CALCITONIN-GENE-RELATED PEPTIDE IN VISCEROSENSITIVE RESPONSE TO COLORECTAL DISTENSION IN RATS

The role of calcitonin gene-related peptide (CGRP) on colorectal diste nsion-induced visceral pain was investigated in conscious rats. Intrac olonic administration of acetic acid (0.6%) resulted in a significantl y increased number of abdominal contractions in response to colorectal balloon distension from 5.8 +/- 1.2 in controls to 16.6 +/- 1.0 in ac etic acid-treated animals (P < 0.05), evidencing sensitization of visc eral afferent pathways and subsequently visceral hyperalgesia. This se nsitization phenomenon was not observed in animals previously treated with systemic capsaicin. Likewise, in animals not treated with capsaic in, use of an intravenous antagonist for CGRP [human CGRP-(8-37)], com pletely reversed the sensitizing effects of acetic acid. Furthermore, intravenous administration of CGRP dose dependently increased the numb er of abdominal contractions in response to colorectal distension from 3.0 +/- 1.1 (CGRP 250 ng) to 17.0 +/- 1.2 (CGRP 500 ng, P < 0.05), as previously observed in acetic acid-treated animals. Finally, intrathe cal administration of hCGRP-(8-37) (midlumbar) also resulted in a tota l dose-dependent reversal of CGRP (500 ng) or acetic acid-induced visc eral hypersensitivity. These results demonstrate that CGRP plays a maj or role in this model of visceral afferent nerve sensitization from ga strointestinal origin.