Studies on endogenous itch mediators and their interaction

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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.