygdala. The latter directly and indirectly modulates paralimbic cortices such as the ventromedial prefrontal cortex (VMPFC), anterior cingulate cortex (ACC) and insula thereby processing the emotional responses to pain and temperature proposed to be dysfunctional in fibromyalgia. In turn, the VMPFC has efferent modulatory projections to the PAG, hypothalamus (Hyp), and amygdala. Descending inhibitory control is exerted by the periaqueductal gray (PAG) and locus coeruleus (LC) via the rostroventral medulla (RVM) where ‘on’ and ‘off’ cells differentially modulate nociceptive signals entering at the spinal cord level.

Sympathetically-maintained pain

That sympathetically-maintained hyperalgesia¹¹⁸ contributes to pain in patients with fibromyalgia is evidenced by the ability of norepinephrine to cause pain in these patients.²¹ Consistent with this, local anesthetics applied to stellate sympathetic ganglia⁷ innervating BAT produces analgesia in patients with fibromyalgia. This suggests sensitization of adrenergic receptors or a failure of these sites to desensitize as they usually do in rats.⁹²–⁹⁴ Adrenergic receptors are upregulated and pronociceptive after sympathectomy, as shown by enhanced nociception produced by norepinephrine after removal of the superior cervical ganglion in rats. ¹¹⁹ Hyperalgesia can also be mediated by α₂-adrenergic receptors on postganglionic sympathetic nerves, such as after application of chloroform to rat paws,¹²⁰ or by increased expression of α₂-adrenergic receptors on primary afferent fibers,¹²¹ such as in rabbits after tissue injury.¹²¹,¹²² Capsaicin-sensitive thermal hyperalgesia in the rat depends on α₁-adrenergic receptors on primary afferent C-fibers¹²³ whereas mechanical hyperalgesia elicited by epinephrine injected intradermally in rats results from activation of G-protein-coupled β_2-adrenergic receptors on primary afferent fibers.¹²⁴ Large-diameter axotomized sensory neurons can be activated by sympathetic stimulation when nerve injury causes basket-like structures to sprout from sympathetic nerves within dorsal root ganglia of rats,¹²⁵ a hyperalgesic condition relieved rather than caused by sympathectomy. ¹²⁶

Primary afferent fibers

After adrenergic fibers activate BAT, primary afferent C-fibers detect heat generated¹²⁷ and feedback to inhibit BAT activity by releasing calcitonin gene-related peptide (CGRP) peripherally and centrally.¹²⁸ Paradoxically, during chronic cold, primary afferent C-fiber activity is needed to recruit BAT by adaptive thermogenesis (i.e. increased UCP1 synthesis and enhanced mass) as desensitization of these afferents prevents recruitment.¹²⁹ Sensitized primary afferent C-fibers projecting to BAT discharge at lower temperatures, enhancing feedback inhibition of thermogenesis (causing hypothermia) and simultaneously causing hyperalgesia in adjacent skin and muscle that is innervated by these sensitized collaterals. Based on the high pain sensitivity at tender points near areas of BAT together with abnormally low body temperature, the symptoms of fibromyalgia may result from sensitized primary afferent C-fibers innervating BAT and adjacent tissues¹²⁸ causing referred pain. Patients with fibromyalgia may respond abnormally to cold and stress as conditions that are frequently comorbid with fibromyalgia inhibit adaptive thermogenesis.

Sensitization

Sensitization of primary afferent C-fibers may occur due to activation of capsaicin-sensitive, transient receptor potential vanilloid (TRPV1) receptors on nociceptors and on temperature-sensing afferents. TRPV1 antagonists induce hyperthermia in rat¹³⁰ indicating these receptors remain tonically active in mammals to protect against hot temperatures causing tissue damage. This tone is provided by oxidized linoleic acid metabolites (OLAMs), such as 9- and 13-HODE acids. OLAMs activate TRPV1 sites on nociceptors causing hyperalgesia^131,132 and elicit a sensation of warmth but decrease body temperature.¹³³ Low doses of TRPV1 agonists enhance pain,^133,134 but high doses desensitize TRPV1 sites. OLAMs are also ligands of PPARγ receptors whose activity is necessary for adaptive thermogenesis. ¹³⁵ By altering concentrations of 9- or 13-HODE, chronic defeat stress in rodents not only causes hyperthermia¹³⁶ and increases UCP1 mRNA,¹³⁷ it also increases thermal^138,139 and mechanical hyperalgesia.¹⁴⁰ Chronic inflammation also increases expression of TRPV1 receptors.¹⁴¹ which could account for both the lower body temperature and mechanical hyperalgesia in fibromyalgia patients as various inflammatory conditions are frequently comorbid with fibromyalgia. Capsaicin-induced hyperalgesia even correlates with overall pain scores in these patients.¹⁴²

Substance P

Substance P, released from primary afferent C-fibers transmitting pain or temperature, causes vasodilation in skin to dissipate heat and induces hyperalgesia. Centrally, substance P sensitizes nociceptive pathways and initiates cooling behaviors.^133,143 Although the high concentration of substance P in the cerebrospinal fluid of patients with fibromyalgia has been postulated to originate from nociceptive fibers, it may originate instead from temperature-sensitive fibers. Regardless of its origin, elevated substance P may account for lower body temperatures and hyperalgesia in patients with fibromyalgia. One model of fibromyalgia based on repeated exposures of rodents to cold¹⁴⁴ depends on spinal substance P activity for hyperalgesia.¹⁴⁵ If substance P decreases body temperature below normal, this may trigger thermogenic activity, enhancing sympathetic tone to BAT. Thus pain may result from the combined effect of substance P along nociceptive pathways together with sympathetically-mediated hyperalgesia in skin and muscle surrounding BAT, similar to the pain of angina.¹¹⁷

Nerve growth factor (NGF)

NGF, elevated in the cerebrospinal fluid of patients with fibromyalgia,³⁴ produces thermal and mechanical hyperalgesia in rodents^146,147 and humans when injected centrally¹⁴⁸ or peripherally into muscle.¹⁴⁹ Sympathetic nerves and primary afferent C-fibers each depend on NGF in target tissues for survival and specialization. ¹⁵⁰ There is competition between adrenergic- and primary afferent C-fibers for NGF in tissues where both exist. Normally NGF originates from target tissues and is transported retrogradely to dorsal root ganglia where it regulates protein synthesis (e.g. substance P and CGRP),¹⁵⁰ including TRPV1 receptors.¹⁵¹ Destruction of one fiber type increases availability of NGF to remaining fibers. For example, postganglionic sympathectomy increases CGRP and substance P¹⁵² due to enhanced NGF along nociceptors in rat.¹⁵³ Sympathectomy increases¹⁵⁴ while sympathetic activity decreases NGF synthesis in rats and mice.^155,156 NGF in mice causes aberrant growth of peripheral ganglia as well as abnormal sympathetic innervation of sensory ganglia^157,158 together with hyperalgesia. In summary, NGF might contribute to the hyperalgesia of fibromyalgia by increasing substance P or TRPV1 receptors and/or by promoting sympathetic tone. ^31,32

Subcortical areas

Of nuclei involved in thermoregulation,¹⁵⁹ the parabrachial, raphe pallidus (RP), and dorsomedial hypothalamus (DMH) are also involved in nociception.^160,161 This convergence may allow thermoregulatory signals to influence nociception. Disinhibition of the DMH activates rostroventral medulla (RVM) ON-cells and suppresses RVM OFF-cell firing causing hyperalgesia in rats.¹⁶² Blocking serotonergic ON-cell activity prevents hyperalgesia, but does not interfere with thermogenesis, suggesting differentiation of autonomic and nociceptive transmission. Non-serotonergic ON-cells facilitate nociception but inhibit BAT activity whereas OFF-cells suppress nociceptive transmission^163,164 and potentiate BAT activity in rat.¹⁶⁵ Although pain and opioids each influence thermogenesis,¹⁶⁵ it is not known whether thermogenesis influences pain such that ON-cells, activated by thermogenesis, potentiate nociception as well as inhibit thermogenic activity. Opioid receptors contribute to antinociception by acting as are pattern generators in RVM raphe nuclei,¹⁶⁶ where mu opioid agonists decrease ON-cell activity and increase OFF-cell activity.^167–170 In contrast, kappa opioid agonists increase nociception in rats by suppressing OFF-cells.¹⁷¹ Repeated cold exposure in mice, similar to that modeling fibromyalgia,¹⁴⁴ increases the pronociceptive effect of kappa opioids¹⁷² and decreases the antinociceptive effect of mu opioid receptors, which are also down-regulated in fibromyalgia.¹⁷³

Thermoregulatory and nociceptive pathways also converge at the parabrachial nucleus receiving somatosensory signals from spinothalamic and trigeminothalamic lamina I neurons in the rat.^174,175 Rat lamina I neurons¹⁶⁰ project specifically to parabrachial neurons responding to cooling¹⁷⁶ and to noxious stimuli,¹⁷⁷ as well as to polymodal nociceptive cells responding to noxious mechanical heat and cold stimuli. ¹⁷⁸ Whereas some neurons respond primarily to cool signals from skin,¹⁷⁹ the majority of parabrachial neurons respond to both tactile and visceral and/or temperature input.¹⁸⁰ Following chronic cold or stress, thermoregulatory and nociceptive signals activate common sites, as indicated by c-fos labeling in rats,¹⁸¹ increasing the role of parabrachial neurons in situations that recruit BAT. The parabrachial nucleus is a major relay for visceral inputs from the nucleus tractus solitarius to the forebrain.¹⁸² This raises the possibility that parabrachial neurons transmit the visceral nociceptive input of abdominal disorders (like irritable bowel syndrome and interstitial cystitis that are common in fibromyalgia) to widespread nociceptive areas.

Cortical Integrators

Cortical areas implicated in fibromyalgia include the insula, amygdala, ventromedial prefrontal cortex (VMPFC), and anterior cingulate cortex (ACC) (). They are frequently referred to in aggregate as limbic/paralimbic cortex; they activate in response to many emotions or when affective processing is required. These regions are involved in the processing of thermal and nociceptive information, perhaps influencing their affective quality. At least some components of these networks appear dysfunctional in fibromyalgia.

The insula is the principal cortical convergence zone for the processing of internal signals that monitor the body’s physiological state (e.g., pH, visceral pressures and motility, heart rate, body temperature).¹⁸³ The insula, also described as interoceptive cortex, modulates conditions within the body. For example, the human insula activates in response to visceral pain,^184,185 and insular infarcts can cause severe hypothermia.¹⁸⁶ Decreased metabolism of the insula occurs in healthy subjects who have detectable BAT and are exposed to environmental heat.¹⁸⁷ Insular activity also correlates inversely with the thermal response during hot flashes induced by adjuvant endocrine therapies¹⁸⁸ and plays a critical role in thermal responses to emotional processing. Human thermosensory cortex lies in the dorsal margin of the middle/posterior insula¹⁸⁹ and activity in the posterior insula participates in processing abnormal somatosensory feedback in fibromyalgia,¹⁹⁰ similar to its role in monkeys.¹⁹¹ Together, the anterior insula and amygdala play a prominent role in anxiety and stress,^192–194 activating in response to aversive sensory stimuli.^{162,195–197}

The ACC also participates in pain and temperature processing. Pressure on the thumb at levels that only activate somatosensory cortex in healthy controls also activate the ACC in patients with fibromyalgia.¹⁹⁸ The VMPFC further connects the ACC, amygdala, and insula to integrate internal signals.¹⁹⁹ Dysfunctional processing of such information is a component of fibromyalgia. For example, the VMPFC monitors internal milieu and is activated by introspection, by self-referential processing²⁰⁰ and by the default mode state. ²⁰¹ Angina arising from cardiac ischemia activates the VMPFC.²⁰² Even self-monitoring one’s heart rate in the absence of angina activates the VMPFC.²⁰³ The VMPFC is the origin of galvanic skin responses, reflecting a component of somatic markers involved in decision-making.²⁰³ Lesions of the VMPFC impair decision-making, reflecting dysfunctional processing of somatic markers.^204,205 The VMPFC plays a role in sickness-related mood changes reflecting a possible overlap between fibromyalgia and depressive symptoms.²⁰⁶ Fibromyalgia patients have reduced grey matter in the VMPFC and amygdala²⁰⁷ similar to that in patients with chronic pain.²⁰⁸ Such structural abnormalities can result from chronic abnormal metabolic activity perhaps through excitotoxic mechanisms.²⁰⁹ Fibromyalgia patients differ from controls in affective processing (acoustic startle eyeblink reflex) mediated by the amygdala.²¹⁰ The VMPFC is also anatomically connected to the lateral and medial hypothalamus and periaqueductal grey,¹⁹⁹ making it a prime crossroad for mediating not only arousal and mood, but also pain and thermal regulation. Emotional arousal is associated with facial thermal signatures indicating an overlap between emotion and thermal regulation. Skin temperature variation in humans is associated with changes in activity within the insula, ACC, and VMPFC.²¹¹

Together these studies demonstrate a convergence of pain and temperature information upon central brain systems including the insula, amygdala, VMPFC, and ACC. These limbic and paralimbic structures are associated with emotion and may color the affective components of pain and sensory processing. Fibromyalgia appears to involve many of these regions.

Conclusions

This review summarizes the literature describing commonalities between the regulation of pain and temperature that may contribute to the widespread pain of fibromyalgia. Both fibromyalgia and thermoregulation are exquisitely sensitive to stress. Acute cold and stress increase the generation of heat by increasing UCP1 activity in BAT while chronically high sympathetic tone increases the synthesis of UCP1, increasing BAT volume (adaptive thermogenesis) to guard against persistent stress. The high sympathetic tone in patients with fibromyalgia aggravates their pain and should initiate adaptive thermogenesis, yet their temperature is lower than healthy individuals. This indicates either insufficient heat production or enhanced heat loss, the latter being unlikely as sympathetic tone tends to curb heat loss. Multiple points along pain and thermoregulatory pathways exist where they may influence each other. In the periphery, warmth and pain are both detected by primary afferent C-fibers that release substance P into the spinal cord, causing hyperalgesia, cooling behaviors and inhibition of BAT activity. In the brain, pain and temperature are regulated by overlapping pathways in subcortical and cortical areas. It is doubtful that body temperature alone influences nociception. Rather, the challenge of maintaining normal body temperatures in the face of acute cold or of initiating adaptive thermogenesis in response to chronic stress may be compromised by conditions that are comorbid with fibromyalgia. For example, inflammatory conditions inhibit the response of BAT to sympathetic stimulation while conditions that sensitize primary afferent C-fibers may prematurely terminate thermogenic activity by enhanced feedback inhibition of BAT, consistent with the lower body temperatures in patients with fibromyalgia. Women may be more susceptible to fibromyalgia because they are inherently less able to initiate adaptive thermogenesis than men. Insufficient activation of BAT may lead to even greater sympathetic tone, compounding the possibility of referred pain via collateral nerves projecting to areas surrounding BAT. Exercise may relieve symptoms of fibromyalgia and improve thermoregulation by gradually decreasing adrenergic activity and providing an alternate source of body heat.

​

Significance

This review summarizes multiple intersections between the regulation of nociception and temperature that may be relevant to fibromyalgia syndrome. The working hypotheses raised may contribute to the elucidation of the etiology of fibromyalgia.

Acknowledgements

The PET scan displayed was generously provided to us by Dr. Wouter D. van Marken Lichtenbelt. We extend special thanks to Ms. Allison Leuin, Drs. I. Jon Russell, Katalin J. Kovács, Tina Clarkson, Barbara Segal, and David Bernlohr for their input and helpful editorial comments on this manuscript. The authors declare no conflict of interest with any institution or company.

Support

AAL is supported by an NIH grant (AT056092) from the National Institutes on Arthritis and Musculoskeletal and Skin Diseases and by a grant from the University of Minnesota Graduate School. JVP is supported by the National Alliance for Research in Schizophrenia and Depression (NARSAD) and the Department of Veterans Affairs USA. JDP is supported by an NIH Institutional Research and Academic Career Development Award (IRACDA) grant (5K12GM074628) from the National Institute of General Medical Sciences.

Abbreviations

Footnotes

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

References

1. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33:160–172. [PubMed] [Google Scholar]2. Jeschonneck M, Grohmann G, Hein G, et al. Abnormal microcirculation and temperature in skin above tender points in patients with fibromyalgia. Rheumatology (Oxford) 2000;39:917–921. [PubMed] [Google Scholar]3. Rodriguez E, Monjo M, Rodriguez-Cuenca S, et al. Sexual dimorphism in the adrenergic control of rat brown adipose tissue response to overfeeding. Pflugers Arch. 2001;442:396–403. [PubMed] [Google Scholar]4. Rodriguez-Cuenca S, Pujol E, Justo R, et al. Sex-dependent thermogenesis, differences in mitochondrial morphology and function, and adrenergic response in brown adipose tissue. J Biol Chem. 2002;277:42958–42963. [PubMed] [Google Scholar]5. Kuroshima A, Habara Y, Uehara A, et al. Cross adaption between stress and cold in rats. Pflugers Arch. 1984;402:402–408. [PubMed] [Google Scholar]6. Julien N, Goffaux P, Arsenault P, et al. Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain. 2005;114:295–302. [PubMed] [Google Scholar]7. Bengtsson A, Bengtsson M. Regional sympathetic blockade in primary fibromyalgia. Pain. 1988;33:161–167. [PubMed] [Google Scholar]8. Pandolf KB. Effects of physical training and cardiorespiratory physical fitness on exercise-heat tolerance: recent observations. Med Sci Sports. 1979;11:60–65. [PubMed] [Google Scholar]9. Rowell LB. Human cardiovascular adjustments to exercise and thermal stress. Physiol Rev. 1974;54:75–159. [PubMed] [Google Scholar]10. Wolfe F, Clauw DJ, Fitzcharles MA, et al. Fibromyalgia Criteria and Severity Scales for Clinical and Epidemiological Studies: A Modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol. 2011;38:1113–1122. [PubMed] [Google Scholar]11. Bennett RM. Emerging concepts in the neurobiology of chronic pain: evidence of abnormal sensory processing in fibromyalgia. Mayo Clin Proc. 1999;74:385–398. [PubMed] [Google Scholar]12. Russell IJ. Advances in fibromyalgia: possible role for central neurochemicals. Am J Med Sci. 1998;315:377–384. [PubMed] [Google Scholar]13. Hapidou EG, Rollman GB. Menstrual cycle modulation of tender points. Pain. 1998;77:151–161. [PubMed] [Google Scholar]14. Buskila D, Neumann L. Musculoskeletal injury as a trigger for fibromyalgia/posttraumatic fibromyalgia. Curr Rheumatol Rep. 2000;2:104–108. [PubMed] [Google Scholar]15. Affleck G, Urrows S, Tennen H, et al. Sequential daily relations of sleep, pain intensity, and attention to pain among women with fibromyalgia. Pain. 1996;68:363–368. [PubMed] [Google Scholar]16. Moldofsky H, Scarisbrick P, England R, et al. Musculosketal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosom Med. 1975;37:341–351. [PubMed] [Google Scholar]17. Skuse D, Albanese A, Stanhope R, et al. A new stress-related syndrome of growth failure and hyperphagia in children, associated with reversibility of growth-hormone insufficiency. Lancet. 1996;348:353–358. [PubMed] [Google Scholar]18. Elert J, Kendall SA, Larsson B, et al. Chronic pain and difficulty in relaxing postural muscles in patients with fibromyalgia and chronic whiplash associated disorders. J Rheumatol. 2001;28:1361–1368. [PubMed] [Google Scholar]19. Okifuji A, Donaldson GW, Barck L, et al. Relationship between fibromyalgia and obesity in pain, function, mood, and sleep. J Pain. 2010;11:1329–1337. [PMC free article] [PubMed] [Google Scholar]20. Dessein PH, Shipton EA, Joffe BI, et al. High frequency of insulin resistence and hyperlipidemia in fibromyalgia. Ann Rheum Dis. 1999;58:137. [Google Scholar]21. Martinez-Lavin M, Vidal M, Barbosa RE, et al. Norepinephrine-evoked pain in fibromyalgia. A randomized pilot study [ISRCTN70707830] BMC Musculoskelet Disord. 2002;3:2. [PMC free article] [PubMed] [Google Scholar]22. Hagen K, Pettersen E, Stovner LJ, et al. No association between chronic musculoskeletal complaints and Val158Met polymorphism in the Catechol-O-methyltransferase gene. The HUNT study. BMC Musculoskelet Disord. 2006;7:40. [PMC free article] [PubMed] [Google Scholar]23. Cohen H, Neumann L, Glazer Y, et al. The relationship between a common catechol-O-methyltransferase (COMT) polymorphism val(158) met and fibromyalgia. Clin Exp Rheumatol. 2009;27:S51–56. [PubMed] [Google Scholar]24. Finan PH, Zautra AJ, Davis MC, et al. COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia. Pain. 2011;152:300–307. [PMC free article] [PubMed] [Google Scholar]25. Garcia-Fructuoso FR, Lao-Villadoniga JI, Beyer K, et al. Relación entre genotipos del gen catecol-o-metiltransferasa y la gravedad de la fibromialgia. Reumatol Clin. 2006;2:168–172. [PubMed] [Google Scholar]26. Gursoy S, Erdal E, Herken H, et al. Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome. Rheumatol Int. 2003;23:104–107. [PubMed] [Google Scholar]27. Martinez-Jauand M, Sitges C, Rodriguez V, et al. Pain sensitivity in fibromyalgia is associated with catechol-O-methyltransferase (COMT) gene. Eur J Pain. 2013;17:16–27. [PubMed] [Google Scholar]28. Marchand S, Arsenault P. Spatial summation for pain perception: interaction of inhibitory and excitatory mechanisms. Pain. 2002;95:201–206. [PubMed] [Google Scholar]29. Kosek E, Hansson P. Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects. Pain. 1997;70:41–51. [PubMed] [Google Scholar]30. Lautenbacher S, Rollman GB. Possible deficiencies of pain modulation in fibromyalgia. Clin J Pain. 1997;13:189–196. [PubMed] [Google Scholar]31. Russell IJ, Orr MD, Littman B, et al. Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum. 1994;37:1593–1601. [PubMed] [Google Scholar]32. Vaeroy H, Helle R, Forre O, et al. Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain. 1988;32:21–26. [PubMed] [Google Scholar]33. Vaeroy H, Nyberg F, Terenius L. No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7. Pain. 1991;46:139–143. [PubMed] [Google Scholar]34. Giovengo SL, Russell IJ, Larson AA. Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia. J Rheumatol. 1999;26:1564–1569. [PubMed] [Google Scholar]35. Laske C, Stransky E, Eschweiler GW, et al. Increased BDNF serum concentration in fibromyalgia with or without depression or antidepressants. J Psychiatr Res. 2007;41:600–605. [PubMed] [Google Scholar]36. Yunus MB, Kalyan-Raman UP, Masi AT, et al. Electron microscopic studies of muscle biopsy in primary fibromyalgia syndrome: a controlled and blinded study. J Rheumatol. 1989;16:97–101. [PubMed] [Google Scholar]37. Vierck CJ., Jr Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia) Pain. 2006;124:242–263. [PubMed] [Google Scholar]38. Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol. 2006;2:90–98. [PubMed] [Google Scholar]39. Clauw DJ, Chrousos GP. Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. 1997;4:134–153. [PubMed] [Google Scholar]40. Crofford LJ. Neuroendocrine abnormalities in fibromyalgia and related disorders. Am J Med Sci. 1998;315:359–366. [PubMed] [Google Scholar]41. Neeck G, Crofford LJ. Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am. 2000;26:989–1002. [PubMed] [Google Scholar]42. Riedel W, Schlapp U, Leck S, et al. Blunted ACTH and cortisol responses to systemic injection of corticotropin-releasing hormone (CRH) in fibromyalgia: role of somatostatin and CRH-binding protein. Ann N Y Acad Sci. 2002;966:483–490. [PubMed] [Google Scholar]43. Weigent DA, Bradley LA, Blalock JE, et al. Current concepts in the pathophysiology of abnormal pain perception in fibromyalgia. Am J Med Sci. 1998;315:405–412. [PubMed] [Google Scholar]44. Adler GK, Kinsley BT, Hurwitz S, et al. Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome. Am J Med. 1999;106:534–543. [PubMed] [Google Scholar]45. Martinez-Lavin M, Hermosillo AG, Rosas M, et al. Circadian studies of autonomic nervous balance in patients with fibromyalgia: a heart rate variability analysis. Arthritis Rheum. 1998;41:1966–1971. [PubMed] [Google Scholar]46. Torpy DJ, Papanicolaou DA, Lotsikas AJ, et al. Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia. Arthritis Rheum. 2000;43:872–880. [PubMed] [Google Scholar]47. Buskila D, Odes LR, Neumann L, et al. Fibromyalgia in inflammatory bowel disease. J Rheumatol. 1999;26:1167–1171. [PubMed] [Google Scholar]48. Barton A, Pal B, Whorwell PJ, et al. Increased prevalence of sicca complex and fibromyalgia in patients with irritable bowel syndrome. Am J Gastroenterol. 1999;94:1898–1901. [PubMed] [Google Scholar]49. Sivri A, Cindas A, Dincer F, et al. Bowel dysfunction and irritable bowel syndrome in fibromyalgia patients. Clin Rheumatol. 1996;15:283–286. [PubMed] [Google Scholar]50. Sperber AD, Atzmon Y, Neumann L, et al. Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications. Am J Gastroenterol. 1999;94:3541–3546. [PubMed] [Google Scholar]51. Veale D, Kavanagh G, Fielding JF, et al. Primary fibromyalgia and the irritable bowel syndrome: different expressions of a common pathogenetic process. Br J Rheumatol. 1991;30:220–222. [PubMed] [Google Scholar]52. Alagiri M, Chottiner S, Ratner V, et al. Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes. Urology. 1997;49:52–57. [PubMed] [Google Scholar]53. Clauw DJ, Schmidt M, Radulovic D, et al. The relationship between fibromyalgia and interstitial cystitis. J Psychiatr Res. 1997;31:125–131. [PubMed] [Google Scholar]54. Arnold LD, Bachmann GA, Rosen R, et al. Vulvodynia: characteristics and associations with comorbidities and quality of life. Obstet Gynecol. 2006;107:617–624. [PMC free article] [PubMed] [Google Scholar]55. Peres MF, Young WB, Kaup AO, et al. Fibromyalgia is common in patients with transformed migraine. Neurology. 2001;57:1326–1328. [PubMed] [Google Scholar]56. Kang JH, Lin HC. Comorbidities in patients with primary Sjogren’s syndrome: a registry-based case-control study. J Rheumatol. 2010;37:1188–1194. [PubMed] [Google Scholar]57. Nothnick WB. Novel targets for the treatment of endometriosis. Expert Opin Ther Targets. 2004;8:459–471. [PubMed] [Google Scholar]58. Palm O, Moum B, Jahnsen J, et al. Fibromyalgia and chronic widespread pain in patients with inflammatory bowel disease: a cross sectional population survey. J Rheumatol. 2001;28:590–594. [PubMed] [Google Scholar]59. Valenca MM, Medeiros FL, Martins HA, et al. Neuroendocrine dysfunction in fibromyalgia and migraine. Curr Pain Headache Rep. 2009;13:358–364. [PubMed] [Google Scholar]61. Willis WD, Al-Chaer ED, Quast MJ, et al. A visceral pain pathway in the dorsal column of the spinal cord. Proc Natl Acad Sci U S A. 1999;96:7675–7679. [PMC free article] [PubMed] [Google Scholar]62. Zhang HQ, Al-Chaer ED, Willis WD. Effect of tactile inputs on thalamic responses to noxious colorectal distension in rat. J Neurophysiol. 2002;88:1185–1196. [PubMed] [Google Scholar]63. Gebhart GF, Ness TJ. Central mechanisms of visceral pain. Can J Physiol Pharmacol. 1991;69:627–634. [PubMed] [Google Scholar]64. Whelton SP, Chin A, Xin X, et al. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136:493–503. [PubMed] [Google Scholar]65. Cole CR, Blackstone EH, Pashkow FJ, et al. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med. 1999;341:1351–1357. [PubMed] [Google Scholar]66. De Meersman RE. Heart rate variability and aerobic fitness. Am Heart J. 1993;125:726–731. [PubMed] [Google Scholar]67. Blomqvist CG, Saltin B. Cardiovascular adaptations to physical training. Annu Rev Physiol. 1983;45:169–189. [PubMed] [Google Scholar]68. Mueller PJ. Exercise training and sympathetic nervous system activity: evidence for physical activity dependent neural plasticity. Clin Exp Pharmacol Physiol. 2007;34:377–384. [PubMed] [Google Scholar]69. Poehlman ET. A review: exercise and its influence on resting energy metabolism in man. Med Sci Sports Exerc. 1989;21:515–525. [PubMed] [Google Scholar]70. Tremblay A, Despres JP, Bouchard C. The effects of exercise-training on energy balance and adipose tissue morphology and metabolism. Sports Med. 1985;2:223–233. [PubMed] [Google Scholar]71. Sinyor D, Schwartz SG, Peronnet F, et al. Aerobic fitness level and reactivity to psychosocial stress: physiological, biochemical, and subjective measures. Psychosom Med. 1983;45:205–217. [PubMed] [Google Scholar]72. Driver HS, Taylor SR. Exercise and sleep. Sleep Med Rev. 2000;4:387–402. [PubMed] [Google Scholar]73. Puetz TW, Flowers SS, O’Connor PJ. A randomized controlled trial of the effect of aerobic exercise training on feelings of energy and fatigue in sedentary young adults with persistent fatigue. Psychother Psychosom. 2008;77:167–174. [PubMed] [Google Scholar]74. Scheuer J, Tipton CM. Cardiovascular adaptations to physical training. Annu Rev Physiol. 1977;39:221–251. [PubMed] [Google Scholar]75. Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003;289:76–79. [PubMed] [Google Scholar]77. Daley AJ, Grimmett C, Roberts L, et al. The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial. Int J Sports Med. 2008;29:778–782. [PubMed] [Google Scholar]78. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–359. [PubMed] [Google Scholar]79. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293:E444–E452. [PubMed] [Google Scholar]80. Rothwell NJ, Stock MJ. Effects of Age on Diet-Induced Thermogenesis and Brown Adipose-Tissue Metabolism in the Rat. International Journal of Obesity. 1983;7:583–589. [PubMed] [Google Scholar]81. Aronson SM, Teodoru CV, Adler M, et al. Influence of cortisone upon brown fat of hamsters and mice. Proc Soc Exp Biol Med. 1954;85:214–218. [PubMed] [Google Scholar]82. Galpin KS, Henderson RG, James WP, et al. GDP binding to brown-adipose-tissue mitochondria of mice treated chronically with corticosterone. Biochem J. 1983;214:265–268. [PMC free article] [PubMed] [Google Scholar]84. Williams G, Kolodny GM. Method for decreasing uptake of 18F–FDG by hypermetabolic brown adipose tissue on PET. AJR Am J Roentgenol. 2008;190:1406–1409. [PubMed] [Google Scholar]85. Frayn KN. The glucose-fatty acid cycle: a physiological perspective. Biochem Soc Trans. 2003;31:1115–1119. [PubMed] [Google Scholar]86. Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–1517. [PMC free article] [PubMed] [Google Scholar]87. Dobert N, Menzel C, Hamscho N, et al. Atypical thoracic and supraclavicular FDG-uptake in patients with Hodgkin’s and non-Hodgkin’s lymphoma. Q J Nucl Med Mol Imaging. 2004;48:33–38. [PubMed] [Google Scholar]88. Rousseau C, Bourbouloux E, Campion L, et al. Brown fat in breast cancer patients: analysis of serial (18)F-FDG PET/CT scans. Eur J Nucl Med Mol Imaging. 2006;33:785–791. [PubMed] [Google Scholar]89. Lichtenbelt WDV, Vanhommerig JW, Smulders NM, et al. Cold-Activated Brown Adipose Tissue in Healthy Men. New England Journal of Medicine. 2009;360:1500–1508. [PubMed] [Google Scholar]90. Rothwell NJ, Stock MJ. Effects of denervating brown adipose tissue on the responses to cold, hyperphagia and noradrenaline treatment in the rat. J Physiol. 1984;355:457–463. [PMC free article] [PubMed] [Google Scholar]91. Lafontan M, Barbe P, Galitzky J, et al. Adrenergic regulation of adipocyte metabolism. Hum Reprod. 1997;12(Suppl 1):6–20. [PubMed] [Google Scholar]92. Nedergaard J. Catecholamine sensitivity in brown fat cells from cold-acclimated hamsters and rats. Am J Physiol. 1982;242:C250–257. [PubMed] [Google Scholar]93. Unelius L, Bronnikov G, Mohell N, et al. Physiological desensitization of beta 3-adrenergic responses in brown fat cells: involvement of a postreceptor process. Am J Physiol. 1993;265:C1340–C1348. [PubMed] [Google Scholar]94. Unelius L, Mohell N, Nedergaard J. Cold acclimation induces desensitization to adenosine in brown fat cells without changing receptor binding. Am J Physiol. 1990;258:C818–C826. [PubMed] [Google Scholar]95. Malo A, Puerta M. Oestradiol and progesterone change beta3-adrenergic receptor affinity and density in brown adipocytes. Eur J Endocrinol. 2001;145:87–91. [PubMed] [Google Scholar]96. Svoboda P, Unelius L, Cannon B, et al. Attenuation of Gs alpha coupling efficiency in brown-adipose-tissue plasma membranes from cold-acclimated hamsters. Biochem J. 1993;295(Pt 3):655–661. [PMC free article] [PubMed] [Google Scholar]97. Horvath B, Spies C, Warden CH, et al. Uncoupling protein 2 in primary pain and temperature afferents of the spinal cord. Brain Research. 2002;955:260–263. [PubMed] [Google Scholar]98. Pedersen SB, Bruun JM, Kristensen K, et al. Regulation of UCP1, UCP2, and UCP3 mRNA expression in brown adipose tissue, white adipose tissue, and skeletal muscle in rats by estrogen. Biochem Biophys Res Commun. 2001;288:191–197. [PubMed] [Google Scholar]99. Kemnitz JW, Glick Z, Bray GA. Ovarian hormones influence brown adipose tissue. Pharmacol Biochem Behav. 1983;18:563–566. [PubMed] [Google Scholar]100. Quevedo S, Roca P, Pico C, et al. Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue. Pflugers Arch. 1998;436:689–695. [PubMed] [Google Scholar]101. Roca P, Rodriguez AM, Oliver P, et al. Brown adipose tissue response to cafeteria diet-feeding involves induction of the UCP2 gene and is impaired in female rats as compared to males. Pflugers Arch. 1999;438:628–634. [PubMed] [Google Scholar]102. Puerta ML, Nava MP, Abelenda M, et al. Inactivation of brown adipose tissue thermogenesis by oestradiol treatment in cold-acclimated rats. Pflugers Arch. 1990;416:659–662. [PubMed] [Google Scholar]103. Nava MP, Fernandez A, Abelenda M, et al. Dissociation between brown adipose tissue thermogenesis and sympathetic activity in rats with high plasma levels of oestradiol. Pflugers Arch. 1994;426:40–43. [PubMed] [Google Scholar]104. Monjo M, Rodriguez AM, Palou A, et al. Direct effects of testosterone, 17 beta-estradiol, and progesterone on adrenergic regulation in cultured brown adipocytes: potential mechanism for gender-dependent thermogenesis. Endocrinology. 2003;144:4923–4930. [PubMed] [Google Scholar]105. Bell RR, McGill TJ, Digby PW, et al. Effects of dietary protein and exercise on brown adipose tissue and energy balance in experimental animals. J Nutr. 1984;114:1900–1908. [PubMed] [Google Scholar]106. Ueno N, Oh-ishi S, Kizaki T, et al. Effects of swimming training on brown-adipose-tissue activity in obese ob/ob mice: GDP binding and UCP m-RNA expression. Res Commun Mol Pathol Pharmacol. 1997;95:92–104. [PubMed] [Google Scholar]107. Scarpace PJ, Yenice S, Tumer N. Influence of exercise training and age on uncoupling protein mRNA expression in brown adipose tissue. Pharmacol Biochem Behav. 1994;49:1057–1059. [PubMed] [Google Scholar]108. Yamashita H, Yamamoto M, Sato Y, et al. Effect of running training on uncoupling protein mRNA expression in rat brown adipose tissue. Int J Biometeorol. 1993;37:61–64. [PubMed] [Google Scholar]109. Sullo A, Brizzi G, Maffulli N. Triiodothyronine deiodinating activity in brown adipose tissue after short cold stimulation test in trained and untrained rats. Physiol Res. 2004;53:69–76. [PubMed] [Google Scholar]110. de Castro JM, Hill JO. Exercise and brain catecholamine relationships with brown adipose tissue and whole-body oxygen consumption in rats. Physiol Behav. 1988;43:9–12. [PubMed] [Google Scholar]111. Nadel ER, Pandolf KB, Roberts MF, et al. Mechanisms of thermal acclimation to exercise and heat. J Appl Physiol. 1974;37:515–520. [PubMed] [Google Scholar]113. Harri M, Dannenberg T, Oksanen-Rossi R, et al. Related and unrelated changes in response to exercise and cold in rats: a reevaluation. J Appl Physiol. 1984;57:1489–1497. [PubMed] [Google Scholar]114. Larueachagiotis C, Rieth N, Goubern M, et al. Exercise-Training Reduces Bat Thermogenesis in Rats. Physiology & Behavior. 1995;57:1013–1017. [PubMed] [Google Scholar]115. Sbarbati A, Cavallini I, Marzola P, et al. Contrast-enhanced MRI of brown adipose tissue after pharmacological stimulation. Magn Reson Med. 2006;55:715–718. [PubMed] [Google Scholar]116. Crisan M, Casteilla L, Lehr L, et al. A reservoir of brown adipocyte progenitors in human skeletal muscle. Stem Cells. 2008;26:2425–2433. [PubMed] [Google Scholar]117. Foreman RD. Neurophysiology of Heart pain. In: Ter Horst TJ, editor. The Nervous system and the Heart. Totowa, NJ: Humana Press; 2000. pp. 343–363. [Google Scholar]118. Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol. 2006;80:53–83. [PubMed] [Google Scholar]119. Bossut DF, Perl ER. Effects of nerve injury on sympathetic excitation of A delta mechanical nociceptors. J Neurophysiol. 1995;73:1721–1723. [PubMed] [Google Scholar]120. Levine JD, Taiwo YO, Collins SD, et al. Noradrenaline hyperalgesia is mediated through interaction with sympathetic postganglionic neurone terminals rather than activation of primary afferent nociceptors. Nature. 1986;323:158–160. [PubMed] [Google Scholar]122. Sato J, Perl ER. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science. 1991;251:1608–1610. [PubMed] [Google Scholar]123. Ren Y, Zou X, Fang L, et al. Involvement of peripheral purinoceptors in sympathetic modulation of capsaicin-induced sensitization of primary afferent fibers. J Neurophysiol. 2006;96:2207–2216. [PubMed] [Google Scholar]124. Khasar SG, McCarter G, Levine JD. Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors. J Neurophysiol. 1999;81:1104–1112. [PubMed] [Google Scholar]125. McLachlan EM, Janig W, Devor M, et al. Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature. 1993;363:543–546. [PubMed] [Google Scholar]126. Kalmari J, Niissalo S, Konttinen YT, et al. Modulation of visceral nociceptive responses of rat spinal dorsal horn neurons by sympathectomy. Neuroreport. 2001;12:797–801. [PubMed] [Google Scholar]127. Shinozaki K, Shimizu Y, Shiina T, et al. A neurophysiological evidence of capsaicin-sensitive nerve components innervating interscapular brown adipose tissue. Auton Neurosci. 2005;119:16–24. [PubMed] [Google Scholar]128. Osaka T, Kobayashi A, Namba Y, et al. Temperature- and capsaicin-sensitive nerve fibers in brown adipose tissue attenuate thermogenesis in the rat. Pflugers Arch. 1998;437:36–42. [PubMed] [Google Scholar]129. Cui J, Zaror-Behrens G, Himms-Hagen J. Capsaicin desensitization induces atrophy of brown adipose tissue in rats. Am J Physiol. 1990;259:R324–R332. [PubMed] [Google Scholar]130. Gavva NR, Bannon AW, Surapaneni S, et al. The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J Neurosci. 2007;27:3366–3374. [PMC free article] [PubMed] [Google Scholar]131. Patwardhan AM, Akopian AN, Ruparel NB, et al. Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents. J Clin Invest. 2010;120:1617–1626. [PMC free article] [PubMed] [Google Scholar]132. Patwardhan AM, Scotland PE, Akopian AN, et al. Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia. Proc Natl Acad Sci U S A. 2009;106:18820–18824. [PMC free article] [PubMed] [Google Scholar]133. Hori T. Capsaicin and central control of thermoregulation. Pharmacol Ther. 1984;26:389–416. [PubMed] [Google Scholar]134. Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 1999;51:159–212. [PubMed] [Google Scholar]135. Park JY, Kawada T, Han IS, et al. Capsaicin inhibits the production of tumor necrosis factor alpha by LPS-stimulated murine macrophages, RAW 264.7: a PPARgamma ligand-like action as a novel mechanism. FEBS Lett. 2004;572:266–270. [PubMed] [Google Scholar]136. Keeney AJ, Hogg S, Marsden CA. Alterations in core body temperature, locomotor activity, and corticosterone following acute and repeated social defeat of male NMRI mice. Physiol Behav. 2001;74:177–184. [PubMed] [Google Scholar]137. Chuang JC, Cui H, Mason BL, et al. Chronic social defeat stress disrupts regulation of lipid synthesis. J Lipid Res. 2010;51:1344–1353. [PMC free article] [PubMed] [Google Scholar]138. King CD, Devine DP, Vierck CJ, et al. Differential effects of stress on escape and reflex responses to nociceptive thermal stimuli in the rat. Brain Res. 2003;987:214–222. [PubMed] [Google Scholar]139. Marcinkiewcz CA, Green MK, Devine DP, et al. Social defeat stress potentiates thermal sensitivity in operant models of pain processing. Brain Res. 2009;1251:112–120. [PMC free article] [PubMed] [Google Scholar]140. Rivat C, Becker C, Blugeot A, et al. Chronic stress induces transient spinal neuroinflammation, triggering sensory hypersensitivity and long-lasting anxiety-induced hyperalgesia. Pain. 2010;150:358–368. [PubMed] [Google Scholar]141. Cortright DN, Szallasi A. Biochemical pharmacology of the vanilloid receptor TRPV1. An update. Eur J Biochem. 2004;271:1814–1819. [PubMed] [Google Scholar]142. Morris V, Cruwys S, Kidd B. Increased capsaicin-induced secondary hyperalgesia as a marker of abnormal sensory activity in patients with fibromyalgia. Neurosci Lett. 1998;250:205–207. [PubMed] [Google Scholar]143. Dib B. Thermoregulatory behaviour induced by intrathecal injection of substance P in the rat. Eur J Pharmacol. 1987;133:147–153. [PubMed] [Google Scholar]145. Kuraishi Y, Satoh M. Participation of spinal cord substance P in hyperalgesia induced by repeated cold stress. Regul Pept. 1993;46:405–406. [PubMed] [Google Scholar]146. Lewin GR, Mendell LM. Nerve growth factor and nociception. Trends Neurosci. 1993;16:353–359. [PubMed] [Google Scholar]147. Lewin GR, Rueff A, Mendell LM. Peripheral and central mechanisms of NGF-induced hyperalgesia. Eur J Neurosci. 1994;6:1903–1912. [PubMed] [Google Scholar]148. Petty BG, Cornblath DR, Adornato BT, et al. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol. 1994;36:244–246. [PubMed] [Google Scholar]149. Svensson P, Cairns BE, Wang K, et al. Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia. Pain. 2003;104:241–247. [PubMed] [Google Scholar]150. Bennett DL. Neurotrophic factors: important regulators of nociceptive function. Neuroscientist. 2001;7:13–17. [PubMed] [Google Scholar]151. Ro JY, Lee JS, Zhang YP. Activation of TRPV1 and TRPA1 leads to muscle nociception and mechanical hyperalgesia. Pain. 2009;144:270–277. [PMC free article] [PubMed] [Google Scholar]152. Ekstrom J, Ekman R. Sympathectomy-induced increases in calcitonin gene-related peptide (CGRP)-, substance P- and vasoactive intestinal peptide (VIP)-levels in parotid and submandibular glands of the rat. Arch Oral Biol. 2005;50:909–917. [PubMed] [Google Scholar]153. Ekstrom J, Reinhold AC. Increases in nerve growth factor immunoreactivity in the submandibular gland, but not in the parotid gland, of the rat following sympathetic denervation. Arch Oral Biol. 2004;49:3–9. [PubMed] [Google Scholar]154. Supowit SC, Ethridge RT, Zhao H, et al. Calcitonin gene-related peptide and substance P contribute to reduced blood pressure in sympathectomized rats. Am J Physiol Heart Circ Physiol. 2005;289:h2169–h2175. [PubMed] [Google Scholar]155. Nisoli E, Tonello C, Benarese M, et al. Expression of nerve growth factor in brown adipose tissue: implications for thermogenesis and obesity. Endocrinology. 1996;137:495–503. [PubMed] [Google Scholar]156. Qin F, Vulapalli RS, Stevens SY, et al. Loss of cardiac sympathetic neurotransmitters in heart failure and NE infusion is associated with reduced NGF. Am J Physiol Heart Circ Physiol. 2002;282:h463–h471. [PubMed] [Google Scholar]157. Albers KM, Wright DE, Davis BM. Overexpression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system. J Neurosci. 1994;14:1422–1432. [PMC free article] [PubMed] [Google Scholar]158. Davis BM, Albers KM, Seroogy KB, et al. Overexpression of nerve growth factor in transgenic mice induces novel sympathetic projections to primary sensory neurons. J Comp Neurol. 1994;349:464–474. [PubMed] [Google Scholar]160. Gauriau C, Bernard JF. Pain pathways and parabrachial circuits in the rat. Exp Physiol. 2002;87:251–258. [PubMed] [Google Scholar]161. Heinricher MM, Tavares I, Leith JL, et al. Descending control of nociception: Specificity, recruitment and plasticity. Brain Res Rev. 2009;60:214–225. [PMC free article] [PubMed] [Google Scholar]163. Fields HL, Heinricher MM, Mason P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci. 1991;14:219–245. [PubMed] [Google Scholar]164. Porreca F, Ossipov MH, Gebhart GF. Chronic pain and medullary descending facilitation. Trends Neurosci. 2002;25:319–325. [PubMed] [Google Scholar]166. Morrison SF. Differential control of sympathetic outflow. Am J Physiol Regul Integr Comp Physiol. 2001;281:R683–R698. [PubMed] [Google Scholar]167. Fields HL, Vanegas H, Hentall ID, et al. Evidence that disinhibition of brain stem neurones contributes to morphine analgesia. Nature. 1983;306:684–686. [PubMed] [Google Scholar]168. Gao K, Chen DO, Genzen JR, et al. Activation of serotonergic neurons in the raphe magnus is not necessary for morphine analgesia. J Neurosci. 1998;18:1860–1868. [PMC free article] [PubMed] [Google Scholar]169. Heinricher MM, Morgan MM, Fields HL. Direct and indirect actions of morphine on medullary neurons that modulate nociception. Neuroscience. 1992;48:533–543. [PubMed] [Google Scholar]170. Heinricher MM, Morgan MM, Tortorici V, et al. Disinhibition of off-cells and antinociception produced by an opioid action within the rostral ventromedial medulla. Neuroscience. 1994;63:279–288. [PubMed] [Google Scholar]171. Meng ID, Johansen JP, Harasawa I, et al. Kappa opioids inhibit physiologically identified medullary pain modulating neurons and reduce morphine antinociception. J Neurophysiol. 2005;93:1138–1144. [PubMed] [Google Scholar]172. Omiya Y, Goto K, Ishige A, et al. Changes in analgesia-producing mechanism of repeated cold stress loading in mice. Pharmacol Biochem Behav. 2000;65:261–266. [PubMed] [Google Scholar]173. Harris RE, Clauw DJ, Scott DJ, et al. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007;27:10000–10006. [PMC free article] [PubMed] [Google Scholar]174. Bester H, Chapman V, Besson JM, et al. Physiological properties of the lamina I spinoparabrachial neurons in the rat. J Neurophysiol. 2000;83:2239–2259. [PubMed] [Google Scholar]175. Hylden JL, Anton F, Nahin RL. Spinal lamina I projection neurons in the rat: collateral innervation of parabrachial area and thalamus. Neuroscience. 1989;28:27–37. [PubMed] [Google Scholar]176. Menendez L, Bester H, Besson JM, et al. Parabrachial area: electrophysiological evidence for an involvement in cold nociception. J Neurophysiol. 1996;75:2099–2116. [PubMed] [Google Scholar]177. Bester H, Menendez L, Besson JM, et al. Spino (trigemino) parabrachiohypothalamic pathway: electrophysiological evidence for an involvement in pain processes. J Neurophysiol. 1995;73:568–585. [PubMed] [Google Scholar]178. Craig AD, Dostrovsky JO. Differential projections of thermoreceptive and nociceptive lamina I trigeminothalamic and spinothalamic neurons in the cat. J Neurophysiol. 2001;86:856–870. [PubMed] [Google Scholar]180. Bernard JF, Huang GF, Besson JM. The parabrachial area: electrophysiological evidence for an involvement in visceral nociceptive processes. J Neurophysiol. 1994;71:1646–1660. [PubMed] [Google Scholar]181. Bhatnagar S, Dallman M. Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress. Neuroscience. 1998;84:1025–1039. [PubMed] [Google Scholar]182. Herbert H, Moga MM, Saper CB. Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat. J Comp Neurol. 1990;293:540–580. [PubMed] [Google Scholar]183. Craig AD. How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci. 2002;3:655–666. [PubMed] [Google Scholar]184. Cohen SJ, Hobson AR, Aziz Q. Processing of visceral sensory signals in the brain. In: Johnson LR, editor. Physiology of the Gastrointestinal Tract. San Diego, CA: Academic Press; 2012. pp. 689–702. [Google Scholar]185. Smith JK, Humes DJ, Head KE, et al. fMRI and MEG analysis of visceral pain in healthy volunteers. Neurogastroenterol Motil. 2011;23 648-e260. [PubMed] [Google Scholar]187. Miao Q, Zhao XL, Zhang QY, et al. Stability in brain glucose metabolism following brown adipose tissue inactivation in chinese adults. AJNR Am J Neuroradiol. 2012;33:1464–1469. [PMC free article] [PubMed] [Google Scholar]188. Joffe H, Deckersbach T, Lin NU, et al. Metabolic activity in the insular cortex and hypothalamus predicts hot flashes: an FDG-PET study. J Clin Endocrinol Metab. 2012;97:3207–3215. [PMC free article] [PubMed] [Google Scholar]189. Craig AD, Chen K, Bandy D, et al. Thermosensory activation of insular cortex. Nat Neurosci. 2000;3:184–190. [PubMed] [Google Scholar]190. Harris RE, Sundgren PC, Pang Y, et al. Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. Arthritis Rheum. 2008;58:903–907. [PubMed] [Google Scholar]191. Mesulam MM, Mufson EJ. Insula of the old world monkey. I. Architectonics in the insulo-orbito-temporal component of the paralimbic brain. J Comp Neurol. 1982;212:1–22. [PubMed] [Google Scholar]192. Britton JC, Phan KL, Taylor SF, et al. Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery. Biol Psychiatry. 2005;57:832–840. [PubMed] [Google Scholar]193. Drevets WC. Neuroimaging abnormalities in the amygdala in mood disorders. Ann N Y Acad Sci. 2003;985:420–444. [PubMed] [Google Scholar]194. Pawlak R, Magarinos AM, Melchor J, et al. Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior. Nat Neurosci. 2003;6:168–174. [PubMed] [Google Scholar]195. Zald DH, Lee JT, Fluegel KW, et al. Aversive gustatory stimulation activates limbic circuits in humans. Brain. 1998;121(Pt 6):1143–1154. [PubMed] [Google Scholar]196. Zald DH, Pardo JV. Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. Proc Natl Acad Sci U S A. 1997;94:4119–4124. [PMC free article] [PubMed] [Google Scholar]197. Zald DH, Pardo JV. The neural correlates of aversive auditory stimulation. Neuroimage. 2002;16:746–753. [PubMed] [Google Scholar]198. Pujol J, Lopez-Sola M, Ortiz H, et al. Mapping brain response to pain in fibromyalgia patients using temporal analysis of FMRI. PLoS One. 2009;4:e5224. [PMC free article] [PubMed] [Google Scholar]199. Price JL. Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions. Ann N Y Acad Sci. 2007;1121:54–71. [PubMed] [Google Scholar]200. Gusnard DA, Akbudak E, Shulman GL, et al. Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Natl Acad Sci U S A. 2001;98:4259–4264. [PMC free article] [PubMed] [Google Scholar]201. Gusnard DA, Raichle ME. Searching for a baseline: Functional imaging and the resting human brain. Nature Reviews Neuroscience. 2001;2:685–694. [PubMed] [Google Scholar]202. Rosen SD, Paulesu E, Frith CD, et al. Central nervous pathways mediating angina pectoris. Lancet. 1994;344:147–150. [PubMed] [Google Scholar]203. Critchley HD, Elliott R, Mathias CJ, et al. Neural activity relating to generation and representation of galvanic skin conductance responses: a functional magnetic resonance imaging study. J Neurosci. 2000;20:3033–3040. [PMC free article] [PubMed] [Google Scholar]204. Damasio ARNeuropsychology. Towards a neuropathology of emotion and mood. Nature. 1997;386:769–770. [PubMed] [Google Scholar]205. Bechara A, Damasio H, Tranel D, et al. Deciding advantageously before knowing the advantageous strategy. Science. 1997;275:1293–1295. [PubMed] [Google Scholar]206. Harrison NA, Brydon L, Walker C, et al. Inflammation Causes Mood Changes Through Alterations in Subgenual Cingulate Activity and Mesolimbic Connectivity. Biological Psychiatry. 2009;66:407–414. [PMC free article] [PubMed] [Google Scholar]207. Burgmer M, Gaubitz M, Konrad C, et al. Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia. Psychosom Med. 2009;71:566–573. [PubMed] [Google Scholar]208. Rodriguez-Raecke R, Niemeier A, Ihle K, et al. Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. J Neurosci. 2009;29:13746–13750. [PMC free article] [PubMed] [Google Scholar]209. Putcha D, Brickhouse M, O’Keefe K, et al. Hippocampal hyperactivation associated with cortical thinning in Alzheimer’s disease signature regions in non-demented elderly adults. J Neurosci. 2011;31:17680–17688. [PMC free article] [PubMed] [Google Scholar]210. Bartley EJ, Rhudy JL, Williams AE. Experimental assessment of affective processing in fibromyalgia. J Pain. 2009;10:1151–1160. [PubMed] [Google Scholar]211. Egan GF, Johnson J, Farrell M, et al. Cortical, thalamic, and hypothalamic responses to cooling and warming the skin in awake humans: a positron-emission tomography study. Proc Natl Acad Sci U S A. 2005;102:5262–5267. [PMC free article] [PubMed] [Google Scholar]

Fibromyalgia and Heat Sensitivity – Daily Life

With much of the U.S. experiencing temperatures in the 90 and 100 degree ranges, I thought it would be a good time to talk about how the heat affects many of us with fibromyalgia.
Most people with fibromyalgia report having some kind of temperature sensitivity.
Some are very sensitive to cold, others are sensitive to heat, and still others react to both.

I’m one of the heat-sensitive people.
I sometimes describe myself as “hyper-sensitive” to heat.
When temperatures get above 70, I’m uncomfortable.
If they reach 75 degrees, I’m miserable.
It feels as if every tissue in my body is swollen and I have difficulty breathing.
I’ve been known to hyperventilate from trying to catch my breath.
When I get overheated, my pain level goes way up and anything touching my skin is extremely painful – including my clothes.

As strange as it may sound to some, heat sensitivity is the most life-altering of all my FM symptoms – even worse than the pain and fatigue.
Before I go anywhere, I have to make sure the temperature will be tolerable for me.
I can’t tell you how many outings and events I’ve had to miss because of this problem.
My children and grandchildren all go to the beach together every other summer, but I can’t go because it’s too hot.
And I’ve had to miss my grandsons’ soccer games and birthday parties that were held outdoors in the summer.
In the summer months, I’m basically held hostage in my own home where I can control the temperature.

Over the years, I’ve tried a number of different techniques and purchased dozens of products in my efforts to stay cool.
Here are a few tips that have worked best for me when I simply can’t avoid the heat:

• Wear soft, lightweight clothing that fits very loosely.
  Stick to light colors because dark colors absorb heat.

• Stay hydrated.
  Make sure you always have a cold drink (preferably water) to sip on.
  Avoid alcohol as it causes you to lose body fluids and tends to make you feel warmer.

• Take a cool bath or shower.

• Sometimes just soaking your feet in cool water (not ice water) can help cool your whole body down.

• If you don’t have an air conditioner, put a bowl of ice in front of a fan to help cool the air.

• Use an ice bag or cold pack.
  A few ice cubes in a sandwich bag, wrapped in a soft cloth works well.
  Rub the cold pack on your arms, legs, neck – wherever you are the warmest – to help cool yourself down.

• Carry a small, hand-held, battery-operated fan with you when you go out.
  They’re very inexpensive and many have the option of filling them with water so you can mist yourself with water as the fan is running.

Now I’d like to hear from you.
If you have fibromyalgia, does the heat bother you?
If so, do you have any tips that help you survive the summer heat?
Please click “Comments” below to share.

Meet Our Writer

Karen Lee Richards

Karen is the co-founder of the National Fibromyalgia Association. She writes for HealthCentral as a patient expert for Pain Management.

Does Warmer Weather Affect Chronic Pain?

While science may not have an exact reason for why pain worsens in the heat, it cannot be ignored. Many patients who suffer from chronic pain report that the change in weather makes their pain worse. Bad weather, such as cold and rainy days, are often associated with pain, but hot and humid summer days are actually worse for chronic pain. 

How Does Barometric Pressure Affect Chronic Pain?

Barometric pressure, also called air pressure, is the weight of the air in the atmosphere. It changes depending on the weather: low pressure means a storm is eminent and high pressure indicates a clear day. Medical theories suggest that a drop in pressure means there is an increased amount of pressure on the joints. However, heat and humidity affects inflamed tissue and affects the way joints expand and contract.  

Heat and Common Chronic Pain Conditions

Many chronic pain conditions are affected by the heat and humidity during the summer months. 

• Arthritis. A study shows that nearly 5% older people with osteoarthritis reported hot weather influences their joint pain. People with inflammatory arthritis experience pain when the temperature changes and humidity increases because it affects the way joint tissue expands and contracts, therefore triggering pain. 
• Headaches & Migraines. Temperature changes trigger tension-type headaches and migraines. The fluctuation in temperature, humidity, and barometric pressure during warmer months can lead to dehydration, which commonly triggers headaches. 
• Fibromyalgia. The National Fibromyalgia Association links weather and fibromyalgia symptoms when the weather is humid. People who suffer from rheumatological conditions have “temperature sensitivity” meaning any extreme temperatures (both hot and cold) can have worsening symptoms and heightened pain.  
• Multiple Sclerosis (MS). While pain has not always been a recognized symptom of MS, it plays a huge role in this chronic neurological disease. Anything that raises the body’s temperature can worsen MS symptoms. This means a hot summer day can make the pain worse and it is so common, that there’s even a name for this: Uhthoff Syndrome. However, once a person cools down, the symptoms typically go away. 

How to Deal With the Heat

If you experience pain during the summertime, here are some tips to beat the heat and reduce your pain:

• Stay Indoors: If the humidity and extreme heat causes flare ups in your pain, spending time in an air-conditioned area will help regulate your body temperature. Too much time outside can affect your joints and make your anti-inflammatory medication less effective. 
• Drink Water: Drinking water and staying hydrated to maintain electrolyte levels and fluids is crucial to avoiding pain that comes from dehydration.  
• Wear Loose Clothing: Wearing linen or light cotton clothing keeps your body cool by allowing it to breath. Tight clothes or heavy fabrics do not allow sweat to evaporate or keep your body cool.
• Swim: Swimming is a great way to alleviate joint pain and to cool off in the summer months. Low-impact cardio like water exercises are great for those who have arthritis or chronic joint pain. 

Weather Doesn’t Trigger Fibromyalgia Symptoms, Study Finds – WebMD

By Mary Elizabeth Dallas

HealthDay Reporter

TUESDAY, June 4 (HealthDay News) — Although some people with fibromyalgia are sensitive to changes in temperature, sunshine and precipitation, new research shows that weather conditions do not affect the pain or fatigue associated with this chronic condition.

“Our analyses provide more evidence against, than in support of, the daily influence of weather on fibromyalgia pain and fatigue,” said study first author Ercolie Bossema from Utrecht University in the Netherlands.

The study, published in the journal Arthritis Care & Research, involved nearly 350 women with fibromyalgia, a chronic syndrome that causes unexplained pain, fatigue, headaches and sleep disturbances. The women were 47 years old, on average, and had been diagnosed almost two years earlier. They were asked about symptoms of pain and fatigue over the course of 28 days, during which time the researchers also recorded weather conditions, including outside temperature, sunshine duration, precipitation, atmospheric pressure and relative humidity, as reported by the Royal Netherlands Meteorological Institute.

Changes in weather showed a significant but small effect on pain or fatigue symptoms for 10 percent of cases. Significant, small differences between patients’ responses to weather also were found in 20 percent of cases.

The researchers said differences among the women’s response to weather conditions did not appear linked to functional or mental health status, demographics or seasonal or weather-related variations.

In the United States, 5 million people have fibromyalgia, many more of them women than men. Although the cause of this chronic pain syndrome is unclear, previous studies have suggested some people with fibromyalgia are more sensitive to certain stimuli. Up to 92 percent of people with this condition report a worsening of symptoms because of weather conditions.

“Previous research has investigated weather conditions and changes in fibromyalgia symptoms, but an association remains unclear,” Bossema said in a journal news release.

The study’s authors said future research on this issue should include more patient characteristics, such as personality traits and beliefs about chronic pain, in order to explain individual differences in weather sensitivity.

Temperature Sensitivity In Fibromyalgia –

Temperature sensitivity affects many women with fibromyalgia, myself included. You can be cold all the time or hot all the time or alternate between being hot or cold.

Pin

For over twenty-five years I had hot flashes and night sweats. I can’t tell you how many times I was totally embarrassed because I could not stop sweating. My hair and clothes would be drenched regardless of the outside temperature. Now I am freezing all the time.

Research shows that people with fibromyalgia have an inability to adapt to changes in temperature along with a lower pain threshold to both hot and cold stimuli. Julie at Counting My Spoons wrote about a study that examined the temperature thresholds for heat and cold in women with fibromyalgia compared to healthy women.

What Causes Temperature Sensitivity

Body temperature is regulated by the hypothalamus. The hypothalamus is a section of the brain responsible for hormone production. It is considered the link between the nervous system and the endocrine system.

The hypothalamus not only controls body temperature. It controls energy levels, the sleep cycle, muscular function, circulation, the gut and defense against infection.

Most fibromyalgia symptoms seem to be due to imbalances in the hypothalamus-pituitary-adrenal axis (HPA axis). These three glands work together to control hormone levels. Disruptions in the HPA axis seem to be at the core of fibromyalgia.

Thyroid hormones also play a role in regulating body temperature. An overactive thyroid (hyperthyroidism) can cause a person to feel too hot, while an underactive thyroid (hypothyroidism) can cause a person to feel too cold.

The thyroid gland is under the control of the pituitary gland. The pituitary gland itself is regulated by the hypothalamus. Anything that disrupts the HPA axis will also suppress thyroid function.

Certain medications interfere with the regulation of body temperature. Some drugs make you sensitive to heat, increasing the risk of heat stroke and some can lower body temperature.

Heat Sensitivity

Some heat sensitive people feel all-over heat sensations that seem to come from within their own body. Along with hot flashes, some people have problems with excessive sweating. Others may only have problems in their hands and feet, including puffiness and aching. Warm or hot weather can be unbearable with heat sensitivity.

To avoid getting overheated:

• Keep your environment cool.
• Wear soft, lightweight clothing that fits loosely. Stick to light colors in warm weather because dark colors absorb heat.
• Stay hydrated. Make sure you always have a cold drink (water is best) to sip on.
• Take a cool bath or shower. Sometimes just soaking your feet in cool water can help cool your body down.
• Use cooling products such as a cold pack or fan. Carry a small, hand-held, battery operated fan with you when you go out.

When the weather gets warm, heat sensitive people with fibromyalgia often experience symptom flare-ups. Research has found that people with fibromyalgia exposed to hot temperatures report increases in: pain, headaches, fatigue, anxiety and depression. They are also more likely to have heat rashes and heat exhaustion or heat stroke.

Heat stroke is a medical emergency. Signs of heat stroke and immediate action to cool the overheated person while waiting for emergency treatment can be found on the Mayo Clinic website.

Cold Sensitivity

People who are cold sensitive often feel chilled to the bone and have a hard time warming up. The cold can be all over or just in your hands and feet. This symptom is usually worse during cold weather, but can occur at any time.

To prevent problems with cold:

• Keep your environment warm.
• Dress warmly, especially in cold weather. Keep your feet covered, wear socks and slippers.
• Drink hot liquids and eat hot meals like soup and oatmeal.
• Take warm baths or showers.
• Keep a blanket handy or use a heating pad or similar microwave products.

An unusual sensitivity to cold in the hands and feet with color changes in the skin sometimes occur in people with fibromyalgia. This condition is called Raynaud’s syndrome, also known as Raynaud’s phenomenon.

Sensitive To Both, Heat and Cold

Some people fluctuate between being hot and being cold. One minute you can be sweating with hot flashes and freezing the next. This can be very challenging. You have to be prepared for either scenario.

• Dress in layers or have extra layers available.
• For night sweats, wear moisture wicking sleepwear or use temperature regulating sheets.

Fluctuations in temperature can make your fibromyalgia feel worse. It’s important to plan ahead. You may have to spend most of your time indoors where you can better control the conditions.

Conclusion

Temperature sensitivity is a common fibromyalgia symptom. Most women with fibromyalgia report being extremely sensitive to cold and/or heat. Essentially, temperature sensitivity may be due to hormonal imbalances in the hypothalamus-pituitary-adrenal axis. Medications can also interfere with the regulation of body temperature.

For many years, I was hot all the time. The warm and hot weather was unbearable so I preferred cold weather. Now it seems as if the switch has been flipped and I am always cold. The hot flashes stopped when I stopped taking antidepressants and Lyrica. So either it was the medications or I made it through menopause. Now, if I could just get warm.

I’d like to hear from you. If you have fibromyalgia, are you sensitive to heat, cold or both? If so, do you have any tips that help? Please leave a comment below to share.

Pin for Later

Pin

Fibromyalgia Can Make Us Sensitive to Temperature Changes

Changing seasons can wreak havoc on the pain levels and the overall sense of wellness of people with fibromyalgia. Not only are we sensitive to temperature changes, but also to barometric changes.

Whether you tend to be sensitive to heat or cold, temperature fluctuations can cause your disease to flare and your pain to increase. It’s interesting how I am more comfortable in an air-conditioned environment in the summer; warm rooms make me feel nauseous. And in the winter I struggle to feel warm, even if the heat is on, making my pain level decidedly worse.

If you are vacillating between hot and cold, it may be helpful to wear layers. That way, you can take off and put on as necessary to accommodate the craziness that’s part of fibromyalgia. Hormonal imbalances and certain medications can be factors as well, especially in women.

Those who are sensitive to heat can experience excessive sweating and hot flashes, and be more prone to heat stroke. It’s especially challenging if you are experiencing excessive heat internally in hot weather. Be sure to stay hydrated and, if possible, in a cooler environment.

Those sensitive to cold (like me) may feel it more in their hands and feet, but it could be all over, too. It makes winters something to dread. I have thought many times of moving somewhere that is less cold than New England. Maybe someday.

Did you know that research shows people with fibromyalgia have an inability to adapt to changes in temperature, as well as a lower pain threshold to both hot and cold stimuli? this probably isn’t news to you, as you are living it, but it’s good to know that research backs up our experience.

Another expert theory states that the thyroid gland is to blame because it helps to control body temperature. Did you know that many fibromyalgia sufferers also have hypothyroidism, which means the thyroid is not functioning properly, leading to temperature sensitivity? I have that issue. My diagnosis of fibromyalgia coincided with my diagnosis of hypothyroidism.

If your thyroid is functioning normally, low blood volume or poor circulation could be the culprit behind your temperature sensitivity.

Severe cold and extreme heat can register as painful experiences in those of us with lower pain thresholds. Perhaps that might explain why temperature sensitivity is so common among those of us who experience pain sensitivity.

Every season has its challenges; I’m either hot or cold. How about you? Do you experience this?

Note: Fibromyalgia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Fibromyalgia News Today, or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to fibromyalgia.

Heat or Cold Therapy for Fibromyalgia

We always have a hard time getting out of a warm shower or bath. The warm water provides a “feel good”, relaxing feeling. Fibromyalgia patients feel a similar way when using heat therapy. The heat applied to the affected area dilates the blood vessels which increases blood flow. Heat therapy is an effective and inexpensive form of chronic pain relief. The rush of blood flow repairs soft tissue, provides more oxygen, increase muscle tone, relaxes tense muscles, and flushes out any waste or toxins to the site.

• Decreases pain, especially around the tender points
• Relax stiff and tight muscles
• Increases flexibility and range of motion
• Decreases fatigue
• Decreases stress, to provide a good night of sleep

Heat should be avoided by people with inflammatory conditions or diseases, such as arthritis. Since fibromyalgia is not an inflammatory disease, sufferers gain pain relief from heat therapy.

There are two types of heat therapy: Superficial and deep heat therapy. Superficial heat therapy heats the skin and skin surface by heating pads and hot packs. Deep heat therapy needs to reach the core muscles by using ultrasound or whirlpool baths. Remember to consult your healthcare provider before beginning your heat therapy.

Helps relax; reduces pain and stiffness throughout the body.

The common source of heat therapy relieves muscles spasms and pain, especially when caused by restless leg syndrome. Soak a facecloth or towel in hot steaming water, place over affected area, and wait 10 minutes.

For many fibromyalgia patients, the baths alleviate pain and stress. The bath circulates water around affected area which increases the circulation. Whirlpools are effective in increasing blood flow to the area.

An electric pad that is place superficially over affected area to reduce pain and stiffness.

This increases skin elasticity and restores moisture in hands and feet. The wax is melted to warm temperature, the affected area is dipped into the wax, pulled out, dipped until you have a good wax covering, wrap a towel around the whole area for 20 minutes, and peel off wax.

Cold therapy is beneficial for many fibromyalgia sufferers to numb the affected area. The cold constricts the blood vessels and decreases blood flow, in turn, reducing inflammation. Common forms of cold therapy:

• Ice bag or frozen vegetables
• Cold pack
• Ice bath

Costochondrite – Medical Center “Liko-Med”

What is costochondritis?

Costochondritis is the inflammation of the cartilage that connects the ribs and the sternum. The inflammatory process causes chest pain on one or both sides. Certain diseases can cause costochondritis, such as arthritis and fibromyalgia, trauma, and a viral or bacterial infection of the respiratory tract. However, the cause of the disease is usually unknown. Costochondritis is considered harmless. It is very often mistaken for a heart attack.The disease is more common in women than in men. As a rule, the inflammation goes away on its own in a few days or weeks.

What to expect?

Costochondritis pain can be very severe, so the disease is often mistaken for a heart attack or lung disease. The inflammation usually goes away on its own within a few days or weeks. Pain relievers, ice, or heat can help reduce pain.

Distribution.

Costochondritis is diagnosed in 14% of adolescents and 30% of adults who complain of chest pain.

Risk factors .

– Belonging to the female sex.

– More than forty years old.

Treatment.

Treatment of costochondritis includes:

– Applying heat or cold to the sore spot.

– The use of anti-inflammatory drugs.

– Avoiding activities that aggravate pain.

– Corticosteroid injections – for severe pain.

What can you do yourself?

Costochondritis is usually treated at home with anti-inflammatory drugs. It is useful to apply ice or heat to the area of ​​inflammation. If this does not help, see your doctor for an assessment of the condition.

How does it get worse?

– Injuries.

– Twisting movements.

– Deep breaths.

– Sleep on an uncomfortable bed without a pillow or mattress.

When to see a doctor?

See a doctor if:

– you began to wake up from pain;

– breathing problems;

– a fever has begun or signs of infection have appeared.

Chest pain that spreads to the left arm, along with sweating, nausea, or general chest pain not concentrated in one area, may be a sign of a heart attack and requires emergency treatment.

What to ask a doctor?

1.How often should I be screened to assess my condition?

2. Do I need to have any tests or X-rays?

3. For what symptoms should you seek medical attention?

4. When will the condition improve?

5. What is the long-term prognosis of the disease?

Making a diagnosis.

Costochondritis is diagnosed based on the patient’s medical history and the results of a physical examination.

90,000 It seems to man that it is cold.A sharp fluctuation in blood pressure

If you are constantly cold but others are not, this can be an unpleasant situation. You may need to wear a jacket when the weather is warm for other people, or the pool and beach water where everyone swims may be too cold for you.

Along with the inconvenience of feeling cold, you may wonder why your temperature perception is not “normal” or “average”. Cold intolerance, also called cold hypersensitivity, is not uncommon and can be caused by a number of health conditions.

When it is constantly cold

You must tell your doctor if you are constantly cold. Your doctor will ask you about other symptoms that can help determine the cause of this intolerance, including changes in appetite, weight changes, mood problems, or trouble sleeping. Below are some of the most common reasons why you might be chilly all the time.

Thyroid disease

Hypothyroidism or low thyroid function is one of the most recognized causes of hypersensitivity to cold.Thyroid disease requires evaluation and treatment.

There are many different types and reasons. If your symptoms are consistent with thyroid disease, your doctor will order blood tests that can determine what kind of hormone problem you may be experiencing.

Thyroid disease can be treated with medication, and most people experience significant improvement in symptoms with treatment.

Anemia

Anemia means your red blood cells are not functioning optimally.There are a number of causes and types of anemia, including hereditary, environmental, and nutritional causes such as deficiencies in iron and vitamin B12 and. Your doctor can diagnose anemia through a simple blood test.

It is important for you to get proper treatment for your anemia, because without treatment, the disease can get worse.

Malnutrition

Malnutrition can be somewhat difficult because it does not necessarily mean that you are not getting enough food. Malnutrition means that the food you eat does not provide the right amount of nutrients.

In fact, an overweight person may be nutritionally deficient and deficient in essential vitamins and minerals. Likewise, a person can eat large amounts of food but be malnourished if a health problem, such as malabsorption or diarrhea, prevents some of the nutrients from being absorbed into the body.

Malnutrition can cause anemia, but can also cause vitamin and mineral deficiencies. If malnutrition is the result of an unhealthy diet, then changing your diet and possibly adding vitamin supplements is the best way to fix the problem.However, if you have a problem with malnutrition as a result of a problem with your digestive system, then you may need medical and possibly even surgical treatment.

Thinness

Often thin people are hypersensitive to cold. This is because fat insulates the body and muscles help the body generate heat through metabolism. If you are very skinny and lack muscle and / or body fat, you may be hypersensitive to cold.

However, not everyone who is thin is hypersensitive to cold.For example, hyperthyroidism can cause a person to be very skinny and feel hot all the time. And athletes who can be very thin can also have a lot of muscle as a result of physical fitness.

Circulation problems

If you are constantly cold, your friends may tell you that you have poor circulation. Circulatory problems can cause the temperature of the hands and fingers to drop. Often, circulatory problems also cause pale hands and feet, or even a bluish tinge.

A specific circulatory condition called Raynaud’s disease is characterized by episodic narrowing of blood vessels, resulting in pale or blue fingers or toes.

If you experience these symptoms, you should talk to your doctor. You cannot fix circulatory problems on your own by shaking or massaging your hands or feet, so it is important to see your doctor about this problem.

Neuropathy

Neuropathy, which is a disorder of the nerves, can cause hypersensitivity of the nerves.This hypersensitivity can cause a cold sensation in the hands or feet all the time, and can also cause an increased sensitivity to cold.

Problems with the pituitary gland

The pituitary gland, located in the brain, regulates many hormones in the body, including the thyroid hormone. Any problem in the function of the pituitary gland that causes this gland to be over or under activity can cause problems with temperature regulation, which makes you feel too hot or too cold all the time.

Hypothalamic problems

The hypothalamus is a small area of ​​the brain that regulates hormones throughout the body and also regulates the pituitary gland. The hypothalamus controls several aspects of the body’s condition, including temperature, hydration, and blood pressure, and regulates the body’s hormones to fine tune these conditions. If the hypothalamus is not functioning properly, you may experience symptoms such as a constant feeling of coldness.

Estrogen

Estrogen is a hormone that regulates female reproduction.Estrogen levels change throughout a woman’s life and throughout a woman’s menstrual cycle and pregnancy.

Fluctuations in estrogen levels can affect sensitivity to cold, causing women to feel colder than usual during some stages of the menstrual cycle.

Parkinson’s disease

Feeling cold is one of the less recognized symptoms of Parkinson’s disease. In general, this is due to changes in autonomic function that can occur with Parkinson’s disease.

Fibromyalgia

Many people with suffer from symptoms that are inconsistent or fluctuate over time. Fibromyalgia can cause many alarming symptoms, including feeling cold all the time or for a while.

Nerve trauma

Nerve damage is usually the result of a traumatic accident that damages all or part of the nerve, resulting in a lack of function. However, in addition to a lack of nerve function, people who experience only partial recovery from nerve damage may experience a persistent cold sensation or hypersensitivity to cold in the area of ​​the body that is supplied with the damaged nerve.

Infectious disease

When you have an infection, such as a cold or “upset stomach,” your body may feel cold and you may even feel chills or shivers. Often times, when you have an infection, you can fluctuate between feeling hot and feeling cold, especially if you have a fever.

The feeling of coldness when you have an infection is largely due to the fact that your body is consuming so much energy that it fights the infection.

Feeling cold as a result of infection should be a temporary situation that resolves after the infection itself has gone away.Many people find that they are cold all the time for several days before they notice more recognizable signs of infection, such as fever, cough, and nausea.

Fatigue

Fatigue can also cause cold. Some people find that their entire body feels colder than usual when they are awake. If you are cold as a result of fatigue or physical exhaustion, this feeling should be eliminated as soon as your body can get enough rest.

Women are more prone to cold

Women are more often cold than men.Thyroid problems and fibromyalgia are more common in women, and of course estrogen fluctuations are only present in women. Women are also more prone to thinness than men.

Summary

Constantly feeling cold can be frustrating and even embarrassing if you always dress warmer than everyone else, or avoid outdoor activities that you think others enjoy.

There are a number of diseases that can cause this condition. Often, even after you have been tested, you cannot get a medical diagnosis.

You may be disappointed if you don’t get an answer to the cause of your problem. However, rest assured that most people who feel cold all the time have no medical problem at all and are perfectly healthy. If you do not have an illness that causes such intolerance, you can use practical methods to solve your problems, for example, choosing comfortable warm clothes and shoes while sitting by the fireplace, consuming warm food and hot drinks.

People often get cold in winter and even in spring, when it is cold and slush outside.But what if a person feels chills in different parts of the body when it’s warm and sunny outside? Many of us believe that there is a problem in their body. This is partially true, but there are many other reasons why people get cold too often.

Women get cold much more often than men. This tendency is explained by the large amount of the hormone estrogen in their body, as well as the fact that their body has more fat and less muscle tissue compared to the male body.

A person’s well-being is strongly influenced by his diet.Therefore, if you eat improperly, for example, fast food and overly fried foods, then your body lacks essential nutrients and vitamins. It is even worse when a person is on a diet and loses weight – because of this, he weakens, and along with it, the immune system weakens.

When a woman begins menopause or pregnancy, a hormonal imbalance occurs in her body. The amount of estrogen rises, which can make you feel cold. Therefore, a sudden change in hormone levels can also cause chills.

When a person eats, the body sends more blood to the stomach to aid digestion. Therefore, there is not enough blood in the rest of the body, which weakens the immune system. In addition, if a person has a very small weight, then he is more prone to chills.

People who suffer from high and low blood pressure often have cold hands and feet. When blood pressure is low, blood flows slowly, so there is not enough blood circulating in the limbs. On the other hand, at high pressure, there are difficulties in blood circulation, due to which also the limbs do not have enough blood.

Some medicines may cause discomfort and chills, especially if the medicines are not suitable for the person.

If a cold is accompanied by rapid weight loss that cannot be restored even with a healthy diet, then there may be problems with the thyroid gland. With thyroid disease, the metabolism slows down, which lowers the body temperature of the body.

Chills in the arms and legs are common in people with Raynaud’s phenomenon. When a healthy person is in the cold, blood rushes to the internal organs.However, in people with Raynaud’s phenomenon, this manifests itself too strongly – the blood drains from the skin, which makes the person feel chills in the limbs and body.

How to raise body temperature?

People who are constantly cold should balance their diet. A proper diet with lots of proteins, vitamins, fats and minerals will ensure good body functioning and return to normal temperature.

You should eat regularly. It has been proven that if there is too long a break between meals, the body does not have enough energy to maintain heat.

Normally, hemoglobin in women should be in the range of 120-140 g / l, in men – 130-160 g / l. In the case of a decrease in these values, treatment is prescribed to increase hemoglobin. As a rule, these are iron preparations and vitamin C.

Also, anemia can result from poor vascular patency as a result of the development of atherosclerosis. Most often, atherosclerotic plaques are the result of malnutrition, which includes a large amount of animal fat, the undigested remains of which are deposited in the form of plaques in our vessels.

Atherosclerosis
is a deadly disease that leads not only to anemia, but also to high blood pressure, the risk of heart attack and stroke, as well as vascular occlusion leading to tissue necrosis and gangrene with subsequent amputation of the limbs.

To reduce the risk of atherosclerosis, you should, if possible, exclude from your menu all products containing animal fat – butter, fatty cottage cheese, sour cream, fatty cheeses, fatty meat.

Fiber-rich foods should also be included in the diet. This allows you to cleanse the intestines, preventing non-digested fat from re-entering the body.

Tell me, why am I constantly freezing?
Even in summer, in the heat, a cold wave can pass somewhere inside and goose bumps appear on the body.
And now, with the onset of cold weather, in general trouble.
No matter how many clothes you put on and how much warm tea you drink, there is still some kind of cold inside.
My feet are almost always cold.
This is probably why the throat often hurts.

What is it connected with and how to get rid of this permanent feeling of coldness?

Asked: Natalya | 14-09-2010

Answer

First of all, when hands and feet are constantly freezing, this is a violation of capillary circulation.
Often this disease is vegetative-vascular dystonia, the basis of the appearance of which is low resistance to stressful situations, increased emotionality, physical inactivity from childhood, the consequences of infectious diseases.
Such symptoms also appear with hormonal changes in adolescence, with cervical osteochondrosis or personality traits such as anxiety, excessive suspiciousness.
Hands and feet get cold with low hemoglobin, diseases.
Similar symptoms are found in Raynaud’s disease, in which there is a spasm of blood vessels, impaired arterial blood supply to the hands and feet, under the influence of cold or emotional overload.
Its origin is unclear, but it is not worth starting it, since it tends to progress, up to peeling of the fingertips, loss of skin elasticity, an eating disorder and all sorts of other troubles may develop.
How can I help?
1. Train your blood vessels.
This is not entirely easy, but necessary.
Start with hot foot baths or contrasting ones.
In the first case, steam your legs well until reddened in a hot shower several times a week, or soak them in hot water for about an hour.
In the second case, lower your feet alternately in hot and cold water.
Go once a week to the sauna, steam bath, steam in the steam room, and then jump into the cold pool.
After the steam room, it will not seem cold to you, and the blood vessels are very well strengthened.
2. Force yourself every day during the day to do 10 exercises to warm up the whole body or sign up for aerobics, go to a fitness club, solarium, swimming pool.
3. Eliminate coffee and spirits, alcohol, smoking for several months from the diet, they cause spasms and vasoconstriction, and not their dilation.
4. If you have low hemoglobin, then a deficiency of iron in the blood will lead you to anemia, in which the body temperature decreases, there is a feeling that the person is slowly cooling down, its deficiency affects the functioning of the thyroid gland
In this case, dried apricots should become your constant food , raisins, pomegranates, salads, fresh fruits and vegetables.
Drink more vitamin and herbal decoctions, compotes, fruit drinks, increasing blood circulation.
5. When going outside, the most important thing is to keep your head, arms and legs warm.
6. Strengthen your immunity.

________________________________________________________________
Best regards, Svetlana Sorokina

Consultant

Women often complain about the eternal feeling of cold, partly because of physiology, partly because of their hypersensitivity to cold conditions.Here are 10 common reasons why your internal thermostat doesn’t reflect reality.

You are underweight

Low body weight (body mass index less than 18.5 points) can make you feel cold for several reasons. Firstly, low values ​​on the scales are equal to low indicators in the level of fat reserves, which should warm us. Secondly, low body weight indicates insufficient calorie intake, this slows down metabolism, which is why the body begins to spend less energy on its own heating.Put on a couple of pounds you need with an emphasis on healthy, homemade foods that are high in protein, vira, and complex carbohydrates.

Your thyroid gland is naughty

Constant coldness is one of the many well-being problems that you “owe” to a failed thyroid gland. You could even say that a persistent feeling of coldness is the surest sign of hypothyroidism (decreased thyroid function and decreased hormone production). Without the necessary hormone levels, the metabolic rate slows down, and the body begins to save on its own heating.Other common signs of hypothyroidism are thinning hair, dry skin, and fatigue. Most often, women who have recently given birth and women over 60 fall into the risk group. Prescription medications will help to remove the thyroid gland from an inhibited state.

You do not have enough iron

Low iron levels are one of the most common causes of persistent freezing. Here’s why: Iron is a key substance in the transport of oxygen by red blood cells throughout the body. Without iron, these blood cells start to do their job worse, and you start to shiver from the cold.Iron deficiency is also dangerous because in this state of affairs, the thyroid gland becomes sluggish, and you add yourself another reason to freeze (see the previous paragraph).

Your blood circulation is impaired

If the palms and feet are constantly icy, but the rest of the body feels quite comfortable, then perhaps you should pay special attention to the blood circulation, which does not have enough strength to “reach” the limbs. Cardiovascular disorders may be the cause of this weakening: the heart does not pump well enough, or the blood vessels are narrowed.Smoking can also constrict blood vessels.

You don’t get enough sleep

Lack of sleep can be an elephant walking the china shop of your nervous system, throwing all your internal mechanisms out of balance, including your body thermostat. It is not entirely clear why this happens, perhaps this is how the body manifests its stress due to insufficient rest. This is confirmed by a study published in the European Journal of Applied Physiology, where 20 young people who were deprived of normal sleep showed a decrease in body temperature.He suffers from lack of sleep and our metabolism, which, again, leads to impaired self-heating and inhibited blood circulation.

You are dehydrated

We are 60% water, and it is water that helps regulate our body temperature. If there is enough fluid in the body, it retains heat and releases it more slowly, keeping the overall temperature comfortable. When there is not enough fluid, the body becomes more sensitive to the ambient temperature. But water warms us not only in this way.It enhances metabolism, the inhibited state of which translates into a lowered body temperature. Try to drink at least 8 glasses of water a day, especially before and after exercise.

You lack vitamin B12

This vitamin is available to us only from animal products, and its lack will make you chatter from the cold. The body needs it to make red blood cells, which carry oxygen throughout the body. Its deficiency can lead to anemia, i.e.That is, a reduced number of red blood cells and, as a result, to chronic “permafrost”. To make up for your B12 deficiency, include lean meats, fish, and dairy products in your diet. Sometimes, it is worth noting that the deficiency of this vitamin occurs due to its lack of absorption. If your diet has enough of this vitamin, but you still feel cold, see your doctor for a blood test for this important vitamin.

You are a woman

Always fighting with your husband for control of the thermostat? It turns out that the feeling of cold also depends on gender.In principle, women are better equipped to keep warm than men. For this purpose, their bodies are “programmed” to distribute blood flow in such a way as to maintain optimal nutrition for vital organs such as the heart and brain – sometimes at the expense of the palms and feet, which makes these parts of the body chronically cold.

You have diabetes

Diabetes not properly controlled, called diabetic neuropathy. A constant attack on nerve tissue can cause cold, numbness, and sometimes pain in the arms and legs.Diabetic neuropathy develops gradually and you may not even be aware of it. Be sure to see your doctor about these symptoms.

You need muscle mass

Muscles help maintain a normal body temperature by generating heat, no muscles – hello, feeling cold! In addition, building up, you start up the metabolism, which at the same time fights against the eternal feeling of cold. Sign up for a gym or get some dumbbells for your home – the increased muscles will become a kind of “blanket” that relieves you of the permafrost.

There are reasons why many people constantly feel chilled, even when they are warmly dressed. Let’s try to figure it out.

Our body can be compared to a house that has an intelligent heating system. The cauldron is the liver, it heats the liquid (blood), the pump is the heart, this organ disperses the blood through the tubes-vessels to all corners of the body. Muscle tissue retains heat like a battery. If this perfect system malfunctions, the person will constantly freeze.

Reasons why a person freezes

The reason for chilliness is physique

The warmest of all people with normal body weight and developed muscles, athletes are the least cold. Skinny girls who do not exercise, have a low metabolic rate and less heat generated, they always shiver from the cold. However, being overweight also makes you freeze more. Excess fat compresses blood vessels, impairs blood flow.

The reason for chilliness is a way of life

Tobacco smoke is the reason why hands and feet are freezing.The fact is that it causes vasoconstriction.

Also, if you are on a diet and reduce your calorie intake, the body will respond to this by reducing the metabolic rate during the cold season. This means that you will be colder than usual.

With a lack of sleep, thermoregulation is also impaired. Anyone who does not sleep enough chills during the day; knowing this, dress warmly after a sleepless night.

The reason for chilliness is low pressure

The reason for chilliness is lack of iron

A low level of hemoglobin in the blood causes a failure in the supply of oxygen to the body.The vessels dilate excessively to increase blood flow and react as if you were in a hot, heated room. The body wastes precious heat and freezes very quickly. It is necessary to find the reason for the lack of hemoglobin, this may be a sign of a serious illness.

The cause of chilliness is hormonal problems

Malfunctions of the endocrine glands are a common cause of chilliness. With a reduced function of the thyroid gland, the metabolic rate decreases and the receipt of heat from the calories delivered with food is inhibited.Such a person gains weight with a moderate diet, and his feet are cold at any time of the day. Pregnant women can also suffer from cold.

Heat exchange is also impaired in diabetes: sometimes the feet freeze to such an extent that they lose sensitivity. If you suspect you have hormonal disorders, immediately contact a specialist.

How to keep warm

1. Stretch your hands, twist your arms at the elbows, then at the shoulder joints. Rotate your torso.Half-sit down and rotate with your knees, pelvis.

2. Carry hot tea with you in a thermos.

3. Give up tight shoes and tight-fitting clothing in cold weather, wear warm socks and gloves in any weather.

4. Shower before bed to keep your feet as warm as possible. For very cold feet, a hot bath with dry mustard is good. You can use a heating pad.

5. Place a large bottle of very hot water under the blanket in advance to warm the sheet.

6. Attend or, if there are no contraindications.

7. And, of course, move more, go in for sports! It’s the most important.

If you find an error, please select a piece of text and press Ctrl + Enter
.

My legs and arms often get cold. It has always been like this for as long as I can remember. It seemed to me that it was due to the low pressure. And for some time now I have had attacks of a terrible cold, it seems that my whole body is getting cold. I can’t get warm even under a few blankets and a heating pad doesn’t help either.At the same time, the pressure, as usual, is about 100/70, and the cold comes from the inside. Tell me what to do at such moments, otherwise it’s scary, especially in the middle of the night, when you wake up all frozen. And maybe someone knows what it is from, which doctor should I go to?

Comments: 11 »

Cold hands and feet, a decrease in body temperature indicate a slowdown in blood circulation and an increase in blood viscosity. The reason is the slagging of the vessels of the liver, kidneys and anemia. Overcooling of the body causes an increased release of adrenaline, disrupts metabolic processes, while the rate of chemical reactions decreases.
To normalize blood circulation and improve blood composition, it is necessary to eat well, take contrasting air and water procedures, and try to maintain an optimistic attitude.
Treatment can only be prescribed by a doctor, depending on the diagnosis.

You need to move more and drink more fluids. Not necessarily water, fresh juices and watery fruits and vegetables are better. Citrus fruits are fine now.

You know, I also have such a problem, the cause of cold extremities can be vegetative-vascular dystonia, iron deficiency, Raynaud’s syndrome.I have low hemoglobin – a lack of iron, my sister went away after the birth of the child, so this is very individual. Contact a therapist, in order to find out the exact reason you need to undergo an examination, only a doctor can prescribe a suitable treatment for you. In any case, eat more vitamins and foods containing iron, exercise, and walk.

And you were not diagnosed with VSD (vegetative-vascular dystonia) in childhood?
Do angiography of blood vessels, circulatory failure at the capillary level, and you freeze !!! and if the binding capacity is low, then the reason is already different.One analysis for iron is not informative!

Of course, first of all, you need to cleanse your body. But in any case, good nutrition is necessary, since without good nutrition, it is almost impossible to improve the blood composition. Also, I would advise you to take a little cinnamon, you can, like tea, it makes the blood thinner, thanks to this, blood circulation will improve, which is very important in this case. Checked on myself.

I have a similar problem, my limbs are very often cold.A hot bath helps, apparently the blood liquefies when it heats up.

I have the same thing! Constantly cold limbs, especially hands, even in the heat! I can count on my fingers the days when my hands were warm! Nightmare 🙂 I am constantly cold, so there are often disputes with colleagues about the open window – everyone is always hot, but I’m cold! But I have VSD and neurocirculatory dystonia of a cardiac type, the diagnosis has been made, but there is no treatment as such in conventional medicine. Therefore, try not to overwork yourself, do self-heating, eat a variety of foods, try to walk more in the fresh air – all these, of course, are general recommendations, but the therapists did not recommend another + tincture of hawthorn, motherwort, etc.and the most important thing is not to stress.
And a hot bath is really salvation, even just to steam your legs is already good! 🙂

Everything is fine, it’s even very good, don’t listen to those who are afraid of diseases and don’t go to the doctors, only harm your body, but rather listen, you are a very spiritually different person, it’s easier to say your soul leaves the body during sleep and walks very far from it and the body cools down, for example, when I sleep at night, not only the body is cold, but it even gets cold in the room, although it’s summer outside and the whole house is warm, even when they come in in the morning they wonder why it’s so cold! I congratulate your body has a highly developed essence, good luck to you!

For some reason, my body from the outside is always cool, although I begin to freeze from the inside at about the pace.15-20 gr. Maybe who knows?

Consider some of the symptoms of illness by sensation of temperature.

Causes of feeling cold

Hypothyroidism – cause of feeling cold

Do you constantly wrap yourself in sweaters or turn on the heaters at full capacity, while others feel great without them? Then this may be one of the eloquent signs of hypothyroidism, a decrease in the activity of the thyroid gland, which produces too few hormones.Although hypothyroidism occurs in both sexes, it often goes unrecognized in adults and older women. Some of the other hallmarks of this condition include weight gain, dry skin, a low hoarse voice, and constipation.

Elderly people often get cold even in summer, so they try to avoid fans and air conditioners. As a result, there is a threat of stroke or heart attack associated with overheating. According to statistics, during the unprecedented heat wave that hit Europe in the summer of 2003, 35,000 people died, most of them elderly.

Main causes of feeling cold

Cold intolerance is a sign of another hormonal disorder – hypopituitarism, dysfunction of the pituitary gland – the main gland of the endocrine system. People with this condition suffer from overwork, infertility and low blood pressure.

Cold intolerance may be a characteristic feature of another hormonal disorder – dysfunction of the hypothalamus, a gland that helps regulate body temperature, appetite, weight and emotions.Dysfunction of the hypothalamus occurs in the presence of a tumor, infections, head trauma, and malnutrition.

A constant cold sensation accompanies anemia. About 20% of people with iron deficiency anemia suffer from cold intolerance.

In rare cases, hypersensitivity to cold is a warning sign of bone cancer or leukemia (cancer of the blood and bone marrow).

If you are often cold, feel numb and weak, fibromyalgia, a disorder of the musculoskeletal system that most women suffer from, may be the cause of the cold sensation.It does not pose a direct threat to life, but it weakens the body.

Causes of feeling hot

Climax – cause of feeling hot

Surely many are familiar with the climax mantra: “It’s hot in here – or is it me?” Constant hot flashes and hot flashes are hallmarks of menopause, but not all women who complain of heat intolerance suffer from hot flashes associated with menopause.

Hyperthyroidism – the cause of the feeling of heat

Moreover, many men also have a hard time coping with high ambient temperatures.Heat intolerance is a classic symptom of hormonal disorders, especially hyperthyroidism, an increased production of thyroid hormone, which increases body temperature and speeds up metabolism. A few more characteristic signs of this dysfunction are nervousness, weight loss, constant hunger and thirst, and bulging. Both men and women suffer from an overactive thyroid gland, but more often this disorder with a sensation of heat occurs in women.

Main causes of feeling hot

Feeling hot can be a reaction to excess caffeine, amphetamines, some antidepressants and thyroid medications.

Increased sensitivity to heat can be a signal of serious conditions – multiple sclerosis, for example. Indeed, exposure to heat and hot water can temporarily worsen the condition of a patient with multiple sclerosis – tremors appear, vision is lost, and memory problems arise.

Heat intolerance is a typical cause of anhidrosis, in which a person does not sweat at all. This condition is a serious life-threatening condition. People who don’t sweat at all risk overheating and heatstroke.

Help from qualified doctors

Which doctor should I go to for help?

The body consists of many different parts and components, and in almost each of them a huge variety of disturbances can develop. Below is a list of professionals to contact for help. But if you feel acute or chronic pain that does not go away, you have bleeding, vomiting, redness and swelling, severe itching, dizziness, blurred consciousness, immediately contact your doctor or call an ambulance.

Feeling cold
can be a sign of various disorders and a consequence of a number of reasons, for example, poor diet or a sedentary lifestyle.

When a person generally does not tolerate cold, this may be a sign of a metabolic problem.
This may also be due to a low body fat index, which prevents the body from maintaining an optimal body temperature.

On the other hand, cold sensation
90,097 could be due to the fact that 90,228 people are suffering from some kind of infection
, for a cold or pneumonia, when there is a constant change in his body temperature.However, in cases of these diseases, the sensation of cold usually subsides as the cause is eliminated.

Cold sweat, which occurs with reduced pressure, as well as a feeling of coldness in various parts of the body (usually in the limbs) cannot go unnoticed, as they cause severe discomfort.

Possible causes:

• Hunger
• Anorexia
• Fatigue
• Infection
• Menopause. In women 90,228, the amount of estrogen fluctuates, which causes a feeling of warmth or, conversely, coldness. This occurs most often during menopause or pregnancy.

• Hypothyroidism
• Low body fat index
• Circulatory disorders

News | Page 2 of 3

News

14 Oct 2017

HEADACHE: to heal or “let it go by itself”?

There is no person who never, not once in his life would have a headache.Taking painkillers in this case is the fastest and often most effective way to solve this problem. When is the moment when you should stop self-medication and see a doctor?

If your head hurts 3 times a week or more
If taking “usual” painkillers no longer brings relief
In case of acute and intense headache (it hurts as badly as it has never hurt in my life)
If the headache is accompanied by weakness in the arm and / or leg (usually on one side of the body), transient loss of vision, speech, sudden loss of memory (in which a person loses orientation in space for a while and forgets where he is and what is he doing).In such cases, you must immediately consult a doctor and undergo a serious examination, including an ultrasound examination of large vessels, ECG, EchoCG, a clinical blood test, urine, blood sugar, detailed blood tests to determine a lipid profile, a tendency to thrombus formation, computed or magnetic resonance imaging brain.

Headache can be the first symptom of a wide variety of diseases: hypertension, vegetative-vascular dystonia, renal and endocrine pathology, brain tumor, stroke, etc.e. Today 45 diseases are known, accompanied by headache. Timely diagnosis and adequate therapy for these conditions will improve your well-being and maintain your health.

It should be noted that headache is not a painful sensation of the nervous tissue of the brain, since it lacks pain receptors. It occurs as a result of exposure to sensitive areas located in the head and / or neck: the skull (periosteum), muscles, nerves, arteries and veins, subcutaneous tissue, eyes, sinuses and mucous membranes.The method for treating headache depends on the identified disease or the cause of the symptom.

Historical reference

Individual mentions of recurrent headaches, reminiscent of the description of a migraine clinic, appeared more than 5,000 years ago. In the XIX-XVI centuries BC, descriptions of headache attacks were also found in Babylonian literature, which was compared to a flash of lightning. For the first time, hemicrania, which is accompanied by vomiting and poor health in general, was described in the Ebers papyrus as “a disease of half of the head.”The first classification of headaches called “De Cephalalgia” was developed by Thomas Willis in 1672. In 1787, Christian Baur divided all headaches into idiopathic (primary) and symptomatic (secondary), and also identified 84 categories of headaches. At the end of the 19th century, in the book “On migraine headaches and other similar diseases” by Edward Living, it was shown the differential difference between migraine and other, similar in clinic, headaches. The clinical symptoms of cluster headache were described by Harris in 1926, but the priority of describing the disease belongs to Ryder (1924).In 1939, Horton also described the clinic for cluster cephalalgia, but unlike Harris, he regarded it as erythromelalgia, and then as histamine cephalalgia. Later, this condition was referred to as Horton’s syndrome. For the first time, Ekbom pointed out the similarity of these conditions in 1947, and since 1952, at the suggestion of Kunkel, the disease is called “cluster cephalalgia”. In 1962, at the National Institute of Diseases of the Nervous System, the Committee on Headache introduced a new definition of headache into practice, and also developed a classification of cephalgia and prosopalgia, which existed for 26 years.In 1988, the International Headache Classification Committee introduced a new classification of head and facial pains, which is still used today. The second version of the classification, published in 2004, has been approved by the World Health Organization.

Classification of headaches

According to the International Classification of Headaches (2nd Edition), all headaches are divided into two large groups: primary (migraine, tension headache, cluster headache and other trigeminal autonomic (autonomous) cephalalgias, other primary headaches) and secondary headaches (associated with head and / or neck trauma, vascular lesions, infections, homeostasis disorders, mental illness, etc.)reasons). Cranial neuralgia and unclassified headache are separately identified.

There are other classifications of headache.

So, according to the mechanism of occurrence, the headache is classified into 6 types: vascular headache, muscle tension headache, liquorodynamic headache, neuralgic headache, mixed headache, psychlgia (central headache).

In all this diversity, I would like to dwell on some types of headaches that we encounter most often, namely:

– tension headache;

– migraine;

– cervicogenic headache;

– headache associated with increased blood pressure;

– abusal headache.

Tension headache (HDN) is the most common type of primary headache. Episodic HDN occurs in more than 70% of people, chronic HDN affects 1-3% of adults. HDN often begins in adolescence, mainly among women (there are two men for every three women). The peak incidence occurs at 20-39 years. The mechanism of HDN development is associated with stress or musculoskeletal problems of the neck.

Attacks of episodic HDN usually last several hours, but can last for several days.Chronic HDN can be continuous and interfere with normal functioning to a much greater extent than episodic HDN.

HDN is characterized by: bilateral localization, compressive / pressing character, pain intensity from mild to moderate, headache does not worsen from normal physical activity, absence of nausea or vomiting, photophobia or phonophobia may be present. The pain is usually monotonous with minor fluctuations in intensity throughout the day. It is often described by patients as a feeling of pressure, tension or constriction around the head like a “helmet” and is much less often presented in the form of pain itself, sometimes extending to the neck or starting from the neck.In some cases, patients report short episodes of acute, one-sided piercing pain.

Often, patients with HDN associate the appearance of painful episodes with stress. The occurrence of episodes of HDN after physical and mental fatigue is just as often noted. Irregular eating and disturbance of sleep and wakefulness are characteristic provoking factors, although factors such as strong odors, smoke, bright light and meteorological factors rarely act as provocateurs of HDN episodes.In the chronic form of HDN, it often occurs at night or in the morning upon awakening.

The diagnosis of HDN is based on the analysis of complaints (the nature of the headache) and the history of the disease (the relationship between headache episodes with negative emotions, chronic stress, prolonged postural overstrain). Examination in patients with HDN reveals tension and soreness of the pericranial muscles.

Considering the great role of muscle-tonic syndrome in the pathogenesis and chronicity of HDN, the treatment of muscle tension should be one of the most important tasks of HDN therapy.Therefore, along with non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants must be included in the treatment regimens for this group of patients. In the presence of emotional and personality disorders, sedatives and antidepressants must be added. In patients with a combination of HDN and migraine, which is often found in clinical practice, it is possible to use triptans. However, in these cases, the patient should be taught to distinguish between episodes of HDN and migraine attacks.

In this group of patients, acupuncture, relaxation training, and post-isometric relaxation are effective as preventive measures.

Migraine is manifested by stereotypical attacks of one-sided pulsating headache, which is accompanied by nausea, vomiting, photo- and phonophobia. The duration of a migraine attack varies from 4 to 72 hours. In many cases, seizures occur as a result of exposure to provoking factors, the most common of which are: stress, disturbances in sleep and wakefulness, menstruation, jet lag, food (cheese, chocolate, citrus fruits, eggs, smoked meats, etc.).) and drinks (red wine, beer, coffee).

There are two main forms of migraine: migraine without aura and migraine with aura. Migraine without aura occurs in 80% of all migraine cases. Many patients can experience migraine attacks with or without an aura. Quite often there are attacks of “aura without headache”, which, unfortunately, are often not recognized and not diagnosed.

Migraine treatment includes two areas: treatment of a migraine attack and prophylactic treatment in the interictal period.Treatment of a migraine attack is divided into: 1) nonspecific – these are simple analgesics – paracetamol; combined analgesics – combinations with caffeine, short-acting barbiturates; non-steroidal anti-inflammatory drugs – aspirin, ibuprofen, indomethacin, diclofenac; drugs for relief of accompanying symptoms; 2) specific therapy is triptans – sumatriptan, zolmitriptan, nonselective agonists of 5-HT1 B / 1B receptors – ergotamine, dihydroergotamine; auxiliary agents – metoclopramide, domperidone; combined drugs – difmeter.Prophylactic drug treatment is prescribed to all patients and is aimed at reducing the frequency of occurrence and severity of headache attacks. When choosing a pharmacological agent, individual characteristics of the patient, characteristics of seizures, and the presence of comorbid disorders are taken into account. For the prevention of migraine attacks, I use β-adrenergic receptor blockers, calcium channel blockers, antiepileptic drugs, antidepressants, nootropics, venotonics, riboflavin (vitamin B12), coenzyme Q10, thioctic (α-lipoic) acid.Non-drug treatment methods are effective for migraines: acupuncture, relaxation training, behavioral therapy.

Cervicogenic headache

The prevalence of cervicogenic headache (CBH) among patients with chronic headaches is 15-20%. CHP is observed mainly in middle-aged people, is 4 times more common among women and has a significant tendency to chronicity. CGB, as a rule, affects representatives of “sedentary” professions, as well as those who, in the process of work, often have to throw their heads back or work with their heads down.The appearance of CHP in most cases is preceded by a prolonged forced position of the neck and head, as well as awkward neck movements associated with overextension or sharp rotation. Other provoking factors are sleep in an uncomfortable position, hypothermia, drafts, stress.

Speaking about the mechanism of development of cervicogenic headache, muscular-tonic and vascular components should be distinguished. Damage to the cervical spine leads to impaired outflow along the vertebral venous plexuses and leads to the formation of central venous stasis.Also, irritation of the autonomic plexus of the vertebral arteries plays a significant role in the formation of CHP.

CGB is a unilateral headache that spreads from the cervico-occipital region to the anterior parts of the head. The intensity of the CHP is most often moderate, sometimes it can be accompanied by nausea, non-systemic dizziness, flashing of flies before the eyes, cervico-brachial pain. It should be noted that the one-sided nature of the headache is characteristic of the onset of the disease. When amplified, it can spread to the other side, but still dominates on the side of origin.Often, CHP is combined with other types of headache.

The main objective sign confirming the cervicogenic nature of headache is musculoskeletal dysfunction in the cervicobrachial region. There is a shortening of the extensors of the neck, the descending portion of the trapezius, scalene muscles, a low level of training of the deep flexors of the neck and interscapular muscles. In chronic CHP, active trigger points are determined in the region of the sternocleidomastoid, scalene, belt, descending portion of the trapezius, levator scapula, subscapularis and supraspinatus muscles, as well as short extensors of the neck (short suboccipital muscles) from the side of the same name.In terms of examination, the doctor will prescribe an X-ray of the cervical spine with functional loads, Doppler ultrasonography of the neck vessels.

Treatment of CHB includes non-drug and drug-based methods.

Manual therapy. Its main goal is to eliminate functional musculoskeletal disorders that cause cervical headache, and thus prevent its subsequent episodes.

Patients are assigned a training system. Its key stage is isometric strengthening of the local muscles of the cervicobrachial region – deep flexors of the neck and interscapular muscles.Postural and ergonomic retraining of the patient involves the exclusion of positions and movements that can lead to overstretching of soft tissue structures and mechanical irritation of the vertebral arteries. According to indications, wearing a Chance collar is recommended.

Drug treatment includes the appointment of NSAIDs and central muscle relaxants (tizanidine, baclofen). In the presence of a vascular component, vasoactive drugs (nicergoline, vinpocetine, ginkgo biloba drugs), actovegin, nootropics are added to therapy, and in case of venous insufficiency, venotonic drugs (venosmin, detralex, normoven, venodiol).In the chronic course of CHB, depressive disorders can join; in such cases, antidepressants should be added.

Headache associated with high blood pressure

With high blood pressure, the headache is dull, pressing, sometimes pulsating in nature with localization (most often) in the occiput. Patients with essential hypertension, as a rule, are already well aware of this character of headache, “feel” that the pressure rises.Therapeutic tactics in this situation is as follows: measure blood pressure, when it rises, take antihypertensive drugs (captopril, captopres, fenigidin, bisoprolol). As a rule, an increase in blood pressure is accompanied by emotional arousal, which, in turn, leads to a further increase in blood pressure numbers. Therefore, we recommend taking sedatives (corvaltab, valerian, sedistres, cardiolin).

However, sometimes patients do not know and do not associate headache with an increase in blood pressure. They take painkillers, which to some extent alleviate their condition, but do not give a noticeable improvement in well-being, and most importantly, the cause of the headache (high blood pressure) is not eliminated, which in turn can lead to rather serious health complications.High blood pressure, untreated hypertension is the risk of heart attack and stroke.

Therefore, when you have a headache, take your blood pressure. If the blood pressure numbers are more than 140/90 mm Hg, you need to take antihypertensive drugs (drugs that lower the blood pressure numbers) and consult a doctor. The doctor will prescribe the necessary examination plan (ECG, Holter monitoring of ECG and blood pressure, dopplerography of the extracranial vessels of the head and neck, ultrasound of the heart) and the question of the need for regular intake of antihypertensive drugs will be resolved, the drug will be selected and the dose will be selected.There are a lot of antihypertensive drugs, which one you need and in what dose, the doctor must decide.

As a rule, prescribing antihypertensive drugs alone is not enough to completely cope with the problem of headache in hypertension. Here you will need a course intake of vascular, nootropic drugs, venotonics, and in some cases, antidepressants.

Abuse headache

Uncontrolled intake of analgesics (especially in combination with barbiturates, caffeine, some sedatives) can cause depression of your own anti-pain brain centers and lead to the so-called abusus (drug) headache.With frequent headaches, it is important to remember: it is extremely dangerous to take pain relievers in large quantities and for more than 15 days a month, and combined analgesics – longer than 10 days. At the same time, there is no specific drug that provokes the development of this disease. The only thing that matters is the duration of use and the dose of the drug.

Treatment of abusal headache is a rather difficult task. First of all, it is necessary to completely cancel the drug, the use of which caused this syndrome.But this should be done carefully and gradually, since abrupt discontinuation of the drug can increase the pain syndrome. Also, depending on the indications, the doctor will prescribe antiemetics, sedatives, antidepressants, and, if necessary, carry out rehydration and detoxification measures.

It should be noted that the prevention of the development of abusal headache is facilitated not only by knowledge about the dangers of abuse of painkillers, but also, first of all, by timely diagnosis and adequate treatment of the patient’s pain syndromes.Headache treatment should consist not only of the treatment of a headache attack, but also of preventive treatment courses, lifestyle modifications, nutrition, moderate physical exertion. It is this approach that will allow you to cope with the problem of headaches, gain health and well-being.

more details

90,000 Increased fatigue and drowsiness, reasons.

The fatigue that many feel at the end of a working day or a hard week is completely normal. But long-term general malaise and increased fatigue are already signs of various diseases and conditions. So, in combination with progressive muscle weakness, shortness of breath, they can be the first symptoms of Pompe disease in adult patients ¹ .

Pompe disease is a genetic disease, the onset of which can occur at any age. It is associated with a hereditary deficiency of the acid alpha-glucosidase enzyme, which leads to the accumulation of glycogen and, as a result, the destruction of the components of all cells of the body, lysosomes ¹ .

Pompe disease is a rare, orphan pathology and causes increased fatigue in isolated cases. What other diseases and conditions can be associated with weakness and fatigue?

Fatigue as a variant of the norm

Physicians understand fatigue as a temporary decrease in the body’s capabilities due to intense exertion, which is manifested by a decrease in working capacity and a feeling of fatigue. The causes of fatigue can be both physical and mental.In the first case, there is a temporary inability of the muscle to maintain optimal physical activity, which is the more pronounced, the stronger the load ² .

Mental fatigue manifests itself in a temporary decrease in maximum cognitive ability due to prolonged periods of mental activity. Symptoms include drowsiness and decreased concentration ² .

In addition, sensory fatigue – visual, auditory – is distinguished, which consists in lowering the threshold of excitability and impairing the corresponding functions (vision, hearing).Regardless of the reasons and manifestations, physiological fatigue disappears after rest. In contrast, pathological fatigue persists for a long time and does not depend on the volume of loads on the body ² .

What is asthenia?

In medicine, pathological fatigue is called asthenia, which in Greek means impotence. Symptoms of asthenia include ² :

• increased fatigue
• irritability combined with physical weakness
• emotional lability – increased excitability is quickly replaced by tearfulness and vice versa
• headaches
• sleep disorders
• intolerance to bright light
• change in mental state
• muscle pain
• inability to relax and other manifestations.

Asthenia, in contrast to overwork, is not the result of physical or mental stress, does not disappear after rest and has a constant course. According to the most approximate data, 12-18% of people around the world face increased fatigue, and with somatic diseases (infections, pathologies of the blood, lungs, etc.), its prevalence can reach 100% ³ .

What diseases cause weakness?

Increased fatigue accompanies various diseases and pathological conditions, including ^2.3 :

• hormonal imbalance
• pathology of the respiratory tract (chronic obstructive pulmonary disease, emphysema)
• cardiovascular diseases
• almost all blood diseases, including anemia
• chronic renal, hepatic failure
• mental illness (depression, in particular major depressive disorder)
• multiple sclerosis
• diabetes mellitus
• infectious diseases (ARVI, hepatitis, tuberculosis)
• fibromyalgia
• obesity
• sleep apnea
• powerful pain syndrome and many others
• malignant processes.

Increased fatigue can also be caused by the intake of certain medications, in particular, chemotherapy, analgesics, antidepressants.

Since asthenia is closely associated with many diseases, it is important to consult a doctor when it develops and find out the causes.

Wrong lifestyle as a cause of increased fatigue

However, it should be remembered that asthenia can be associated not only with a serious pathological process in the body, but also with an unhealthy lifestyle and an unbalanced diet.

Unbalanced diet

Several studies have found that consuming excess amounts of simple carbohydrates can cause fatigue throughout the day. This is due to the ability of these nutrients to rapidly raise blood glucose levels, which in turn results in the immediate release of large amounts of insulin, which removes sugar from the blood to the cells. A sharp increase and a subsequent equally sharp decrease in sugar levels and causes a feeling of fatigue ⁴ .

Another reason for increased fatigue is a low-calorie diet. With a negative balance between calories from food and energy expenditure, metabolism slows down, which can be associated with a feeling of fatigue. To prevent a slowdown in metabolism, most people need to get at least 1200 calories a day ⁵ .

It is important to consume enough protein, which increases the metabolic rate more intensively than carbohydrates and fats ⁵ .In addition, studies have shown that fatigue is reduced with an increase in branched-chain amino acids, which are the building blocks of protein. So that the metabolism is intense enough to prevent fatigue, protein should be consumed at every meal ⁶ .

Vitamin deficiency

It is known that a deficiency of certain vitamins and microelements, in particular, vitamin D, can lead to asthenia.Low blood levels of this vital nutrient can have a negative impact on performance and quality of life in general ⁷ . The results of clinical studies indicate that a decrease in the level of solar vitamin in the blood in women of less than 29 ng / ml is associated with significantly more frequent complaints of increased fatigue compared with a level of more than 30 ng / ml ⁸ .

Many biochemical processes occurring in the body every day are accompanied by the loss of fluid, which is important to compensate.Studies have shown that even minor fluid losses can lead to decreased energy levels, decreased alertness and increased fatigue ⁹ .

Sleep disorders

One of the most obvious causes of increased fatigue is chronic lack of sleep. During sleep, hormones are released that regulate metabolism and energy levels, and toxic metabolic products that accumulate during activity are removed. The metabolic rate is significantly reduced, which allows for recovery processes ¹⁰ .

Current guidelines suggest that the average nighttime sleep for adults is seven hours. At the same time, sleep should be calm and uninterrupted. A short nap can also help boost energy levels throughout the day. Studies have shown that a well-defined sleep schedule with a clear time frame for falling asleep and a length of rest can reduce fatigue and eliminate sleep problems ¹⁰ .

At the same time, prolonged sleep during daylight hours contributes to the violation of circadian rhythms and a failure of the biological clock.This is another common cause of chronic fatigue. Circadian rhythm disorders are also associated with jet lag (jet lag), night shift work, regular sleep deprivation, the habit of falling asleep with a light source, and other factors ¹⁰ .

Hypodynamics and stress

One of the most common causes of increased fatigue among middle-aged and elderly people is low physical activity ⁸ . Studies have shown that people with low levels of activity have insufficient strength and stamina, which limits the ability to exercise.However, with the start of training, fatigue decreases. At the same time, the effectiveness of training is manifested even with minimal loads ¹¹ .

Another scourge of our time is chronic stress. It has been proven that they are associated with increased fatigue, asthenia ¹² .

References

1. Hagemans M.L.C. et al. Impact of late-onset Pompe disease on participation in daily life activities: Evaluation of the Rotterdam Handicap Scale // Neuromuscul.Disord. Elsevier, 2007. Vol. 17, No. 7. P. 537-543.
2. Pizova N.V. Fatigue, asthenia and chronic fatigue. What it is? // Cons. medicum. 2012.Vol. 14, No. 2.
3. Shakirova I.N., Dyukova G.M. Asthenia is an interdisciplinary problem // Difficult patient. 2012. T. 10, No. 5. P. 14-16.
4. Chen M.K. The epidemiology of self-perceived fatigue among adults // Prev. Med. (Baltim). Academic Press, 1986. Vol. 15, no. 1. P. 74–81.
5. Westerterp K.R. Diet induced thermogenesis.// Nutr. Metab. (Lond). BioMed Central, 2004. Vol. 1, No. 1. P. 5.
6. Blomstrand E. A Role for Branched-Chain Amino Acids in Reducing Central Fatigue // J. Nutr. 2006. Vol. 136, No. 2. P. 544S – 547S.
7. Johnson K., Sattari M. Vitamin D deficiency and fatigue: an unusual presentation // Springerplus. 2015. Vol. 4, No. 1. P. 584.
8. Ecemis G.C., Atmaca A. Quality of life is impaired not only in vitamin D deficient but also in vitamin D-insufficient pre-menopausal women.// J. Endocrinol. Invest. 2013. Vol. 36, No. 8. P. 622-627.
9. Ganio M.S. et al. Mild dehydration impairs cognitive performance and mood of men // Br. J. Nutr. 2011. Vol. 106, No. 10. P. 1535-1543.
10. Hartzler B.M. Fatigue on the flight deck: The consequences of sleep loss and the benefits of napping // Accid. Anal. Prev. 2014. Vol. 62. P. 309-318.
11. de Vries J.D. et al. Exercise as an Intervention to Reduce Study-Related Fatigue among University Students: A Two-Arm Parallel Randomized Controlled Trial // PLoS One / ed.