https://www.science.org/doi/10.1126/scitranslmed.abj9954
Beneficial inflammation
Chronic pain can develop from an acute pain state. The mechanisms mediating the transition from acute to chronic pain remain to be elucidated. Here, Parisien et al. focused on the immune system using samples from patients and animal models. Transcriptomic analysis in immune cells from subjects with low back pain showed that neutrophil activation–dependent inflammatory genes were up-regulated in subjects with resolved pain, whereas no changes were observed in patients with persistent pain. In rodents, anti-inflammatory treatments prolonged pain duration and the effect was abolished by neutrophil administration. 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.
Abstract
The transition from acute to chronic pain is critically important but not well understood. Here, 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.
Transcriptomic changes were compared between patients whose LBP was resolved at 3 months with those whose LBP persisted. 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 up-regulation of inflammatory responses was protective against the transition to chronic pain.
In mouse pain assays, early treatment with a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led to prolonged pain despite being analgesic in the short term; such a prolongation was not observed with other analgesics. Depletion of neutrophils delayed resolution of pain in mice, whereas peripheral injection of neutrophils themselves, or S100A8/A9 proteins normally released by neutrophils, prevented the development of long-lasting pain induced by an anti-inflammatory drug.
Analysis of pain trajectories of human subjects reporting acute back pain in the UK Biobank identified elevated risk of pain persistence for subjects taking NSAIDs. Thus, despite analgesic efficacy at early time points, the management of acute inflammation may be counterproductive for long-term outcomes of LBP sufferers.
Science daily article on this research:
Discovery reveals blocking inflammation may lead to chronic pain
Findings may lead to reconsideration of how we treat acute pain
https://www.sciencedaily.com/releases/2022/05/220512092711.htm
Beneficial inflammation
Chronic pain can develop from an acute pain state. The mechanisms mediating the transition from acute to chronic pain remain to be elucidated. Here, Parisien et al. focused on the immune system using samples from patients and animal models. Transcriptomic analysis in immune cells from subjects with low back pain showed that neutrophil activation–dependent inflammatory genes were up-regulated in subjects with resolved pain, whereas no changes were observed in patients with persistent pain. In rodents, anti-inflammatory treatments prolonged pain duration and the effect was abolished by neutrophil administration. 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.
Abstract
The transition from acute to chronic pain is critically important but not well understood. Here, 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.
Transcriptomic changes were compared between patients whose LBP was resolved at 3 months with those whose LBP persisted. 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 up-regulation of inflammatory responses was protective against the transition to chronic pain.
In mouse pain assays, early treatment with a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led to prolonged pain despite being analgesic in the short term; such a prolongation was not observed with other analgesics. Depletion of neutrophils delayed resolution of pain in mice, whereas peripheral injection of neutrophils themselves, or S100A8/A9 proteins normally released by neutrophils, prevented the development of long-lasting pain induced by an anti-inflammatory drug.
Analysis of pain trajectories of human subjects reporting acute back pain in the UK Biobank identified elevated risk of pain persistence for subjects taking NSAIDs. Thus, despite analgesic efficacy at early time points, the management of acute inflammation may be counterproductive for long-term outcomes of LBP sufferers.
Science daily article on this research:
Discovery reveals blocking inflammation may lead to chronic pain
Findings may lead to reconsideration of how we treat acute pain
https://www.sciencedaily.com/releases/2022/05/220512092711.htm