Articles: pain-clinics.
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The peripheral inflammatory response is an attractive therapeutic target for pain treatment. Neutrophils are the first circulating inflammatory cells recruited to sites of injury, but their contribution to pain outcomes is unclear. We performed a systematic review and meta-analysis of original preclinical studies, which evaluated the effect of preemptive neutrophil depletion on pain outcomes (PROSPERO registration number: CRD42022364004). ⋯ Analyses regarding intervention unveiled a lower pain reduction for some commonly used methods for neutrophil depletion, such as injection of antineutrophil serum or an anti-Gr-1 antibody, than for other agents such as administration of an anti-Ly6G antibody, fucoidan, vinblastine, CXCR1/2 inhibitors, and etanercept. In conclusion, the contribution of neutrophils to pain depends on pain etiology (experimental model), pain outcome, and the neutrophil depletion strategy. Further research is needed to improve our understanding on the mechanisms of these differences.
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Visual exposure to dim, green, light has been found to reduce pain levels in patients living with migraine, low back pain, and fibromyalgia. Preclinical studies discovered that the analgesic effect of green light was due to the central release of endogenous opioids and a reduction in inflammatory cytokines in the cerebrospinal fluid. The present study assessed the effect of green light therapy (GLT) on joint pain in a rat model of osteoarthritis (OA) and investigated the role of endolipids. ⋯ Serum lipidomics indicated an increase in circulating analgesic endolipids in response to GLT, particularly the N-acyl-glycines. Partial blockade of the endocannabinoid system with the G protein receptor-18/cannabinoid-1 receptor antagonist AM281 (500 μg/kg i.p.) attenuated GLT-induced analgesia. These data show for the first time that GLT acts to reduce OA pain by upregulating circulating analgesic endolipids, which then engage the endocannabinoid system.
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Preclinical research supports a critical role for nervous system glia in pain pathophysiology. This systematic review of human trials of potential glia-modulating drugs for the prevention or treatment of pain followed a predefined search strategy and protocol registration. We searched for English language, randomized, double-blind trials comparing putative glia-modulating drugs to placebo or other comparators. ⋯ Only 6 trials reported a positive effect of the treatment (pentoxifylline-4 trials; minocycline-2 trials), whereas 11 trials reported mixed results and 9 trials reported no effect. This review does not provide convincing evidence of efficacy of current pharmacological targets of nervous system glial function for pain treatment or prevention. However, in light of ample preclinical evidence of the importance of neuroimmune signalling and glial functions in pain pathophysiology, continued strategic human research is anticipated to identify (1) drugs with maximal activity as selectively targeted glial modulators, (2) the necessary timing and duration of pharmacological glial modulation needed for pain prevention or treatment for specific injuries or pain conditions, and (3) the best design of future clinical trials of glial-targeted drugs for pain treatment and/or prevention.