Characterization of the glutamatergic system for induction and maintenance of allodynia

Glutamate is the main excitatory neurotransmitter in the central nervous system and has been shown to be involved in spinal nociceptive processing. We previously demonstrated that intrathecal (i.t.) administration of prostaglandin (PG) E-2 and PGF(2 alpha) induced touch-evoked pain (allodynia) through the glutamatergic system by different mechanisms. In the present study, we characterized glutamate receptor subtypes and glutamate transporters involved in induction and maintenance of PGE(2)- and PGF(2 alpha)-evoked allodynia. In addition to PGE(2) and PGF(2 alpha). N-methyl-D-aspartate (NMDA) and alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not kainate, induced allodynia. PGE(2)- and NMDA-induced allodynia were observed 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 GluR epsilon1(-/-) mice, but not in GluR epsilon4(-/-) mice. The induction of allodynia by PGE(2) and NMDA was abolished by the NMDA receptor epsilon2 (NR2B) 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 DL-threo-beta -benzyloxyaspartate (DL-TBOA) blocked all the allodynia induced by PGE(2), PGF(2 alpha), NMDA, and AMPA. These results demonstrate that there are two pathways for induction of allodynia mediated by the glutamatergic 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.