Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, 24105, Kiel, Germany.
Pain. 2023 Mar 1;164(3):534-542. doi: 10.1097/j.pain.0000000000002735. Epub 2022 Jul 20.
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.
辣椒素是一种瞬时受体电位香草素 1 的激动剂，用于治疗周围神经性疼痛的局部治疗。其作用机制包括可还原的受体失功能和退化以及随后的皮肤伤害感受器的再生。在这里，我们假设一种伤害感受传入纤维的亚类，即肽能血管活性伤害感受器的功能恢复加速，这可能是辣椒素镇痛的潜在原因。在这项非干预性探索性试验中，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。评估了基线疼痛评分、合并症和生活质量。在受影响的皮肤中进行了功能性激光散斑对比分析（评估肽能伤害感受器功能特性的热诱发神经源性血管舒张）和定量感觉测试。治疗后 4 周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 周进行电话访谈。局部辣椒素治疗可显著降低疼痛强度，最大程度在 4 周时。同时，热诱发的神经源性血管舒张平均与预处理值相似。一半的患者不仅表现出功能恢复，而且血管舒张也得到改善，表明神经纤维再生。与恶化的患者相比，在第 4 周时热诱发神经源性血管舒张改善的患者疼痛减轻更大。血管舒张程度与疼痛减轻显著相关。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修饰作用在应用后 4 周就已经发生。
