REDUCTION OF CARRAGEENAN EDEMA AND THE ASSOCIATED C-FOS EXPRESSION IN THE RAT LUMBAR SPINAL-CORD BY NITRIC-OXIDE SYNTHASE INHIBITOR

1 Three hours after intraplantar carrageenin (6 mg/150 mu l of saline) Fos-like immunoreactivity (Fos-LI) was mainly observed in 1,4 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, N-G-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 superficial 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 100 mg 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.