Mechanism of action of botulinum toxin on the internal anal sphincter.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Jones
O M
OM
Department of Pharmacology, University of Oxford, Oxford, UK. oliverjones10@hotmail.com
Brading
A F
AF
Mortensen
N J McC
NJ
D001003:Anal Canal / Q000187:drug effects*; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009465:Neuromuscular Agents / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D013552:Swine
D009465:Neuromuscular Agents; D018722:Nicotinic Agonists; D004246:Dimethylphenylpiperazinium Iodide; D019274:Botulinum Toxins, Type A