Involvement of glutamate receptors in allodynia induced by prostaglandins E 2 and F 2α injected into conscious mice

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Abstract
In order to investigate the involvement of glutamate receptor systems in allodynia induced by prostaglandin (PG) E 2 or F 2 α , we co-administered antagonists for N- methyl- d -aspartate (NMDA). non-NMDA, or metabotropic glutamate receptors intrathecally with PGE 2 or PGF 2 α and examined their effects on the allodynia evoked in conscious mice by non-noxious brushing of the flanks. MK-801, a non-competitive NMDA receptor channel blocker, and d -AP-5, a selective NMDA receptor antagonist, dose-dependently blocked PGH 2 -induced allodynia with an IC 50 of 1.60 and 0.52 μg/mouse, respectively. A glycine binding-site antagonist for the NMDA receptor, 7-CI-KYNA, did not influence it. None of these NMDA receptor antagonists inhibited PGF 2 α -evoked allodynia. Non-NMDA receptor antagonists GAMS and CNQX inhibited both PGE 2 - and PGF 2 α -induced allodynia. On the other hand, l -AP-3 and l -AP-4, putative metabotropic glutamate receptor antagonists, dose-dependently antagonized the allodynia induced by PGF 2 α with an IC 50 of 0.92 and 3.26 ng/mouse, respectively, but not that induced by PGE 2 . Intrathecal administration of l -glutamate produced allodynia over a wide range of low doses from 0.1 pg to 0.1 μg/mouse, and the maximal effect was observed at 1 ng. Similar to allodynia induced by prostaglandins, the response lasted over a 50-min experimental period. These results demonstrate that both PGE 2 - and PGF 2 α -evoked allodynia are mediated through a pathway that includes the glutamate receptor system but that subtypes of glutamate receptors involved and sites of action in the spinal cord may he different between them.