May 9, 2015

Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Biological and Pharmaceutical Bulletin
Vol. 38 (2015) No. 5 p. 635-644



http://doi.org/10.1248/bpb.b15-00090
Reviews
Yasushi Kuraishi1)
1) Laboratory of Applied Pharmacology, Graduate School of Medicine and 
Pharmaceutical Sciences, University of Toyama
 Released on J-STAGE 20150501  
Keywords: pruritus, animal model, scratching, biting, keratinocyte, itch mediator
Itch is a sensation that provokes a desire to scratch. Mast-cell histamine was thought to be a key itch mediator. However, histamine and mast-cell degranulation were reported not to elicit scratching in animals. It was difficult to investigate the pathophysiology of itching and to evaluate the antipruritic efficacy of chemical agents in the early 1990 s. We showed that hind-paw scratching and biting were elicited by stimulation with pruritogenic agents in mice. Those results demonstrated for the first time that cutaneous itching could be evaluated behaviorally in animals. We established various animal models of pathological itch of the skin (dry skin, mosquito allergy, surfactant-induced pruritus, and herpes zoster) and mucus membranes (pollen allergy). Mast-cell histamine did not play a key role in itching in any animal model examined except for the pollen allergy model. Histamine is not an exclusive itch mediator of mast cells; tryptase and leukotriene B4 released from mast cells also act as itch mediators. Epidermal keratinocytes release several itch mediators, such as leukotriene B4, sphingosylphosphorylcholine, thromboxane A2, nociceptin, nitric oxide, and histamine, which may play important roles in pathological itching. Appropriate animal models of pathological itching are needed for pharmacological evaluation of the antipruritic efficacy of chemical agents.

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