Capsaicin, an agonist at the transient receptor potential vanilloid 1, is used for the topical treatment of peripheral neuropathic pain. Reversible receptor defunctionalization and degeneration and subsequent regeneration of cutaneous nociceptors are discussed as its mechanism of action. Here, we hypothesize an accelerated functional recovery of a subclass of nociceptive afferents, the peptidergic vasoactive nociceptors, as the potential cause of capsaicin analgesia. In this noninterventional exploratory trial, 23 patients with peripheral neuropathic pain were treated with one topical high-concentration capsaicin application. Baseline pain ratings, comorbidities, and quality of life were assessed. Functional laser speckle contrast analysis (heat-evoked neurogenic vasodilatation to assess functional properties of peptidergic nociceptors) and quantitative sensory testing were performed in the affected skin. Four weeks after treatment, functional laser speckle contrast analysis and questionnaires were repeated. Telephone interviews were conducted at weeks 2, 10, and 12. Topical capsaicin treatment induced a significant reduction in pain intensity with a maximum at 4 weeks. At the same time, heat-evoked neurogenic vasodilatation was on average similar to pretreatment values. Half of the patients not only showed a functional recovery but also an improvement in vasodilatation, indicating regeneration of nerve fibers. Patients with improved heat-evoked neurogenic vasodilatation at week 4 showed a greater pain reduction than those with deterioration. The degree of vasodilatation significantly correlated with pain reduction. These findings suggest that (1) regeneration of peptidergic nociceptors may be the mechanism behind capsaicin-induced analgesia and (2) that a disease-modifying effect of capsaicin on these fibers already occurs 4 weeks after application.

辣椒素是瞬时受体电位香草酸 1 的激动剂，用于局部治疗周围神经性疼痛。讨论了可逆性受体去功能化和退化以及随后皮肤伤害感受器的再生作为其作用机制。在这里，我们假设伤害性传入的一个亚类（肽能血管活性伤害性感受器）的加速功能恢复是辣椒素镇痛的潜在原因。在这项非介入性探索性试验中，23 名周围神经性疼痛患者接受了一次局部高浓度辣椒素应用治疗。评估基线疼痛等级、合并症和生活质量。在受影响的皮肤中进行功能性激光散斑对比分析（热诱发神经源性血管舒张以评估肽能伤害感受器的功能特性）和定量感觉测试。治疗四周后，重复进行功能性激光散斑对比分析和问卷调查。在第 2、10 和 12 周进行了电话采访。局部辣椒素治疗可显着降低疼痛强度，在第 4 周时达到最大程度。同时，热诱发的神经源性血管舒张平均与治疗前的值相似。一半的患者不仅表现出功能恢复，而且血管舒张也有所改善，表明神经纤维再生。第 4 周热诱发神经源性血管舒张改善的患者比恶化的患者疼痛减轻幅度更大。血管舒张程度与疼痛减轻显着相关。这些发现表明，(1) 肽能伤害感受器的再生可能是辣椒素诱导镇痛的机制，(2) 辣椒素对这些纤维的疾病缓解作用在施用后 4 周就已经出现。