신경병통증 모델 쥐의 척수내에서 흥분성아미노산 수용체

Abstract

It has been proposed that excitatory amino acid (EAA) receptors mediate sensitzation of central neurons that may play a crucial role in the generation of neuropathic pain. We performed experiments using a rat model of peripheral neuropathy to provide direct evidence that EAA receptors are involved in mediating hyperexcitability of dorsal horn neurons in the spinal cord. The results obtained were as follows: 1) Rats that received an unilateral ligation of L5 and L6 spinal nerves showed behaviorally increased mechanical sensitivity of the hindpaw on the side of nerve ligation. 2) Wide dynamic range (WDR) spinal dorsal horn neurons on the side of the ligation showed enhanced brush-and pinch-evoked responses. 3) WDR neurons on the side of the ligation were classified into three groups, based on responses to iontophoretically applied EAA receptor ligands: neurons responsive preferentially to NMDA (15 of 40, 37.5%), neurons responsive preferentially to AMPA (20 of 40, 50%), non-NMDA receptor agonist, and neurons responsive well to both NMDA and AMPA (5 of 40, 12.5%). 4) AMPA responsive neurons were suppressed by GAMS, non-NMDA receptor antagonist, only in their brush evoked response, whereas NMDA responsive neurons were suppressed by AP-5, NMDA receptor antagonist, only in their pinch-evoked response. The results suggest that following a peripheral nerve injury, spinal WDR neurons are enhanced in their mechanical responsiveness where increased response to innocuous mechanical stimulus is mediated by non-NMDA receptor while that to noxious one is by NMDA receptor.