Jones O M, Brading A F, Mortensen N J McC
Department of Pharmacology, University of Oxford, Oxford, UK.
Br J Surg. 2004 Feb;91(2):224-8. doi: 10.1002/bjs.4394.
Botulinum toxin is an effective treatment for anal fissure. Manometric studies support an apparent action of botulinum toxin on the internal anal sphincter (IAS). This aim of this study was to establish the underlying mechanism.
Porcine IAS strips were suspended in a superfusion organ bath and allowed to equilibrate. Electrical field stimulation (EFS) was applied with parameters that induced nitrergic relaxation followed by noradrenaline-mediated contraction. These responses were compared before and after addition of botulinum toxin.
All strips developed myogenic tone, which was slightly increased following the addition of botulinum toxin. EFS-induced nitrergic relaxation was unaffected by toxin treatment. However, EFS-induced contraction was significantly reduced by toxin treatment. 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic agonist, caused muscle strip contraction, which was blocked by guanethidine, implying the presence of sympathetic ganglia within the IAS. Botulinum toxin significantly attenuated DMPP-induced contraction.
In the treatment of anal fissure the major effect of botulinum toxin on the IAS is blockade of sympathetic (noradrenaline mediated) neural output. This is probably a postganglionic action, involving a reduction in noradrenaline release at the neuromuscular junction. Botulinum toxin has no significant effect on nitrergic transmission, which is probably not vesicular in nature.
肉毒杆菌毒素是治疗肛裂的一种有效方法。压力测定研究支持肉毒杆菌毒素对肛门内括约肌（IAS）有明显作用。本研究的目的是确定其潜在机制。
将猪的IAS条带悬挂于灌注器官浴槽中使其平衡。施加电场刺激（EFS），其参数可诱导由一氧化氮介导的舒张，随后是去甲肾上腺素介导的收缩。在添加肉毒杆菌毒素前后比较这些反应。
所有条带均产生肌源性张力，添加肉毒杆菌毒素后略有增加。毒素处理不影响EFS诱导的由一氧化氮介导的舒张。然而，毒素处理显著降低了EFS诱导的收缩。烟碱激动剂1,1 - 二甲基 - 4 - 苯基哌嗪碘化物（DMPP）引起肌条收缩，这被胍乙啶阻断，这意味着IAS内存在交感神经节。肉毒杆菌毒素显著减弱了DMPP诱导的收缩。
在肛裂治疗中，肉毒杆菌毒素对IAS的主要作用是阻断交感神经（去甲肾上腺素介导）神经输出。这可能是一种节后作用，涉及神经肌肉接头处去甲肾上腺素释放减少。肉毒杆菌毒素对一氧化氮能传递无显著影响，一氧化氮能传递可能本质上不是囊泡性的。
