title: Effect of SB-750364, a specific TRPV1 receptor antagonist, on injury-induced ectopic discharge in the lingual nerve.
abstract: Abnormal neural activity generated at a site of nerve injury is thought to contribute to the development of dysaesthesia. Vanilloid receptor 1 (TRPV1), a transducer of noxious stimuli, may be involved in the initiation of this abnormal activity and could provide a useful therapeutic target. We investigated the effect of a specific TRPV1 antagonist (SB-750364) on injury-induced discharge in the lingual nerve. In 12 anaesthetised adult ferrets the left lingual nerve was sectioned and animals were allowed to recover for 3-7 days. In terminal experiments under general anaesthesia, the nerve was re-exposed and electrophysiological recordings made from spontaneously active axons in fine filaments dissected from the nerve central to both the injury site and the junction with the chorda tympani. SB-750364 was infused via the cephalic vein in order to achieve three increasing but stable systemic blood levels of the compound (0.3, 1.0 and 3.0 microM). Twenty-eight spontaneously active units were studied, with discharge frequencies ranging from 0.02 to 4.9 Hz. There was a significant reduction in spontaneous activity in 17 units (61%) at 1.0 microM or less of SB-750364 (p<0.01; Friedman test with Dunn's multiple comparisons). A further 4 units (14%) showed a significant reduction in activity at 3.0 microM (p<0.01). In the remaining 7 units (25%) the discharge was unaffected (p>0.05). These data show that the TRPV1 antagonist SB-750364 can reduce the level of spontaneous activity initiated in some axons following lingual nerve injury.
authors.affiliation: Department of Oral & Maxillofacial Surgery, School of Clinical Dentistry, University of Sheffield, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Biggs
authors.forename: Julian M
authors.initials: JM
authors.lastname: Yates
authors.forename: Alison R
authors.initials: AR
authors.lastname: Loescher
authors.forename: Nick M
authors.initials: NM
authors.lastname: Clayton
authors.forename: Peter P
authors.initials: PP
authors.lastname: Robinson
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Boissonade
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D020209:Cranial Nerve Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005289:Ferrets; D008036:Lingual Nerve / Q000187:drug effects* / Q000503:physiopathology; D061222:Lingual Nerve Injuries; D008297:Male; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C494484:TRPV1 receptor