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 Ca(2+)-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.
Ortiz
Mario I
MI
Sección Externa de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D.F., Mexico.
Torres-López
Jorge E
JE
Castañeda-Hernández
Gilberto
G
Rosas
Rodolfo
R
Vidal-Cantú
Guadalupe C
GC
Granados-Soto
Vinicio
V
D015761:4-Aminopyridine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000008:administration & dosage; D005905:Glyburide / Q000494:pharmacology; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D000700:Analgesics; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D004008:Diclofenac; D005557:Formaldehyde; D001030:Apamin; D019789:Tetraethylammonium; D009020:Morphine; D020110:Pinacidil; D014044:Tolbutamide; D015761:4-Aminopyridine; D005905:Glyburide