The effect of carbamazepine on injury-induced ectopic discharge in the lingual nerve.
Previous studies have shown that the development of ectopic activity from damaged axons following nerve injury may contribute to the aetiology of sensory disturbances, including dysaesthesia. Pharmacological manipulation of this activity could provide a method of treatment for this intractable condition. In this study we have investigated the effect of carbamazepine, an anti-convulsant, as it is known to have membrane stabilising properties. In eight anaesthetised adult ferrets the left lingual nerve was sectioned and the animals allowed to recover for 3 days. Then, in terminal experiments under general anaesthesia, the nerve was re-exposed and electrophysiological recordings were made from spontaneously active units in fine filaments dissected from the nerve proximal to the injury site. Carbamazepine in a modified cyclodextrin (hydroxypropyl-beta-cyclodextrin) was administered intravenously in increments, in order to achieve a progressively increasing systemic concentration, and serum levels were determined at the point that activity ceased. Twenty-one spontaneously active units were studied, with conduction velocities of 2.1-28.9 m s(-1) and discharge frequencies of 0.25-15.3 Hz. Spontaneous activity ceased in 13 units with a serum concentration of carbamazepine ranging from 3.5 to 8.4 mg/l, which was within the normal therapeutic range (4-12 mg/l). Four units ceased activity with carbamazepine levels above the therapeutic range (15.4-17.2 mg/ml), but the remaining four continued to discharge throughout the recording period. These data suggest that systemic carbamazepine can reduce the level of spontaneous activity initiated in some axons following lingual nerve injury.
Department of Oral and Maxillofacial Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK. j.m.yates@sheffield.ac.uk
Julian M
JM
Yates
Keith G
KG
Smith
Peter P
PP
Robinson
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001369:Axons / Q000187:drug effects*; D002220:Carbamazepine / Q000008:administration & dosage*; D020209:Cranial Nerve Injuries / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D007262:Infusions, Intravenous; D008036:Lingual Nerve / Q000187:drug effects* / Q000503:physiopathology; D061222:Lingual Nerve Injuries; D009431:Neural Conduction / Q000187:drug effects
D000927:Anticonvulsants; D002220:Carbamazepine