ANTICONVULSANTS SUPPRESS C-FOS PROTEIN EXPRESSION IN SPINAL-CORD NEURONS FOLLOWING NOXIOUS THERMAL-STIMULATION

The expression of the nuclear immediate-early gene-encoded protein c-F os in spinal cord dorsal horn neurons of the rat following noxious the rmal stimulation was compared in carbamazepine-, valproate- and phenyt oine-treated animals. Single intraperitoneal injection of carbamazepin e (50 mg/kg), valproate (300 mg/kg) or intravenous injection of phenyt oine (20 mg/kg) before noxious stimulation reduced the number of c-Fos immunoreactive neurons to 65-80% of control levels in superficial lam inae and to 30-60% in deep laminae of the dorsal horn. Pretreatment wi th carbamazepine or valproate for 4 or 8 days combined with an injecti on immediately before noxious stimulation further significantly decrea sed the number of c-Fos neurons in the deep dorsal horn only in animal s treated with valproate. The observation that activity-dependent gene expression in the spinal cord is effectively modulated by anticonvuls ants discloses a novel therapeutic potential of these compounds. Presu mably via an acute suppression of high-frequency repetitive firing and /or altered synaptic transmission of intraspinal or descending neurotr ansmitter systems these drugs gain access to neuroplastic mechanisms w hich might be relevant for the restoration of physiological levels of neuronal excitability in the central nervous system. (C) 1995 Academic Press, Inc.