Increased spinal N-methyl-D-aspartate receptor function after 20 h of carrageenan-induced inflammation

Spinal N-methyl-D-aspartate (NMDA) receptors are thought to be important in starts of central hyperexcitability induced by e.g. inflammation or painfu l neuropathies. The carrageenan model of inflammatory pain has been and sti ll is widely used as is the NMDA receptor antagonist 2-amino-5-phosphonopen tanoic acid (AP5) to investigate NMDA receptor function. Here we present tw o novel findings using electrophysiological technique: the NMDA receptor fu nction in the spinal cord is increased following 20 h of carrageenan-induce d inflammation and further that only the D-isomer of AP5 is active in the s pinal cord. Exogenous NMDA (0.5 and 5 nmol) applied onto the dorsal spinal cord produced a significantly greater facilitation and D-APS (1.25 mu mol) a significantly greater inhibition of the C-fibre evoked response of the wi de dynamic range (WDR) neurones studied in carrageenan (20 h after injectio n) compared to control rats. The present and two recent studies suggest cen tral changes are different and possibly greater in the later (20 h) compare d to the earlier (2-6 h) phase or carrageenan-induced inflammation. In conc lusion, 20 h of carrageenan-induced inflammation increases the function of spinal NMDA receptor involved in nociceptive transmission and in addition t he D-isomer of AP5 should be used when NMDA receptor antagonism is wanted i n the spinal cord. (C) 2001 International Association for the Study of Pain . Published by Elsevier Science B.V. All rights reserved.