Acute inflammatory response via neutrophil activation protects against the development of chronic pain

医学 炎症 止痛药 慢性疼痛 免疫系统 急性疼痛 外围设备 转录组 免疫学 内科学 麻醉 物理疗法 基因表达 生物化学 化学 基因
作者
Marc Parisien,L. Lima,Concetta Dagostino,Nehmé El-Hachem,Gillian L. Drury,Audrey V. Grant,Jonathan Huising,Vivek Verma,Carolina B. Meloto,Jaqueline Raymondi Silva,Gabrielle Guanaes Silva Dutra,Teodora Markova,Hong Dang,Philippe A. Tessier,Gary D. Slade,Andrea G. Nackley,Nader Ghasemlou,Jeffrey S. Mogil,Massimo Allegri,Luda Diatchenko
出处
期刊:Science Translational Medicine [American Association for the Advancement of Science (AAAS)]
卷期号:14 (644) 被引量:167
标识
DOI:10.1126/scitranslmed.abj9954
摘要

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.
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