Peripheral nerve injury is associated with local inflammation and neuropathic pain. In this study we investigated the local expression of the inducible isoform of nitric oxide synthase (iNOS) following a chronic constriction injury (CCl) to the sciatic nerve, a rat model of neuropathic pain. Western blot analysis and immunohistochemical co-localization methods were used to identify temporal and spatial expression of iNOS and its cells of origin. Changes in mRNA were analyzed by RT-PCR and iNOS specific primers. We report that CCl injury induced local iNOS expression in both macrophages and Schwann cells within and distal to the injury site. The local increase in iNOS mRNA expression paralleled both the temporal and spatial protein expression. This study supports the hypothesis that CCl is associated with a local inflammatory reaction mediated at least in part by iNOS. Local activation of the iNOS-NO system may play an important role in the pathogenesis of peripheral nerve injury and neuropathic pain. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.