Role of alpha- and beta-calcitonin gene-related peptide in postoperative small bowel ileus

Ablation of a-calcitonin gene-related polypeptide (CGRP) containing neurons with the afferent neurotoxin capsaicin improves postoperative foregut transit in a rodent model. Similarly, administration of a selective alpha-CGRP antibody or hCGRP((8-37)), a CGRP receptor antagonist, improves postoperative gastric emptying. Unlike the stomach, which contains only alpha-CGRP, the small bowel additionally contains beta-CGRP. The role of the latter in postoperative small bowel transit is unknown. The purpose of this study was to evaluate the effect of an alpha-CGRP antibody and hCGRP((8-37)) on postoperative small bowel transit. Male Sprague-Dawley rats underwent placement of duodenal catheters and were randomly assigned to 1 of 11 groups. Four groups were pretreated with 1% capsaicin. One week later, all animals underwent standardized laparotomy following administration of a control antibody or the alpha-CGRP mono-clonal antibody, or during infusion of hCGRP((8-37)) at varying doses. Small bowel transit was measured 25 minutes postoperatively. The alpha-CGRP antibody sped postoperative transit when given alone or in combination with capsaicin. In contrast, animals treated with hCGRP((8-37)) showed no significant improvement in postoperative transit, and the beneficial effect of capsaicin was blocked. Unlike their similar effects on postoperative gastric emptying, we found that hCGRP((8-37)) and the alpha-CGRP antibody had differing effects on postoperative small bowel transit. The reason for this is unknown but may be related to their differing specificities for alpha- and beta-CGRP.