Characterization of spinal amino acid release and touch-evoked allodynia produced by spinal glycine or GABA(A) receptor antagonist

Intrathecal strychnine (glycine antagonist) or bicuculline (GABAA antagonis t) yields a touch-evoked agitation that is blocked by N-methyl-D-aspartate receptor antagonism. We examined the effects of intrathecal strychnine and bicuculline on touch-evoked agitation and the spinal release of amino acids . Fifty-two Sprague-Dawley rats were prepared under halothane anesthesia wi th a lumbar intrathecal catheter and a loop dialysis catheter. Four days af ter implantation, rats were randomized to receive an intrathecal injection of N-methyl-D-aspartate (3 mu g), strychnine (3 mu g) or bicuculline (10 mu g), or a combination of N-methyl-D-aspartate with bicuculline or strychnin e. The agitation produced by brief light tactile stroking of the flank (tac tile allodynia), and the spontaneous spinal release of glutamate, taurine a nd serine was measured. Intrathecal N-methyl-D-aspartate, strychnine and bi cuculline produced similar touch-evoked allodynia. Intrathecal bicuculline and N-methyl-D-aspartate alone evoked a transient spinal release of glutama te and taurine, but not serine, in the 0-10 min sample, while strychnine di d not affect spinal transmitter release at any time. As GABA(A) but not glycine receptor inhibition at equi-allodynic doses incr eases glutamate release, while the allodynia of both is blocked by N-methyl -D-aspartate receptor antagonism, we hypothesize that GABA(A) sites regulat e presynaptic glutamate release, while glycine regulates the excitability o f neurons postsynaptic to glutamatergic terminals. (C) 1999 IBRO. Published by Elsevier Science Ltd.