포르말린 시험에서 쥐의 척수강 내로 투여한 Adenosine 수용체 작용제들의 항침해효과
Antinociceptive Effects of Intrathecal Adenosine Receptors Subtype Agonists in the Formalin Test
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Abstract
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, A1, A2A, A2B and A3, 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%, 50μl) was injected into the hind paw of male Sprague-Dawley rats. Intrathecal adenosine receptors subtype agonists (adenosine A1 receptor agonist, CPA: 0.3, 0.8, 2.7 nM; adenosine A2A receptor agonist, DPMA: 5.8, 19.2, 57.6 and 191.8 nM; adenosine A3 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 ED50 was CPA ＞ DPMA ＞＞ IB-MECA. Conclusions: Spinal A1 and A2A receptors may be involved in the modulation of the facilitated state, as well as acute nociception, while the A3 receptor was involved in the regulation of only the facilitated state.
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