Involvement of glutamate receptors in allodynia induced by prostaglandins E2 and F2 alpha injected into conscious mice.

Abstract

In order to investigate the involvement of glutamate receptor systems in allodynia induced by prostaglandin (PG) E2 or F2 alpha, we co-administered antagonists for N-methyl-D-aspartate (NMDA), non-NMDA, or metabotropic glutamate receptors intrathecally with PGE2 or PGF2 alpha 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 PGE2-induced allodynia with an IC50 of 1.60 and 0.52 microgram/mouse, respectively. A glycine binding-site antagonist for the NMDA receptor, 7-Cl-KYNA, did not influence it. None of these NMDA receptor antagonists inhibited PGF2 alpha-evoked allodynia. Non-NMDA receptor antagonists GAMS and CNQX inhibited both PGE2- and PGF2 alpha-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 PGF2 alpha with an IC50 of 0.92 and 3.26 ng/mouse, respectively, but not that induced by PGE2. Intrathecal administration of L-glutamate produced allodynia over a wide range of low doses from 0.1 pg to 0.1 microgram/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 PGE2- and PGF2 alpha-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 be different between them.

• Authors: Toshiaki Minami, Isao Nishihara, Rumiko Uda, Seiji Ito, Masayoshi Hyodo, Osamu Hayaishi
• Journal: Pain (Pain) Vol. 57 Issue 2 Pg. 225-231 (May 1994) ISSN: 0304-3959 [Print] United States
• PMID: 7916453 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Neurotransmitter Agents
• Receptors, Metabotropic Glutamate
• Receptors, N-Methyl-D-Aspartate
• Glutamic Acid
• Dinoprost
• Dinoprostone

Topics

• Animals
• Dinoprost (pharmacology)
• Dinoprostone (pharmacology)
• Glutamates (pharmacology)
• Glutamic Acid
• Injections, Spinal
• Mice
• Neurotransmitter Agents (pharmacology)
• Pain (physiopathology)
• Receptors, Metabotropic Glutamate (antagonists & inhibitors)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Spinal Cord (physiology)
• Synaptic Transmission (drug effects)