by Dr. David Borenstein, Medically Reviewed by Dr. C.H. Weaver M.D. 6/2022
On Tuesday, May 17, 2022, Gina Kolata reported on a study released in Science Translational Medicine reported by Marc Parisien and colleagues.1 The title of the article was “Acute inflammatory response via neutrophil activation protects against the development of chronic pain.” The main conclusion of the paper was that the use of nonsteroidal anti-inflammatory drugs may increase the risk of developing chronic low back pain. The article quoted Dr. James Weinstein, a former editor of the journal Spine, stating that individuals should run when their back hurts instead of taking nonsteroidals.
The investigators took blood cells from 98 acute low back pain patients who were followed for 3 months. The investigators studied gene markers of neutrophils, white cells that mediate inflammation. These markers were higher in individuals who had an inflammatory response and resolved their acute pain. Individuals with chronic low back pain had none of these inflammatory markers. Individuals who took NSAIDs for pain had a greater risk of extinguishing the inflammatory response and which resulted in chronic pain. They also replicated the study in patients with temporomandibular joint disease with acute pain. Those who recovered had a more intense and rapid inflammatory responses. Another part of the paper reported on experiments with mice with a model of nerve compression with sciatica. Treatments with dexamethasone, a steroid, resulted in a potential for chronic pain. The authors use repository data of 500,00 individuals who have medical conditions and drug use. A total of 2,163 people had acute low back pain, with 461 developing a chronic condition. Individuals who took NSAIDs had two times the risk of developing chronic back pain.
The limitations of this paper were multiple, some of which were listed by the authors. There was no control group without pain for the 98 patients with LBP. For example, were the neutrophil markers increased in individuals who did not have any pain? Also, the authors never interacted with the 98 patients with LBP. Was all the acute LBP exactly the same entity? Did they have muscle spasms, herniated disks, osteoarthritis, or spinal stenosis? Were individuals (age, sex, prior back events)who resolved their acute LBP treated exactly the same as individuals who developed chronic low back pain? Did the chronic LBP patients take NSAIDs for the entire 3 months or for only a week? Did those acute LBP individuals who had resolution of their pain take any NSAIDs during the entire 3 months of the study? Were they allowed any other category of medicine? Which NSAIDs were prescribed? Did they have long or short half-lives? Did the chronic LBP patients change NSAIDs during the 3month trial? Did all the study individuals go to physical therapy? Or were they encouraged to exercise in any way? Is chronic LBP just acute LBP that goes on longer or does it have a different mechanism? This study suggests individuals without an inflammatory response are destined to develop chronic LBP not because of NSAIDs but the lack of a neutrophil response as part of their usual immune function. Exactly how many of these individuals exist in the population is not answered by this study.
My editorial comment differs from that of this study. While an article by Chou2 reported on a systematic review of the use of NSAIDs for the treatment of back pain is used by Paisien et al, to state that “NSAIDs are minimally effective at best” I beg to differ. Asa rheumatologist who has used this class of agents for 40 years, they have had a beneficial effect on the functional outcome of my patients. Pain scores are useful, but is the patient functional when using a NSAID? Their chronic pain may be present but to what level? Are they able to do their activities of daily living? Also, the first NSAID may not work. On occasion, 3 or more NSAIDs need to be tried to find the agent that is effective and tolerated.
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I do believe that exercise is an important part of therapy for a wide range of musculoskeletal conditions. As I say to my patients “Motion is the Lotion.” Medicine is not the end goal. If individuals improve, drug therapy is not needed. Despite what was reported in The New York Times, the use of NSAIDs for the treatment of acute conditions is not over. Just ask the next gout patient you see if they will give up their NSAID of choice!
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- Parisien M et al: Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Sci Transl Med 14:eabj9954 (2022)
- Chou R et al: Systemic pharmacologic therapies for low back pain: A systematic review for an American College of Physicians clinical practice guideline. Ann Intern Med 166:480-492, 2017