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.

The expression of the nitric oxide synthase enzyme in periodontal disease and orofacial pain: systematic review

“…At the end of the selection process, 11 articles were obtained. Nine studies observed the expression of NOS and/or NO through the clinical and laboratory studies 7,14,[16][17][18][19][20][21][22] . The methodological parameters used to evaluate the periodontal condition were the following: PI = plaque index (%), CEJ = cementoenamel junction, GI = gingival index, BP= bleeding on probing (%), CAL = clinical attachment level (mm), and probing depth .About laboratory studies, the incisional gingival biopsies and laboratory tests by immunohistochemistry were described.…”

“…Among the 11 articles included in this systematic review, 5 studies looked at the expression of NOS and/or NO and their metabolites in PD 3,7,[19][20][21] and other 5 studies quantified the expression of NOS, NO and metabolites in OP 14,17,18,22,24 . Only one article revealed the expression of NOS simultaneously in patients with and OP 16 .…”

Avaliação da sensibilidade mecânica, ansiedade e neuroplasticidade cortical motora em ratos submetidos à doença periodontal experimental

“…A doença periodontal (DP) é frequente na população mundial e embora tenha tratamento conhecido e eficaz nem sempre é reconhecida, uma vez que seus sinais e sintomas são considerados irrelevantes pelos pacientes. Savioli et al, 2004;Savioli et al, 2010;Savioli et al, 2012;Siqueira et al, 2010;Fernandes et al, 2007;Fabri et al, 2009;Fabri et al, 2014a;Fabri et al, 2014b;Fabri et al, 2014c;Rolim et al, 2014 . Em outro estudo brasileiro contendo uma amostra maior de pacientes adultos e idosos foi verificado que a prevalência de dor no segmento orofacial foi de 55,5%.…”

“…Não houve diferenças para os demais parâmetros (Tabela 5). (Fabri et al, 2009;Fabri et al, 2014b). Entretanto os resultados do presente estudo devem ser interpretados com cautela e mais estudos serão necessários para avaliar a relação DP, número de dentes afetados e nocicepção.…”

“…O tratamento da DP em pacientes com dores crônicas orofaciais também foi capaz de melhorar o perfil psicológico e diminuir o uso de descritores de dor(Fabri et al, 2014a). Outro estudo do grupo observou que ao longo do curso da doença periodontal não tratada são expressadas grandes quantidades de óxido nítrico, graças à presença da molécula óxido nítrico sintase, principalmente no tecido gengival de pacientes com dores crônicas craniofaciais e DP concomitantes(Fabri et al, 2014b). Esta presença massiva de mediadores da inflamação, interleucinas e citocinas, nos pacientes com DP não tratada pode explicar o menor efeito das medicações imunobiológicas em pacientes com doenças reumatológicas como a artrite reumatoide(Savioli et al, 2012).A DP parece ter também uma correlação com o aumento da hipersensibilidade dentinária.…”