Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
J Neurophysiol. 2010 Jul;104(1):271-9. doi: 10.1152/jn.00938.2009. Epub 2010 May 19.
Itching is a common symptom in dermatologic diseases and causes restless scratching of the skin, which aggravates the condition. The mechanism of the itch sensation, however, is enigmatic. The present study included behavioral tests and electrophysiological recordings from rat dorsal root ganglion (DRG) neurons in vivo to analyze the response to pruritic stimuli induced by topical application of 5-hydroxytryptamine (5-HT) to the skin. Topically applied 5-HT to the rostral back evoked scratching, whereas application of the vehicle did not. Following subcutaneous injection of the opioid receptor antagonist naloxone, the number of scratches decreased, suggesting that the scratching was preferentially mediated by itch but not pain sensation. To elucidate the firing properties of DRG neurons in response to topically applied 5-HT, intracellular recordings were made from DRG neurons in vivo. None of the Abeta and Adelta neurons responded to 5-HT; in contrast, 25 of 91 C neurons (27%) exhibited repetitive firing in response to 5-HT, which could be classified into two firing patterns: one was a transient type, characterized by low firing frequency that decreased within 5 min; the other was a long-lasting type, having high firing frequency that continued increasing after 5 min. The time course of the firing pattern of long-lasting C neurons was comparable to the scratching behavior. Intriguingly, the long-lasting-type neurons had a significantly smaller fast afterhyperpolarization than that of the 5-HT-insensitive neurons. These observations suggest that the long-lasting-firing C neurons in rat DRG sensitive to 5-HT are responsible for conveying pruritic information to the spinal cord.
瘙痒是皮肤科疾病的常见症状,会导致患者不停地搔抓皮肤,从而使病情恶化。然而,瘙痒感觉的产生机制仍不清楚。本研究通过对大鼠背根神经节(DRG)神经元进行行为学测试和电生理学记录,分析了皮肤外用 5-羟色胺(5-HT)诱导的瘙痒刺激的反应。将 5-HT 涂抹于大鼠背部引起搔抓行为,而涂抹载体则无此反应。皮下注射阿片受体拮抗剂纳洛酮后,搔抓次数减少,表明搔抓主要由瘙痒而不是疼痛介导。为了阐明 DRG 神经元对 5-HT 外用的反应特性,我们对体内 DRG 神经元进行了细胞内记录。无 Abeta 和 Adelta 神经元对 5-HT 有反应;相比之下,91 个 C 神经元中有 25 个(27%)对 5-HT 表现出重复放电,可分为两种放电模式:一种是短暂型,其特征是在 5 分钟内频率降低的低频放电;另一种是持续型,具有在 5 分钟后持续增加的高频放电。持续型 C 神经元的放电模式与搔抓行为的时间进程相当。有趣的是,持续型神经元的快速后超极化幅度显著小于 5-HT 不敏感神经元。这些观察结果表明,对 5-HT 敏感的大鼠 DRG 中的持续放电 C 神经元负责将瘙痒信息传递到脊髓。