DISTINCT ELECTROPHYSIOLOGICAL EFFECTS OF 2 SPINALLY ADMINISTERED MEMBRANE STABILIZING DRUGS, BUPIVACAINE AND LAMOTRIGINE

A selective blockade of the relay of messages by C-fibres into the spi nal cord is a logical approach to the reduction of nociceptive transmi ssion. 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 follo wing noxious and innocuous stimulation. Dorsal horn neuronal responses following acute repetitive C-fibre electrical stimulation (three time s the C-fibre threshold at 0.5 Hz) were recorded in intact halothane a naesthetised rats. Wind up, an enhanced C-fibre evoked response of dor sal horn neurones, and an associated post discharge were observed foll owing repetitive stimulation. The effects of spinally administered bup ivacaine and lamotrigine on the dorsal horn neuronal responses were in vestigated. Spinal bupivacaine (25-1000 mu g/50 mu l) dose dependently reduced the C-fibre evoked responses (r(2) = 0.5, P < 0.0003), wind u p (r(2) = 0.4, P < 0.002) and the post discharge (r(2) = 0.34, P < 0.0 05) of these neurones. The effects of bupivacaine were long lasting, u p to 120 min post-administration. The A beta-fibre evoked responses we re not dose-dependently reduced by bupivacaine. Spinal lamotrigine (50 -1000 mu g/50 mu l) did not significantly reduce the C- or A beta-fibr e evoked responses. In contrast there was a tendency for wind up and p ost discharge to be facilitated by lamotrigine. Although both bupivaca ine and lamotrigine are sodium channel blockers, the effects of the tw o drugs on the C-fibre and A beta-fibre evoked responses were complete ly different. Bupivacaine reduced C-fibre evoked responses whereas lam otrigine had a tendency to facilitate responses. The profile of sodium channel blockers would appear highly diverse and the status of lamotr igine as a potential analgesic remains unclear. (C) 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.