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.
La enfermedad periodontal (EP) es una patología crónica que pueden tener acción local y sistémica. A pesar de que hay una serie de mediadores inflamatorios implicados en la EP, los mecanismos implicados en el dolor craneofacial crónico asociado con la EP aún no están elucidados. El objetivo fue evaluar la inmunoreactividad de la sustancia P (SP), óxido nítrico sintetasas neuronal (nNOS) e inducible (iNOS) en muestras gingivales de pacientes con enfermedad periodontal severa con y sin dolor craneofacial crónico. Fueron obtenidas muestras gingivales durante la cirugía periodontal rutinaria de 20 pacientes que presentaron con EP y dolor craneofacial crónico (Grupo PPC) y 18 pacientes sólo con PD (Grupo PD). Después de la extirpación quirúrgica, el tejido se sometió a las técnicas histológicas de rutina y se tiñó por inmunohistoquímica con anticuerpos contra el SP, nNOS e iNOS. Se evaluaron el contenido de SP, nNOS e iNOS en el tejido gingival total, así como la superficie gingival, epitelio y tejido conectivo mediante análisis de imagen. Se observó alta expresión de nNOS en el tejido gingival obtenido a partir de pacientes PPC (p<0,001) en comparación a los pacientes con EP, particularmente en el área de epitelio (p<0,001). Además, la expresión de iNOS se incrementó en el tejido conjuntivo gingival (p= 0,003) del grupo PPC. No hubo diferencia en la expresión de SP entre los grupos. Nuestros resultados sugieren que el óxido nítrico, en particular derivado de nNOS, modula no sólo PD, sino también el dolor craneofacial crónico, ya que los pacientes con esta asociación presentan un aumento de la expresión de nNOS e iNOS en el tejido gingival.
ABSTRACT
Gengivite e periodontite são doenças periodontais imunoinflamatórias caracterizadas por infecções localizadas crônicas geralmente associadas a uma inflamação insidiosa. Essa revisão narrativa discute doenças periodontais e mecanismos que influenciam a resposta imune e a autoimunidade na área das doenças reumáticas pediátricas (DRP), particularmente a artrite idiopática juvenil (AIJ), lúpus eritematoso sistêmico juvenil (LESJ) e dermatomiosite juvenil (DMJ). Foi notada maior frequência de gengivite nessas doenças em comparação com controles sadios, enquanto casos de periodontite foram achados raros. Em pacientes com AIJ, a gengivite e a periodontite estavam relacionadas a fatores mecânicos, artrite crônica com incapacitação funcional, desregulação da resposta imunoinflamatória, dieta e medicamentos, principalmente corticosteroides e ciclosporina. Em pacientes com LESJ, a gengivite estava associada a períodos mais longos da doença, doses elevadas de corticosteroides, hiperativação dos linfócitos B e elevação da imunoglobulina G. São escassos os dados sobre doenças periodontais na população com DMJ; nos pacientes ativos, foi observado um padrão gengival singular, caracterizado por eritema gengival, dilatação dos capilares e formação arbustiforme. Em conclusão, gengivite foi a doença periodontal mais comum em pacientes com DRP. A associação observada com a atividade da doença reforça a necessidade de futuros estudos, com o intuito de determinar se a resolução dessa complicação irá influenciar o curso ou a gravidade da doença.
Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation. This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity.