Yamaoka Junichi, Kawana Seiji
Department of Dermatology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, Japan.
Exp Dermatol. 2007 Sep;16(9):737-45. doi: 10.1111/j.1600-0625.2007.00593.x.
When mice were scratched with brushes on their dorsal skins, they began to scratch themselves with their hind paws. Thus, self-scratching behaviour was induced in mice in response to skin-scratching stimulation. If the second skin-scratching stimulation was given within a few days, the induction of the second self-scratching behaviour was significantly suppressed compared with the first one. Thereafter, mice gradually recovered from this unresponsive state within a week. Thus, a transient unresponsive state of self-scratching behaviour is induced by skin-scratching stimulation. Pretreatment with a tachykinin receptor NK-1R antagonist L-703606 or capsaicin significantly suppressed self-scratching behaviour, while pretreatment with a neutral endopeptidase inhibitor phosphoramidon significantly enhanced it. Pretreatment with a calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) did not affect the following self-scratching behaviour. From these results, it is suggested that substance P (SP) signalling through its receptor NK-1R at least in part mediates the induction of self-scratching behaviour. After skin-scratching stimulation, immunoreactivity of SP both in the peripheral nerve fibres and in the dorsal root ganglion (DRG) neurons was significantly decreased and was well-correlated with suppression of self-scratching behaviour. From these findings, it is suggested that the induction of unresponsive states of self-scratching behaviour may be at least in part caused by the depleted states of SP in peripheral nerve fibres and/or in DRG neurons. The induction of a transient unresponsive state after skin-scratching may possibly happen also in patients with pruritus. Thus, further studies to elucidate the precise mechanisms are required.
当用刷子刮擦小鼠背部皮肤时，它们开始用后爪搔抓自己。因此，对皮肤搔抓刺激产生反应，在小鼠中诱导出了自我搔抓行为。如果在几天内给予第二次皮肤搔抓刺激，与第一次相比，第二次自我搔抓行为的诱导受到显著抑制。此后，小鼠在一周内逐渐从这种无反应状态中恢复。因此，皮肤搔抓刺激可诱导自我搔抓行为的短暂无反应状态。用速激肽受体NK-1R拮抗剂L-703606或辣椒素预处理可显著抑制自我搔抓行为，而用中性内肽酶抑制剂磷酰胺预处理则显著增强该行为。用降钙素基因相关肽（CGRP）受体拮抗剂CGRP(8-37)预处理不影响随后的自我搔抓行为。从这些结果表明，P物质（SP）通过其受体NK-1R发出的信号至少部分介导了自我搔抓行为的诱导。皮肤搔抓刺激后，外周神经纤维和背根神经节（DRG）神经元中SP的免疫反应性均显著降低，且与自我搔抓行为的抑制密切相关。从这些发现表明，自我搔抓行为无反应状态的诱导可能至少部分是由外周神经纤维和/或DRG神经元中SP的耗竭状态引起的。皮肤搔抓后短暂无反应状态的诱导在瘙痒患者中也可能发生。因此，需要进一步研究以阐明其确切机制。
