Expression of PSD-95/SAP90 is critical for N-methyl-D-aspartate receptor-mediated thermal hyperalgesia in the spinal cord

PSD-95/SAP90, a molecular scaffold protein, attaches the N-methyl-D-asparta te receptor to cellular signaling pathways through PSD-95/DLG/Z0-1 domain i nteractions at neuronal synapses.(5,9) This suggests that PSD-95/SAP90 migh t be involved in many physiological and pathophysiological actions triggere d via the N-methyl-D-aspartate receptor in the central nervous system. Were , we present evidence that suppression of the expression of PSD-95/SAP90 in the spinal cord significantly attenuated facilitation of the tail-hick ref lex triggered through N-methyl-D-aspartate receptor activation but not base line tail-flick reflex latency. Moreover, PSD-95/SAP90's messenger RNA and protein were enriched in the spinal cord and selectively distributed in the superficial dorsal horn, where PSD-95/SAP90 overlapped with the N-methyl-D -aspartate receptor. In spinal cord neurons, PSD-95/SAP90 interacted with t he N-methyl-D-aspartate receptor subunits 2A/2B. It is indicated that activ ation of the N-methyl-D-aspartate receptor in spinal hyperalgesia results i n association of the N-methyl-D-aspartate receptor with PSD-95/SAP90 and th at PSD-95/SAP90 is required for noxious thermal hyperalgesia triggered via the N-methyl-D-aspartate receptor at the spinal cord level. The present fin dings may provide novel insights into the mechanisms for persistent sensiti zation of the somatosensory system. (C) 2000 IBRO. Published by Elsevier Sc ience Ltd. All rights reserved.