The peripheral antinociceptive effect of nalbuphine is associated with activation of ATP-sensitive K+ channels.
There is evidence that local peripheral administration of codeine and morphine produces antinociception through the activation of the ATP-sensitive K(+)-channel. Therefore we evaluated the participation of this channel in the antinociceptive action produced by nalbuphine in the formalin test. Female Wistar rats (160-200 g) were injected in the dorsal surface of the right hind paw with 50 microl of formalin (5%). Nociception was quantified as the number of flinches of the injected paw during 1 hr, whereas a reduction of the number of flinches was considered antinociception. Rats received a s.c. injection (50 microl) into the dorsal surface of the right hind paw of vehicle or increasing doses of nalbuphine (100-400 microg/paw) 20 min before formalin injection into the ipsilateral paw. To determine whether nalbuphine-induced peripheral antinociception was mediated by K(+)-channels, the effect of pretreatment (10 min before formalin injection) with the appropriate vehicle or the ATP-sensitive K(+)-channel inhibitor glibenclamide (25-100 microg/paw) on the antinociceptive effect induced by local peripheral nalbuphine (400 microg/paw) was assessed. Morphine was used as positive antinociceptive control. Local peripheral injection of nalbuphine produced a dose-dependent antinociception during both phases of the test. Local pretreatment with glibenclamide prevented nalbuphine-induced antinociception in a dose-dependent fashion in both phases of the test. Our data suggest that nalbuphine activates ATP-sensitive K(+)-channels in order to produce its peripheral antinociceptive effect.
Ortiz
Mario I
MI
Laboratorio de Farmacología Del Area Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma Del Estado de Hidalgo, Eliseo Ramírez Ulloa 400, Col. Doctores, Pachuca, Hgo. 42090. mario_i_ortiz@hotmail.com
Fernández-Martínez
Eduardo
E
Ponce-Monter
Héctor
H
Pérez-Hernández
Nury
N
Macías
Arturo
A
Rangel-Flores
Eduardo
E
Castañeda-Hérnandez
Gilberto
G
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000819:agonists*; D009020:Morphine / Q000494:pharmacology; D009266:Nalbuphine / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D017933:Peripheral Nervous System / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000701:Analgesics, Opioid; D054086:KATP Channels; D026902:Potassium Channel Blockers; D009020:Morphine; D009266:Nalbuphine; D005905:Glyburide