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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.
J Pharmacol Exp Ther. 2004 Jul; 310(1):223-9.JP

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+Show Affiliations

Department of Anesthesiology, University of California-San Diego, La Jolla, California 92093-0818, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

15007101

Citation

Jones, Toni L., and Linda S. Sorkin. "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." The Journal of Pharmacology and Experimental Therapeutics, vol. 310, no. 1, 2004, pp. 223-9.
Jones TL, Sorkin LS. 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. J Pharmacol Exp Ther. 2004;310(1):223-9.
Jones, T. L., & Sorkin, L. S. (2004). 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. The Journal of Pharmacology and Experimental Therapeutics, 310(1), 223-9.
Jones TL, Sorkin LS. 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. J Pharmacol Exp Ther. 2004;310(1):223-9. PubMed PMID: 15007101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Jones,Toni L, AU - Sorkin,Linda S, Y1 - 2004/03/08/ PY - 2004/3/10/pubmed PY - 2004/9/8/medline PY - 2004/3/10/entrez SP - 223 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 310 IS - 1 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15007101/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_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15007101 DB - PRIME DP - Unbound Medicine ER -