Fight fire with fire: Neurobiology of capsaicin-induced analgesia for chronic pain
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2020-11-10Journal
Pharmacology and TherapeuticsPublisher
Elsevier Inc.Type
Article
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Capsaicin, the pungent ingredient in chili peppers, produces intense burning pain in humans. Capsaicin selectively activates the transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptive primary afferents, and underpins the mechanism for capsaicin-induced burning pain. Paradoxically, capsaicin has long been used as an analgesic. The development of topical patches and injectable formulations containing capsaicin has led to application in clinical settings to treat chronic pain conditions, such as neuropathic pain and the potential to treat osteoarthritis. More detailed determination of the neurobiological mechanisms of capsaicin-induced analgesia should provide the logical rationale for capsaicin therapy and help to overcome the treatment's limitations, which include individual differences in treatment outcome and procedural discomfort. Low concentrations of capsaicin induce short-term defunctionalization of nociceptor terminals. This phenomenon is reversible within hours and, hence, likely does not account for the clinical benefit. By contrast, high concentrations of capsaicin lead to long-term defunctionalization mediated by the ablation of TRPV1-expressing afferent terminals, resulting in long-lasting analgesia persisting for several months. Recent studies have shown that capsaicin-induced Ca2+/calpain-mediated ablation of axonal terminals is necessary to produce long-lasting analgesia in a mouse model of neuropathic pain. In combination with calpain, axonal mitochondrial dysfunction and microtubule disorganization may also contribute to the longer-term effects of capsaicin. The analgesic effects subside over time in association with the regeneration of the ablated afferent terminals. Further determination of the neurobiological mechanisms of capsaicin-induced analgesia should lead to more efficacious non-opioidergic analgesic options with fewer adverse side effects. Copyright 2020 The AuthorsSponsors
This work was supported by the National Institutes of Health R01 DE027731 and R35 DE030045 to MKC.Identifier to cite or link to this item
http://hdl.handle.net/10713/15185ae974a485f413a2113503eed53cd6c53
10.1016/j.pharmthera.2020.107743
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