Calcitonin gene-related peptide and spinal afferents partly mediate postoperative colonic ileus in the rat.
BACKGROUND
Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide contained in intrinsic and extrinsic neurons of the gastrointestinal wall that has been shown to be released by noxious stimulation, to be involved in nociception, to inhibit gastrointestinal motility, and to partly mediate postoperative gastric ileus. We hypothesized that abdominal surgery-induced release of CGRP might inhibit postoperative colonic motility and food intake.


METHODS
Colonic transit, stool pellet number, stool pellet weight, and food intake were measured for 48 hours after induction of postoperative ileus in rats. CGRP was immunoneutralized by preoperative injection of CGRP monoclonal antibody, or visceral afferent nerve fibers containing CGRP were functionally ablated by topical capsaicin treatment of the vagus nerves or of the celiac/superior mesenteric ganglia before abdominal surgery.


RESULTS
Abdominal surgery increased colonic transit time and decreased 24-hour cumulative stool pellet number, stool pellet weight, and food intake. CGRP immunoneutralization reversed postoperative inhibition of colonic transit, 24-hour cumulative stool pellet number, stool pellet weight, and food intake by 77%, 82%, 80%, and 52%, respectively. Whereas ablation of vagal afferent nerve fibers had no effect, spinal afferent nerve fiber ablation reversed postoperative inhibition of 24-hour cumulative stool pellet number, stool pellet weight, and food intake by 41%, 38%, and 19%, respectively.


CONCLUSIONS
CGRP and spinal afferent nerve fibers partly mediate postoperative colonic ileus and inhibition of food intake in the rat. By the magnitude of reversal of postoperative ileus, CGRP seems to be an important mediator of postoperative colonic ileus. Our results for the first time show involvement of a neuropeptide and spinal afferents in the mediation of postoperative colonic ileus and postoperative inhibition of food intake in rats.
Zittel
T T
TT
CURE/Gastroenteric Biology Center, West Los Angeles VA Medical Center, Calif., USA.
Lloyd
K C
KC
Rothenhöfer
I
I
Wong
H
H
Walsh
J H
JH
Raybould
H E
HE
D000005:Abdomen / Q000601:surgery*; D000344:Afferent Pathways / Q000737:chemistry / Q000503:physiopathology*; D000818:Animals; D000911:Antibodies, Monoclonal; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis*; D002211:Capsaicin / Q000494:pharmacology; D003108:Colonic Diseases / Q000209:etiology / Q000503:physiopathology*; D003672:Defecation; D005247:Feeding Behavior; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000503:physiopathology; D005772:Gastrointestinal Transit; D007415:Intestinal Obstruction / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D011183:Postoperative Complications / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry / Q000503:physiopathology*; D013152:Splanchnic Circulation; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin