Mechanism of Spinal Transmission in Tactile Allodynia

Abstract

Intrathecal (i.t.) injection of strychnine (STR : glycine antagonist) or bicuculline (BIC : GABA-A receptor antagonist) results in tactile-allodynia that can be blocked by N-methyl D-aspartate (NMDA) receptor antagonists. These glycine and GABA-A receptors tonically regulate activity in spinal glutamatergic terminals and i.t. STR and BIC enhance the spinal release of amino acids (AAs). Under halothane (1.5 %) anesthesia Sprague-Dawley rats were implanted with a lumber i.t. loop dialysis catheter and an i.t. injection catheters. Four days after implantation, rats were randomized to receive an i.t. injection of STR (3μg) or BIC (10μg). Before and after injections the touch-evoked agitation (TEA) was scored and dialysate samples were collected periodically and analyzed for glutamate (Glu) and taurine (Tau) concentration by HPLC with EC detector. To assess the contribution of NMDA receptors which themvelves exert an excitatory effect upon spinal glutamatergic neuron, the effects of i.t. NMDA (3μg) on spinal AAs release and TEA scores were also examined. Interthecal NMDA and BIC evoked a transient spinal release of Glu and Tau in the 0-10 min sample and prominent allodynia, whereas STR did not affect spinal transmitter release at any time. These results suggest that the development of allodynia may result from either a loss of GABA-A or glycine inhibition. The spinal mechanisms underlying these two actions appear to differ, the former facilitating spinal glutamate release, the latter not.