Pain
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Neuropathic pain remains difficult to treat, with drug development hampered by an incomplete understanding of the pathogenesis of the condition, as well as a lack of biomarkers. The problem is compounded by the scarcity of relevant human peripheral tissues, including skin, nerves, and dorsal root ganglia. Efforts to obtain such samples are accelerating, increasing the need for standardisation across laboratories. ⋯ We achieved consensus on minimal recommended phenotyping, harmonised wet laboratory protocols, statistical design, reporting, and data sharing. Here, we also share a variety of relevant standard operating procedures as supplementary protocols. We envision that our recommendations will help unify human tissue research in the field and accelerate our understanding of how abnormal interactions between sensory neurons and their local peripheral environment contribute towards neuropathic pain.
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Pain perception is closely tied to the brain's anticipatory processes, particularly involving the suppression of sensorimotor α-oscillations, which reflect the system's readiness for incoming pain. Higher sensorimotor α-oscillation levels are correlated with lower pain sensitivity. Alpha transcranial alternating current stimulation (α-tACS) can enhance these oscillations, potentially reducing pain perception, with effects that may be sustained and influenced by the certainty of pain expectations. ⋯ In anticipatory brain oscillations, real α-tACS enhanced somatosensory α1-oscillations and increased midfrontal θ-oscillations in conditions of certainty, with θ-oscillation modulation showing sustained effects. Mediation analysis revealed that α-tACS reduced pain reactivity by enhancing somatosensory α1-oscillations but increased pain reactivity through the enhancement of midfrontal θ-oscillations, with the latter effect being more pronounced. These findings suggest that while α-tACS may provide pain relief through somatosensory α-oscillation augmentation, its stronger and longer-lasting impact on midfrontal θ-oscillations could lead to hyperalgesia, particularly in the context of certain pain expectations.
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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.
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We developed the SupportPrim PT clinical decision support system (CDSS) using the artificial intelligence method case-based reasoning to support personalised musculoskeletal pain management. The aim of this study was to evaluate the effectiveness of the CDSS for patients in physiotherapy practice. A cluster randomised controlled trial was conducted in primary care in Norway. ⋯ No significant between-group differences were found for GPE. For PSFS, there was a significant difference favouring the control group, but this was less than the prespecified difference of 15%. We identified several study limitations and recommend further investigation into artificial intelligence applications for managing musculoskeletal pain.
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Chemotherapy-induced peripheral neuropathic pain aggravates cancer survivors' life burden. Electroacupuncture (EA) has exhibited promising analgesic effects on neuropathic pain in previous studies. We investigated whether EA was effective in a paclitaxel-induced neuropathic pain mouse model. ⋯ Electroacupuncture effectively alleviated paclitaxel-induced mechanical allodynia, and the effect was attenuated by the chemogenetic activation of astrocytes in the RVM. In addition, inhibiting astrocytic calcium activity by using either IP3R2 knockout (IP3R2 KO) mice or microinjection of AAV-mediated hPMCA2 w/b into the RVM to reduce non-IP3R2-dependent Ca2+ signaling in astrocytes exhibited an analgesic effect on neuropathic pain, which mimicked the EA effect. The current study revealed the pivotal role of the RVM astrocytes in mediating the analgesic effects of EA on chemotherapy-induced peripheral neuropathic pain.