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ANALGESIA

Expression of Adenosine A_2A Receptors in the Rat Lumbar Spinal Cord and Implications in the Modulation of N-Methyl-d-Aspartate Receptor Currents

Emmanuel Guntz, MD^*, Hélène Dumont, MD^*, Els Pastijn, MD^*, Alban de Kerchove d’Exaerde, PhD, Karima Azdad, PhD, Maurice Sosnowski, MD, PhD^*, Serge N. Schiffmann, MD, PhD, and David Gall, PhD

From the *Department of Anesthesiology, Hôpital Universitaire Saint-Pierre, and Laboratory of Neurophysiology, Université Libre de Bruxelles, Brussels, Belgium.

Address correspondence and reprint requests to Dr. E. GUNTZ, Rue haute, 322, 1000 Brussels. Address e-mail to eguntz{at}ulb.ac.be.

Abstract

BACKGROUND: The presence of A_2A receptors in the dorsal horn of the spinal cord remains controversial. At this level, activation of N-methyl-d-aspartate (NMDA) receptors induces wind-up, which is clinically expressed as hyperalgesia. Inhibition of NMDA receptor currents after activation of A_2A receptors has been shown in rat neostriatal neurons. In this study, we sought to establish the presence of adenosine A_2A receptors in the lamina II of the rat lumbar dorsal horn neurons and investigated whether the activation of A_2A receptors is able to modulate NMDA receptor currents.

METHODS: Experiments were conducted in the rat lumbar spinal cord. The presence of adenosine A_2A receptor transcripts inside the lumbar spinal cord is assessed with the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Western blot experiments are performed at the same level. The RT-PCR technique is also performed specifically in the lamina II, and the presence of adenosine A_2A receptor transcripts is assessed in neurons from the lamina II with the single-cell RT-PCR technique. The effect of adenosine A_2A receptor activation on NMDA receptor currents is studied by the whole-cell configuration of the patch clamp technique.

RESULTS: RT-PCR performed on the lumbar spinal cord revealed the presence of adenosine A_2A receptor transcripts. Western blot experiments revealed the presence of A_2A receptors in the lumbar spinal cord. RT-PCR performed on the substantia gelatinosa also revealed the presence of adenosine A_2A receptor transcripts. Finally, single cell RT-PCR revealed the presence of adenosine A_2A receptor transcripts in a sample of lamina II neurons. Patch clamp recordings showed an inhibition of NMDA currents during the application of a selective A_2A agonist.

CONCLUSIONS: These results demonstrate the presence of A_2A receptor on neurons from the substantia gelatinosa of the rat lumbar dorsal horn and the inhibition of NMDA-induced currents by the application of a selective A_2A receptor agonist. Therefore, A_2A receptor ligands could modulate pain processing at the spinal cord level.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999