Articles: chronic.
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A well-recognized molecular entity involved in pain-related neuroplasticity is the N-methyl-D-aspartate receptor (NMDAR), which is crucial for developing chronic pain. Likewise, the pannexin 1 (Panx1) channel has been described as necessary for initiating and maintaining neuropathic pain, driving nociceptive signals dependent on spinal NMDAR through several possible mechanisms. Through behavioral, pharmacological, and molecular approaches, our study in male rats has revealed several key findings: (1) neurons located in spinal cord laminae I and II express functional Panx1 channels in both neuropathic and sham rats. ⋯ Notably, while 10Panx successfully alleviates hyperalgesia, it does not alter pSrc expression; and (4) NMDA-stimulated YOPRO-1 uptake in neurons of laminae I-II of spinal cord slices were prevented by the NMDAR antagonist D-AP5, the Src inhibitor PP2 (but not PP3), as well as with the 10Panx and carbenoxolone. Therefore, NMDAR activation in dorsal horn neurons triggers an NMDAR-Src-Panx1 signaling pathway, where Panx1 acts as an enhancing effector in neuropathic pain. This implies that disrupting the NMDAR-Panx1 communication (eg, through Src inhibitors and/or Panx1 blockers) may offer a valuable strategy for managing some forms of chronic pain.
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This systematic review and meta-analysis critically examined the evidence for peer support interventions to reduce pain and improve health outcomes in community-dwelling adults with chronic musculoskeletal pain (PROSPERO CRD42022356850). A systematic search (inception-January 2023) of electronic databases and grey literature was undertaken to identify relevant randomised controlled trials, with risk of bias and GRADE assessments performed on included studies. Meta-analyses used a generic, inverse-variance, random-effects model, calculating mean difference (MD) or standardised mean difference (SMD). ⋯ Pooled health service utilisation outcomes showed unclear estimates. Self-management, quality of life, and social support outcomes had mixed evidence. Despite low-very low evidence certainty, peer support interventions demonstrated small improvements over usual care and waitlist controls for some clinical outcomes, suggesting that peer support may be useful as an adjunct to other treatments for musculoskeletal pain.