Jones O M, Moore J A, Brading A F, Mortensen N J Mc C
Department of Pharmacology, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Colorectal Dis. 2003 Nov;5(6):552-7. doi: 10.1046/j.1463-1318.2003.00484.x.
Botulinum toxin is an effective treatment for anal fissure, though there is a lack of agreement over the optimal site for its injection. This reflects our current ignorance of its mechanism, and whether it has any action on the nerves of the internal anal sphincter (IAS). This study set out to resolve this issue through use of a pig model.
Eight pigs were studied in pairs: one of each pair received a botulinum toxin injection into the anal sphincter, whilst the other acted as its control. Manometry was performed every two weeks under anaesthesia. Pigs were slaughtered at between four and six weeks after injection and the properties of the IAS compared in vitro.
Whilst maximum anal resting pressure (MARP) increased slowly in control pigs during the experimental period, reflecting weight gain, a fall was observed in treated pigs. In vitro, IAS strips from control pigs generated 400 mg of spontaneous tone per gram of tissue (+/- 45; standard error), compared to 250 (+/- 25) mg/g tissue from treated pigs (P < 0.01). Electric Field Stimulation at 50 Hz produced 150 (+/- 22) mg contraction/gram tissue in IAS strips from control pigs compared to 53 (+/- 13) mg/g tissue in treated pigs (P < 0.0005). This contractile response was blocked by guanethidine.
Botulinum toxin has a significant action on the IAS. It reduces myogenic tone and contractile responses of this tissue to sympathetic nerve stimulation. Further studies are required to clarify its mechanism of action more precisely.
肉毒杆菌毒素是治疗肛裂的一种有效方法，尽管对于其注射的最佳部位尚无定论。这反映出我们目前对其作用机制以及它是否对内括约肌（IAS）神经有任何作用并不了解。本研究旨在通过使用猪模型来解决这个问题。
八只猪两两分组进行研究：每组中的一只猪接受肉毒杆菌毒素注射到肛门括约肌，而另一只作为对照。在麻醉状态下每两周进行一次测压。在注射后四到六周宰杀猪，并在体外比较IAS的特性。
在实验期间，对照猪的最大肛门静息压力（MARP）随着体重增加而缓慢上升，而在接受治疗的猪中则观察到下降。在体外，对照猪的IAS条每克组织产生400毫克的自发张力（±45；标准误差），相比之下，接受治疗的猪为250（±25）毫克/克组织（P < 0.01）。50赫兹的电场刺激在对照猪的IAS条中产生150（±22）毫克收缩/克组织，而在接受治疗的猪中为53（±13）毫克/克组织（P < 0.0005）。这种收缩反应被胍乙啶阻断。
肉毒杆菌毒素对IAS有显著作用。它降低了该组织的肌源性张力以及对交感神经刺激的收缩反应。需要进一步研究以更精确地阐明其作用机制。
