Abstract

While increasing evidence points to a role for the nitric oxide (NO)/ cyclic guanosine 3,5-monophosphate (GMPc) cascade in hyperalgesia and allodynia, participation of the NO/GMPc pathway in synaptic processing in the spinal cord, i.e. wind-up activity, is less clear. We studied the effects of intrathecal administration of N?-nitro-L-arginine methyl ester (L-NAME) and methylene blue, inhibitors of NO synthase and guanylate cyclase respectively, on wind-up activity developed in a C-fiber reflex response paradigm. 5, 10 and 20 ?g i.t. of L-NAME or methylene blue did not modify spinal wind-up in normal rats, while a dose-dependent inhibition of wind-up was observed in monoarthritic rats. Results suggest that the NO/GMPc pathway plays a non-significant role in wind-up activity evoked in normal animals, while it may be essential in chronic pain processing. © 2003 Elsevier Ireland Ltd. All rights reserved.