Capsaicin-induced neuropathy: loss of cutaneous nerves and its functional consequences after multiple injections of capsaicin into the hindpaw of mice

• Main Authors: Hao Chiang, 姜昊
• Other Authors: Sung-Tsang Hsieh
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/87943018359404206420

碩士 === 國立臺灣大學 === 解剖學暨生物細胞學研究所 === 96 === Environmental chemical pollutants and certain medication for chemotherapy are the inducers of toxic neuropathy, which affect the structure and functions of peripheral nerves. Most neurotoxins affect both large and small-diameter neurons, rendering confusion when trying to elucidate the specific effects on different types of neurons. Capsaicin (8-methyl-N-vanillyl-6-noneamide), the main ingredient in hot chili peppers, evoked the pungent sensation on subjects. Meanwhile, it could be applied topically to alleviate pain in patients with neuropathic pain. In this study, we asked whether repeated local injection of capsaicin could serve as a model of small-fiber neuropathy and how behavioral changes developed. 10 μl Capsaicin (1%) was injected daily into one side of the hindpaw of mice for 7 days; the other side was injected with vehicle solution. Using immunuhistochemistry, pan-neuronal marker protein gene product 9.5 (PGP9.5) (+) epidermal nerve density was reduced by 31%, peptidergic neuron marker calcitonin gene-related peptide (CGRP) (+) nerve density by 60%, and substance P (SP) (+) nerve density by 97% after capsaicin treatment on post-injection day 7 (PID7). Accompanying with denervation of epidermis, animals with capsaicin treatment exhibited marked reduction of sensitivity to thermal and mechanical stimuli on PID7 compared with the contralateral side. Unmyelinated axons of medial plantar nerve showed signs of Wallerian-like degeneration under capsaicin treatment. To assess whether capsaicin-induced neuropathy could be reversed, capsaicin injection ceased at PID7. Animals were kept alive and their behaviors were evaluated weekly until PID42. On PID42, both mechanical and thermal responses returned to normal. However, there was difference in the pattern of skin reinnervation among epidermal nerves of different phenotypes. Epidermal nerve density of SP (+) nerve fibers was reduced by 78%, whereas PGP9.5 (+) and CGRP (+) nerve fibers nearly replenished on PID42. These findings provided a model of capsaicin-induced neuropathy and indicated different vulnerability to capsaicin among different types of epidermal nerves.