Acute pain is commonly treated with anti-inflammatory drugs. However, this practice may be short-sighted. According to a new study, inflammation may prevent acute pain from turning into chronic pain.
A transcriptome-wide analysis of peripheral immune cells from subjects with low back pain showed that neutrophil activation–dependent inflammatory genes were upregulated in subjects with resolved pain, whereas no changes were observed in patients with persistent pain. This finding—which suggests that anti-inflammatory drugs might be analgesic in the short term but prolong pain in the long term—was replicated in an independent cohort of patients with another musculoskeletal pain condition, temporomandibular disorder (TMD).
This work, which was carried out by McGill University researchers and their colleagues in Italy, was detailed in a paper (“Acute inflammatory response via neutrophil activation protects against the development of chronic pain”) that appeared in Science Translational Medicine. Besides presenting the transcriptomic findings, the paper described how rodent pain models were used to elucidate the mechanism mediating the transition from acute to chronic pain. Finally, the paper indicated that data from a large human cohort (UK Biobank) was used to clarify the relationship between back pain and the use of anti-inflammatory drugs.
“[We] investigated the pathophysiological mechanisms underlying the transition from acute to chronic low back pain (LBP) and performed transcriptome-wide analysis in peripheral immune cells of 98 participants with acute LBP, followed for 3 months,” the article’s authors wrote. “We found thousands of dynamic transcriptional changes over 3 months in LBP participants with resolved pain but none in those with persistent pain. Transient neutrophil-driven upregulation of inflammatory responses was protective against the transition to chronic pain.
“In rodents, anti-inflammatory treatments prolonged pain duration, and the effect was abolished by neutrophil administration,” the authors added. “Last, clinical data showed that the use of anti-inflammatory drugs was associated with increased risk of persistent pain, suggesting that anti-inflammatory treatments might have negative effects on pain duration.”
The senior authors of the article were McGill University’s Luda Diatchenko, MD, PhD, and Jeffrey S. Mogil, PhD, and Policlinico Monza’s Massimo Allegri, MD.
“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” said Diatchenko. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.” Mogil added that neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage. “Inflammation occurs for a reason,” he remarked, “and it looks like it’s dangerous to interfere with it.”
Experimentally blocking neutrophils in mice prolonged the pain up to 10 times the normal duration. Treating the pain with anti-inflammatory drugs and steroids like dexamethasone and diclofenac also produced the same result, although they were effective against pain early on.
These findings are also supported by a separate analysis of 500,000 people in the United Kingdom that showed that those taking anti-inflammatory drugs to treat their pain were more likely to have pain two to ten years later, an effect not seen in people taking acetaminophen or anti-depressants.
“Our findings suggest it may be time to reconsider the way we treat acute pain,” Allegri noted. “Luckily, pain can be killed in other ways that don’t involve interfering with inflammation.”
“We discovered that pain resolution is actually an active biological process,” Diatchenko declared. “These findings should be followed up by clinical trials directly comparing anti-inflammatory drugs to other pain killers that relieve aches and pains but don’t disrupt inflammation.”