Calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors mediate development, but not maintenance, of secondary allodynia evoked by first-degree burn in the rat.

Abstract

Intrathecal pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists blocks development of spinal sensitization in a number of pain models. In contrast, secondary mechanical allodynia evoked by thermal injury (52.5 degrees C for 45 s) applied to the hind paw of the rat is not blocked by intrathecal pretreatment with NMDA receptor antagonists. It is, however, blocked by antagonists to the non-NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/KA) and calcium-permeable AMPA/KA receptors. These findings suggest a role for these receptors in the development of spinal sensitization. The present study used the same thermal injury model to assess the effects of the AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and specific calcium-permeable AMPA/KA receptor antagonists philanthotoxin (PHTx) and joro spider toxin (JST) when given as postinjury treatments. Intrathecal saline injection at 5 and 30 min postinjury had no effect on thermal injury-evoked allodynia as measured by calibrated von Frey filaments. In contrast, 36 nmol of CNQX given at either time point reversed allodynia. Intrathecal 13 nmol of PHTx or 9 nmol of JST (higher doses than that required for pretreatment) reversed allodynia at the 5-min time point, but neither drug was antiallodynic at the 30-min time point. Thus, secondary mechanical allodynia in this model is not maintained by calcium-permeable AMPA/KA receptors, but instead requires activation of calcium-impermeable AMPA/KA receptors. This finding supports a role for AMPA/KA receptor function in responses occurring during spinal sensitization.

• Authors: Toni L Jones, Linda S Sorkin
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 310 Issue 1 Pg. 223-9 (Jul 2004) ISSN: 0022-3565 [Print] United States
• PMID: 15007101 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Excitatory Amino Acid Antagonists
• JSTX spider toxin
• Receptors, AMPA
• Receptors, Kainic Acid
• Spider Venoms
• 6-Cyano-7-nitroquinoxaline-2,3-dione
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
• Kainic Acid
• Calcium

Topics

• 6-Cyano-7-nitroquinoxaline-2,3-dione (pharmacology)
• Animals
• Burns (physiopathology)
• Calcium (metabolism)
• Disease Models, Animal
• Excitatory Amino Acid Antagonists (pharmacology)
• Injections, Spinal
• Kainic Acid (pharmacology)
• Motor Cortex
• Pain (physiopathology)
• Pain Threshold
• Rats
• Receptors, AMPA (physiology)
• Receptors, Kainic Acid (physiology)
• Spider Venoms (pharmacology)
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (pharmacology)