Abstract
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 N(G)-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 Ca(2+)-activated-K(+) channel blockers, respectively) or margatoxin (voltage-dependent K(+) channel blocker), but not N(G)-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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Analgesics / administration & dosage
-
Analgesics / pharmacology*
-
Animals
-
Apamin / administration & dosage
-
Apamin / pharmacology
-
Behavior, Animal / drug effects
-
Charybdotoxin / administration & dosage
-
Charybdotoxin / pharmacology
-
Diclofenac / analogs & derivatives
-
Dose-Response Relationship, Drug
-
Enzyme Inhibitors / administration & dosage
-
Enzyme Inhibitors / pharmacology
-
Female
-
Formaldehyde
-
Glyburide / administration & dosage
-
Glyburide / pharmacology
-
Guanylate Cyclase / antagonists & inhibitors
-
Hindlimb / drug effects
-
Hindlimb / pathology
-
Injections, Spinal
-
Injections, Subcutaneous
-
Methiothepin / administration & dosage
-
Methiothepin / pharmacology
-
NG-Nitroarginine Methyl Ester / administration & dosage
-
NG-Nitroarginine Methyl Ester / pharmacology
-
Naloxone / administration & dosage
-
Naloxone / pharmacology
-
Neurotoxins / administration & dosage
-
Neurotoxins / pharmacology
-
Nitric Oxide Synthase / antagonists & inhibitors
-
Organic Chemicals / administration & dosage
-
Organic Chemicals / pharmacology*
-
Oxadiazoles / administration & dosage
-
Oxadiazoles / pharmacology
-
Pain / chemically induced
-
Pain / prevention & control
-
Pain Measurement / methods
-
Quinoxalines / administration & dosage
-
Quinoxalines / pharmacology
-
Rats
-
Rats, Wistar
-
Scorpion Venoms
Substances
-
1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
-
Analgesics
-
Enzyme Inhibitors
-
Neurotoxins
-
Organic Chemicals
-
Oxadiazoles
-
Quinoxalines
-
Scorpion Venoms
-
Charybdotoxin
-
Diclofenac
-
Formaldehyde
-
Apamin
-
Naloxone
-
Methiothepin
-
margatoxin
-
Nitric Oxide Synthase
-
Guanylate Cyclase
-
Glyburide
-
NG-Nitroarginine Methyl Ester
-
lumiracoxib