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A recent Canadian study offers important clue to why some back pain becomes chronic. The study suggests that taking anti-inflammatory drugs for acute pain inhibits healing, while also indicating that inflammation is the key to healing. The study, conducted by researchers at McGill University, found that neutrophils, a type of white blood cell that helps the body fight infection and dominates the early stages of inflammation, play a key role in resolving pain.[1]
In the last phase of the study, they examined data from the United Kingdom Biobank, a database of medical information obtained from half a million volunteers. Researchers found those taking anti-inflammatory drugs, like ibuprofen, naproxen, and diclofenac to treat their pain, were much more likely to have pain two to ten years later
By comparing blood samples between patients who had their pain resolved and those who didn’t, scientists found that people whose pain went away had experienced a lot of inflammation driven by neutrophils. Therefore the preliminary conclusion is that it might be better to endure the pain of an acute injury than to take anti-inflammatories.[2]
Anti-Inflammatories (NSAIDs)
Non-Steroidal Anti-inflammatory Drugs (NSAIDs) and cortico-steroids. have been a mainstay in treating ligament injuries, and sports injuries for many years, and are still widely prescribed and used, despite the fact that their efficacy and safety have been questioned by many studies, and many experts:
There are valid reasons to expect that NSAIDs might have an adverse effect on healing, since prostaglandin-induced inflammation is an early sequel in the cascade of injury- induced events. This response normally results in the recruitment of cells into the injured area where they remove necrotic debris and initiate the healing process. However, NSAIDs are known to specifically block the cyclooxygenase enzymes which catalyze the conversion of arachidonic acid to prostaglandins which would otherwise play a significant role in ligament healing.[3]
A study that looked into the use of the NSAID “piroxicam” in the Australian military for the treatment of acute ankle sprains found that while recruits were able to resume training more rapidly, over the long-term, those in the piroxicam-treated group experienced an increase in ankle instability. Multiple studies have been conducted on the cyclooxygenase-2 (COX-2) inhibitor class of NSAIDs, and researchers have concluded that the use of these medications inhibits ligament healing, and thus, leads to impaired mechanical strength.[4]
In a study, 180 rabbits received rotator cuff repairs. Immediately post-op the rabbits were given either a placebo, or one of two NSAIDs (celecoxib or indomethacin), for 2 weeks post-op. Five of the tendons in the NSAID group completely failed to heal whereas all the tendons in the control group healed, and collagen organization and maturation was significantly poorer in the NSAID group at 4 and at 8 weeks post-op. The study concludes that if the results of this study are verified in a larger animal model, the common practice of administering non-steroidal anti-inflammatory drugs after rotator cuff repair should be reconsidered.[5]
Another study demonstrated that NSAIDs provided short-term improvements in the initial week following the injury, but after 4 weeks the rabbits treated with NSAIDs had significantly decreased torque and tension production of their affected muscles. This study concluded that a brief course of NSAIDs provide short-term benefit, but created a detriment in long-term muscle function.[6]
NSAIDs have also been shown to delay fracture healing. Data from animal studies suggest that NSAIDs, which inhibit COX-2, can impair fracture healing due to the inhibition of the endochondral ossification pathway.[7]
Corticosteroid Injections
While Corticosteroid injections have been shown effective in decreasing inflammation and pain in ligament injuries for up to six to eight weeks, they also inhibit the histological, biochemical, and biomechanical properties of ligament healing. A review of 41 “high-quality” studies involving 2,672 patients, published in The Lancet, revealed only short-lived benefit from corticosteroid injections.[8]
Steroid injections into ligaments and tendons have also been known to inhibit fibroblast function and thus collagen synthesis even to the extent of causing collagen necrosis at the injection site.
Another article in The Lancet entitled “Corticosteroids: Short Term Gain for Long Term Pain,” concluded that: Non-steroidal anti-inflammatory drugs have no randomised trial evidence, expert opinion support, or a plausible mechanism to promote tendon healing, and might inhibit tendon healing. The evidence for specific exercise therapy is more encouraging than the evidence for corticosteroid injection, and exercise therapy is likely to promote protein synthesis via cell signaling (mechanotransduction). Specific exercise therapy might produce more cures at 6 and 12 months than one or more corticosteroid injections.[9]
Another problem with NSAIDS and corticosteroids is that patients may feel no discomfort and ignore early symptoms of ligament injury, which could cause further damage to the ligament, and thus, delay definitive healing. Pain is often signal of improper body use, which can cause joint and tissue damage, so masking pain allows one to continue the misuse without correcting it.
NSAIDs & Exercise
Many people take NSAIDS before or during exercise either to offset pre-existing joint pain (for example: osteoarthritis joint pain) so that one can exercise without discomfort, or to prevent muscle and tendon soreness that result from exercising.
Athletes at all levels and in a wide variety of sports swear by their painkillers. Approximately one-fourth to one-third of Olympic athletes report using NSAIDs three days prior to data collection for doping control. In some sports, this reported value is greater than 50%.[10] A study published on the website of the British Journal of Sports Medicine found that, at the 2008 Ironman Triathlon in Brazil, almost 60 percent of the racers reported using non-steroidal anti-inflammatory painkillers, which include ibuprofen, at some point in the three months before the event, with almost half downing pills during the race itself.[11] Although many athleted use NSAIDs before physical activity to reduce pain and inflammation, this claim lacks lscientific support, particularly when considering the underlying pathology of many sports related injuries.
Stuart Warden, assistant professor and director of physical therapy research at Indiana University says that: the prophylactic use of NSAIDs inhibits COX-mediated prostoglandin (PG) synthesis and has been found to reduce tissue adaptation to mechanical loading. The mechanical loading associated with exercise typically increases bone formation to alter bone mass and size to optimize skeletal strength. Numerous animal studies have demonstrated that loading-induced bone formation is substantially blunted when NSAIDs are administered prior to the introduction of a mechanical stimulus.
Warden goes on to say that a recent randomized controlled trial suggested that individuals taking NSAIDs prior to exercise exhibited an impaired skeletal adaptive response. These NSAID-mediated reductions in bone adaptation have the potential to reduce exercise-induced improvements in bone mass, size, and strength which over time can leave the skeletal system vulnerable to future injury, such as stress fracture.[12]
The painkillers also blunt the body’s response to exercise at a deeper level. Normally, the stresses of exercise activate a particular molecular pathway that increases collagen, and leads, eventually, to creating denser bones and stronger tissues. If “you’re taking ibuprofen before every workout, you lessen this training response,” Warden says. Your bones don’t thicken and your tissues don’t strengthen as they should. They may be less able to withstand the next workout. In essence, the pills athletes take to reduce the chances that they’ll feel sore may increase the odds that they’ll wind up injured — and sore.[13]
Warden also points out that there is a subset of athletes who are at risk of renal problems when they combine the use of anti-inflammatories with exercise, because the COX isozymes and prostaglandins have and important role in maintaining renal blood flow and the rate of glomular filtration. These effects are minimal under normal conditions, but can be become critical in conditions of stress, such endurance exercise. Renal blood flow and glomerular filtration rate are reduced by 40% to 50% during strenuous exercise and lead to a reduction in free water clearance. Inhibition of the COX isozymes and PGs exacerbate these changes. The clinical consequence includes an elevated risk of developing potentially life-threatening hyponatremia in endurance athletes who prophylactically use NSAIDs.[14]
Warden’s concerns are borne out by another study on runners in the Western States Endurance Run: a 100-mile test of human stamina held annually in the Sierra Nevada Mountains of California. Those runners taking over-the-counter ibuprofen pills before and during the race displayed significantly more inflammation and other markers of high immune system response afterward than the runners who hadn’t taken anti-inflammatories. The ibuprofen users also showed signs of mild kidney impairment and, both before and after the race, of low-level endotoxemia, a condition in which bacteria leak from the colon into the bloodstream.[15]
The Disturbing Dangers of Anti-Imflammatories
Over 100,000 people are hospitalized for GI bleeding from NSAID-related gastrointestinal complications, and there are at least 16,500 NSAID-related deaths a year among arthritis patients alone, and these values are considered “conservative.”
The figures for all NSAID users would be overwhelming, yet the scope of this problem is generally under-appreciated. If deaths from gastrointestinal toxic effects from NSAIDs were tabulated separately in the National Vital Statistics reports, these effects would constitute the 15th most common cause of death in the United States. Yet these toxic effects remain mainly a “silent epidemic,” with many physicians and most patients unaware of the magnitude of the problem. Furthermore these mortality statistics do not include deaths ascribed to the use of over-the-counter NSAIDS.”[16]
Gut problems can be exacerbated by combining exercise and NSAIDs. Dr. Kim van Wijck, has done several studies on the relationship of exercise, the intestines to anti-inflammatories. In the first study, healthy men cycled for 60 minutes at 70% of maximum workload capacity. Splanchnic hypoperfusion was assessed using gastric tonometry. Splanchnic hypoperfusion is common in various pathophysiological conditions, and is often considered to lead to gut dysfunction. Dr. van Wijck found strenuous physical exercise leads to loss of epithelial integrity, which may give rise to increased intestinal permeability with bacterial translocation and inflammation.[17]
In a second study, Dr. van Wijck and his colleagues added and interesting twist. This time they compared blood leakage in the small intestine with in several ways.
- Simply resting for an hour without exercising
- Taking 400 mg of Ibuprofen the night before and the morning of the visit to the lab and then resting for and hour.
- Exercising briskly on a stationary bike for an hour.
- Taking 400 mg of Ibuprofen the night before and the morning of the visit to the lab and then exercising briskly on a stationary bike for an hour.
At the end of each rest or ride, researchers drew blood to check whether the men’s small intestines were leaking.[18]
Dr. van Wijck found that blood levels of a protein indicating intestinal leakage were, in fact, much higher when the men combined bike riding with ibuprofen than during the other experimental conditions when they rode or took ibuprofen alone. Notably, the protein levels remained elevated several hours after exercise and ibuprofen.[19]
Conclusion
Many of the authors and researchers cited in this article came to a similar conclusion. Why are anti-inflammatories and steroid injections the treatment of choice for “inflammation” and traumatic injury, when there are many indications that they cause damage to the body on many levels? Many researchers have also noted that exercise and letting the natural inflammatory process take its course seems to achieve better results than the use of anti-inflammatories.
Perhaps it is because of fear of pain. One question the Canadian study (mentioned at the beginning of this article) raised for me was: is there actually a purpose to the pain itself? Perhaps pain is the messenger, and by killing the messenger we disrupt an internal communication system that manages the healing process. Perhaps we need to experience the pain to jump-start the healing process, and therefore fooling the body by killing pain through drugs that interrupt the inflammatory process and dull the pain is counter-productive.
A final series of questions from Dr, Bahram Jam:
I have always been puzzled by the proposal that when an injury occurs, we must immediately act to reduce and eliminate inflammation. I just have one question to ask: why? Can anyone answer why the normal inflammatory response post-acute trauma is not good for healing? For me, it is similar to proposing that the blood coagulation mechanism that occurs after an acute cut is pathological and must be reduced. Why?
Our mammalian ancestors spent hundreds of millions of years evolving and specifically humans have spent about 7 million years in the making. Survival of a species relies on effective physiological repairing of an injury when it inevitably occurs. Do we truly believe that the body’s natural inflammatory response that has evolved over millions of years is somehow wrong? If it is not wrong, then why do we try so hard to prevent, minimize and reduce inflammation? When did inflammation after an acute injury become a harmful toxic agent that must be eliminated at all costs?[20]
Notes:
[1] “Canadian study offers important clue to why some back pain becomes chronic Many take anti-inflammatory drugs for acute pain, but study suggests inflammation is key to healing” Peggy Lam CBC News · Posted: May 20, 2022 4:00 AM
[2] Ibid
[3] “Ligament Injury and Healing: A Review of Current Clinical Diagnostics and Therapeutics” Barbara Woldin, Ross Hauser et al. The Open Rehabilitation Journal · January 2013: DOI: 10.2174/1874943701306010001
[4] “Ligament Injury and Healing: A Review of Current Clinical Diagnostics and Therapeutics” Barbara Woldin, Ross Hauser et al.
[5] “Indomethacin and celecoxib impair rotator cuff tendon- to-bone healing” Cohen DB1, Kawamura S, Ehteshami JR, Rodeo SA. American Journal of Sports Medicine. 2006 Mar;34(3):362- 9.
[6] “Anti-inflammatory medication after muscle injury. A treatment resulting in short-term improvement but subsequent loss of muscle function.” Mishra DK1, Fridén J, Schmitz MC, Lieber RL. Journal of Bone Joint Surgery Am. 1995 Oct;77(10):1510-9
[7] “NSAIDs and fracture healing” Geusens, Piet; Emans, Pieter J.; de Jong, Joost J.A.; van den Bergh, JoopCurrent Opinion in Rheumatology: July 2013 – Volume 25 – Issue 4 – p 524-531. doi: 10.1097/BOR.0b013e32836200b8
[8] “Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials.” Brooke K Coombes , Leanne Bisset, Bill Vicenzino. Lancet:2010 Nov 20;376(9754):1751-67. doi: 10.1016/S0140-6736(10)61160-9
[9] “Corticosteroids: short-term gain for long-term pain?” Alexander Scott and Karim M Khan. The Lancet: Volume 376, ISSUE 9754, P1714-1715, November 20, 2010: https://doi.org/10.1016/S0140-6736(10)61308-6
[10] “Prophylactic use of nsaids by athletes: a risk/benefit assessment.” Stuart J. Warden, The Physician and Sports Medicine: ISSN – 0091-3847,April 2010, No. 1, Volume 38.
[11] “Phys Ed: Does Ibuprofen Help or Hurt During Exercise?” Gretchen Reynolds. The New York Times. September 1, 2009.
[12] “Prophylactic use of nsaids by athletes: a risk/benefit assessment.” Stuart J. Warden, The Physician and Sports Medicine: ISSN – 0091-3847,April 2010, No. 1, Volume 38.
[13] “Phys Ed: Does Ibuprofen Help or Hurt During Exercise?” Gretchen Reynolds. The New York Times. September 1, 2009.
[14] “Prophylactic use of nsaids by athletes: a risk/benefit assessment.” Stuart J. Warden,
[15] “Ibuprofen use, endotoxemia, inflammation, and plasma cytokines during ultramarathon competition.” David C. Neuman et al. Brain Behavior Immunology: 2006 Nov;20(6):578-84.
[16] “Recent considerations in nonsteroidal anti-inflammatory drug gastropathy” G. Singh et als. American Journal of Medicine 1998 Jul 27;105(1B):31S-38S. doi: 10.1016/s0002-9343(98)00072-2.
[17] “Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men.” Van Wick K. et al PLoS ONE. 2011;6:e22366. doi: 10.1371/journal.pone.0022366.
[18] “Aggravation of Exercise-Induced Intestinal Injury by Ibuprofen in Athletes. “Wan Wick, Kim et Al. Medicine & Science in Sports & Exercise: December 2012 – Volume 44 – Issue 12 – p 2257-2262 doi: 10.1249/MSS.0b013e318265dd3d.
[19] ”For Athletes, Risks From Ibuprofen Use” Gretchen Reynolds The New York Times December 5, 2012
[20] “Paradigm Shifts: Use of Ice & NSAIDS Post Acute Soft Tissue Injuries (Part 1 of 2)”. Dr. Bahram Jam, http://physicaltherapyweb.com/paradigm-shifts-use-icensaids-post-acute-soft-tissue-injuries-part-1-2
