Activation of peripheral ATP-sensitive K+ channels mediates the antinociceptive effect of Crotalus durissus terrificus snake venom.
The role of peripheral potassium channels on the antinociceptive effect of Crotalus durissus terrificus venom, a mixed delta- and kappa-opioid receptor agonist, was investigated in hyperalgesia induced by carrageenin or prostaglandin E(2). Rat paw pressure test was applied before and 3 h after the intraplantar (i.pl.) injection of the nociceptive stimuli. Oral administration of venom 2 h after carrageenin or prostaglandin E(2) induces antinociception. Local pretreatment with 4-aminopyridine and tetraethylammonium (blockers of voltage-dependent K(+) channel) or charybdotoxin and apamin (inhibitors of large- and small-conductance Ca(2+)-activated K(+) channel, respectively) did not modify venom effect. On the other hand, glybenclamide, an inhibitor of ATP-sensitive K(+) channel abolished antinociception induced by the venom. Glybenclamide also inhibited the antinociceptive effect of [D-Pen(2.5)] enkephalin (DPDPE), a delta opioid receptor agonist, but did not modify the effect of (+)-trans-(1R,2R)-U-50488 (U50488), a kappa opioid receptor agonist. Diazoxide and pinacidil, two ATP-sensitive K(+) channel openers, injected by intraplantar route, induced a long-lasting increment of pain threshold of the animals and produced antinociception in both models of hyperalgesia. These results suggest that the antinociceptive effect of crotalid venom is mediated by activation of ATP-sensitive K(+) channels at peripheral afferent neurons.
Picolo
Gisele
G
Laboratório de Fisiopatologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 São Paulo, SP, Brazil.
Cassola
Antônio Carlos
AC
Cury
Yara
Y
D000255:Adenosine Triphosphate / Q000502:physiology*; D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003435:Crotalid Venoms / Q000378:metabolism / Q000494:pharmacology*; D017839:Crotalus; D008297:Male; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D003435:Crotalid Venoms; D015221:Potassium Channels; D000255:Adenosine Triphosphate