Zittel T T, Lloyd K C, Rothenhöfer I, Wong H, Walsh J H, Raybould H E
CURE/Gastroenteric Biology Center, West Los Angeles VA Medical Center, Calif., USA.
Surgery. 1998 May;123(5):518-27. doi: 10.1067/msy.1998.88090.
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.
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.
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.
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.
降钙素基因相关肽（CGRP）是一种广泛分布的神经肽，存在于胃肠道壁的内在和外在神经元中，已被证明可通过有害刺激释放，参与痛觉感受，抑制胃肠蠕动，并部分介导术后胃麻痹。我们推测腹部手术诱导的CGRP释放可能会抑制术后结肠蠕动和食物摄入。
在大鼠术后肠梗阻诱导后48小时测量结肠转运、粪便颗粒数量、粪便颗粒重量和食物摄入量。术前注射CGRP单克隆抗体使CGRP免疫中和，或者在腹部手术前通过对迷走神经或腹腔/肠系膜上神经节进行辣椒素局部处理，使含有CGRP的内脏传入神经纤维功能丧失。
腹部手术增加了结肠转运时间，减少了24小时累积粪便颗粒数量、粪便颗粒重量和食物摄入量。CGRP免疫中和分别使术后结肠转运、24小时累积粪便颗粒数量、粪便颗粒重量和食物摄入量的抑制作用逆转了77%、82%、80%和52%。而切断迷走神经传入纤维没有效果，切断脊髓传入神经纤维分别使术后24小时累积粪便颗粒数量、粪便颗粒重量和食物摄入量的抑制作用逆转了41%、38%和19%。
CGRP和脊髓传入神经纤维部分介导了大鼠术后结肠麻痹和食物摄入抑制。就术后肠梗阻逆转的程度而言，CGRP似乎是术后结肠麻痹的重要介质。我们的结果首次表明一种神经肽和脊髓传入神经参与了大鼠术后结肠麻痹和术后食物摄入抑制的介导。
