About all

Rheumatoid arthritis and stress: Can Mental Stress Cause Rheumatoid Arthritis?

Can Mental Stress Cause Rheumatoid Arthritis?

Rheumatoid arthritis is a painful condition that requires effort every single day to manage. One of the biggest contributors to rheumatoid arthritis is stress, so keeping stress levels under control is key for anyone who struggles with this autoimmune condition.
 
Older adults with rheumatoid arthritis may experiences new stressors that cause flare-ups. Symptom management is especially important for seniors. If you or a loved one has rheumatoid arthritis, you should understand the connection between stress and autoimmune diseases as well as common stress reduction techniques that can help keep symptoms at bay.
 

What Is Rheumatoid Arthritis?

 
Rheumatoid arthritis is an autoimmune disease that affects your joints. It triggers your immune system to attack your body’s healthy cells, leading to tissue damage and chronic joint pain. In severe cases, rheumatoid arthritis can also damage the heart, lungs, and other organs.
 
The following are some of the most common symptoms of rheumatoid arthritis:
 

  • Swollen, tender, or painful joints
  • Joint stiffness
  • Identical symptoms on both sides of the body
  • Fatigue
  • Fever
  • Unexplained weight loss
  • Weakness

 

Rheumatoid Arthritis and Older Adults

 
Rheumatoid arthritis is usually diagnosed in middle-aged adults, but it creates some unique challenges for seniors. Older adults can be diagnosed with rheumatoid arthritis later in life, and those who have had the disease for many years can continue to struggle with symptoms as they age.
 
Rheumatoid arthritis is progressive. As you get older, the wear and tear on your joints may have become significant. It also can be incredibly difficult to deal with if you’re facing the normal signs of aging. You may find it harder to stay active as you age, which can make symptoms worse. Keeping up with medication management and treatments can be challenging for older adults as well.
 
Because rheumatoid arthritis can be so painful and difficult for seniors, you should do everything in your power to keep the symptoms under control. This means visiting your doctor regularly, maintaining a healthy lifestyle, and managing your stress.
 

Stress and Rheumatoid Arthritis

 
Research suggests a strong connection between stress and rheumatoid arthritis. Any form of stress can take a toll on your mind and body, and stressful events are especially harmful for people with autoimmune diseases. When you experience a stressful event, your body enters “fight or flight” mode. This can affect your hormone levels and weaken your immune system.
 
Studies show that stress can cause rheumatoid arthritis flare-ups. The stress takes a mental toll, too. The emotional effects of intense stress may make the chronic pain and other symptoms feel more difficult to manage. You may struggle to keep up with treatments or maintain a healthy lifestyle when you’re facing chronic stress.
 

Can Stress Cause Rheumatoid Arthritis?

 
Stress can worsen an existing case of rheumatoid arthritis, but it may also trigger the onset of the illness. Many people report going through a stressful or traumatic event shortly before their rheumatoid arthritis symptoms developed. There’s also a correlation between childhood trauma and rheumatoid arthritis later in life.
 
Older adults are susceptible to a number of different stressors, so stress may play a role in the onset of rheumatoid arthritis in seniors. A serious fall, the loss of a spouse, and a change in living situation are just a few of the many stressful life changes older adults go through. Any one of these stressors could trigger an autoimmune issue.
 

Reducing Stress to Manage Rheumatoid Arthritis

 
All seniors should make efforts to reduce their stress and maintain a healthy, peaceful lifestyle. However, this is especially vital for older adults with rheumatoid arthritis. Stress can take a severe physical toll on your body, so incorporating stress management techniques throughout your day is necessary for both your physical and your mental health.
 

The Following Are Some of the Best Ways for Older Adults to Reduce Stress

 

Get Plenty of Sleep

 
Many older adults struggle to get a good night of sleep. Your sleep cycle may change as you age, and learning to manage your sleeping patterns can be challenging. Stress is so much easier to manage when you’re well-rested, though. Try to keep the same sleep schedule every night, and maintain a relaxing routine before you go to bed so that falling asleep is easier.
 

Exercise Regularly

 
Joint pain and mobility issues can make exercise a challenge for older adults. However, incorporating movement into your day has powerful benefits for your mental and physical health. Low-intensity exercises like walking, swimming, and yoga can all help to reduce your stress. Consult your doctor for advice if you’re concerned about starting an exercise regimen.
 

Join a Support Group

 
Your friends and family can be a great source of support and comfort. They probably don’t understand what it’s like to have rheumatoid arthritis, though. Chronic illnesses are intensely isolating. Connecting with others who can relate to your experiences is a great way to feel less alone. You can also pick up some stress management tips from others who share your symptoms.
 

Attend Counseling for Seniors

 
Chronic stress can feel impossible to overcome on your own. Whether you’re going through a difficult life event or you’re just a naturally high-stress person, professional support may be necessary to ease your anxiety and learn to keep calm.
 
Therapy is an opportunity to explore the root causes of your stress and to understand why you may have such a strong response to stressful events. As you gain a better understanding of your thoughts and emotions, you can start to utilize coping skills so that your stress doesn’t take such an intense toll on your mind and body.
 
Blue Moon Senior Counseling offers therapy for older adults with rheumatoid arthritis and other chronic health issues. We understand the link between mental health issues and rheumatoid arthritis, and we’re happy to help as you learn to take control over your stress. To learn more about our services, please contact us today.

How Stress Affects Rheumatoid Arthritis

Written by R. Morgan Griffin

  • Make Exercise a Priority
  • Calm Your Mind
  • Make Some Lifestyle Changes
  • Tackle Stress at Work
  • Get Support

Stress can make rheumatoid arthritis (RA) symptoms worse. Take action to keep that from happening.

Researchers still don’t fully understand the link between stress and RA. It may involve things related to your body’s stress response and inflammation.

Use these proven methods to curb stress.

When your joints ache, you might not feel like going for a brisk walk or swimming laps. Try your best to do something.

Being active is especially good for people with RA. It eases pain, improves mood, lowers stress, and helps keep joints mobile.

Go for cardio (aerobic exercise). Pick activities that are easy on your joints, like swimming and walking.

Also do strength training. You can use light weights, machines at the gym, resistance bands, or your own body weight (think push-ups and lunges).

Don’t forget flexibility. Tai chi and gentle types of yoga are good for that. They can also be relaxing.

If you’re not active already, ask your doctor what’s OK for you to do. And pace yourself. You may need to take it easier when you have a flare.

If your symptoms get in the way of exercise, work with a physical therapist who specializes in treating people with RA. You’ll learn ways to build strength, feel better, and zap stress.

Studies show that meditation can help improve mood, reduce distress, and ease pain. It can be as simple as focusing on your breathing. Your mind will wander to other topics. That’s OK. Just turn your attention back to your breath, or whatever else you choose to focus on.

You could also try guided imagery. Picture in your mind places or situations you find relaxing. Try to use all your senses, and imagine seeing it, smelling it, and feeling it.

Work around problems. When RA symptoms flare up, everyday tasks can be harder to do. Look for solutions. If typing hurts your hands, try voice recognition software for your computer. In the kitchen, you might find that new utensils with bigger grips make cooking easier. These little changes can take some of the stress off you.

Keep up with your sleep. Get up and go to bed at the same time each day to set a regular sleep cycle. If you can, don’t take work home from the office. Turn off the TV, computer, and phone at least an hour before bed.

Do what you love. Think about the things you enjoy doing, such as having coffee with a friend, reading, or seeing a movie. Build those activities into your weekly schedule.

Don’t smoke. Some people with RA smoke to deal with the stress of their condition, but that’s not a good idea. Studies have found that smoking can make rheumatoid arthritis worse and make medication less effective.

Stretch. Aim to take a break every half-hour to stretch, walk around, and clear your head. When you can’t, stretch at your desk. Try to move all your joints. Arch your back. Shrug your shoulders. Stretch your arms above your head. Make claws with your hands. Flex your ankles and toes.

Breathe deeply. Take a few deep breaths with your eyes closed or open. Inhale through the nose, feeling your chest expand. Then exhale through your mouth. Repeat.

Relax your muscles. Slowly relax all the muscle groups in your body, starting with your feet and ending with your head. First, tense the muscles for about 8 seconds. Then relax them and feel the tension melt away.

Focus on a soothing image. Keep pictures on your desk or a slideshow of pictures on your computer that relax you. Try a favorite vacation spot, pictures of loved ones, or adorable kittens. Anything that makes you smile or feel calm helps.

Listen. Slip on a pair of headphones for a few minutes. Play a song that gives you happy, soothing thoughts. Or listen to relaxing natural sounds, like ocean waves or a waterfall.

Smell. Certain scents — like lavender, chamomile, and sandalwood — can ease stress for some people. Keep a bottle of scented hand lotion on your desk and use it when you need a little “aromatherapy.” Get products with real essential oils instead of artificial scents.

Write in a journal. When you’re feeling anxious, clear off your desk and take out a pad — or clear your screen and open a new file — and write for a few minutes. Studies show that writing down what you’re feeling can make you feel better and even lower your blood pressure. If keeping a journal feels awkward, write an email about your feelings to a close friend. When you’re done, you can decide whether to send it or just keep it to yourself.

Think about what’s stressing you out. We often try to push stuff out of our heads to calm down. But facing it head-on can help. What is it that bothers you? Are you behind on a project? Did your boss say something that upset you? Once you have a clearer sense of the problem, you can come up with a solution. You’ll feel more in control and less tense.

Partner with your doctor. Let them know how you’re doing. Tell them about any problems you have. Bring up any questions or concerns you have.

See a therapist. Talk to a psychologist, social worker, or counselor. Even a few appointments can help you find ways to handle your challenges.

Join a support group. You can talk with other people who know what you’re going through because they face similar challenges. Online support groups are another option.

Top Picks

Is arthritis caused by stress?

Publication author

Muchaeva Svetlana Erdni-Garyaevna
Reflexologist, hirudotherapist
Experience 33 years

In 2008, at the Paris Congress of the European League Against Rheumatism (EULAR), a sensational report was made by Swedish specialists from the Stockholm Institute of Environmental Medicine that nervous stress can trigger the development of rheumatoid arthritis. According to one of the leading specialists of the Institute, Annmarie Wesley, a nervous system disorder due to stress not only increases the risk of developing this disease, but also aggravates the course of the disease and makes it difficult to treat.

Meanwhile, in Tibetan medicine, such a connection between a disorder of the nervous system (Rlung system – Tib.) and the state of the joints has been known for many centuries. This is written in ancient Tibetan medical treatises.

From the point of view of Tibetan medicine, a disorder of the Rlung system causes a chain reaction in the body, starting with an imbalance in the regulatory system Bad-kan (Tib.), which is simultaneously responsible for the immune system and the condition of the joints. In modern medicine, this is called a violation of neuroendocrine regulation, leading in particular to a deterioration in immunity. There was even such a science – psychoneuroimmunology, which studies the effect of stress and nervous disorders on the immune system.

In turn, an imbalance in the immune system causes autoimmune processes such as rheumatoid arthritis and psoriatic arthritis (psoriasis).

That is why in the treatment of joint diseases, Tibetan medicine acts not only locally on the area of ​​inflammation, but also on the whole body to improve metabolic processes, strengthen the balance of the immune system and, of course (!), to restore the balance of the nervous system.

If there are such signs of Rlung imbalance as insomnia, neuroses, depression, panic attacks, arthritis is treated against the background of herbal medicine and treatment with procedures to eliminate the imbalance of the nervous system, eliminate the effects of stress, harmonize the psycho-emotional state, restore sleep, increase stress resistance.

This allows you to restore the balance of immunity and significantly (sometimes several times) increase the effectiveness of the main treatment of the joints.

On the other hand, increased resistance to stress has another effect. The fact is that stress causes not only a malfunction of the immune system, but also muscle spasms, including in the joints. These muscle spasms lead to clamping (compression) of blood vessels, disruption of blood microcirculation and blood supply to the joints, and therefore to a deterioration in their nutrition. Thus, nervous stress exacerbates the development of joint diseases, both inflammatory and non-inflammatory (in particular, they provoke the development of arthrosis of the joints).

Tibetan medicine relieves muscle spasms in arthritis with the help of acupressure, acupuncture and moxibustion, restoring blood supply to the joints, improving their nutrition and increasing local immunity, and on the other hand, increasing stress resistance, prevents their renewal. Such complex therapy makes it possible to successfully treat arthritis and arthrosis (including coxarthrosis and gonarthrosis), not only of autoimmune origin, but also of a different etiology.

Share

Psychological stress and rheumatoid arthritis – interference of pathogenetic mechanisms | Tuaeva

1. Kobayashi S, Momohara S, Kamatani N, et al. Molecular aspects of rheumatoid arthritis: role of environmental factors. FEBS J. 2008;275(18):4456-62. doi: 10.1111/j.1742-4658.2008.06581.x

2. Arleevskaya M, Kravtsova O, Lemerle J, et al. How Rheumatoid Arthritis Can Result from Provocation of the Immune System by Microorganisms and Viruses. Frontiers in Microbiology. 2016; 7:1296. doi: 10.3389/fmicb.2016.01296

3. PD horizons. Homeostasis. Moscow: Medicine; 1981. 576 p. [Gorizontov PD. Gomeostaz [Homeostasis]. Moscow: Meditsina; 1981. 576 p. (In Russ.)]

4. Korshunov NI, Grigor’eva EA, Kapustina LV, et al. The problems, mental disorders and quality of life of rheumatoid arthritis patients. Ter Arkh. 1991;63(8):100-4.

5. Hanly J, Fisk J, McCurdy G. Neuropsychiatric syndromes in patients with systemic lupus erythematosus and rheumatoid arthritis. J Rheumatol. 2005;32(8):1459-66.

6. Lu M, Guo H, Lin M, at al. Bidirectional associations between rheumatoid arthritis and depression: a nationwide longitudinal study. scientific reports. 2016;6(1):20647. doi: 10.1038/srep20647

7. Farmer A, Korszun A, Owen M, et al. Medical disorders in people with recurrent depression. Brit J Psychiatry. 2008;192(05):351-5. doi: 10.1192/bjp.bp.107.038380

8. Van’t Land H, Verdurmen J, ten Have M, et al. The association between arthritis and psychiatric disorders; results from a longitudinal population-based study. J Psychosomat Res. 2010;68(2):187-93. doi: 10.1016/j.jpsychores.2009.05.011

9. Söderlin M, Bergsten U, Svensson B, for the BARFOT study group. Patient-reported events preceding the onset of rheumatoid arthritis: Possible clues to aetiology. Musculoskeletal Care. 2010;9(1):25-31. doi: 10.1002/msc.193

10. Rezvani A, Aytüre L, Arslan M, et al. Affective temperaments in patients with rheumatoid arthritis. Int J Rheum Dis. 2014;17(1):34-8. doi: 10.1111/1756-185X.12033

11. Gadek-Michalska A, Tadeusz J, Rachwalska P, et al. Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems. Pharmacol Rep. 2013;65(6):1655-62. doi: 10.1016/S1734-1140(13)71527-5

12. McInnis C, Wang D, Gianferante D, et al. Response and habituation of pro- and anti-inflammatory gene expression to repeated acute stress. Brain Behav Immun. 2015;46:237-48. doi: 10.1016/j.bbi.2015.02.006

13. Szabo Y, Newton T, Miller J, et al. Acute stress induces increases in salivary IL-10 levels. stress. 2016;19(5):499-505. doi: 10.1080/10253890.2016.1206885

14. Shcherbatykh SE. Influence of the parameters of higher nervous activity of students on the nature of the course of examination stress. Journal of Higher Nervous Activity. I.P. Pavlova. 2000;(6):959-65 [Shcherbatykh YuV. The influence of the parameters of the higher nervous activity of students on the nature of the exam stress. Zhurnal Vysshey Nervnoy Deyatel’nosti im. I.P. Pavlova. 2000;(6):959-65 (In Russ.)].

15. Snow W, Stoesz B, Kelly D, et al. Roles for NF-κB and Gene Targets of NF-κB in Synaptic Plasticity, Memory, and Navigation. Mol Neurobiol. 2013;49(2):757-70. doi: 10.1007/s12035-013-8555-y

16. O’Connor K, Johnson J, Hansen M, et al. Peripheral and central proinflammatory cytokine response to a severe acute stressor. Brain Res. 2003;991(1-2):123-32. doi: 10.1016/j.brainres.2003.08.006

17. Marsland A, Walsh C, Lockwood K, et al. The effects of acute psychological stress on circulating and stimulated inflammatory markers: A systematic review and meta-analysis. Brain Behav Immun. 2017;64:208-19. doi: 10.1016/j.bbi.2017.01.011

18. Shields G, Kuchenbecker S, Pressman S, et al. Better cognitive control of emotional information is associated with reduced proinflammatory cytokine reactivity to emotional stress. stress. 2016;19(1):63-8. doi: 10.3109/10253890.2015.1121983

19. Fernandes S, Koth A, Parfitt G, et al. Enhanced cholinergictone during the stress induce a depressive-like state in mice. Behav Brain Res. 2018;347:17-25. doi: 10.1016/j.bbr.2018.02.044

20. Theoharides T, Spanos C, Pang X, et al. Stress-induced intracranial mast cell degranulation: a corticotropin-releasing hormonemediated effect. endocrinology. 1995;136(12):5745-50. doi: 10.1210/endo.136.12.7588332

21. Herman J, McKlveen J, Solomon M, et al. Neural regulation of the stress response: glucocorticoid feedback mechanisms. Braz J Med Biol Res. 2012;45(4):292-8. doi: 10.1590/S0100-879X2012007500041

22. Ishii Y, Yamaizumi A, Kawakami A, et al. Anti-inflammatory effects of noradrenaline on LPS-treated microglial cells: Suppression of NFκB nuclear translocation and subsequent STAT1 phosphorylation. Neurochem Int. 2015;90:56-66. doi: 10.1016/j.neuint.2015.07.010

23. Elenkov I, Chrousos G. Stress Hormones, Th2/Th3 patterns, Pro/Anti-inflammatory Cytokines and Susceptibility to Disease. Trends Endocrinol Metabolism. 1999;10(9):359-68. doi: 10.1016/S1043-2760(99)00188-5

24. Bicknell R. Endogenous opioid peptides and hypothalamic neuroendocrine neurones. J Endocrinol. 1985;107(3):437-46. doi: 10. 1677/joe.0.1070437

25. Pfeiffer A, Herz A. Endocrine Actions of Opioids. Horm Metabol Res. 1984;16(08):386-97. doi: 10.1055/s-2007-1014801

26. Henry M, Gendron L, Tremblay M, et al. Enkephalins: Endogenous Analgesics with an Emerging Role in Stress Resilience. Neural Plast. 2017;2017:1-11. doi: 10.1155/2017/1546125

27. Plein L, Rittner H. Opioids and the immune system – friend or foe. Brit J Pharmacol. 2017;175(14):2717-25. doi: 10.1111/bph.13750

28. Ninkovic J, Roy S. Role of the mu-opioid receptor in opioid modulation of immune function. Amino Acids. 2011;45(1):9-24. doi: 10.1007/s00726-011-1163-0

29. McLaughlin P, McHugh D, Magister M, et al. Endogenous opioid inhibition of proliferation of T and B cell subpopulations in response to immunization for experimental autoimmune encephalomyelitis. BMC Immunol. 2015;16(1):24. doi:10.1186/s12865-015-0093-0

30. Joana P, Amaia A, Arantza A, et al. Central immune alterations in passive strategy following chronic defeat stress. Behav Brain Res. 2016;298:291-300. doi: 10.1016/j.bbr.2015.11.015

31. Pertsov S, Koplik E, Stepanyuk V, et al. Blood Cytokines in Rats with Various Behavioral Characteristics during Emotional Stress and Treatment with Interleukin-1β. Bull Exper Biol Med. 2009;148(2):196-9. doi: 10.1007/s10517-009-0668-y

32. Aschbacher K, Epel E, Wolkowitz O, et al. Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and future depressive symptoms. Brain Behav Immun. 2012;26(2):346-52. doi: 10.1016/j.bbi.2011.10.010

33. Swierkot J, Nowak B, Czarny A, et al. The Activity of JAK/STAT and NF-κB in Patients with Rheumatoid Arthritis. Adv Clin Expert Med. 2016;25(4):709-17. doi: 10.17219/acem/61034

34. Arleevskaya M, Shafigullina A, Filina Y, et al. Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women. Frontiers Immunol. 2017;8:1725. doi: 10.3389/fimmu.2017.01725

35. Anacker C, Zunszain P, Carvalho L, Pariante C. The glucocorticoid receptor: Pivot of depression and of antidepressant treatment? Psychoneuroendocrinology. 2011;36(3):415-25. doi: 10.1016/j.psyneuen.2010.03.007

36. Gouin JP, Glaser R, Malarkey WB, et al. Childhood abuse and inflammatory responses to daily stressors. Ann Behav Med. 2012;44(2):287-92. doi: 10.1007/s12160-012-9386-1

37. Chrousos G, Torpy D, Gold P. Interactions between the Hypothalamic-Pituitary-Adrenal Axis and the Female Reproductive System: Clinical Implications. Ann Intern Med. 1998;129(3):229. doi: 10.7326/0003-4819-129-3-199808010-00012

38. Cutolo M, Sulli A, Pizzorni C, et al. Hypothalamic-Pituitary Adrenocortical and Gonadal Functions in Rheumatoid Arthritis. Ann N Y Acad Sci. 2003;992(1):107-17. doi: 10.1111/j.1749-6632.2003.tb03142.x

39. Straub R, Paimela L, Peltomaa R, et al. Inadequately low serum levels of steroid hormones in relation to interleukin-6 and tumor necrosis factor in untreated patients with early rheumatoid arthritis and reactive arthritis. Arthritis Rheum. 2002;46(3):654-62. doi: 10.1002/art.10177

40. Masi A, Rehman A, Chatterton R, et al. Controlled Cohort Study of Serum Gonadal and Adrenocortical Steroid Levels in Males Prior to Onset of Rheumatoid Arthritis (pre-RA): A Comparison to pre-RA Females and Sex Differences among the Study Groups. Intern J Rheumatol. 2013;2013:1-11. doi: 10.1155/2013/284145

41. Neeck G, Klüter A, Dotzlaw H, et al. Involvement of the Glucocorticoid Receptor in the Pathogenesis of Rheumatoid Arthritis. Ann N Y Acad Sci. 2002;966(1):491-5. doi:10.1111/j.1749-6632.2002.tb04252.x

42. Fruchter O, Kino T, Zoumakis E, et al. The Human Glucocorticoid Receptor (GR) Isoform β Differentially Suppresses GRα-Induced Transactivation Stimulated by Synthetic Glucocorticoids. J Clin Endocrinol Metabol. 2005;90(6):3505-9. doi: 10.1210/jc.2004-1646

43. Duma D, Jewell C, Cidlowski J. Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification. J Steroid Biochem Mol Biol. 2006;102(1-5):11-21. doi:10.1016/j.jsbmb.2006.09.009

44. Weaver I, Cervoni N, Champagne F, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7(8):847-54. doi: 10.1038/nn1276

45. McGowan P, Sasaki A, D’Alessio A, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12(3):342-8. doi: 10.1038/nn.2270

46. Stockman J. Association of FKBP5 Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in Adults. Yearbook Pediatrician. 2009;2009:103-4. doi: 10.1016/S0084-3954(08)79072-9

47. Miller G, Murphy M, Cashman R, et al. Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers. Brain Behav Immun. 2014;41:191-9. doi: 10.1016/j.bbi.2014.05.016

48. Kozaci D, Chernajovsky Y, Chikanza I. The differential expression of corticosteroid receptor isoforms in corticosteroid-resistant and -sensitive patients with rheumatoid arthritis . Rheumatology. 2006;46(4):579-85. doi: 10.1093/rheumatology/kel276

49. Van Oosten M, Dolhain R, Koper J, et al. Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis. Arthritis Res Ther. 2010;12(4):R159. doi: 10.1186/ar3118

50. Koopman F, Tang M, Vermeij J, et al. Autonomic Dysfunction Precedes Development of Rheumatoid Arthritis: A Prospective Cohort Study. EBioMedicine. 2016;6:231-7. doi: 10.1016/j.ebiom.2016.02.029

51. Adlan A, Lip G, Paton J, et al. Autonomic function and rheumatoid arthritis – A systematic review. Semin Arthritis Rheum. 2014;44(3):283-304. doi: 10.1016/j.semarthrit.2014.06.003

52. Rovensky J, Imrich R, Penesova A, et al. Adrenomedullary Response to Hypoglycemia in First-degree Relatives of Patients with Rheumatoid Arthritis. Ann N Y Acad Sci. 2008;1148(1):552-5. doi: 10.1196/annals.1410.070

53. Wahle M, Hanefeld G, Brunn S, et al. Failure of catecholamines to shift T-cell cytokine responses towards a Th3 profile in patients with rheumatoid arthritis. Arthritis Res Ther. 2006;8(5):R138. doi:10.1186/ar2028

54. Elbeialy A, Elbarbary M, Kamel M. Peripheral Beta-Endorphin in Rheumatoid Arthritis: A Correlation with the Disease Activity. Scand J Rheumatol. 1997;26(2):88-91. doi: 10.3109/03009749709115824

55. Takeba Y, Suzuki N, Kaneko A, et al. Endorphin and enkephalin ameliorate excessive synovial cell functions in patients with rheumatoid arthritis. J Rheumatol. 2001;28(10):2176-83.

56. Yin H, Zhang F, Yu M, et al. Beta-Endorphin Ameliorates Synovial Cell Hyperfunction in the Collagen-Induced Arthritis Rat Model by Specific Downregulation of NF-kappa B Activity. neuroendocrinology. 2005;81(1):10-8. doi: 10.1159/000084828

57. Mousa S, Straub R, Schafer M, Stein C. Beta-endorphin, Metenkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis. Ann Rheum Dis. 2007;66(7):871-9. doi: 10.1136/ard.2006.067066

58. Maxwell L, Barrett B, Chase J, et al.