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.

辣椒素是辣椒中的辛辣成分，会在人体中产生强烈的灼痛感。辣椒素选择性地激活瞬时受体电位香草素 1 (TRPV1)，它富含伤害性初级传入神经，并支持辣椒素诱导的灼痛机制。矛盾的是，辣椒素长期以来一直被用作镇痛剂。含有辣椒素的局部贴剂和可注射制剂的开发已导致在临床环境中用于治疗慢性疼痛状况，例如神经性疼痛和治疗骨关节炎的潜力。更详细地确定辣椒素诱导镇痛的神经生物学机制应为辣椒素治疗提供逻辑依据，并有助于克服治疗的局限性，其中包括治疗结果和程序不适的个体差异。低浓度的辣椒素诱导伤害感受器末端的短期去功能化。这种现象在数小时内是可逆的，因此可能无法解释临床益处。相比之下，高浓度的辣椒素导致由表达 TRPV1 的传入末端的消融介导的​​长期去功能化，从而导致持续数月的长效镇痛。最近的研究表明，辣椒素诱导的 Ca 高浓度的辣椒素导致由表达 TRPV1 的传入末端的消融介导的​​长期去功能化，导致持续数月的长效镇痛。最近的研究表明，辣椒素诱导的 Ca 高浓度的辣椒素导致由表达 TRPV1 的传入末端的消融介导的​​长期去功能化，导致持续数月的长效镇痛。最近的研究表明，辣椒素诱导的 Ca²⁺ /calpain 介导的轴突末端消融对于在神经性疼痛小鼠模型中产生长效镇痛是必要的。结合钙蛋白酶，轴突线粒体功能障碍和微管解体也可能导致辣椒素的长期影响。随着消融的传入末端的再生，镇痛效果随着时间的推移而减弱。进一步确定辣椒素诱导镇痛的神经生物学机制应该会导致更有效的非阿片类镇痛剂选择，并且副作用更少。