1. Adenosine A2A receptors and peripheral nociception
- Author
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Hussey, Martin John
- Subjects
615.71 - Abstract
Adenosine is a neuromodulator with complex effects on nociceptive pathways. Mice lacking the adenosine A2A receptor are hypoalgesic and a role for the A2A receptor in sensitizing afferent fibres projecting to the spinal cord has been suggested. To test this hypothesis adenosine A2A receptor knockout mice and wildtype controls were used in behavioural and autoradiographic experiments. Adenosine A2A receptor knockout mice had substantially reduced spinal cord NMDA glutamate binding whereas spinal cord AMPA glutamate receptor binding was increased, spinal cord substance P receptor binding was unaffected. Additionally, there was reduced uptake of [14C]-2-deoxyglucose into spinal cord sections from adenosine A2A receptor knockout mice. In the formalin test there was a significant reduction in nociceptive behaviour displayed by adenosine A2A receptor knockout mice during both phases of the test. The selective adenosine A2A antagonist SCH58261 also antagonized both phases of the formalin test in wildtype mice. Spinal cord NMDA glutamate receptor binding was significantly reduced following formalin injection in wildtype mice whereas AMPA glutamate receptor binding and uptake of [14C]-2-deoxyglucose were significantly increased following formalin injection in wildtype mice. There were no significant changes in any of the measures examined in spinal cords from adenosine A2A receptor knockout mice. Following repeated PGE2 injection and mechanical paw pressure, spinal cord NMDA glutamate receptor binding and uptake of [14C]-2-deoxyglucose into the spinal cord was significantly greater in adenosine A2A receptor knockout mice compared to wildtype mice. This may reflect loss of inhibitory adenosine A2A receptors located on inflammatory cells. The reduced response to formalin injection and decrease in NMDA glutamate receptor binding could reflect reduced peripheral sensory input to the spinal cord and be responsible for the hypoalgesia in adenosine A2A receptor knockout mice. These results support a key role for adenosine A2A receptors in peripheral nociceptive pathways.
- Published
- 2007