Characterization of the glutamatergic system for induction and maintenanceof allodynia

Glutamate is the main excitatory neurotransmitter in the central nervous sy stem and has been shown to be involved in spinal nociceptive processing. We previously demonstrated that intrathecal (i.t.) administration of prostagl andin (PG) E-2 and PGF(2 alpha) induced touch-evoked pain (allodynia) throu gh the glutamatergic system by different mechanisms. In the present study, we characterized glutamate receptor subtypes and glutamate transporters inv olved in induction and maintenance of PGE(2)- and PGF(2 alpha)-evoked allod ynia. In addition to PGE(2) and PGF(2 alpha). N-methyl-D-aspartate (NMDA) a nd alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but no t kainate, induced allodynia. PGE(2)- and NMDA-induced allodynia were obser ved in NMDA receptor epsilon4 (NR2D) subunit knockout (GluR epsilon4(-/-)) mice. hut not in epsilon1 (NR2A) subunit knockout (GluR epsilon1(-/-)) mice . Conversely, PGF(2 alpha)- and AMPA-induced allodynia were observed in Glu R epsilon1(-/-) mice, but not in GluR epsilon4(-/-) mice. The induction of allodynia by PGE(2) and NMDA was abolished by the NMDA receptor epsilon2 (N R2B) antagonist CP-101.606 and neonatal capsaicin treatment. PGF(2 alpha)- and AMPA-induced allodynia were not affected by CP-101.606 and by neonatal capsaicin treatment. On the other hand, the glutamate transporter blocker D L-threo-beta -benzyloxyaspartate (DL-TBOA) blocked all the allodynia induce d by PGE(2), PGF(2 alpha), NMDA, and AMPA. These results demonstrate that t here are two pathways for induction of allodynia mediated by the glutamater gic system and suggest that the glutamate transporter is essential for the induction and maintenance of allodynia. (C) 2001 Elsevier Science B.V. All rights reserved.