Effects of intrasphincteric botulinum toxin on the lower esophageal sphincter in piglets

Background: The toxin of Clostridium botulinum (BoTx) inhibits the release of acetylcholine from nerve terminals and causes paralysis of skeletal muscle. The present study examined the hypothesis that BoTx may have a similar effect on gastrointestinal smooth muscle. Methods: Baseline lower esophageal sphincter (LES) pressures were obtained in five piglets, and normal saline was injected endoscopically into the LES. One week later, LES pressure was measured again, followed by injection of BoTx into the LES. After another week, LES pressure was measured again. Results: Compared with a baseline LES pressure of 8.2 ± 1.5 mm Hg, LES pressure decreased to 3.2 ± 1.0 mm Hg after BoTx injection, a reduction of about 60% (P < 0.01). By contrast, LES pressure did not change significantly after normal saline injection. The animals showed no evidence of toxicity. Data from other experiments showed that after injection with toxin, the LES responds normally to bethanechol and pentagastrin but displays a paradoxical response to edrophonium and cholecystokinin. Conclusions: BoTx is a potent inhibitor of resting LES tone. Its relatively specific anticholinergic effect may help clarify the role of cholinergic and noncholinergic pathways in the regulation of gastrointestinal sphincters.