Pharmacological evidence for the activation of K+ channels by diclofenac

The involvement of K+ channels in the antinociceptive action of diclofenac was assessed in the formalin test. Local administration of diclofenac produced a dose-dependent antinociceptive effect due to a local action because drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with glibenclamide and tolbutamide (ATP-sensitive K+ channel inhibitors), charybdotoxin and apamin (large- and small-conductance Ca2+-activated K+ channel blockers, respectively), 4-aminopyridine or tetraethylammonium (voltage-dependent K+ channel inhibitors) prevented diclofenac-induced antinociception. Given alone, K+ channel inhibitors did not modify formalin-induced nociceptive behavior. Pinacidil (an ATP-sensitive K+ channel opener) also produced antinociception which was blocked by glibenclamide. The peripheral antinociceptive effect of morphine (positive control) was blocked by glibenclamide and 4-aminopyridine but not by charybdotoxin or apamin. The results suggest that the peripheral antinociceptive effect of diclofenac may result from the activation of several types of K+ channels, which may cause hyperpolarization of peripheral terminals of primary afferents. (C) 2002 Elsevier Science B.V. All rights reserved.