Caring Medical - Where the world comes for ProlotherapyWhen NSAIDs make pain worse

Prolotherapy Knee articular cartilage repair without surgery

Ross Hauser, MD

In this article, Ross Hauser MD explains why chronic non-steroidal anti-inflammatory drug (NSAIDs) usage can make pain worse in the long-term and accelerate the need for joint replacement.

Below is a quote from new research in the medical journal Pain. In this statement doctors suggest that the reason joint replacement is recommended and performed is because NSAIDs do not work.

“Difficulty in managing advanced osteoarthritis pain often results in joint replacement therapy. Improved understanding of mechanisms driving NSAID-resistant ongoing osteoarthritis pain might facilitate development of alternatives to joint replacement therapy.”1

Other new research on failings of NSAIDs: The bullet points:

In our practice we see patients of all ages. We see the high school athlete, we see the great-grand parent. If both have knee problems – from sports related injury or age deterioration, both prior to their visit with us, they will likely be prescribed an NSAID. Why? Because doctors believe that NSAIDs still offer the best of both worlds – an anti-inflammatory medication and a pain reliever.

As such, NSAIDs are still considered the first-line treatment for osteoarthritis related pain despite significant side effects including PREVENTING HEALING and ACCELERATE osteoarthritis and joint deterioration.

A significant public health concern

Research from 2015 is “alarming.” Doctors note that due to the high risk of life-threatening side effects, NSAIDs are not favored for treating persistent non-cancerous pain in the elderly. 

Does Medicare pay for this? One research group says yes Medicare pays for inappropriate treatments.

Now listen to these staggering numbers – between 2000 and 2007 there were 206 MILLION doctor visits recorded for patients with an average age of 75. Most of the NSAIDs users had Medicare (75%), and about 25% were prescribed with adjuvant medications considered inappropriate for their age.

Compared to men, women were 1.79 times more likely to be prescribed NSAIDs. The researchers of this study concluded: “We recommend investigating the appropriateness (or inappropriateness) of the high prevalence of NSAIDs use among older patient.4

Treating or Suppressing Joint Pain?

Why have researchers failed to develop effective and safe disease modifying osteoarthritis drugs (DMOADs) for the millions of patients suffering from this serious and disabling disease? Because drugs do not repair damaged cartilage in joints.6

The treatment assumption is that stopping inflammation assists recovery.

Mostly because of a lack of adequate information provided by the prescribing physician, many patients are under the mistaken impression that these drugs not only reduce pain, but also promote healing. Nothing could be further from the truth. Inflammation is an integral part of the healing process.

No available evidence suggests that NSAIDs are able to promote the healing process

Non-steroidal anti-inflammatory drugs all inhibit release of prostaglandins and the healing process of soft tissues.

When a ligament or tendon is injured, prostaglandins are released which initiate vasodilation in non-injured blood vessels.

This enables healthy blood vessels to increase blood flow and immune cell flow to the injured area to begin the repair process.

The use of anti-inflammatories inhibits the release of prostaglandins thus ultimately decreasing the blood flow to the injured area.

Proteoglycans are essential for the elasticity and compressive stiffness of articular cartilage and suppression of their synthesis has significant adverse effects on the joint.

The key question regarding the healing of any injury is, “What exactly does any therapy do to the fibroblastic cells that actually grow the ligament and tendon tissue?” Treatments that stimulate fibroblast proliferation will cause ligament and tendon repair and will help with healing (Prolotherapy). Therapies that interfere with or destroy fibroblastic growth will be detrimental to the healing (NSAIDs)

Recently doctors reported that the use of NSAIDs prevented post-surgical healing,7 and as far back as 1995, in a classic study from the University of North Carolina, School of Medicine, Division of Orthopaedic Surgery, Sports Medicinesection found how detrimental NSAIDs use was in healing soft tissue. They separated study patients into groups:

All the tendons underwent injury through repetitive motion, similar to what would happen to an athlete in training. Seventy-two hours after the injury, it was noted that compared to controls the only group that showed increased levels of prostaglandins (inflammation) was the exercised group. The group that was exercised and received the NSAID, as well as the NSAID group, had statistically significant lower levels of prostaglandins (specifically Prostaglandin E2) in the tendons.

The researchers also measured DNA synthesis in the fibroblasts (repair mechanism). This showed which fibroblasts were proliferating. Again, the exercised group was the only group that exhibited elevated levels of DNA synthesis in the fibroblasts. Compared to the control group there was 100 percent more growth of fibroblasts in the exercise group. The tendons treated with NSAIDs had no DNA synthesis noted.

This showed there was no fibroblastic growth occurring. The group that exercised and took the NSAID showed a little bit of growth. The paper also stated a fact that many researchers in this field are wondering, “Despite the lack of scientific data, NSAIDs are widely used, often as the mainstay of treatment.”8  More than twenty years later – little has changed.

NSAIDs and the RICE treatment nearly eliminate the body’s ability to heal.

NSAIDs have been shown to delay and hamper the healing in all of the soft tissues, including muscles, ligaments, tendons, and cartilage. Anti-inflammatories can delay healing and delay it significantly, even in muscles with their tremendous blood supply. In combination with RICE therapy (Rest, Ice, Compression, and Elevation) NSAIDs will nearly eliminate the body’s ability to heal itself.

In one study on muscle strains, Piroxicam essentially wiped out the entire inflammatory proliferative phase of healing.In a study in The Journal of Hand Surgery, it was found that the ibuprofen doses used in the study caused the strength of the flexor tendons to decrease.10

NSAIDs a false sense of healing makes things worse

From the above studies, it is clear that NSAIDs inhibit the fibroblastic growth process and thus diminish the individual’s chance of healing. NSAIDs are used because they decrease pain, but they do so at the expense of hurting the healing of the injured soft tissue. A good example of this is a study on the use of Piroxicam in the treatment of acute ankle sprains in the Australian military.

Compared with the placebo group, the subjects treated with Piroxicam had less pain, were able to resume training more rapidly, were treated at lower cost, and were found to have increased exercise endurance on resumption of activity. At first glance in reviewing this study, NSAIDs appear to be great, but the real question is…did they help the ligament injury heal?

To test ligament healing, the ankles were tested via the anterior drawer test. During this test the ankle was moved forward to determine the laxity in the ligaments. In this study, at every date of testing after the initial injury, days three, seven, and fourteen, the Piroxicam-treated group demonstrated greater ligament instability.

At the time of the initial injury the ligament instability in the Piroxicam group and the control group were exactly the same. This study showed that the NSAID stopped ligament healing, yet the person felt better. The authors noted, “This result is of concern in that it may reflect a paradoxically adverse effect of the NSAID-derived analgesia in allowing subjects to resume activity prematurely.”11

Recently doctors tried to make the case that injecting Piroxicam and Hyaluronic Acid in combination reduced inflammation and acted effectively against knee osteoarthritis.12 This is effectively argued against in the companion paper Hyaluronic Acid Injections for knee osteoarthritis.

NSAIDs and the acceleration of the arthritis process

NSAIDs are truly anti-inflammatory in their mechanism of action. Since all tissues heal by inflammation, one can see why long-term use of these medications will have harmful effects. Osteoarthritis and other chronic pain disorders are not an ibuprofen or other NSAID deficiency. Their chronic long-term use will not cure, and will actually hamper soft tissue healing and accelerate the arthritic process.

In our own research article The Acceleration of Articular Cartilage Degeneration in Osteoarthritis by Nonsteroidal Anti-inflammatory Drugs, we noted: “For those using NSAIDs compared to the patients who do not use them, joint replacements occur earlier and more quickly and frequently. Massive NSAID use in osteoarthritic patients since their introduction over the past forty years is one of the main causes of the rapid rise in the need for hip and knee replacements, both now and in the future.”13

Other authors agree:

Summary Points NSAIDs negative impact on articular cartilage repair

In summary, NSAIDs remain among the most commonly used drugs in the world for the treatment of osteoarthritis despite potential for significant side effects and their negative impact on articular cartilage.”13

In 1995 a classic study revealed that after one year treatment with NSAIDs, the joint space in the knee showed significant deterioration – twice that of a group treated with placebo. 16 More than 20 years later, little has changed.

Please see our article Painkillers, prescription pain medications why we dont recommend them on this site.

Our treatment solutions

Please see our article: The use of Stem Cell Therapy in the treatment of joint and spine degeneration for new research on the use of stem cells for osteoarthritis.

  • Ross Hauser MD – Danielle Steilen, MMS, PA-C – Tim Speciale, DO

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1 Havelin J, Imbert I, Cormier J, Allen J, Porreca F, King T. Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis. J Pain. 2016 Mar;17(3):374-82.

2. Molto A, Granger B, Wendling D, Dougados M, Gossec L. Joint Bone Spine. 2016 May 26. Use of nonsteroidal anti-inflammatory drugs in early axial spondyloarthritis in daily practice: Data from the DESIR cohort.

3. da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, Trelle S. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2016 May 21;387(10033):2093-105.

4. Rianon N, Knell ME, Agbor-Bawa W, Thelen J, Burkhardt C, Rasu RS. Persistent nonmalignant pain management using nonsteroidal anti-inflammatory drugs in older patients and use of inappropriate adjuvant medications. Drug Healthc Patient Saf. 2015 Jan 29;7:43-50. doi: 10.2147/DHPS.S67425. eCollection 2015.

5. Danelich IM, Wright SS, Lose JM, Tefft BJ, Cicci JD, Reed BN. Safety of Nonsteroidal Antiinflammatory Drugs in Patients with Cardiovascular Disease. Pharmacotherapy. 2015 May 4. doi: 10.1002/phar.1584.

6. Buttgereit F, Burmester GR, Bijlsma JW. Non-surgical management of knee osteoarthritis: where are we now and where do we need to go? RMD Open. 2015 Feb 18;1(1):e000027. doi: 10.1136/rmdopen-2014-000027. eCollection 2015.

7. Ji C, Xiong Y, Pan X, Guo X, et al. Effect of non-steroidal anti-inflammatory drugs on the increasing the incidence of colonic anastomosis in rats. Int J Clin Exp Pathol. 2015 Jun 1;8(6):6126-34. eCollection 2015.

8. Almekinders, L. An in vitro investigation into the effects of repetitive motion and nonsteroidal anti-inflammatory medication on human tendon fibroblasts. American Journal of Sports Medicine. 1995; 23:119-123.

9. Greene, J. Cost-conscious prescribing of nonsteroidal anti-inflammatory drugs for adults with arthritis. Archives of Internal Medicine. 1992; 152:1995-2002.

10. Kulick, M. Oral ibuprofen: evaluation of its effect on peritendinous adhesions and the breaking strength of a tenorrhaphy. The Journal of Hand Surgery. 1986; 11A:100-119.

11. Slatyer, M. A randomized controlled trial of Piroxicam in the management of acute ankle sprain in Australian regular army recruits. American Journal of Sports Medicine. 1997; 25:544-553.

12. Park CW, Ma KW, Jang SW, Son M, Kang MJ. Comparison of piroxicam pharmacokinetics and anti-inflammatory effect in rats after intra-articular and intramuscular administration. Biomol Ther (Seoul). 2014 May;22(3):260-6. doi: 10.4062/biomolther.2014.037.

13. Hauser RA. The Acceleration of Articular Cartilage Degeneration in Osteoarthritis by Nonsteroidal Anti-inflammatory Drugs. Journal of Prolotherapy. 2010; 1(2):305-322.

14. Hochberg MC, Perlmutter DL, Hudson JI, Altman RD. Preferences in the management of osteoarthritis of the hip and knee: results of a survey of community-based rheumatologists in the United States. Arthritis Care Res. 1996;9(3):170–176.

15. Krijthe BP, Heeringa J, Hofman A, Franco OH, Stricher BH. Non-steroidal anti-inflammatory drugs and the risk of atrial fibrillation: a population-based follow-up study. BMJ Open. 2014; 4(4): doi:10.1136/bmjopen-2013-004059

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