Involvement of nitric oxide in serotonin-induced scratching in mice.

BACKGROUND: Serotonin is a pruritogenic substance in humans and animals, but the mechanisms of action through which serotonin induces itch response are not yet understood. AIM: To examine the possible role of nitric oxide (NO) in the profile of scratching behaviour due to intradermal injection of serotonin in mice. METHODS: Intradermal injection of serotonin (14.1-235 nmol per site) into the nape of the neck was used to elicit itch in mice. Scratching behaviour was evaluated by counting the number of bouts during 60 min after injection. To determine the possible involvement of the nitrergic system in serotonin-induced scratching, L-NG-nitroarginine methyl ester [L-NAME; a nonselective nitric oxide synthase (NOS) inhibitor], aminoguanidine [a selective inducible (i)NOS inhibitor] and L-arginine (an NO precursor) were administered intraperitoneally to control and serotonin-injected animals. RESULTS: Intradermal serotonin caused scratching in mice with a bell-shaped dose-response correlation, and the peak effective dose was 141 nmol per site. The majority of scratching bouts in animals occurred 5-10 min after injection. Ineffective doses of L-NAME (3 mg/kg IP) and aminoguanidine (100 mg/kg IP) decreased the scratching induced by intradermal serotonin injection in animals (P < 0.001 and P < 0.001), while an subeffective dose of L-arginine (100 mg/kg IP) augmented the scratching effect of serotonin (P < 0.001). CONCLUSIONS: We show for the first time that the scratching induced by intradermal serotonin is mediated by NOS, especially iNOS, activation. We conclude that NO may play a role in mediating itch responses. NO and NOS could be new targets for antipruritic agents.

Altered manifestations of skin disease at sites affected by neurological deficit.

BACKGROUND: The contribution of the nervous system to inflammation in general and inflammatory skin disease in particular has been underappreciated. It is now apparent that an intact neural component is required for the conventional clinical manifestations of many inflammatory skin diseases. OBJECTIVES: To investigate the relationship between nerve damage and skin disease. METHODS: Previous individual reports since 1966 were collected systematically and the clinical observations described therein were placed within current concepts of neurogenic inflammation. RESULTS: We reviewed the literature and identified 23 cases of alterations in the appearance or distribution of skin disorders in patients with acquired central or peripheral neural damage or dysfunction. In 19 cases, near or complete resolution of pre-existing skin lesions occurred in areas directly or indirectly supplied by a subsequently injured nervous system. Exacerbation or new onset of skin lesions occurred in only four cases. The neural deficits described included damage within the peripheral or central nervous system resulting in pure sensory, pure motor or combined sensory and motor deficits. CONCLUSIONS: These cases highlight the importance of neural innervation and neurogenic inflammation in the development of inflammatory skin disease and prompt further examination of the use of neural blockade as an adjunctive therapy in the treatment of inflammatory dermatoses.