HISTAMINE-INDUCED EDEMA IN THE RAT PAW - EFFECT OF CAPSAICIN DENERVATION AND A CGRP RECEPTOR ANTAGONIST

Histamine is known to cause edema and excitation of small-diameter pri mary afferent neurons. In the present study we wanted to investigate t o which extent afferent neurons participate in histamine-induced edema and, subsequently, determine possible inhibitory effects of a tachyki nin NK1 receptor and CGRP receptor antagonist on the histamine respons e. Intraplantar injection of histamine (0.5 mu mol) into the rat hind paw caused a 34% increase of paw volume. In capsaicin-denervated rats, this effect of histamine was nearly abolished. The calcitonin gene-re lated peptide (CGRP) receptor antagonist CGRP-(8-37), but not the tach ykinin NK1 receptor antagonist SR140333, caused significant inhibition of the edema response. Further indication that CGRP can promote the h istamine action was obtained in capsaicin-denervated rats, where co-in jection of CGRP (0.3 pmol) increased the edema response to intrapianta r histamine. In additional experiments, plasma protein extravasation i n the paw skin was evaluated after close arterial infusion of histamin e. Also in these experiments CGRP-(8-37), but not SR140333, significan tly reduced the histamine effect. The observation that in the rat hind paw a CGRP receptor antagonist, but not a tachykinin NK1 receptor ant agonist, attenuates histamine-induced vascular leakage raises the poss ibility that in some tissues CGRP receptor antagonists may be superior to tachykinin NK1 receptor antagonists in reducing histamine-induced neurogenic inflammatory responses.