Participation of potassium channels in the antinociceptive effect of docosahexaenoic acid in the rat formalin test

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that has shown gastroprotective, cardioprotective, neuroprotective, anti-inflammatory and antinociceptive effects in different models. However, its action mechanism is still not well-defined. Reports indicate that some PUFAs regulate potassium (K⁺) channels in ventricular myocytes of rodents. As a result, the aim of this study was to evaluate the probable participation of K⁺channels in the antinociceptive effect of DHA. The rat paw 1% formalin test was used to assess nociception and antinociception. Fifty microliters of formalin solution were administered subcutaneously in the paw, and the number of flinches were quantified. Rats were treated with local peripheral administration of DHA (100–1778 µg/paw) or diclofenac (10–300 µg/paw). The antinociception of DHA was evaluated with and without the local pretreatment of K⁺channel blockers. DHA and diclofenac produced dose-dependent antinociceptive effects during the second phase (P<0.05). Local peripheral administration of tolbutamide and glibenclamide (K_ir6.1-2; ATP-sensitive K⁺channel blockers); iberiotoxin and charybdotoxin (K_Ca1.1; big conductance calcium-activated K⁺channel blockers); apamin and dequalinium (K_Ca2.1–3; small conductance Ca²⁺-activated K⁺channel blockers); but not by 4-aminopyridine and tetraethylammonium (K_V; voltage-gated K⁺channel blockers) reverted the DHA-induced antinociceptive effect. It is concluded that big- and small-conductance Ca²⁺-activated K⁺channels and ATP-sensitive K⁺channels are activated by DHA to produce local antinociception on the rat formalin test.