Deletion of the adenosine A 2A receptor in mice enhances spinal cord neurochemical responses to an inflammatory nociceptive stimulus

摘要

Knockout mice lacking the adenosine A 2A receptor are less sensitive to nociceptive stimuli, and this may be due to the presence of pronociceptive A 2A receptors on sensory nerves. In support of this hypothesis, we have recently shown that in A 2A receptor knockout mice there are marked reductions in the changes of two markers of spinal cord neuronal activity, [ 3H]MK801 binding to NMDA receptors and uptake of [ 14C]-2-deoxyglucose, in response to formalin injection. We now report that following a more prolonged inflammatory stimulus, consisting of intraplantar injections of PGE 2 and paw pressure, there was in contrast an increase in [ 3H]MK801 binding and [ 14C]-2-deoxyglucose uptake in the spinal cords of the A 2A receptor knockout mice which was much greater than in the wild-type mice. This increase suggests that when there is a pronounced inflammatory component to the stimulus, loss of inhibitory A 2A receptors on inflammatory cells outweighs the loss of pronociceptive A 2A receptors on peripheral nerves so that overall there is an increase in nociceptive signalling. This implies that although A 2A antagonists have antinociceptive effects they may have only limited use as analgesics in chronic inflammatory pain.