Involvement of potassium channels and nitric oxide in tramadol antinociception.
It has been considered that tramadol, a centrally acting analgesic, shows its effect via opiatergic, noradrenergic, and serotonergic systems. It has a low affinity for opioid receptors, and its effect can be partly blocked by naloxone. Since the noradrenergic and serotonergic mechanisms are still unknown, other systems which are associated with pain and analgesia may have a role on the antinociceptive effect of tramadol. The aim of this study was to evaluate the effects of K+ channels and nitrergic systems on the antinociceptive action of tramadol. The antinociceptive effects of tramadol were determined in mice by the hot plate test. To examine the effects of K+ channels and the nitrergic system nonspecific voltage-dependent K+ channel blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA), nitric oxide (NO) precursor L-arginine, and the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were used. Our results indicated that 4-AP, TEA, and L-arginine reduced the antinociceptive effect of tramadol. However, L-NAME augmented the antinociceptive effect of tramadol. The reduction of the effects of tramadol by L-arginine was reversed by L-NAME. The results of our study suggest that nonspecific voltage-dependent K+ channels and nitrergic system have a role on the antinociceptive effect of tramadol in mice hot plate test.
Yalcin
Ipek
I
Department of Pharmacology, Faculty of Medicine, Cukurova University, TR-01330, Balcali, Adana, Turkey.
Aksu
Fazilet
F
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D015221:Potassium Channels / Q000502:physiology*; D014147:Tramadol / Q000494:pharmacology*
D000700:Analgesics; D015221:Potassium Channels; D009569:Nitric Oxide; D014147:Tramadol