Studies on endogenous itch mediators and their interaction

尽管抗组胺药不能抑制许多皮炎疾病的瘙痒感觉，但组胺（一种从肥大细胞释放的经典瘙痒介质）通常被认为是皮肤中的主要瘙痒介质。在这项研究中，为了阐明皮肤瘙痒的机制，我们研究了皮肤中初级传入末梢、肥大细胞等产生和释放的几种内源性物质皮内注射的抓挠诱导效力。组胺（100 nmol/部位）可诱发ICR小鼠的沟道相关行为（抓挠注射部位），但对ddY、BALB/c、C57/BL、WBB 6 F1 +/+和CH 3/He品系小鼠无此作用。5-羟色胺剂量依赖性地引起ICR和ddY小鼠的抓挠行为。P物质、强啡肽A（1-13）和生长抑素也能引起抓挠行为，而VIP、CGRP、神经激肽A、神经激肽B、PAF和L-精氨酸在所测剂量下无明显作用。P物质和5-羟色胺的抓挠诱导效应具有与人类瘙痒相似的几个特征，这表明这些物质诱导的抓挠是由于瘙痒感。强啡肽A（1-13）的促收缩作用与P物质或生长抑素的促收缩作用大致相加。吗啡是一种已知会引起人类瘙痒的阿片类生物碱，在脑池内而不是皮内注射后引起抓挠，研究结果表明阿片类和μ-阿片受体参与中枢神经系统而不是外周的瘙痒。虽然L-精氨酸本身并不引起抓挠，但它增强了低剂量P物质的抓挠诱导作用，这表明一氧化氮增强了某些过敏性疾病的瘙痒。

Although it has been claimed that antihistamines can not inhibit itch sensation of many pruritic diseases, histamine, a classical itch mediator released from mast cells, are generally considered to be a major itch mediator in the skin. In this study, to elucidate the mechanisms of itch in the skin, we examined the scratch-inducing potencies of intradermal injections of several endogenous substances that are produced in and released from primary afferent terminals, mast cells, etc. in the skin. Histamine (100 nmol/site) eliciteditch-related behavior (scratching of the injected site) in ICR mice, but not in mice of ddY,BALB/c, C57/BL,WBB6F1 +/+ or CH3/He strain. Serotonin dose-dependently elicited scratching behavior in ICR and ddY mice. Substance P,dynorphin A (1-13) and somatosatatin also produced scratching behavior, while VIP,CGRP,neurokinin A,neurokinin B,PAF and L-arginine were without apparent effects at doses examined. Scratch-inducing effects of substance P and serotonin had several features similar to those of itch in humans, suggesting scratching induced by these substances are due to an itch sensation. Scratch-inducing effect of dynorpjin A(1-13) were roughly additive to that of either substance P or somatostatin. Morphine, an opioid alkaloid known to produce itch in humans, elicited scratching following intracisterna rather than intradermal injection, findings suggesting that opioid and mu-opioid receptors are involved in itch in the central nervous systems rather than in the periphery. Although L-ariginine itself did not elicit scratching, it enhanced scratch-inducing effects of lower doses of substance P,finding suggesting that nitric oxide enhances itch of some pruritic diesase.