Calcitonin Gene Related Peptide Receptors

Almost all DRG neurons supplying the viscera of the rat, mouse, and guinea pig express CGRP (2,118,235,236), and there is experimental evidence that this peptide contributes to visceral pain in two different ways. First, intraperitoneal administration of exogenous CGRP or acetic acid-induced release of endogenous CGRP triggers a visceromotor pain reaction (237-239). These findings suggest that, within the peritoneal cavity, CGRP triggers events that indirectly increase the sensory gain of primary afferent neurons (63). Second, CGRP appears to be a cotransmitter of spinal afferents involved in visceral pain and hyperalgesia. Thus, the vis-ceromotor pain response that rats exhibit following colorectal distension or intraperitoneal injection of acetic acid is attenuated by CGRP receptor blockade (142,238). More importantly, the mechanical hyperalgesia in the rat colon due to acetic acid-induced inflammation or repeated distension is reversed by the CGRP receptor antagonist CGRP8-37 (142,240). Since in this respect intrathecal administration of CGRP8-37 is more potent than intravenous administration of the CGRP receptor antagonist or a monoclonal CGRP antibody, it has been concluded that the site of CGRP-mediated hyperalgesia is primarily in the spinal cord (240). The available evidence indicates, therefore, that CGRP receptor antagonists have potential in the treatment of visceral hyperalgesia. This conjecture is corroborated by the discovery that the nonpeptide CGRP receptor antagonist BIBN 4096 BS is effective in the treatment of acute migraine attacks (241).

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