Reduced response to the formalin test and lowered spinal NMDA glutamate receptor binding in adenosine A2A receptor knockout mice

被引:46
作者
Hussey, Martin J.
Clarke, Geoffrey D.
Ledent, Catherine
Hourani, Susanna M. O.
Kitchen, Ian [1 ]
机构
[1] Univ Surrey, Sch Biomed & Mol Sci, Guildford GU2 7XH, Surrey, England
[2] Univ Surrey, European Inst Hlth & Med Sci, Guildford GU2 7XH, Surrey, England
[3] Univ Libre Bruxelles, Inst Rech Interdisciplinaire Biol Humaine & Mol, B-1070 Brussels, Belgium
基金
英国生物技术与生命科学研究理事会;
关键词
mouse; nociception; spinal cord; formalin test; adenosine A(2A) receptor; NMDA glutamate receptor; NK1; receptor; SCH58261; adenosine A(2A) antagonist;
D O I
10.1016/j.pain.2006.10.014
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Adenosine is a neuromodulator with complex effects on pain pathways. Mice lacking the adenosine A(2A) receptor are hypoalgesic, and have altered analgesic responses to receptor-selective opioid agonists. These and other findings suggest a role for the adenosine A2A receptor in sensitizing afferent fibres projecting to the spinal cord. To test this hypothesis formalin (20 mu l, 5%) was injected into the paw and nociceptive responses were measured in wildtype and adenosine A2A receptor knockout mice. There was a significant reduction in nociception associated with sensory nerve activation in the knockout mice as measured by time spent biting/licking the formalin-injected paw and number of flinches seen during the first phase, but only the number of flinches was reduced during the second inflammatory phase. In addition, the selective adenosine A(2A) antagonist SCH58261 (3 and 10 mg/kg) also antagonised both phases of the formalin test. We also labelled NMDA glutamate and NK1 receptors in spinal cord sections as an indirect measure of nociceptive transmission from peripheral sites to the spinal cord. [H-3]-Substance P binding to NK1 receptors was unaltered but there was a substantial reduction in binding of [H-3]-MK801 to NMDA glutamate receptors in all regions of the spinal cord from knockout mice. The decrease in NMDA glutamate receptor binding may reflect reduced peripheral sensory input to the spinal cord during development and could relate to the hypoalgesia in this genotype. These results support a key role for the adenosine A2A receptor in peripheral nociceptive pathways. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:287 / 294
页数:8
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