Antinociceptive Effects of Intrathecal Adenosine Receptors Subtype Agonists in the Formalin Test

Background: Adenosine has shown an antinociceptive action, which is mediated via spinal adenosine receptors. Previous studies have revealed the presence of four subtypes of adenosine receptor, , in the spinal cord. The aim of this study was to determine the role of these subtypes for the control of nociception evoked by a formalin injection at the spinal level. Methods: Rats were implanted with lumbar intrathecal catheters. For nociception administration, a formalin solution (5%, 50 ) was injected into the hind paw of male Sprague-Dawley rats. Intrathecal adenosine receptors subtype agonists (adenosine receptor agonist, CPA: 0.3, 0.8, 2.7 nM; adenosine receptor agonist, DPMA: 5.8, 19.2, 57.6 and 191.8 nM; adenosine receptor agonist, IB-MECA: 19.6, 58.8, 196 and 587.9 nM) were administered 10 min before the formalin injection, and the formalin-induced nociceptive behavior (flinching response) observed for 60 min. Results: The intrathecal administrations of CPA and IB-MECA produced limited and no antinociception effect on the phase 1 response in the formalin test, respectively, but both agents depressed the phase 2 response. Intrathecal DPMA suppressed both the phase responses. The rank of potencies during phase 2, as defined by the was CPA > DPMA > > IB-MECA. Conclusions: Spinal receptors may be involved in the modulation of the facilitated state, as well as acute nociception, while the receptor was involved in the regulation of only the facilitated state.