McCafferty D M, Wallace J L, Sharkey K A
Gastrointestinal and Neuroscience Research Groups, Faculty of Medicine, University of Calgary, Alberta, Canada.
Am J Physiol. 1997 Feb;272(2 Pt 1):G272-80. doi: 10.1152/ajpgi.1997.272.2.G272.
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.
我们评估了初级传入神经消融（成年期或新生期用辣椒素进行全身治疗）、初级传入神经激活（结肠内注射辣椒素）和交感神经切除术[6-羟基多巴胺（6-OHDA）]对2,4,6-三硝基苯磺酸（TNBS）诱导的大鼠结肠炎发展的影响。我们还研究了在初级传入神经消融或交感神经切除术后利多卡因是否有效。通过宏观评分、髓过氧化物酶（MPO）活性测定和组织学评估结肠炎。成年大鼠全身用辣椒素治疗会增加宏观损伤评分。与用赋形剂处理的对照组相比，新生大鼠用辣椒素治疗并未显著增加损伤评分或MPO活性。然而，所有用辣椒素处理的组死亡率更高。结肠内注射辣椒素治疗并未改变结肠炎的严重程度。与对照组相比，化学交感神经切除术导致损伤评分降低且组织学改善。在6-OHDA预处理的大鼠中，给予利多卡因可使宏观和组织学评分以及MPO活性几乎降至对照水平。然而，在辣椒素处理的大鼠中给予利多卡因可减轻宏观损伤，但并未改善MPO活性或组织学。这些数据表明，对辣椒素敏感的神经在实验性结肠炎中起保护作用，而交感神经则促进结肠炎的发展。利多卡因的有益作用似乎主要归因于其对肠神经的作用。
