Botulinum toxin injection inhibits myogenic tone and sympathetic nerve function in the porcine internal anal sphincter.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Jones
O M
OM
Department of Pharmacology, University of Oxford, John Radcliffe Hospital, Oxford, UK. oliver.jones@pharm.ox.ac.jp
Moore
J A
JA
Brading
A F
AF
Mortensen
N J Mc C
NJ
D001003:Anal Canal / Q000187:drug effects*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007267:Injections; D013552:Swine; D013564:Sympathetic Nervous System / Q000187:drug effects
D018679:Cholinergic Agonists; D002217:Carbachol; D001905:Botulinum Toxins