title: Deletion of the adenosine A(2A) receptor in mice enhances spinal cord neurochemical responses to an inflammatory nociceptive stimulus.
abstract: 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, [(3)H]MK801 binding to NMDA receptors and uptake of [(14)C]-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 [(3)H]MK801 binding and [(14)C]-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.
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hussey
authors.forename: G D
authors.initials: GD
authors.lastname: Clarke
authors.forename: C
authors.initials: C
authors.lastname: Ledent
authors.forename: I
authors.initials: I
authors.lastname: Kitchen
authors.forename: S M O
authors.initials: SM
authors.lastname: Hourani
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001345:Autoradiography; D003847:Deoxyglucose / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010146:Pain / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D000963:Antimetabolites; D018691:Excitatory Amino Acid Antagonists; D043705:Receptor, Adenosine A2A; D016291:Dizocilpine Maleate; D003847:Deoxyglucose