Tr. Tolle et al., ANTICONVULSANTS SUPPRESS C-FOS PROTEIN EXPRESSION IN SPINAL-CORD NEURONS FOLLOWING NOXIOUS THERMAL-STIMULATION, Experimental neurology, 132(2), 1995, pp. 271-278
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.