Tachykininergic mediation of viscerosensitive responses to acute inflammation in rats: Role of CGRP

Tachykinins, colocalized with calcitonin gene-related peptides (CGRP) in sensory afferents, are involved in viscerosensitive responses. We investigated the role of tachykinins and CGRP in both nociceptive and visceromotor responses to inflammation. Visceral pain was assessed by abdominal muscle contrac tions. Gastric emptying was evaluated after gavage with reconstituted milk containing Cr-51-labeled sodium chromate. Acetic acid or 9 parts per thousand NaCl was injected intraperitoneally before the meal. RP-67580, SR-48968, human CGRP [hCGRP-(8-37)], or their vehicles were injected before acetic acid or saline. RP-67580, SR-48968, or their vehicles were injected before CGRP and the meal. GR-73632 or GR-76349 was injected before the meal. Acetic acids inhibited gastric emptying and increased the number of abdominal contractions. RP-67580 reduced the inhibition of gastric emptying without affecting the abdominal response. SR-48968 only reduced the acetic acid-induced increase of abdominal contractions. hCGRP-(8-37) reduced both responses induced by acetic acid. CGRP mimicked the effects of acetic acid. RP-67580 abolished CGRP-induced gastric emptying inhibition, whereas SR-48968 only diminished visceral pain. GR-73632 reduced gastric emptying, and GR-64349 increased abdominal response. In inflammation, neurokinin receptors (NK1 and NK2) mediate the gastric emptying inhibition and visceral pain, respectively. These responses involve a release of CGRP.