PERIPHERAL CGRP RELEASE AS A MARKER FOR NEUROGENIC INFLAMMATION - A MODEL SYSTEM FOR THE STUDY OF NEUROPEPTIDE SECRETION IN RAT PAW SKIN

The local release of pro-inflammatory neuropeptides in the periphery h as been associated with the development of neurogenic inflammation. Ho wever, there is an increasing number of reports demonstrating tissue-d ependent differences regarding the mechanisms engaged by these neurope ptides to initiate and maintain the inflammatory response in the targe t tissue. Since skin is often involved in tissue injury, the present s tudies were designed to develop a model for assessing cutaneous peptid e secretion as a marker for neurogenic inflammation in skin tissue. sk in tissue. Calcitonin gene-related peptide (CGRP), as one of several n europeptides known to be involved in neurogenic inflammation, was chos en to study capsaicin-induced effects on peripheral neurosecretion. Th e corial surface of the hairy skin of a rat hindlimb was superfused in vitro, and the basal and capsaicin-evoked peripheral release of immun oreactive CGRP (iCGRP) was measured using a radioimmunoassay, The main objectives of these studies were to characterize the various properti es of this release including dose-dependency, exocytosis and receptor- mediation as well as the effects of acute and long-term capsaicin dese nsitization. Capsaicin significantly and dose-dependently increased th e release of iCGRP at concentrations ranging from 3 to 300 mu M. Omiss ion of calcium ions or treatment with the competitive capsaicin recept or antagonist capsazepine completely inhibited the capsaicin-induced i CGRP release. Superfusion of the skin with 100 mu M capsaicin followin g a conditioning stimulation with capsaicin at concentrations ranging from 0.3 to 100 mu M led to an acute, dose-dependent desensitization o f the CGRP response. In addition, chronic desensitization following th e neonatal injection of capsaicin completely abolished the acute iCGRP response to capsaicin. The method described here should prove to be a valuable tool for the evaluation of the processes regulating the peri pheral, cutaneous release of pro-inflammatory neuropeptides. This stra tegy, therefore, may lead to a better understanding of the mechanisms involved in the development and maintenance of neurogenic inflammation , particularly in the skin. (C) 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.