A comparative study of the ability of calcitonin gene-related peptide and adrenomedullin(13 - 52) to modulate microvascular but not thermal hyperalgesia responses

Calcitonin gene-related peptide (CGRP), a neuropeptide, is a potent vasodilator. Adrenomedullin (ADM) is suggested to be produced by vascular cells in inflamed tissue. ADM shares some structural homology with CGRP. We have compared the ability of CGRP and ADM to modulate microvascular and thermal hyperalgesic responses in rat skin. Vasodilator activity was assessed by laser Doppler flowmetry, inflammatory oedema by the extravascular accumulation of intravenously-injected labelled albumin, and neutrophil accumulation by tissue myeloperoxidase, in dorsal skin. Hyperalgesia was assessed by a thermal hyperalgesimeter in paw skin. ADM (10-300 pmol) was 3 fold less potent than CGRP (3-100 pmol) as a direct vasodilator. CGRP (30 pmol) potentiated oedema formation induced by mediators of increased microvascular permeability, as expected (P