EFFECTS OF BOTULINUM TOXIN-A ON THE SPHINCTER OF ODDI - AN IN-VIVO AND IN-VITRO STUDY

Background-Botulinum toxin A is a potent inhibitor of the release of a cetylcholine from nerve endings. Local injection of botulinum toxin ha s recently been suggested to be helpful in sphincter of Oddi dyskinesi a by decreasing sphincter of Oddi pressure. Aims-To explore the mechan ism of action of botulinum toxin A on sphincter of Oddi (SO) muscle. M ethods-Four piglets underwent duodenoscopy and SO manometry was perfor med. After obtaining a baseline pressure, the SO was injected with nor mal saline and the experiment repeated after one week. The SO was then injected endoscopically with botulinum toxin (40 U) with follow up ma nometry one week later. The sphincter of Oddi was removed from 10 pigs , cut into three rings, and placed in an organ bath. The force of cont raction was measured and registered on a polygraph. Rings were stimula ted by 70 V (10 Hz, 0.5 ms) electrical field stimulation for 20 second s, exogenous acetylcholine (100 mu M), and KCl (125 mM). Botulinum tox in (0.1 U/ml) or atropine (1 mu M) was added to the incubation medium and the stimulation was repeated. Results-Mean basal SO pressure in th e pigs remained unchanged after saline injection but decreased to abou t 50% of baseline value following botulinum toxin injection (p=0.04). The contractions induced by direct stimulation of SO smooth muscle wit h KCI were not significantly affected by either atropine or botulinum toxin. In all rings exogenous acetylcholine induced contractions, whic h were totally blocked by atropine, but not by botulinum toxin. Electr ical field stimulation induced contractions that were inhibited by bot h atropine and botulinum toxin. Conclusion-Botulinum toxin inhibits pi g sphincter of Oddi smooth muscle contractions by a presynaptic cholin ergic mechanism, similar to that described in skeletal muscle.