Effects of chemical sympathectomy and sensory nerve ablation on experimental colitis in the rat.

ABSTRACT

We assessed the effects of primary afferent nerve ablation (systemic treatment with capsaicin during adult or neonatal periods), primary afferent nerve activation (intracolonic capsaicin), and sympathectomy [6-hydroxydopamine (6-OHDA)] on the development of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. We also examined whether lidocaine was effective after ablation of primary afferent nerves or sympathectomy. Colitis was assessed by macroscopic scoring, measurement of myeloperoxidase (MPO) activity, and histology. Systemic capsaicin treatment in adults increased the macroscopic damage score. Capsaicin treatment of neonates did not significantly increase damage score or MPO activity compared with vehicle-treated controls. However, all capsaicin-treated groups had a higher mortality. Intracolonic capsaicin treatment did not alter the severity of colitis. Chemical sympathectomy resulted in a decreased damage score and improved histology compared with controls. In 6-OHDA pretreated rats, lidocaine administration reduced the macroscopic and histological scores and MPO activity almost to control levels. However, lidocaine administration in capsaicin-treated rats attenuated the macroscopic damage but did not improve MPO activity or histology. These data suggest that capsaicin-sensitive nerves play a protective role in experimental colitis and sympathetic nerves contribute to the development of colitis. The beneficial effects of lidocaine appear to be due primarily to its action on enteric nerves.