Reduction of carrageenin oedema and the associated c-Fos expression in the rat lumbar spinal cord by nitric oxide synthase inhibitor

Abstract

1. Three hours after intraplantar carrageenin (6 mg/150 microliters of saline) Fos-like immunoreactivity (Fos-LI) was mainly observed in L4 and L5 segments of the dorsal horn. Both superficial (I-II) and deep laminae (V-VI) neurones were labelled. 2. We have studied the effect of systemic administration of a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on carrageenin evoked c-Fos expression and thus the contribution of nitric oxide to this expression. 3. Pre-administration of L-NAME (10, 25, 50, 100 mg kg-1, i.v.) dose-dependently reduced the number of superificial and deep laminae Fos-LI neurones, 100 mg kg-1 produced a 63 +/- 2% and 72 +/- 4% reduction of Fos-LI neurones respectively, P < 0.0001 for both superficial and deep neurones. 4. Pre-administered L-NAME dose-relatedly reduced the carrageenin-evoked paw and ankle oedema, with 100 mg kg-1 of L-NAME resulting in a 74 +/- 2% and 103 +/- 2% reduction respectively. 5. Post-administration of L-NAME (10 mg kg-1, i.v.) reduced the number of superficial and deep laminae Fos-LI neurones (65 +/- 7% and 53 +/- 8% reduction respectively, P < 0.01 for both superficial and deep neurones). 6. Post-administered L-NAME reduced both the paw and ankle oedema (52 +/- 8% and 62 +/- 10% reduction respectively, P < 0.0001 for both paw and ankle). 7. Pre-administered D-NAME (100 mg kg-1, i.v.), the inactive isomer of L-NAME, produced a weak reduction of the number of superficial laminae Fos-LI neurones (26 +/- 8% reduction, P<0.05), without influencing the deep Fos-LI neurones (5 +/- 8% enhancement) or the oedema.8. Systemic L-arginine (1200 mg kg-1) did not reverse the reduction of the total number of Fos-LI neurones induced by 100mg kg-1 of L-NAME, or the effect of L-NAME on the paw and ankle oedema.9. Intraplantar L-arginine (30 mg) did not reverse the effect of L-NAME (100 mg kg-1) on the total number of Fos-LI neurones. However, the inhibitory effects of L-NAME on the paw and ankle oedema were partially reversed by intraplantar L-Arginine (34 +/- 9% and 45 +/- 11% reduction of carrageenin oedema respectively) with these effects being significant as compared to the effect of L-NAME alone(P<0.05 for both).10. There is a strong correlation between the reduction of the number of Fos-LI neurones and the oedema by L-NAME, clearly demonstrating a predominant role of peripheral NO in the development of one of the signs of carrageenin inflammation.