title: Distinct electrophysiological effects of two spinally administered membrane stabilising drugs, bupivacaine and lamotrigine.
abstract: A selective blockade of the relay of messages by C-fibres into the spinal cord is a logical approach to the reduction of nociceptive transmission. Here we compared the effect of two distinctly different sodium channel blockers, the local anaesthetic bupivacaine and the novel anti-epileptic lamotrigine, on the responses of dorsal horn neurones following noxious and innocuous stimulation. Dorsal horn neuronal responses following acute repetitive C-fibre electrical stimulation (three times the C-fibre threshold at 0.5 Hz) were recorded in intact halothane anaesthetised rats. Wind up, an enhanced C-fibre evoked response of dorsal horn neurones, and an associated post discharge were observed following repetitive stimulation. The effects of spinally administered bupivacaine and lamotrigine on the dorsal horn neuronal responses were investigated. Spinal bupivacaine (25-1000 microg/50 microl) dose dependently reduced the C-fibre evoked responses (r2 = 0.5, P < 0.0003), wind up (r2 = 0.4, P < 0.002) and the post discharge (r2 = 0.34, P < 0.005) of these neurones. The effects of bupivacaine were long lasting, up to 120 min post-administration. The Abeta-fibre evoked responses were not dose-dependently reduced by bupivacaine. Spinal lamotrigine (50-1000 microg/50 microl) did not significantly reduce the C- or Abeta-fibre evoked responses. In contrast there was a tendency for wind up and post discharge to be facilitated by lamotrigine. Although both bupivacaine and lamotrigine are sodium channel blockers, the effects of the two drugs on the C-fibre and Abeta-fibre evoked responses were completely different. Bupivacaine reduced C-fibre evoked responses whereas lamotrigine had a tendency to facilitate responses. The profile of sodium channel blockers would appear highly diverse and the status of lamotrigine as a potential analgesic remains unclear.
authors.affiliation: Department of Pharmacology, University College London, UK. v.chapman. @ucl.ac.uk
authors.forename: V
authors.initials: V
authors.lastname: Chapman
authors.forename: M A
authors.initials: MA
authors.lastname: Wildman
authors.forename: A H
authors.initials: AH
authors.lastname: Dickenson
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D007278:Injections, Spinal; D000077213:Lamotrigine; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D000927:Anticonvulsants; D026941:Sodium Channel Blockers; D014227:Triazines; D000077213:Lamotrigine; D002045:Bupivacaine