EC Pharmacology And Toxicology

We have recently demonstrated that tramadol acts peripherally to induce antinociceptive action through nitric oxide and potas- sium channels but not opioid and cannabinoid receptors in rats. However, since its actions in the periphery have not been eluci- dated fully, the noradrenergic, serotonergic, and dopaminergic systems were evaluated in the peripheral antinociception of tramadol against prostaglandin-induced hyperalgesia E 2 . The method of removing rat paws subjected to compression was used to measure the nociceptive threshold. The non-selective α2 -adrenergic yohimbine receptor antagonist (20, 40 μg) partially reversed tramadol analgesia, while the selective α2C -adrenergic receptor antagonist rauwolscine (10, 15, 20 μg) totally antagonized the analgesia. On the contrary, antagonists of the other α2-adrenergic receptor subtypes, α2A, α2B and α2D , BRL44480, imiloxane and RX821002 (20 μg), respectively, did not alter antinociception. As for the serotonergic system, the 5-HT1B, 5-HT1D, and 5-HT3 receptor antagonists, isamoltane, BRL 15572, and ondansetron (100 ng, 1 and 10 μg), respectively, managed to block tramadol antinociception, but the antagonists of tramadol the other evaluated receptors, 5-HT2A and 5-HT7, ketanserin and SB269970 (10 μg), respectively, were not able to exert the same effect. D2, D3, and D4 receptor antagonists, remoxipride (4.20 μg), U99194 (32 μg), and L-745.870 (32 μg), respectively, did not change the tramadol-induced antinociception, suggesting that dopaminergic signaling may not be implicated in this antinociception. Our data suggest the peripheral antinociceptive action induced by tramadol when administered in a model of PGE 2-induced hyperalgesia and that this effect should involve the α2C -adrenergic receptors, the 5-HT1B , 5-HT1D and 5-HT3 serotoner- gic receptors. was unrelated to the activation of dopaminergic receptors

 Keywords: Tramadol; Norepinephrine; Serotonin; Antinociception; Monoamines

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