McCafferty D M, Sharkey K A, Wallace J L
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Am J Physiol. 1994 Apr;266(4 Pt 1):G560-7. doi: 10.1152/ajpgi.1994.266.4.G560.
Neuropeptides liberated from enteric neurons have been suggested to contribute to the inflammatory process in colitis. Based in part on this evidence, lidocaine enemas have recently been suggested as a treatment for ulcerative colitis, but their effects have yet to be fully characterized. We have assessed the effects of lidocaine on the development and maintenance of colitis induced by trinitrobenzenesulfonic acid (TNBS) in rats. In the initial experiments, rats were given lidocaine [5-100 mg/kg intrarectally] 30 min before TNBS administration, and the severity of colitis was assessed 6-24 h later. In subsequent experiments, rats received lidocaine intrarectally or subcutaneously 30 min before TNBS administration and once daily for 7 days. The severity of colitis was assessed by blind macroscopic scoring, measurement of myeloperoxidase activity, and histological evaluation. Lidocaine dose dependently reduced the severity of colitis and the infiltration of granulocytes at 24 h and 7 days post-TNBS. At the latter time point, lidocaine was also found to improve the histological appearance of the tissue and significantly reduce mucosal mast cell hyperplasia. Beneficial effects were also evident when intrarectal lidocaine treatment was initiated after induction of colitis or when lidocaine was given subcutaneously. Granulocyte infiltration into the colon could also be attenuated by a substance P receptor antagonist. These results suggest that lidocaine can exert anti-inflammatory effects in colitis, perhaps by virtue of its effects on intrinsic and/or extrinsic nerves.
有研究表明，从肠神经元释放的神经肽会促进结肠炎的炎症过程。部分基于这一证据，近来有人建议将利多卡因灌肠剂用作溃疡性结肠炎的一种治疗方法，但其效果尚未得到充分阐明。我们评估了利多卡因对三硝基苯磺酸（TNBS）诱导的大鼠结肠炎的发生和维持的影响。在最初的实验中，在给予TNBS前30分钟给大鼠直肠内注射利多卡因[5 - 100 mg/kg]，并在6 - 24小时后评估结肠炎的严重程度。在随后的实验中，在给予TNBS前30分钟给大鼠直肠内或皮下注射利多卡因，并每天一次，持续7天。通过盲法宏观评分、髓过氧化物酶活性测定和组织学评估来评估结肠炎的严重程度。利多卡因剂量依赖性地降低了TNBS给药后24小时和7天时结肠炎的严重程度以及粒细胞浸润。在后者这个时间点，还发现利多卡因改善了组织的组织学外观并显著减少了黏膜肥大细胞增生。当在结肠炎诱导后开始直肠内利多卡因治疗或给予皮下利多卡因时，有益效果也很明显。P物质受体拮抗剂也可减弱粒细胞向结肠的浸润。这些结果表明，利多卡因可能通过其对内在和/或外在神经的作用，在结肠炎中发挥抗炎作用。
