Evidence for the participation of the nitric oxide-cyclic GMP pathway in the antinociceptive action of meloxicam in the formalin test
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The involvement of the nitric oxide-cyclic GMP pathway in the antinociceptive action of the cyclooxygenase-2 preferential inhibitor meloxicam was assessed in the rat formalin test. Rats received local pretreatment with saline or meloxicam and then 50 μl of dilute formalin (1%25). Local administration of meloxicam produced a dose-dependent antinociception in the second phase of the formalin test. The antinociception produced by meloxicam was due to a local action as its administration in the contralateral paw was ineffective. Local pretreatment of the paws with saline or N(G)-D-nitro-arginine methyl ester (D-NAME) did not affect the antinociception produced by meloxicam. However, N(G)-L-nitro-arginine methyl ester (L-NAME, a NO synthesis inhibitor) or 1H-(1,2,4)-oxadiazolo(4,2- a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) blocked in a dose-dependent way the effect of meloxicam. It is concluded that the peripheral antinociceptive effect of meloxicam involves a local NO-cyclic GMP pathway. © 2000 Elsevier Science B.V.
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cGMP; Meloxicam; N(G)-L-nitro-arginine methyl ester (L- NAME); Nitric oxide (NO); ODQ (1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one) 1h 1,2,4 oxadiazolo[4,3 a]quinoxalin 1 one; cyclic GMP; cyclooxygenase 2 inhibitor; formaldehyde; meloxicam; n(g) nitroarginine methyl ester; nitric oxide; sodium chloride; animal behavior; animal experiment; antinociception; article; controlled study; dose response; drug mechanism; female; hyperalgesia; inflammation; nonhuman; priority journal; rat; Analgesics, Non-Narcotic; Animals; Cyclic GMP; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Formaldehyde; Guanylate Cyclase; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxadiazoles; Pain; Pain Measurement; Quinoxalines; Rats; Rats, Wistar; Thiazines; Thiazoles
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