Possible activation of the NO-cyclic GMP-protein kinase G-K+ channels pathway by gabapentin on the formalin test.
The effect of modulators of the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway on the local peripheral antinociceptive action induced by gabapentin was assessed in the rat 1% formalin test. Local peripheral administration of gabapentin produced a dose-dependent antinociception in the second phase of the test. Gabapentin-induced antinociception was due to a local action as its administration in the contralateral paw was ineffective. Local peripheral pretreatment of the paws with NG-L-nitro-arginine methyl ester (L-NAME, a nitric oxide synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) and KT-5823 (a protein kinase G inhibitor) dose-dependently reduced gabapentin-induced antinociception. Likewise, glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), 4-aminopyridine or tetraethylammonium (non-selective inward rectifier K+ channel inhibitors) or charybdotoxin (large-conductance Ca2+-activated-K+ channel blocker), but not apamin (small-conductance Ca2+-activated-K+ channel blocker) or naloxone (opioid receptor antagonist), reduced the antinociception induced by gabapentin. Our data suggest that gabapentin could activate the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway in order to produce its peripheral antinociceptive effect in the rat 1% formalin test.
Ortiz
Mario I
MI
Area Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico. mario_i_ortiz@hotmail.com
Medina-Tato
David A
DA
Sarmiento-Heredia
Denisse
D
Palma-Martínez
Jazmín
J
Granados-Soto
Vinicio
V
D015761:4-Aminopyridine / Q000494:pharmacology; D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D005260:Female; D000077206:Gabapentin; D005905:Glyburide / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010147:Pain Measurement; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D002227:Carbazoles; D003509:Cyclohexanecarboxylic Acids; D007211:Indoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; C073601:KT 5823; D001030:Apamin; D009569:Nitric Oxide; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D014044:Tolbutamide; D015761:4-Aminopyridine; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester