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Genetic deletion of the adenosine A(2A) receptor in mice reduces the changes in spinal cord NMDA receptor binding and glucose uptake caused by a nociceptive stimulus

Hussey, MJ, Clarke, GD, Ledent, C, Kitchen, I and Hourani, SMO (2010) Genetic deletion of the adenosine A(2A) receptor in mice reduces the changes in spinal cord NMDA receptor binding and glucose uptake caused by a nociceptive stimulus NEUROSCIENCE LETTERS, 479 (3). 297 - 301. ISSN 0304-3940

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Abstract

Mice lacking the adenosine A2A receptor are less sensitive to nociceptive stimuli, and A2A receptor antagonists have antinociceptive effects. We have previously shown a marked reduction in the behavioural responses to formalin injection in A¬2A receptor knockout mice. This may be due to the presence of pronociceptive A2A receptors on sensory nerves, and if so spinal cords from A2A receptor knockout mice may have altered neurochemical responses to a nociceptive stimulus. We tested this hypothesis by studying two parameters known to change with spinal cord activity, NMDA glutamate receptor binding and [14C]-2-deoxyglucose uptake, following intraplantar formalin injection in wild-type and A2A receptor knockout mice. In naïve untreated A2A knockout mice [14C]-2-deoxyglucose uptake in all regions of the spinal cord was significantly lower compared to the wild-type, similar to the reduced NMDA receptor binding that we have previously observed. Following formalin treatment, there was an decrease in [3H]MK801 binding to NMDA receptors and an increase in [14C]-2-deoxyglucose uptake in the spinal cords of wild-type mice, and these changes were significantly reduced in the A2A knockout mice. In addition to altered behavioural responses, there are therefore corresponding reductions in spinal cord neurochemical changes induced by formalin in mice lacking adenosine A2A receptors. These observations support the hypothesis that activation of A2A receptors enhances nociceptive input into the spinal cord and suggests a possible role for A2A antagonists as analgesics.

Item Type: Article
Additional Information: NOTICE: this is the author’s version of a work that was accepted for publication in Neuroscience Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuroscience Letters, 479(3), August 2010, DOI 10.1016/j.neulet.2010.05.084.
Uncontrolled Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Adenosine A(2A) receptors, Nociception, Spinal cord, Knockout mice, DORSAL-HORN NEURONS, FORMALIN TEST, SUBSTANTIA-GELATINOSA, RAT, PAIN, MODULATION, EXPRESSION, ANTAGONISTS, INACTIVATION, HYPERALGESIA
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Divisions: Faculty of Health and Medical Sciences > Biochemistry and Physiology
Depositing User: Susanna Hourani
Date Deposited: 02 Dec 2011 12:08
Last Modified: 23 Sep 2013 18:48
URI: http://epubs.surrey.ac.uk/id/eprint/7457

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