Dural application of IL-6 primes animals to systemic NO donors. Animals treated with meningeal IL-6 (n=8 IL-6/SNP 3mg/kg , n=7 IL-6/Vehicle) respond to systemic SNP; producing both facial (A) and hindpaw (B) allodynia at 72 hours post IL-6 while animals treated with Vehicle (n=5 for all groups)did not respond to SNP. Withdrawal thresholds to tactile stimuli applied to the face (A) and the hindpaw (B) after systemic SNP given 72 hours post IL-6. Significant differences among means for each group were determined by analysis of variance followed by Bonferroni post hoc test. Facial: time F (3, 88) = 1.578, P =0.2004, treatment F (3, 88) = 9.588,P <0.0001; Hind paw: time F (3, 80) = 1.172, P =0.3256 treatment F (3, 80) = 20.31, P < 0.0001.