[Involvement of L-arginine-nitric oxide-cyclic GMP pathway in the peripheral antinociceptive effect induced by parecoxib].
OBJECTIVE
The present study was undertaken to determine whether the local antinociceptive activity of parecoxib is mediated, at least in part, through the L-arginine-NO-cGMP pathway using the pain-induced functional impairment model in the rat.


METHODS
A comparative and experimental study was designed using 48 female Wistar rats, weighing between 180 and 200 g. Pain was induced through the injection of 0.05 ml of 30% uric acid into the knee joint of the right hind limb.


RESULTS
Administration of parecoxib (i.v.) generated a dose-dependent antinociceptive effect in rats injected with uric acid. Intra-articular (i.a.) pre-treatment with 1 H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, an inhibitor-soluble guanylyl cyclase) (5 and 10 mg i.a.) reversed the antinociceptive effect of parecoxib (1 mg/kg i.v). However, ipsilateral i.a. pre-treatment with 3-morpholino-sydnonimine-HCl (SIN-1, a non-enzymatic donor of NO) (50 and 500 mg i.a.) potentiated the antinociceptive effect induced by parecoxib (0.3 mg/kg i.v). Intra-articular pre-treatment with L-arginine (a NO substrate) (60 and 600 mg i.a.) did not modify the antinociceptive effect induced by parecoxib (0.3 mg/kg i.v.). Student t-test was used to compare the two groups of data.


CONCLUSIONS
The present results suggest that, in addition to cyclo-oxygenase-2 inhibition, the antinociceptive effect of parecoxib could also involve activation of the L-arginine-NO-cyclic GMP pathway at the peripheral level.
Martínez-Quiroz
Zoraida Irene
ZI
Clínica del Dolor, Instituto Nacional de Ciencias Médicas de Nutrición Salvador Zubirán, Mexico.
López-Muñoz
Francisco Javier
FJ
Guevara-López
Uriah Medardo
UM
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D005260:Female; D007555:Isoxazoles / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000700:Analgesics; D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D009569:Nitric Oxide; D001120:Arginine; C409945:parecoxib; D006152:Cyclic GMP