Low back pain is the leading global cause (as well as within the U.S.) of years lived with disability (YLDs) in both men and women, with an incidence that increased 30% over a 17-year period. Estimated to account for roughly twice the burden (4.3 million years of lived with disability per year) of any health condition, JAMA Network Open cites 13% of U.S. adults as having chronic low back pain. While acute low back pain is often given minimal attention, the transition to chronic pain is substantial.
For instance, this same JAMA article reports that in a cohort of over 5,000 people with acute low back pain, 32% transition to chronic pain at 3 months, with a number of risk factors for progression, including obesity, smoking, higher baseline disability, as well as depression or anxiety. This study also used a 9-item instrument, the Subgroups for Targeted Treatment (STarT) Back tool (SBT), to identify people at greater risk for chronic pain. The risk for transitioning to chronic pain was also found to be independently associated with “early exposure to guideline nonconcordant care”, i.e., care not consistent with current guidelines, such as prescriptions for opioids, initial use of diagnostic imaging, etc. The results of a prospective cohort study published in 2025 in the journal PAIN suggest that how “acute” back pain is defined influenced the transition from acute to chronic back pain, with a strong case for a strict definition of acute low back pain, noting several predictors of progression to chronic pain, including pain intensity, disability, and depression.
Other trials raise concerns for the regular use of NSAIDs for acute low back pain. NSAIDs are frequently recommended or taken over the counter despite a Cochrane review finding that although NSAIDs have some short-term benefits for pain and reduced disability from acute low back pain, these benefits are small compared to placebo; “The magnitude of these effects is small and probably not clinically relevant” (italics added).
In addition to NSAIDs' well-established risks of mucosal injury, which may result in both overt and occult bleeding, acute kidney injury, etc., a study published in Science Translational Medicine raises the possibility that they may also promote chronic pain. This report was comprised of several analyses, most importantly a transcriptomics study of 98 participants with acute low back pain (part of a larger study, PainOMICs), a validation cohort with temporomandibular disorder (TMD), animal research with NSAIDs, and analysis of individuals with low back pain in the UK Biobank cohort.
In the transcriptomics analysis, among participants with acute low back pain, there was a substantial difference in transcriptomic changes between people whose pain persisted after three months and people whose pain resolved. Among people whose pain resolved, several thousand genes were differentially expressed over time, while no change was observed with persistent pain. A functional analysis indicated that with pain resolution, there was an acute neutrophil activation–dependent elevation of the inflammatory response that did not occur among people whose pain persisted (replicated in the validation cohort). In other words, the acute inflammatory response played a crucial role in preventing the transition from acute to chronic pain. This is consistent with the idea that acute inflammation programs its own resolution.
This research team then used assays in mice to evaluate various analgesics and anti-inflammatories, and found that although steroids (dexamethasone) and NSAIDs (diclofenac) improved pain, they also prolonged the resolution of various types of pain states (neuropathic, myofascial, and especially inflammatory), while analgesics without anti-inflammatory properties did not affect the duration of pain. This implies that the use of anti-inflammatory medications for acute inflammation may interrupt a process necessary for the resolution of inflammation.
The last analysis conducted by this team utilized data from the large UK Biobank cohort. They found that people with acute back pain who reported using NSAIDs were at a 1.76-fold greater risk for progressing to chronic back pain, adjusted for multiple potentially related factors. No effect of other medications was observed, including analgesics and antidepressants. These analyses should invite some degree of skepticism about the benign nature of NSAIDs; not only are benefits “probably not clinically relevant,” but they may interfere with pathways needed for the resolution of inflammation, potentially promoting the progression from acute to chronic low back pain.
Perhaps the best approach to supporting the resolution of inflammation has been documented for omega-3 fatty acids and their derivatives. Although only limited clinical trial data exist for low back pain, “pro-resolving mediators” are derived from omega-3 fatty acids, especially DHA and EPA. A growing body of evidence points to the resolution of inflammation as an active, not passive process, and one that depends primarily on lipid mediators derived from omega-3 fatty acids, including resolvins, protectins, and maresins. Supplementation with “specialized pro-resolving mediators” has shown efficacy for osteoarthritis and an ability to upregulate neutrophil and monocyte activity; hopefully, clinical trials will soon evaluate their effect on low back pain.
Related Biotics Research Products: