A critical re-evaluation of the specificity of action of perivagal capsaicin
A critical re-evaluation of the specificity of action of perivagal capsaicin
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DOI：
10.1113/jphysiol.2012.246827
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发表时间：
2013-03-01
影响因子：
5.5
通讯作者：
Travagli, R. A.
中科院分区：
文献类型：
--
作者：
Browning, K. N.;Babic, T.;Travagli, R. A.
迷走神经周围应用辣椒素（1% 溶液）被认为会引起迷走神经传入 C 纤维的选择性变性，并已广泛用于检查许多胃肠 (GI) 神经肽的作用部位。然而，辣椒素和胃肠道神经肽的作用可能不仅限于迷走神经传入纤维，因为其他非感觉神经元已表现出对辣椒素的敏感性，并且这些神经肽的脑干微注射可诱导与全身应用时获得的胃肠道效应相似的效应。本研究的目的是检验迷走神经周围辣椒素诱导控制胃肠道功能的迷走神经传出神经退化的假设。单侧迷走神经周围施用 0.11% 辣椒素 30 分钟后，进行了 714 天的实验。免疫组织化学分析表明，迷走神经切断术后，辣椒素诱导大鼠迷走神经背运动核（DMV）神经元树突变性，胆碱乙酰转移酶降低，但一氧化氮合酶免疫反应性增加。电生理记录显示 DMV 输入电阻和兴奋性降低，部分原因是大电导钙依赖性钾电流的表达以及静息电位下瞬态向外钾窗口电流的打开。此外，促甲状腺激素释放激素兴奋的DMV神经元数量以及对TRH DMV微量注射的胃动力反应均显着减少。我们的数据表明，迷走神经周围施用辣椒素会诱导 DMV 神经元变性并降低迷走神经运动反应。因此，不能认为迷走神经周围辣椒素治疗对迷走神经传入 C 纤维具有选择性，因此，在使用迷走神经周围辣椒素评估胃肠道神经肽的作用机制时需要小心。
Perivagal application of capsaicin (1% solution) is considered to cause a selective degeneration of vagal afferent C fibres and has been used extensively to examine the site of action of many gastrointestinal (GI) neuropeptides. The actions of both capsaicin and GI neuropeptides may not be restricted to vagal afferent fibres, however, as other non-sensory neurones have displayed sensitivity to capsaicin and brainstem microinjections of these neuropeptides induce GI effects similar to those obtained upon systemic application. The aim of the present study was to test the hypothesis that perivagal capsaicin induces degeneration of vagal efferents controlling GI functions. Experiments were conducted 714days after 30min unilateral perivagal application of 0.11% capsaicin. Immunohistochemical analyses demonstrated that, as following vagotomy, capsaicin induced dendritic degeneration, decreased choline acetyltransferase but increased nitric oxide synthase immunoreactivity in rat dorsal motor nucleus of the vagus (DMV) neurones. Electrophysiological recordings showed a decreased DMV input resistance and excitability due, in part, to the expression of a large conductance calcium-dependent potassium current and the opening of a transient outward potassium window current at resting potential. Furthermore, the number of DMV neurones excited by thyrotrophin-releasing hormone and the gastric motility response to DMV microinjections of TRH were decreased significantly. Our data indicate that perivagal application of capsaicin induced DMV neuronal degeneration and decreased vagal motor responses. Treatment with perivagal capsaicin cannot therefore be considered selective for vagal afferent C fibres and, consequently, care is needed when using perivagal capsaicin to assess the mechanism of action of GI neuropeptides.