title: The effect of substance P on the spontaneous discharge from injured inferior alveolar nerve fibres in the ferret.
abstract: Previous studies in our laboratory have shown that, at a site of inferior alveolar nerve (IAN) injury, there is a close association between the development of spontaneous neural activity and the accumulation of neuropeptides in the damaged axons. As this ectopic activity may contribute to the development of sensory disturbances after injury, we have examined further this relationship by determining the potential role of one neuropeptide, substance P (SP), in the initiation or modulation of the spontaneous discharge. Thirty-six adult ferrets were anaesthetised, the IAN sectioned, and the animals allowed to recover for 3-4 days. In terminal experiments under general anaesthesia, electrophysiological recordings were made from axons in fine filaments dissected from the nerve, central to the injury site. The effect of SP (2 x 10(-12), 10(-6) and 10(-4) M) and SP-antagonist (10(-4) M) applied either close-arterially or topically to the injury site was determined. Of the 101 units studied, 59% were spontaneously active. Close-arterial administration of SP increased the level of spontaneous discharge in a dose-dependent manner, with higher concentrations affecting more units (2 x 10(-12) M, 14%; 10(-6) M, 58%; 10(-4) M, 85%). SP also initiated spontaneous discharge in some previously silent units. Activity in 46% of units also increased in response to the SP-antagonist. None of the units responded to topical application of either SP or SP-antagonist. This study shows that SP can both initiate and modulate the spontaneous discharge from damaged axons, and this mechanism may be a potential therapeutic target in the management of sensory disturbances after nerve injury.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Smith
authors.forename: Alison R
authors.initials: AR
authors.lastname: Loescher
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Boissonade
authors.forename: Peter P
authors.initials: PP
authors.lastname: Robinson
mesh_terms: D000287:Administration, Topical; D000818:Animals; D020209:Cranial Nerve Injuries / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D005289:Ferrets; D007269:Injections, Intra-Arterial; D008297:Male; D008340:Mandibular Nerve / Q000187:drug effects* / Q000503:physiopathology; D009412:Nerve Fibers / Q000187:drug effects*; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D061221:Trigeminal Nerve Injuries
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; C496429:substance P (6-11), Tyr(6)-D-Phe(7)-D-His(9)-; D013373:Substance P