Nolano M, Simone D A, Wendelschafer-Crabb G, Johnson T, Hazen E, Kennedy W R
The Salvadore Maugeri Foundation, Campoli MT, Italy.
Pain. 1999 May;81(1-2):135-45. doi: 10.1016/s0304-3959(99)00007-x.
Capsaicin applied topically to human skin produces itching, pricking and burning sensations due to excitation of nociceptors. With repeated application, these positive sensory responses are followed by a prolonged period of hypalgesia that is usually referred to as desensitization, or nociceptor inactivation. Consequently, capsaicin has been recommended as a treatment for a variety of painful syndromes. The precise mechanisms that account for nociceptor desensitization and hypalgesia are unclear. The present study was performed to determine if morphological changes of intracutaneous nerve fibers contribute to desensitization and hypalgesia. Capsaicin (0.075%) was applied topically to the volar forearm four times daily for 3 weeks. At various time intervals tactile, cold, mechanical and heat pain sensations were assessed in the treated and in contralateral untreated areas. Skin blisters and skin biopsies were collected and immunostained for protein gene product (PGP) 9.5 to assess the morphology of cutaneous nerves and to quantify the number of epidermal nerve fibers (ENFs). Capsaicin resulted in reduced sensitivity to all cutaneous stimuli, particularly to noxious heat and mechanical stimuli. This hypalgesia was accompanied by degeneration of epidermal nerve fibers as evidenced by loss of PGP 9.5 immunoreactivity. As early as 3 days following capsaicin application, there was a 74% decrease in the number of nerve fibers in blister specimens. After 3 weeks of capsaicin treatment, the reduction was 79% in blisters and 82% in biopsies. Discontinuation of capsaicin was followed by reinnervation of the epidermis over a 6-week period with a return of all sensations, except cold, to normal levels. We conclude that degeneration of epidermal nerve fibers contributes to the analgesia accredited to capsaicin. Furthermore, our data demonstrate that ENFs contribute to the painful sensations evoked by noxious thermal and mechanical stimuli.
辣椒素局部应用于人体皮肤时，由于伤害感受器受到刺激，会产生瘙痒、刺痛和灼烧感。反复应用后，这些积极的感觉反应之后会出现一段长时间的痛觉减退，通常被称为脱敏或伤害感受器失活。因此，辣椒素已被推荐用于治疗多种疼痛综合征。导致伤害感受器脱敏和痛觉减退的确切机制尚不清楚。本研究旨在确定皮内神经纤维的形态变化是否有助于脱敏和痛觉减退。将0.075%的辣椒素每天4次局部应用于掌侧前臂，持续3周。在不同时间间隔，对治疗区域和对侧未治疗区域的触觉、冷觉、机械性和热痛觉进行评估。收集皮肤水疱和皮肤活检样本，并用蛋白基因产物（PGP）9.5进行免疫染色，以评估皮肤神经的形态并量化表皮神经纤维（ENF）的数量。辣椒素导致对所有皮肤刺激的敏感性降低，尤其是对有害热刺激和机械刺激。这种痛觉减退伴随着表皮神经纤维的退化，PGP 9.5免疫反应性的丧失证明了这一点。早在应用辣椒素3天后，水疱样本中的神经纤维数量就减少了74%。辣椒素治疗3周后，水疱中的减少率为79%，活检样本中的减少率为82%。停止使用辣椒素后，表皮在6周内重新神经支配，除冷觉外的所有感觉恢复到正常水平。我们得出结论，表皮神经纤维的退化有助于辣椒素所致的镇痛作用。此外，我们的数据表明，ENF对有害热刺激和机械刺激引起的疼痛感觉有贡献。
