The Expression of Nitric Oxide in the Gingival Tissue in Subjects with Periodontitis and Chronic Pain

Abstract

Periodontal disease (PD) is a chronic infection that may have local and systemic rebound. Although a series of inflammatory mediators are involved in PD, the mechanisms involved in chronic craniofacial pain associated with it require elucidation. The aim of this study was to evaluate the immunoreactivity of substance P (SP), neuronal (nNOS) and inducible (iNOS) nitric oxide synthases in gingival samples of patients with severe PD with and without chronic craniofacial pain. Gingival specimens were obtained during routine periodontal surgery while managing 20 patients with both PD and chronic craniofacial pain (CFP Group) and 18 patients with only PD (PD Group). Following surgical removal, the tissue underwent routine histological techniques and was stained by immunohistochemistry with antibodies against SP, nNOS and iNOS. Using an image analysis system, we assessed the SP, nNOS and iNOS content in total gingival tissue as well as in both epithelial and connective gingival area. We observed high expression of nNOS in gingival tissue obtained from CFP patients (p<0.001), particularly in the epithelium area (p<0.001) comparatively to PD patients. In addition, the iNOS expression was also increased in the CFP group in the connective gingival tissue (p=0.003). There was no difference concerning SP expression between the groups. Our results suggest that nitric oxide, particularly derived from nNOS, modulates not only PD but also chronic craniofacial pain, since patients with this association presented an increase in nNOS and iNOS expression in gingival tissue.