Spinal and peripheral adenosine A(1) receptors contribute to antinociception by tramadol in the formalin test in mice.

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Sawynok J, Reid AR, Liu J

Spinal and peripheral adenosine A(1) receptors contribute to antinociception by tramadol in the formalin test in mice.

Eur J Pharmacol. 2013 Aug 15;714(1-3):373-8. doi: 10.1016/j.ejphar.2013.07.012. Epub 2013 Jul 16.

PubMed ID

23872384 [ View in PubMed

]

Abstract

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-HT(7) 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 A(1)/A(2)A receptor antagonist) and SCH58261 (selective A(2)A receptor antagonist) were given systemically, while DPCPX (selective A(1) 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 mug also inhibited the action of systemic tramadol. Spinal SB269970 (selective 5-HT(7) receptor antagonist) 3-10 mug 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 mug administered on the ipsilateral, but not contralateral, side. Intraplantar DPCPX also reversed antinociception by systemic tramadol. These results indicate that adenosine A(1) receptors contribute to antinociception by tramadol in the mouse formalin model, and that spinal and peripheral sites are involved in these actions. 5HT(7) receptors in the spinal cord do not appear to be involved in the recruitment of A(1) receptor mechanisms when tramadol is given systemically in this model.

DrugBank Data that Cites this Article

Drugs

Tramadol

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tramadol	Adenosine receptor A1	Protein	Humans	Yes	Agonist	Details