Peripheral and spinal mechanisms of antinociceptive action of lumiracoxib

The possible participation of the nitric oxide (NO)-cyclic GMP-K+ channel pathway, serotonergic or opioidergic system on lumiracoxib-induced local or intrathecal antinociception was assessed in the formalin test. Local or intrathecal administration of lumiracoxib dose-dependently produced antinociception in the second phase of the test. Moreover, local or intrathecal pretreatment with NG-l-nitro-arginine methyl ester (l-NAME, NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor), glibenclamide (ATP-sensitive K+ channel blocker), charybdotoxin and apamin (large- and small-conductance Ca2+-activated-K+ channel blockers, respectively) or margatoxin (voltage-dependent K+ channel blocker), but not NG-d-nitro-arginine methyl ester (d-NAME) or vehicle, significantly prevented lumiracoxib-induced antinociception. The intrathecal injection of methiothepin (serotonin receptor antagonist) reduced lumiracoxib-induced intrathecal antinociception. Local peripheral or intrathecal naloxone did not modify either local or intrathecal lumiracoxib-induced antinociception. Results suggest that lumiracoxib activates the NO-cyclic GMP-K+ channels to produce local and intrathecal antinociception. Data also suggest that lumiracoxib activates the intrathecal serotonergic system, but not opioid receptors either at peripheral or spinal sites.