title: Probable activation of the opioid receptor-nitric oxide-cyclic GMP-K+ channels pathway by codeine.
abstract: There is evidence that local peripheral administration of morphine produces antinociception through the activation of the nitric oxide (NO)-cyclic GMP-K(+) channels pathway. Therefore we evaluated the possible participation of this pathway in the antinociceptive action produced by codeine in the rat 5% formalin test. Local peripheral injection of codeine produced a dose-dependent antinociception during the first and second phases of the test. Local pretreatment of the paws with the NO synthase inhibitor N(G)-L-nitro-arginine methyl ester (L-NAME), the soluble guanylyl cyclase inhibitor methylene blue, the ATP-sensitive K(+) channel inhibitors glibenclamide and tolbutamide, the non-selective voltage-gated K(+) channel inhibitors 4-aminopyridine (4-AP) and tetraethylammonium (TEA) and the opioid receptor blocker naloxone prevented codeine-induced antinociception in both phases of the test. L-NAME, methylene blue, K(+) channel blockers and naloxone by themselves did not modify formalin-induced nociceptive behavior. Our data suggest that codeine could activate the opioid receptor-NO-cyclic GMP-K(+) channels pathway in order to produce its peripheral antinociceptive effect in the formalin test.
authors.affiliation: Laboratorio de Farmacología Area Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo ExHacienda la Concepción Carr, Mexico. mario_i_ortiz@hotmail.com
authors.forename: Mario I
authors.initials: MI
authors.lastname: Ortiz
authors.forename: Jhanet
authors.initials: J
authors.lastname: Castro-Olguín
authors.forename: Nayeli
authors.initials: N
authors.lastname: Peña-Samaniego
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernández
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003061:Codeine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D015221:Potassium Channels; D011957:Receptors, Opioid; D009569:Nitric Oxide; D009270:Naloxone; D019789:Tetraethylammonium; D014044:Tolbutamide; D015761:4-Aminopyridine; D006152:Cyclic GMP; D005905:Glyburide; D008751:Methylene Blue; D003061:Codeine; D019331:NG-Nitroarginine Methyl Ester