Spinal and peripheral adenosine A₁ receptors contribute to antinociception by tramadol in the formalin test in mice

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• 作者：Jana Sawynok ; Allison R. Reid ; Jean Liu
• 关键词：Tramadol ; Adenosine ; Formalin
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：714
• 期：1-3
• 页码：373-378
• 全文大小：1197 K

文摘

Tramadol, an analgesic used alone or combined with acetaminophen, has a complex mechanism of action involving opioid and amine mechanisms. In this study, we explored the involvement of spinal and peripheral adenosine A₁ receptors in antinociception by tramadol, and determined whether spinal serotonin 5-HT₇ receptors were linked to spinal A₁ receptor actions. Antinociception was examined using the 2 % formalin test in mice. Tramadol was administered systemically (intraperitoneal) or peripherally (intraplantar). Caffeine (non-selective A₁/A_2A receptor antagonist) and SCH58261 (selective A_2A receptor antagonist) were given systemically, while DPCPX (selective A₁ receptor antagonist) was given systemically, spinally (lumbar puncture), or peripherally. Systemic tramadol 35 mg/kg produced antinociception against phase 2 formalin-evoked flinching behaviors, particularly in the earlier parts (phase 2A). Systemic caffeine (10 mg/kg) and DPCPX (1 mg/kg), but not SCH58261 (3 mg/kg), inhibited antinociception by systemic tramadol. Spinal DPCPX 3 ¦Ìg also inhibited the action of systemic tramadol. Spinal SB269970 (selective 5-HT₇ receptor antagonist) 3-10 ¦Ìg did not alter the effect of systemic tramadol. Intraplantar tramadol produced antinociception against flinching behaviors, and this action was reversed by intraplantar DPCPX 4.5 ¦Ìg administered on the ipsilateral, but not contralateral, side. Intraplantar DPCPX also reversed antinociception by systemic tramadol. These results indicate that adenosine A₁ receptors contribute to antinociception by tramadol in the mouse formalin model, and that spinal and peripheral sites are involved in these actions. 5HT₇ receptors in the spinal cord do not appear to be involved in the recruitment of A₁ receptor mechanisms when tramadol is given systemically in this model.