Effects of botulinum toxin A on the sphincter of Oddi: an in vivo and in vitro study

Abstract

Background: Botulinum toxin A is a potent inhibitor of the release of acetylcholine from nerve endings. Local injection of botulinum toxin has recently been suggested to be helpful in sphincter of Oddi dyskinesia by decreasing sphincter of Oddi pressure.

Aims: To explore the mechanism of action of botulinum toxin A on sphincter of Oddi (SO) muscle.

Methods: Four piglets underwent duodenoscopy and SO manometry was performed. After obtaining a baseline pressure, the SO was injected with normal saline and the experiment repeated after one week. The SO was then injected endoscopically with botulinum toxin (40 U) with follow up manometry 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 contraction was measured and registered on a polygraph. Rings were stimulated by 70 V (10 Hz, 0.5 ms) electrical field stimulation for 20 seconds, exogenous acetylcholine (100 microM), and KCl (125 mM). Botulinum toxin (0.1 U/ml) or atropine (1 microM) was added to the incubation medium and the stimulation was repeated.

Results: Mean basal SO pressure in the pigs remained unchanged after saline injection but decreased to about 50% of baseline value following botulinum toxin injection (p = 0.04). The contractions induced by direct stimulation of SO smooth muscle with KCl were not significantly affected by either atropine or botulinum toxin. In all rings exogenous acetylcholine induced contractions, which were totally blocked by atropine, but not by botulinum toxin. Electrical field stimulation induced contractions that were inhibited by both atropine and botulinum toxin.

Conclusion: Botulinum toxin inhibits pig sphincter of Oddi smooth muscle contractions by a presynaptic cholinergic mechanism, similar to that described in skeletal muscle.

Figure 1

(A) Representative tracings of sphincter of Oddi smooth muscle contractions induced by electrical field stimulation (EFS), and the effects of botulinum toxin and atropine. Small arrows indicate washes with fresh physiological salt solution. (B) Representative tracings of the sphincter of Oddi smooth muscle contractions induced by exogenous acetylcholine (ACH), and the effects of botulinum toxin and atropine. Small arrows indicate washes with fresh physiological salt solution.