Abstracts
1997 Digestive Disease Week

Calcitonin gene-related peptide and spinal afferents partly mediate postoperative colonic ileus in the rat.

TT Zittel*#, KCK Lloyd#, I Rothenhofer*, H Wong#, JH Walsh#, HE Raybould#. *University Hospital, Department of General Surgery, Tubingen, Germany, and #CURE/Gastroenteric Biology Center, UCLA, Los Angeles.

INTRODUCTION. Calcitonin gene-related peptide (CGRP) has been shown to be released from visceral sensory neurons by noxious stimulation and to inhibit gastric emptying and gastrointestinal transit. We have recently shown that CGRP partly mediates postoperative gastric ileus in anethetized rats (Ann Surg 219:79-87). To further elucidate the role of CGRP in postoperative ileus, we investigated the effects of CGRP blockade and visceral afferent nerve ablation on postoperative colonic ileus.

METHODS. Male Sprague-Dawley rats were equipped with a polyethylen catheter in the ascending colon. 2 weeks later, abdominal surgery (AS) was simulated by laparotomy and manipulation of the cecum for 5 min under halothane anesthesia. Prior to AS, rats were pretreated with i.p. injection of either CGRP monoclonal antibody (MAb, 2 mg) or KLH MAb (2 mg). In separate experiments, vagus nerve (VN) or celiac/superior mesenteric ganglia (CSMG) were treated with vehicle or capsaicin to ablate visceral afferent nerve fibers 2 weeks prior to AS. At the end of AS, carmine red 0.3 ml was injected into the ascending colon. Colonic transit was measured as time in hours to the first appearence of carmine red in the feces and number and weight of stool pellets were recorded for 24 h.

RESULTS. AS significantly reduced colonic transit and stool pellets number and weight compared to unoperated controls or halothane. CGRP Mab prior to AS completely reversed AS-induced inhibition of colonic transit and reduction of stool pellet number and weight. Capsaicin treatment of CSMG partly reversed AS-induced reduction of stool pellet number and weight, but had no effect on colonic transit. Capsaicin treatment of VN had no effect on postoperative colonic ileus.

                                                     AS +       AS +
                     control    halothane AS         CGRP MAb   KLH MAb
colonic transit (h)  8.8±0.9    10.5±1.1  14.2±1.2*  10.3±1.2#  13.7±1.9
pellet number (no)   49±3       45±5      30±3*      42±4#      21±7
pellet weight (g)    12.7±1.0   11.2±1.0  6.9±0.8*   11.7±1.6#  5.7±2

                     AS +          AS +           AS +         AS +
                     vehicle VN    capsaicin VN   vehicle CSMG capsaicin CSMG
colonic transit (h)  24.0±8.5      27.6±2.7       15.4±1.9     15.6±1.6
pellet number (n)    15±2          16±3           18±5         25±2§
pellet weight (gm)   2.9±0.4       3.1±0.5        4.0±1.1      6.3±1.1§
* p<0.05 vs control or halothane; # p<0.05 vs AS; § p<0.05 vs AS + vehicle CSMG

CONCLUSIONS. Our data indicate that CGRP and spinal afferent neurons mediate postoperative colonic ileus in rats. CGRP might be released in part by spinal sensory neuron in the CSMG thereby activating inhibitory reflex pathways.