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Naproxen knee pain: Comparison of the analgesic efficacy and safety of nonprescription doses of naproxen sodium and Ibuprofen in the treatment of osteoarthritis of the knee

Osteoarthritis of the knee: Which painkillers are effective? – InformedHealth.org

Created: July 18, 2019; Next update: 2021.

Osteoarthritis pain can often be treated effectively with anti-inflammatory painkillers. But higher doses are often needed. Due to the possible associated risks, it’s recommended that the painkillers be taken as needed rather than all the time.

Osteoarthritis is typically treated with painkillers known as non-steroidal anti-inflammatory drugs (NSAIDs). These medications have an anti-inflammatory and pain-relieving effect. Examples of NSAIDs include diclofenac, ibuprofen and naproxen. Two other anti-inflammatory painkillers with a similar effect are celecoxib and etoricoxib. These are COX-2 inhibitors (also known as coxibs). They are taken as tablets or directly applied to the painful joint in the form of a gel or cream.

Some NSAIDs can be bought at pharmacies without a prescription – for example, to treat a headache or menstrual pain. To achieve noticeable pain relief in osteoarthritis, though, higher doses are often needed, and they have to be prescribed by a doctor.

NSAIDs and coxibs can relieve pain effectively, but they can also have side effects. The risk of serious side effects depends on your age and any other medical conditions you may have. But anti-inflammatory painkillers aren’t suitable for everyone. People who already have other illnesses, like kidney problems or stomach ulcers, may not be able to take them or may have to go for regular check-ups. Sometimes reducing the dose is enough. Other reasons not to take NSAIDs or coxibs may include interactions with certain medications like acetylsalicylic acid (ASA). Alternatively, you can apply a cream or gel with a drug like diclofenac to your knee. Studies show that this can effectively relieve pain in some people with osteoarthritis of the knee. The drug etofenamate is available in the form of a cream or gel too. But its effectiveness hasn’t been studied in good-quality studies.

Some people worry too much about the possible risks associated with painkillers. A few also worry about becoming dependent on them. But unlike opiate-based painkillers (opioids), NSAIDs and coxibs have no addictive effect. Other people worry that taking painkillers might prevent them from feeling alarm signals sent by their bodies. There’s no medical reason to worry, though: Chronic pain tells you much less about the condition of your joints than you might think.

It’s best to use anti-inflammatory painkillers in addition to other treatments, like exercise therapy. If you’re thinking of taking painkillers right before exercising, it’s a good idea to ask your doctor first.

How are NSAIDs and coxibs used?

There are a number of different NSAIDs and coxibs. The table below lists the names and doses of the drugs that are most commonly used to relieve osteoarthritis pain:

Drug Typical single dose Maximum daily dose
Celecoxib behandlung-jztable1_1_1_2_1 hd_b_i3275.behandlung-jztable1_1_1_1_2″ rowspan=”1″ colspan=”1″>
100 to 200 mg 
400 mg
Diclofenac 50 to 100 mg (extended release) 150 mg
Etoricoxib 30 to 60 mg 60 mg
Ibuprofen 400 to 800 mg 2,400 mg
Naproxen behandlung-jztable1_1_1_6_1″ rowspan=”1″ colspan=”1″>
250 to 500 mg 
1,000 mg

Experts recommend that you only use these medications when the pain is bad rather than using them continuously. That can lower the risk of side effects.

It’s best to start at a low dose and increase it if necessary. It’s important not to exceed the maximum daily dose of a drug.

What can I expect from NSAIDs and coxibs?

Anti-inflammatory painkillers don’t always make the pain go away completely, but they usually relieve it. A group of researchers from Bern analyzed high-quality studies on the effects of NSAIDs, coxibs, and acetaminophen (paracetamol) in osteoarthritis – a total of more than 70 studies with almost 60,000 participants. The most effective painkillers were diclofenac (150 mg per day) and etoricoxib (60 mg per day). Acetaminophen isn’t effective for osteoarthritis.

Whether or not a drug works will also depend on whether you have any other medical conditions and are using any other medication. That’s why it’s helpful to talk with your doctor before starting a treatment. She or he may check your kidney function, among other things, to make sure that you can safely use certain medications.

How common are side effects when taking NSAIDs and coxibs?

The most common side effects of anti-inflammatory painkillers are stomach problems. They range from minor problems like indigestion and stomach ache to more serious problems like gastritis (inflammation of the stomach lining), ulcers, and bleeding in the stomach or bowel (gastrointestinal bleeding). Taking medications with a meal can help.

Medications to protect the stomach, like omeprazole or pantoprazole, can effectively prevent gastrointestinal problems. They are from a group of drugs known as proton pump inhibitors (PPIs) and reduce the production of acid in the stomach. Studies show that this makes gastrointestinal complications relatively rare:

  • When taken for one year together with a PPI, high-dose diclofenac or etoricoxib lead to gastrointestinal complications in 0. 2 to 0.4% of people.

  • This risk is higher with high-dose ibuprofen or naproxen, at 0.6 to 1.6%.

Proton pump inhibitors can interfere with the effects of other medications, though. There’s also some evidence to suggest that the long-term use of PPIs can increase the risk of bone fractures.

High-dose NSAIDs and coxibs can also increase the likelihood of developing cardiovascular diseases such as heart attacks and strokes: by less than 1% per year. Naproxen is an exception. In studies, this medication had little influence on the risk of cardiovascular diseases.

What are the possible reasons not to take NSAIDs and coxibs?

Various factors increase the risk of gastrointestinal problems. These problems are more common in people who

  • are over 65 years old,

  • have already had gastritis, an ulcer or stomach bleeding,

  • have a bacterial infection with Helicobacter pylori,

  • drink a lot of alcohol,

  • take blood-thinning heart medicines, for example anticoagulants like warfarin or acetylsalicylic acid (the drug in medicines like “Aspirin”),

  • take corticosteroids (“steroids”),

  • take a selective serotonin reuptake inhibitor (SSRI) antidepressant,

  • take several anti-inflammatory painkillers at the same time, or

  • have certain gastrointestinal conditions like Crohn’s disease or ulcerative colitis.

If your risk of stomach bleeding or other serious complications is very high, it can be a good idea to talk with your doctor about other treatments.

People who have cardiovascular disease or several risk factors for it should also carefully consider the advantages and disadvantages of treatment with an NSAID or coxib. Treating pain with naproxen may be a good option for them since it doesn’t affect the heart or the circulatory system.

Is the painkiller metamizole (“Novalgin”) an alternative?

Metamizole is a fever-reducing and inflammation-reducing painkiller similar to NSAIDs. But there are no studies on its effectiveness in people with osteoarthritis or comparing it with other treatments. Although this drug is often used in Germany, it’s not approved for the treatment of osteoarthritis and is not recommended by medical societies.

The use of metamizole is the subject of debate because it can lead to a rare but serious side effect known as agranulocytosis. This side effect causes a big drop in the number of certain white blood cells in the body, which can be life-threatening. Possible signs of agranulocytosis are fever, sore throat, and inflamed mucous membranes. The risk of this side effect is estimated to be far below 0.1%.

Are opioid painkillers helpful in osteoarthritis?

Opioids are prescription painkillers that are used in emergency and intensive care to induce anesthesia and to treat cancer-related pain. Morphine is the best-known opioid drug. Other opioids include buprenorphine, codeine, hydromorphone, oxycodone, tapentadol, tilidine and tramadol.

Opioids can relieve acute pain very effectively. But, contrary to popular belief, this is not true for chronic osteoarthritis pain: Studies now show that they often don’t help in osteoarthritis any better than NSAIDs do. There’s also some evidence that they could become less effective after only a few weeks.

Opioids may be a good choice if several drugs are needed for the short-term treatment of severe pain or to bridge the time until surgery. They’re also an option for people who can’t take NSAIDs.

When it comes to osteoarthritis pain, though, opioids shouldn’t be used routinely or for longer time periods. They can cause side effects like constipation, nausea, lack of sexual desire, dizziness, and tiredness, as well as affect your ability to drive. There’s also a low risk of a life-threatening overdose. So it’s very important to follow your doctor’s instructions on how to take them, and not to increase the dose without talking to your doctor first. The same is true for opioid skin patches (fentanyl patches).

Experts recommend not using opioids for longer than one to three months because they can be physically addictive. According to estimates from studies, about 6% of people become addicted after using them for a longer time.

The use of opioids is not recommended for people who already have a headache disorder, fibromyalgia, inflammation of the pancreas, inflammatory bowel disease or an addiction problem.


  • Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382(9894): 769-779. [PMC free article: PMC3778977] [PubMed: 23726390]

  • Busse JW, Craigie S, Juurlink DN, Buckley DN, Wang L, Couban RJ et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ 2017; 189(18): E659-E666. [PMC free article: PMC5422149] [PubMed: 28483845]

  • Da Costa BR, Nüesch E, Kasteler R, Husni E, Welch V, Rutjes AW et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev 2014; (9): CD003115. [PubMed: 25229835]

  • Da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet 2017; 390(10090): e21-e33. [PubMed: 28699595]

  • Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie (DGOOC). S2k-Leitlinie: Gonarthrose. AWMF-Registernr.: 033-004. January 18, 2018.

  • Häuser W, Bock F, Engeser P, Tölle T, Willweber-Strumpf A, Petzke F. Langzeitanwendung von Opioiden bei nichttumorbedingten Schmerzen. Dtsch Arztebl Int 2014; 111(43): 732-740. [PMC free article: PMC4238316] [PubMed: 25404530]

  • Hurley M, Dickson K, Hallett R, Grant R, Hauari H, Walsh N et al. Exercise interventions and patient beliefs for people with hip, knee or hip and knee osteoarthritis: a mixed methods review. Cochrane Database Syst Rev 2018; (4): CD010842. [PMC free article: PMC6494515] [PubMed: 29664187]

  • Smith SR, Deshpande BR, Collins JE, Katz JN, Losina E. Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review. Osteoarthritis Cartilage 2016; 24(6): 962-972. [PMC free article: PMC4996269] [PubMed: 26844640]

  • IQWiG health information is written with the aim of helping
    people understand the advantages and disadvantages of the main treatment options and health
    care services.

    Because IQWiG is a German institute, some of the information provided here is specific to the
    German health care system. The suitability of any of the described options in an individual
    case can be determined by talking to a doctor. We do not offer individual consultations.

    Our information is based on the results of good-quality studies. It is written by a
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Pain Relievers Like Ibuprofen and Naproxen May Worsen Arthritis Inflammation

According to new research, taking anti-inflammatory pain relievers like ibuprofen and naproxen for osteoarthritis may actually worsen inflammation in the knee joint over time.

Taking anti-inflammatory pain relievers like ibuprofen and naproxen for osteoarthritis may worsen inflammation in the knee joint over time. This is according to a new scientific study being presented at the annual meeting of the Radiological Society of North America (RSNA) next week.

As the most common form of arthritis, osteoarthritis (OA) affects more than 32 million adults in the U.S. and more than 500 million people worldwide. It occurs most frequently in the hands, hips, and knees. In people with osteoarthritis, the cartilage that cushions the joint gradually wears away. This is why it is sometimes called degenerative joint disease or “wear and tear” arthritis. Arthritis is often accompanied by inflammation, or swelling, of the joint, which can be painful.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for osteoarthritis pain and inflammation. Common NSAIDs include Ibuprofen (Advil, Motrin) and naproxen (Aleve). However, little is known about the long-term effects of these drugs on disease progression.

“To date, no curative therapy has been approved to cure or reduce the progression of knee osteoarthritis,” said the study’s lead author, Johanna Luitjens, postdoctoral scholar in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco. “NSAIDs are frequently used to treat pain, but it is still an open discussion of how NSAID use influences outcomes for osteoarthritis patients. In particular, the impact of NSAIDs on synovitis, or the inflammation of the membrane lining the joint, has never been analyzed using MRI-based structural biomarkers.”

The fat pad adjacent to the kneecap (Hoffa’s fat pad, infrapatellar fat pad) can change in signal on MRI when the knee is inflamed. (A) Normal knee without signs of inflammation. (B) Arrow pointing on a circumscribed area with higher signal (bright lines) in the area of the fat pad (normally dark), which is indicative of a beginning inflammatory reaction. (C) The whole fat pad has a higher signal (light grey color with white lines), which is a sign of progressive inflammation of the knee joint. Credit: RSNA and Johanna Luitjens

Dr. Luitjens and colleagues set out to analyze the association between NSAID use and synovitis in patients with osteoarthritis of the knee and to assess how treatment with NSAIDs affects joint structure over time.

“Synovitis mediates development and progression of osteoarthritis and may be a therapeutic target,” Dr. Luitjens said. “Therefore, the goal of our study was to analyze whether NSAID treatment influences the development or progression of synovitis and to investigate whether cartilage imaging biomarkers, which reflect changes in osteoarthritis, are impacted by NSAID treatment.”

For the study, 277 participants from the Osteoarthritis Initiative cohort with moderate to severe osteoarthritis and sustained NSAID treatment for at least one year between baseline and four-year follow-up were included in the study and compared with a group of 793 control participants who were not treated with NSAIDs. All participants underwent 3T MRI of the knee initially and after four years. Images were scored for biomarkers of inflammation.

Cartilage thickness, composition, and other MRI measurements served as noninvasive biomarkers for evaluating arthritis progression.

The results showed no long-term benefit of NSAID use. Joint inflammation and cartilage quality were worse at baseline in the participants taking NSAIDs, compared to the control group, and worsened at four-year follow-up.

“In this large group of participants, we were able to show that there were no protective mechanisms from NSAIDs in reducing inflammation or slowing down the progression of osteoarthritis of the knee joint,” Dr. Luitjens said. “The use of NSAIDs for their anti-inflammatory function has been frequently propagated in patients with osteoarthritis in recent years and should be revisited, since a positive impact on joint inflammation could not be demonstrated.”

According to Dr. Luitjens, there are several possible reasons why NSAID use increases synovitis.

“On the one hand, the anti-inflammatory effect that normally comes from NSAIDs may not effectively prevent synovitis, with progressive degenerative change resulting in worsening of synovitis over time,” she said. “On the other hand, patients who have synovitis and are taking pain-relieving medications may be physically more active due to pain relief, which could potentially lead to worsening of synovitis, although we adjusted for physical activity in our model.

Dr. Luitjens noted that prospective, randomized studies should be performed in the future to provide conclusive evidence of the anti-inflammatory impact of NSAIDs.

Co-authors are Charles McCulloch, Ph.D., Thomas Link, M.D., Ph.D., Felix Gassert, M.D., Gabby Joseph, Ph.D., and John Lynch, Ph.D.

Meeting: 108th Scientific Assembly and Annual Meeting of the Radiological Society of North America

What is the most effective drug in the treatment of patients with knee osteoarthritis?


Despite the high prevalence
gonarthritis (knee osteoarthritis), currently a limited number
studies comparing therapeutic strategies with each other.

In this connection, the results
meta-analysis published in January 2015 in the Annals of Internal

The authors of the publication analyzed
randomized clinical trials (RCTs) that have
comparison of two or more drugs used in the treatment of primary
knee osteoarthritis. The following drugs were included in the analysis: acetaminophen
(paracetamol), celecoxib, diclofenac, ibuprofen, naproxen, intra-articular
corticosteroid and hyaluronic acid injections and oral and injectable

RCT results were taken from MEDLINE,
EMBASE, Web of Science, Google Scholar, Cochrane Central Register of Controlled
Trials, US Food and Drug Administration registry, ClinicalTrials.gov, information
on the websites of pharmaceutical companies. A total of 137 studies were found with 33
243 participants from 1980 to 2014. Of these, 129 (n=32,129) assessed pain
syndrome, in 76 (n=24059) joint function and in 55 (n=18267) stiffness


All drugs reduced pain in patients
after 3 months compared with oral placebo. Hyaluronic acid
was more effective than any other drugs (effect size 0.63 (95% CI, 0.39 –
0.88). The least effective was acetaminophen (effect size 0.18 (95% CI,
0.04 -0.33),

Only slightly more effective than acetaminophen
celecoxib, which is very surprising since previous studies
demonstrated a good effect of COX-2 inhibitors.

Injections were more effective in reducing pain than
than oral medication, and placebo injections are more effective than
most oral non-steroidal anti-inflammatory drugs. At
In this study, the researchers drew attention to the fact that injections can relieve pain
by introducing any fluid into the intraarticular space.

Analysis of the results of RCTs assessing the reduction
rigidity showed that naproxen, ibuprofen, diclofenac and celecoxib were
more effective than oral placebo and acetaminophen, and injections
hyaluronic acid was superior in effect to intra-articular injection

To improve joint function, all interventions
other than corticosteroid injections were more effective than oral placebo.
Naproxen, ibuprofen, diclofenac and celecoxib were more effective
acetaminophen. Hyaluronic acid was more effective than placebo injections and

Retrieved : Raveendhara R. Bannuru, MD;
Christopher H. Schmid, PhD; David M. Kent, MD; Elizaveta E. Vaysbrot, MD; John
B. Wong, MD; and Timothy E. McAlindon, MD. Comparative Effectiveness of
Pharmacologic Interventions for Knee Osteoarthritis: A Systematic Review and
Network meta-analysis. Annals of Internal Medicine. January 2015, Vol. 162. No.
19 13 . .

Joint pain | Nalgezin

Pain in the knee joint

The knee joint is enclosed in a sealed joint capsule (bag), inside the joint capsule there is a synovial membrane containing synovial fluid. Synovial fluid ensures the normal mobility of the cartilage that covers the articular surfaces of the bones. The function of cartilage is to glide and cushion during movement. The upper and lower parts of the joint are separated by two discs (menisci).

The main causes of knee pain are:
  • wear of the patella and cartilage which occurs when the patella is displaced and this puts pressure on the femur and cartilage,
  • arthrosis
  • joint wear and tear causes the release of inflammatory factors leading to pain,
  • knee injury (stress, sprains/dislocations, ligament tears, articular cartilage injuries),
  • tissue damage induces secretion of inflammatory factors resulting in pain,
  • inflammation of the tendons and sheaths due to excessive or repeated pressure on the knee joint.
There are other factors that contribute to the development of pain in the knee joint:
  • thigh muscle weakness
    often due to weakness and stiffness of the thigh muscles, a dislocation of the patella develops, which leads to tissue damage and, as a result, the development of pain,
  • flat feet
    flat feet cause weight to be distributed incorrectly across the foot, causing the knee joints to move in an unusual way, which will eventually lead to pain,
  • being overweight
    being overweight puts more stress on your spine, causing bone damage and pain.
Pain in the knee can be relieved if
  • rest is provided, minimizing movement as much as possible,
  • avoid hypothermia of the sore knee, therefore warm compresses are preferred,
  • maintain optimal body weight.
  • do special gymnastics.

Pain in the elbow joint

The elbow joint consists of three bones – the bone of the upper arm or humerus and two bones of the forearm: the radius and the ulna.

The most common causes of elbow pain are:
  • inflammation of the tendons due to excessive stress on the joint
    inflammation leads to the secretion of inflammatory factors, which causes pain,
  • co-infections
    formation of inflammatory factors as a reaction to infections, which in turn causes pain,
  • sprain
    tissue damage causes secretion of inflammatory factors that cause pain,
  • rheumatism
    in rheumatism, pain is caused by inflammation (arthritis) or wear and tear of the joint (arthrosis), both of which involve the secretion of inflammatory factors that lead to the development of pain.
Elbow pain can be relieved if:
  • to provide rest to the joint and eliminate stress that causes pain (if the pain is caused by increased stress),
  • apply cold compresses for 30 minutes,
  • do special gymnastics.

Pain in the shoulder joint

Pain in the shoulder joint can be caused by many causes:

  • trauma
    trauma leads to the development of inflammation, the synthesis of inflammatory factors, which leads to pain,
  • increased load
    increased load leads to tissue damage, synthesis of inflammatory factors, which causes pain,
  • rheumatism
    in rheumatism the pain is caused by inflammation (arthritis) or wear and tear of the joint (arthrosis), both of which cause the secretion of inflammatory factors that lead to the development of pain,
  • pain from other parts of the body (for example, from the neck, head, organs in the chest or abdomen).

Shoulder pain and mobility of the shoulder joint may worsen if additional stress is placed on the affected joint.

Pain in the shoulder joint can be relieved by:
  • resting the joint and eliminating stress that causes pain (if the pain is caused by increased stress),
  • use warm compresses,
  • carry out special gymnastics.

Pain in the hip joint

The main cause of pain in the hip joint is arthrosis, which promotes the synthesis of inflammatory factors that cause pain.

Pain in the hip joint can be relieved by:
  • resting the joint and eliminating stress that causes pain (if the pain is caused by increased stress),
  • carry out special gymnastics.


Rheumatism is accompanied by pain in the joint, which is most often the result of degenerative changes (arthrosis), less often the result of inflammation (arthritis). These changes cause a more or less noticeable rigidity of the body, interfere with movement and are often accompanied by swelling and pain in the joints.

There are several types of joint diseases:

Arthritis – inflammation of the joint

Arthritis – an inflammatory rheumatic disease. This autoimmune disease is characterized by the development of edema of the synovial membranes, which causes pain, local fever and swelling around the joints. Further, there is a rapid division of cells in the focus of inflammation, which leads to a thickening of the synovial membrane. Inflamed cells release an enzyme that attacks bones and cartilage, leading to joint deformity, increased pain, and loss of movement.

Usually, arthritis primarily affects the small joints (fingers and toes), later it also affects the ankle, wrist, knee and elbow joints. The disease can spread to other organs.

Arthrosis is a lesion of the cartilage tissue of the articular surfaces

Arthrosis affects not only the articular cartilage, but the entire joint. This is a degenerative-dystrophic disease that usually develops with age.

Over the years, the cartilage loses its integrity, it begins to crumble and gradually becomes thinner or completely disappears. After this, increased bone formation and the appearance of bone growths or osteophytes begin. There is pain, especially with overload, and there is also morning stiffness of the joints, stiffness after a period of rest and limited movement.

The causes of the development of the disease are not fully understood. Arthrosis can be the result of mechanical and biological factors, as well as occur as a result of trauma, metabolic disorders. Osteoarthritis is often caused by genetic factors.

What can be done for rheumatism?

The doctor must first make a diagnosis and prescribe the appropriate treatment. Responsibility of patients and comprehensive rehabilitation are very important for the successful treatment of this disease, which requires the joint efforts of the doctor, patient and physiotherapist.

What can you do on your own to alleviate the illness?
  • Reduce physical activity,
  • Exercise regularly to help:
    • weight loss with overweight,
    • maintaining muscle tone,
    • symptom control,
  • recommended swimming, cycling and short walks with frequent rest stops,
  • for moderate pain – analgesic Nalgezin, which has an anti-inflammatory effect and relieves pain.