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

Ablation of α-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 α-CGRP antibody or hCGRP(8–37), a CGRP receptor antagonist, improves postoperative gastric emptying. Unlike the stomach, which contains only α-CGRP, the small bowel additionally contains β-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 a-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 α-CGRP monoclonal antibody, or during infusion of hCGRP(8–37) at varying doses. Small bowel transit was measured 25 minutes postoperatively. The a-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 α-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 α- and β-CGRP.