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UNIVERSIDADE ESTADUAL DE CAMPINAS

FACULDADE DE ODONTOLOGIA DE PIRACICABA

JOSUÉ JÚNIOR ARAÚJO PIEROTE

Efeito de dessensibilizante experimental na redução da

sensibilidade dolorosa associada ao clareamento dental: estudo

clínico duplo-cego controlado longitudinal

Effect of experimental desensitizer on the reduction of pain

sensitivity associated with tooth bleaching: longitudinal controlled

double-blind clinical trial

PIRACICABA 2019

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JOSUÉ JÚNIOR ARAÚJO PIEROTE

Efeito de dessensibilizante experimental na redução da

sensibilidade dolorosa associada ao clareamento dental: estudo

clínico duplo-cego controlado longitudinal

Effect of experimental desensitizer on the reduction of pain

sensitivity associated with tooth bleaching: longitudinal controlled

double-blind clinical trial

Tese apresentada à Faculdade de Odontologia de Piracicaba da Universidade Estadual de Campinas como parte dos requisitos para obtenção do título de Doutor em Clínica Odontólogica, na Área de Dentística.

Thesis presented to the Piracicaba Dental School of the University of Campinas in partial fulfillment of the requirements for degree of Doctor in Clinical Dentistry, in Dentistry área.

Orientador: Prof. Dr. Flavio Henrique Baggio Aguiar

Este exemplar corresponde à versão entregue para a banca de defesa da tese do aluno Josué Júnior Araújo Pierote e orientada pelo Prof. Dr. Flavio Henrique Baggio Aguiar

PIRACICABA 2019

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DEDICATÓRIA

Dedico este trabalho à memória da minha tia Maria Alzenira Araujo Passos, pelos maravilhosos momentos que tivemos juntos, e por sempre ter me incentivado aos estudos. Seu sonho era que eu e minha irmã estudássemos e alcançássemos uma excelente qualificação profissional. Com toda certeza ela estaria extremamente orgulhosa desse trabalho. À você, minha querida tia, eu dedico o meu trabalho.

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AGRADECIMENTOS

Em primeiro lugar, agradeço à Deus, por me conceder força e me conduzir ao longo desta jornada recompensadora e me proporcionar uma família maravilhosa e amigos amorosos que são insubstituíveis na minha vida.

Agradeço à Faculdade de Odontologia de Piracicaba da Universidade Estadual de Campinas, na pessoa do seu diretor, Prof. Dr. Francisco Haiter Neto. À Coordenadoria de Pós-Graduação da Faculdade de Odontologia Piracicaba da Universidade de Campinas, na pessoa da coordenadora, Profª. Dra. Karina Gonzales Silvério Ruiz. À Coordenadoria do curso de Pós-Graduação em Clínica Odontológica da Faculdade de Odontologia Piracicaba da Universidade de Campinas, na pessoa do coordenador, Prof. Dr. Valentim Adelino Barão

O agradecimento a Coordenação de Aperfeiçoamento de Pessoa de Nível Superior – Brasil (CAPES) pois o presente trabalho foi realizado com o apoio da mesma – Código de Financiamento 001.

Agradeço aos membros componentes da banca de qualificação, Prof. Dr. Luis Roberto Marcondes Martins, Profa. Dra. Giselle Marchi Baron, Profa. Dra. Lucia Trazzi Prieto e Profa. Dra. Vanessa Cavalli Gobbo, por terem aceitado participar do exame de qualificação, como parte dos requisitos para a obtenção do Título de Doutor em Clínica Odontológica Área de concentração Dentística.

Agradeço aos membros componentes da banca de defesa, Prof. Dr. Flávio Henrique Baggio Aguiar, Prof. Dr. Luis Alexandre Maffei Sartini Paulillo, Profa. Dra. Débora Alves Nunes Leite Lima, Profa. Drª. Marcoeli Silva de Moura, Profa. Drª. Cíntia Tereza Pimenta Araújo, Profa. Drª. Roberta Tarkany Basting Hofling, Profa. Drª. Ana Cecília Corrêa Aranha e Profa. Drª Flávia Lucisano Botelho do Amaral por terem aceitado participar do exame de defesa, como parte dos requisitos para a obtenção do Título de Doutor em Clínica Odontológica com área de concentração Dentística.

Ao meu eterno orientador e amigo, Prof. Dr. Luís Alexandre Maffei Sartini Paulillo, por todos os ensinamentos e pelo carinho, paciência e atenção despendida durante estes anos, sem os quais seria impossível a realização desta tese. Nos momentos que mais precisei ele estava ao meu lado com palavras amigas, de

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confiança e força, me mostrando que o caminho poderia ser difícil, mas que era nossa escolha ser feliz.

Ao meu orientador, Prof. Dr. Flávio Henrique Baggio Aguiar e minha Co-orientadora Profa. Dra. Débora Alves Nunes Leite Lima, por aceitarem me orientar em virtude da aposentadoria do professor Luis Alexandre, por todo o carinho, ensinamentos e atenção ao longo destes anos.

Aos professores da Área de Dentística, Prof. Dr. Flávio Henrique Baggio Aguiar, Profa. Drª. Débora Alves Nunes Leite Lima, Profa. Drª. Gisele Maria Marchi, Prof. Dr. Luis Roberto Marcondes Martins, Profa. Drª. Vanesssa Cavalli Gobbo e Prof. Dr. Marcelo Giannini, pela colaboração em minha formação acadêmica.

Aos meus professores de graduação Profa. Drª. Marcoeli Silva de Moura, Prof. Dr. Raimundo Rosendo Prado Junior, Profa. Drª. Ana Cristina Vasconcelos Fialho e Prof. Dr. Guilherme Ferrer Pompeu por seu brilhantismo profissional e amor pela arte do ensino que foram uma inspiração para a minha jornada científica.

Aos alunos da graduação e aos meus pacientes que me ajudaram a crescer como profissional.

As minhas irmãs de orientação de Doutorado da Pós-Graduação em Clínica Odontológica – Área de Dentística: Lucia Trazzi Prieto e Isabel Ferreira Barbosa. Obrigado pelo carinho, pela atenção e pela força que me deram em todos os momentos.

Aos meus pais, Alzira e Josué, e minha irmã Nayane, por serem as maiores bênçãos da minha vida, por sonharem meus sonhos, por serem fonte das minhas alegrias e exemplos de seres humanos que desejo seguir. Vocês são o principal motivo dos meus esforços, pois fazê-los felizes e orgulhosos são as inspirações que me fazem acordar todos os dias vencendo qualquer cansaço para continuar minha jornada. Eu amo vocês.

À minha família, os momentos em que penso em vocês fazem toda dificuldade ser pequena, e tudo valer a pena. Agradeço, também, a minha avó Maria Bernarda por todas as ligações aos domingos, pois com suas ligações eu consegui ter mais forças para iniciar a semana de uma forma mais leve.

Agradeço aos meus amigos de sempre, Lana Vargas, Heloisa Clara, Kelly Cristina, James Pacheco vocês estão desde o começo comigo e participaram de

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cada vitória, cada conquista, riram e choraram comigo, me deram força e conselhos, obrigada por saber que a qualquer momento eu tenho vocês.

Aos meus amigos e companheiros de pós-graduação, Renato Assis Machado, Mariana Dias Flor, Rodrigo Barros Esteves Lins, Giovana Fontanetti, Priscila Regis, Janaina Damasceno, Joyce Figueiredo, Camila Coelho, Marco Tulio e Danielle Ferreira meus maiores presentes desses anos de Mestrado e Doutorado. Obrigado por estarem comigo em todos os momentos, pelo companheirismo e amizade. Vocês sabem o quanto foram importantes durante esse tempo e que sem vocês eu não teria conseguido.

Agradeço a todos que direta ou indiretamente me auxiliaram e tornaram este projeto em uma realidade, muito obrigado.

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RESUMO

Introdução: A utilização de dessensibilizantes associados ao clareamento dental é

uma alternativa para o tratamento da sensibilidade dolorosa, a qual é considerada o principal efeito colateral relacionado a esse procedimento clínico. Objetivo: Avaliar clinicamente o efeito de géis e dentifrícios dessensibilizantes, na redução da sensibilidade dolorosa e variação de cor durante o tratamento clareador realizado em consultório, por meio de estudo clínico duplo cego controlado longitudinal.

Metodologia: Um estudo longitudinal prospectivo com 108 pacientes foi realizado,

sem distinção de gênero, submetidos ao clareamento dental em consultório utilizando peróxido de hidrogênio a 35% em três sessões clínicas com intervalo de uma semana entre as mesmas. Foram aplicados géis dessensibilizantes previamente ao procedimento clareador e dada a orientação da utilização de dentifrícios dessensibilizantes ao longo do tratamento. Os voluntários foram divididos aleatoriamente em 9 grupos experimentais (n=12), como descritos a seguir: GT/S – glicerina e espessante/sucralose; NF/S - nitrato de potássio e fluoreto de sódio/sucralose; NA/S - nitrato de potássio e arginina/sucralose; GT/AC – glicerina e espessante/arginina e carbonato de cálcio; NF/AC - nitrato de potássio e fluoreto de sódio/arginina e carbonato de cálcio; NA/AC - nitrato de potássio e arginina/arginina e carbonato de cálcio; GT/PN – glicerina e espessante/nitrato de potássio; NF/PN - nitrato de potássio e fluoreto de sódio/nitrato de potássio; NA/PN - nitrato de potássio e arginina/nitrato de potássio. A avaliação da sensibilidade utilizou a escala numérica analógica com escores de 0 a 10, sendo realizada imediatamente após a primeira sessão (S1), 24 horas após a primeira sessão (S2), imediatamente após a segunda sessão (S3), 24 horas após a segunda sessão (S4), imediatamente após a terceira sessão (S5), 24 horas após a terceira sessão (S6) e 24 semanas após o início do clareamento (S7). A variação de cor (ΔE) utilizou o espectrofotômetro para obtenção das coordenadas (L,a,b) utilizando o sistema CIELab antes do clareamento, 4 semanas e 24 semanas após o início do clareamento. Os dados de sensibilidade dolorosa foram submetidos ao teste de análise de variância multifatorial (MANOVA) com medidas repetidas e Teste de Lambda Wilks (p<0,05). Para a análise da variação de cor o teste de análise de variância inteiramente casual foi aplicado (p<0,05). Resultados: Os grupos NF/AC, NA/AC, NF/PN e NA/PN apresentaram menores valores de sensibilidade e redução da sensibilidade ao longo das sessões clínicas. Além disso, todos os grupos não apresentaram sensibilidade na avaliação de 24 semanas. Os valores de cor entre os grupos 4 semanas após o inicio do tratamento clareador não apresentaram diferença estatística (p=0,074). Houve semelhança estatística entre todos os grupos, na avaliação de cor no período 4 semanas (p=0,084) e 24 semanas (p=0,118), após o início do clareamento dental de consultório. Conclusão: O uso de dessensibilizantes contendo nitrato de potássio e flureto de sódio ou nitrato de potássio e arginina associados a dentifrícios contento arginina e carbonato de cálcio ou nitrato de potássio apresentaram redução significativa da sensibilidade ao longo das sessões clínicas, sem influenciar no resultado final do clareamento dental de consultório.

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ABSTRACT

Introduction: The use of desensitizers associated with tooth bleaching is an alternative for the treatment of pain sensitivity, which is considered the main side effect related to this clinical procedure. Objective: To assess clinically the effect of desensitizing gels and dentifrices on the reduction of pain sensitivity and color variation during in-office tooth bleaching through a longitudinal double-blind controlled clinical trial. Methods: A longitudinal prospective study was performed with 108 patients of both sexes subjected to in-office tooth bleaching using 35% hydrogen peroxide in three clinical sessions, with a one-week interval between them.

Desensitizing gels were applied prior to bleaching and instructions were provided on the use of desensitizing dentifrices during the treatment. The volunteers were divided randomly into nine experimental groups (n=12), as follows: GT/S - glycerin and thickener/sucralose; NF/S - potassium nitrate and sodium fluoride/sucralose; NA/S - potassium nitrate and arginine/sucralose; GT/AC - glycerin and thickener/arginine and calcium carbonate; NF/AC - potassium nitrate and sodium fluoride/arginine and calcium carbonate; NA/AC - potassium nitrate and arginine/arginine and calcium carbonate; GT/PN - glycerin and thickener/potassium nitrate; NF/PN - potassium nitrate and sodium fluoride/potassium nitrate; NA/PN - potassium nitrate and arginine/potassium nitrate. Sensitivity was assessed with the numerical analogue scale containing scores from 0 to 10, performed immediately after the first session (S1), 24 hours after the first session (S2), immediately after the second session (S3), 24 hours after the second session (S4), immediately after the third session (S5), 24 hours after the third session (S6), and 24 weeks after the onset of bleaching (S7). A spectrophotometer was used to obtain the color variation (ΔE) data (L, a, b), which were used in the CIELab system and assessed before bleaching and four and 24 weeks after the onset of bleaching. The pain sensitivity data were subjected to multivariate analysis of variance (MANOVA) with repeated measures and Lambda Wilks test (p<0.05). For the analysis of color variation, the completely randomized analysis of variance was applied (p<0.05). Results: The NF/AC, NA/AC, NF/PN, and NA/PN groups presented lower sensitivity values and reduced sensitivity throughout the clinical sessions. In addition, none of the groups showed sensitivity at the 24-week assessment. There was no statistical difference for color values among the groups four weeks after the onset of bleaching (p=0.074). The color assessment of all groups was statistically similar four weeks (p=0.084) and 24 weeks (p = 0.118) after the onset of in-office tooth bleaching. Conclusion: The use of desensitizers containing potassium nitrate and sodium fluoride or potassium nitrate and arginine associated with dentifrices containing arginine and calcium carbonate or potassium nitrate showed a significant reduction of sensitivity during the clinical sessions, without affecting the result of in-office tooth bleaching.

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SUMÁRIO

1. Introdução...12

2. Capítulo Único: Effects of desensitizing products on the reduction of pain sensitivity caused by in-office tooth bleaching: a 24-week follow-up...16

3. Conclusão...36

4. Referências...37

5. Apêndice 5.1 Apêndice 1: Materiais e métodos...42

6. Anexos 6.1. Anexo 1: Termo de consentimento livre e esclarecido...56

6.2. Anexo 2: Ficha clínica...60

6.3. Anexo 3: Carta de aprovação do Comitê de Ética em Pesquisa...63

6.4. Anexo 4: Protocolo de aprovação (ClinicalTrials)...64

6.5. Anexo 5: Comprovante de submissão (Journal of Dentistry)...65

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1.INTRODUÇÃO

A Odontologia estética está em constante mudança e diferentes protocolos de tratamentos para dentes com alteração de cor vêm sendo desenvolvidos ou aprimorados (Soeteman et al., 2018). Dentre esses, o clareamento dental é um dos tratamentos mais procurados para a melhoria da aparência estética, sendo conceituado como um procedimento conservador e eficiente (Karadas, 2015; Corcodel et al., 2017).

Por outro lado, este procedimento pode ocasionar algumas alterações na morfologia dos tecidos dentais mineralizados (Tanaka et al., 2010; Zeczkowski et al., 2015). Entretanto, esses efeitos sobre os tecidos dentários não foram completamente esclarecidos. Estudos mostram que alterações na morfologia e propriedades dos tecidos podem ocorrer, tais como, aumento da permeabilidade e da rugosidade superficial (Hosoya et al., 2003; Camargo et al., 2007; Markovic et al., 2007); diminuição da microdureza superfícial e subsuperficial (Efeoglu et al., 2007; Al-Salehi et al., 2007); alterações topográficas visualizadas em Microscopia Eletrônica de Varredura (Gomes et al., 2009; D'Amario et al., 2012) e perda de íons Cálcio e Fósforo do elemento dental para o gel clareador (Al-Salehi et al., 2007; Lee et al., 2006).

Porém, a intensidade e casuística dessas alterações variam de acordo com diferentes métodos e modelos de estudos (Attin et al., 2004), sendo que para o clareamento de dentes vitais existem três abordagens. O clareamento em consultório, em que se utiliza altas concentrações do agente ativo, entre 30 a 40% de peróxido de hidrogênio, ou 35 a 37% de peróxido de carbamida (Armênio et al., 2008; Basting et al., 2012; He et al., 2012; Alqahtani, 2014). A segunda abordagem é denominada clareamento caseiro, na qual são utilizadas concentrações mais baixas do peróxido de hidrogênio, entre 3,6 e 10%, ou de seu precursor, o peróxido de carbamida, entre 10 e 22%, necessitando de períodos mais prolongados de aplicação, de 1 a 8 horas por dia, por no mínimo 2 semanas (Haywood et al., 1990; Armênio et al., 2008; Alqahtani, 2014).

A terceira abordagem de clareamento de dentes vitais é a denominada “over-the-counter”. Na década de noventa houve o desenvolvimento de produtos de baixa concentração de peróxido de hidrogênio, 3 a 6%, para livre

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comercialização (Haywood, 1990). São produtos aplicados pelo próprio paciente através de dentifrícios, tiras adesivas ou enxaguatórios bucais, sem acompanhamento profissional (Alqahtani, 2014) e são definidos como “over - the - conter” (OTC) (Lima et al., 2013; Devji et al., 2017).

Independente do tipo de tratamento clareador utilizado, o mecanismo de ação é o mesmo. O gel contém como componente ativo o peróxido de hidrogênio, ou seu precursor, o peróxido de carbamida, em diferentes concentrações (Abouassi et al., 2011; Alqahtani, 2014). O peróxido de hidrogênio é um agente oxidante capaz de difundir-se pelo esmalte dental e dissociar-se em radicais livres instáveis, peridroxil, hidroxila e oxigênio que reagem com as moléculas dos pigmentos orgânicos. Essa reação leva à quebra das ligações duplas de carbono resultando em moléculas menores que promovem uma mudança no espectro de absorção da luz, interferindo na sua reflexão, o que resulta no clareamento do dente (Alqahtani, 2014; Young et al., 2017).

No entanto, o efeito oxidante do peróxido de hidrogênio não é específico, pois além de reagir com os pigmentos, também pode reagir com a matriz orgânica do dente (Abouassi et al., 2011; Browning et al., 2012), promovendo uma alteração morfológica da estrutura dental, a qual apesar de acontecer por um curto período de tempo, é considerada um dos efeitos adversos decorrentes do clareamento dental, porém não o único. Outro efeito adverso está relacionado com os tecidos moles, pois seu contato com o gel clareador promove queimaduras esbranquiçadas. Essas queimaduras são transitórias, desde que o tempo de contato do gel com o tecido mole não seja prolongado, porém causam desconforto ao paciente (Alqahtani, 2014).

Entretanto, o principal efeito adverso da técnica de clareamento é a sensibilidade dental (Bonafe et al., 2014; Haywood et al., 1990; Kossatz et al., 2011) sendo relatada por pelo menos dois terços dos pacientes em algum momento do tratamento (Armênio et al., 2008). A dor varia de leve a intolerável, podendo corresponder a 9,5% de abandono do tratamento no caso do clareamento caseiro e 4,3% em relação ao clareamento de consultório (Basting et al., 2012). Esta sensibilidade dolorosa pode estar relacionada à técnica utilizada, ao tempo de aplicação e concentração do gel clareador e, ainda, à resposta individual de cada paciente (He et al., 2012).

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A etiologia dessa sensibilidade é complexa, porém acredita-se que esteja relacionada à quantidade de radicais livres do peróxido de hidrogênio que chegam à polpa (Armênio et al., 2008; Basting et al., 2012; Camargo et al., 2007; Costa et al., 2010). O peróxido de hidrogênio aumenta a permeabilidade do esmalte possibilitando a difusão dos íons oxigênio através da dentina, que podem atingir a polpa (Basting et al., 2012; Cooper et al., 1992; Thitinanthapan et al., 1999). A sensibilidade resulta da ação dos mediadores inflamatórios, tais como a substância-P que é o neuropeptídeo responsável pela vasodilatação e aumento do fluxo sanguíneo pulpar, que permite a chegada das células inflamatórias ao local (Caviedes-Bucheli et al., 2008), levando à reação inflamatória transitória que promove a dor (Bonafe et al., 2014; Caviedes-bucheli et al., 2008). Este processo ocorre quando há níveis insuficientes de antioxidantes (peroxidases, oxigenases e catalases) ou, então, essas são incapazes de remover adequadamente os radicais livres (Bonafe et al., 2014; Costa et al., 2010).

Algumas técnicas clínicas podem ser utilizadas visando a eliminação desses efeitos adversos, entre estas estão a diminuição da concentração de peróxido de hidrogênio, diminuição no tempo e frequência de aplicação do gel clareador (Armênio et al., 2008; Basting et al., 2012), administração de analgésicos/antiinflamatórios (Coldebella et al., 2009) e a utilização de produtos dessensibilizantes (Bonafe et al., 2014; Browning et al., 2012; Tay et al., 2009), na forma de gel ou dentifrícios (Armênio et al., 2008; Basting et al., 2012; Haywood et al., 2005).

Os produtos dessensibilizantes utilizam dois mecanismos de ação. Podem agir obliterando os canalículos da dentina e, assim, impedir a movimentação dos fluidos dentinários e, ainda auxiliar na remineralização da dentina (Basting et al., 2012; Bonafe et al., 2014), sendo esses produtos à base de fluoreto, arginina e/ou carbonato de cálcio.

O fluoreto de sódio, a arginina e carbonato de cálcio atuam obliterando os canalículos da dentina, impedindo assim o movimento dos fluidos dentinários e auxiliando na remineralização da mesma (Basting et al., 2012; Bonafe et al., 2014). Além disso, a associação de arginina e carbonato de cálcio é capaz de ser depositada sobre superfícies de dentina para bloquear fisicamente e selar os túbulos dentinários (Basting et al., 2012; Bonafe et al., 2014).

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O segundo modo de ação é pelo bloqueio da atividade nervosa da polpa, através da diminuição da excitabilidade sensorial dos nociceptores. O nitrato de potássio atua diminuindo a capacidade de repolarização das fibras nervosas presentes na polpa dental, após sofrerem despolarização devido ao impulso de dor (Basting et al., 2012; Bonafe et al., 2014).

O nitrato de potássio difunde-se através do esmalte e dentina até as terminações nervosas das fibras sensoriais, reduzindo a excitabilidade das fibras nervosas, inibindo o movimento dos íons sódio e potássio ao redor das fibras sensoriais, resultando na modulação ou supressão da sensação de dor (Basting et al., 2012; Bonafe et al., 2014).

Entretanto, mesmo com a diversidade de produtos dessensibilizantes no mercado comercial, a sensibilidade ainda é relatada pela maioria dos pacientes que realizam clareamento. Com isso, a formulação de produtos dessensibilizantes ainda é necessária, com o objetivo de reduzir ao máximo ou extinguir a sensibilidade dolorosa dos pacientes. Uma alternativa seria um produto que combinasse os dois mecanismos de redução da sensibilidade, ou seja, por meio da obliteração dos canalículos dentinários promovida por substâncias contendo arginina e por meio do bloqueio da atividade nervosa promovido por substâncias contento nitrato de potássio.

Com isso, esse trabalho teve como objetivo a formulação de um dessensibilizante experimental à base de arginina e nitrato de potássio, e a avaliação de seu desempenho clínico, bem como de outros dessensibilizantes e dentifrícios comerciais, por meio de um estudo clínico duplo cego controlado com avaliação longitudinal na redução da sensibilidade dolorosa e variação de cor durante o clareamento dental em consultório.

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2. CAPÍTULO ÚNICO

Effects of desensitizing products on the reduction of pain sensitivity caused by in-office tooth bleaching: a 24-week follow-up

*Artigo submetido a revista Journal of Dentistry (Annex 5)

Authors: Josué Junior Araujo Pierotea, Lucia Trazzi Prietoa, Carlos Tadeu dos Santos Diasb, Débora Alves Nunes Leite Nunesa, Flávio Henrique Baggio Aguiara, Luis Alexandre Maffei Sartini Paulilloa

a Department of Restorative Dentistry, School of Dentistry of Piracicaba, University of Campinas, Av. Limeira, 901, Piracicaba, SP 13414-903, Brazil

b Department of Agronomic engineer, Department of Exact Sciences, ESALQ University of São Paulo, Av. Padua Dias, 11, Piracicaba, SP 13418-900, Brazil

Corresponding author: J.J.A.Pierote ([email protected]), Piracicaba Dental School Dental School, University of Campinas, Av. Limeira, 901, P.O. BOX 52, Piracicaba, SP 13414-903, Brazil. Tel.: +55 19 2106 5339/5218.

E-mail addresses: [email protected] (J.J.A.Pierote), [email protected] (L.T.Prieto), [email protected] (C.T.S.Dias), [email protected] (D.N.L.Lima), [email protected] (F.H.B. Aguiar), [email protected] (L.A.M.S.Paulillo)

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ABSTRACT

Objective: To assess clinically the effect of desensitizing gels and dentifrices on

the reduction of pain sensitivity and color variation during in-office tooth bleaching through. Methods: A longitudinal double-blind controlled clinical trial was performed with 108 patients subjected to in-office tooth bleaching in three clinical sessions, with a one-week interval between them. Desensitizing gels were applied prior to bleaching and instructions were provided on the use of desensitizing dentifrices during the treatment. The volunteers were divided randomly into nine experimental groups (n=12), as follows: GT/S-glycerin and thickener/sucralose; NF/S-potassium nitrate and sodium fluoride/sucralose; NA/S-potassium nitrate and arginine/sucralose; GT/AC-glycerin and thickener/arginine and calcium carbonate; NF/AC-potassium nitrate and sodium fluoride/arginine and calcium carbonate; NA/AC-potassium nitrate and arginine/arginine and calcium carbonate; GT/PN-glycerin and thickener/potassium nitrate; NF/PN-potassium nitrate and sodium fluoride/potassium nitrate; NA/PN-potassium nitrate and arginine/potassium nitrate. Sensitivity was assessed with the numerical analogue scale containing scores from 0 to 10. A spectrophotometer was used to obtain the color variation (ΔE). The pain sensitivity data were subjected to multivariate analysis of variance (MANOVA) (p<0.05). For the analysis of color variation, the completely randomized analysis of variance was applied (p<0.05). Results: The NF/AC, NA/AC, NF/PN, and NA/PN groups presented lower sensitivity values and reduced sensitivity throughout the clinical sessions. In addition, none of the groups showed sensitivity at the 24-week assessment. There was no statistical difference for color values among the groups four weeks after the onset of bleaching (p=0.074). The color assessment of all groups was statistically similar four weeks (p=0.084) and 24 weeks (p=0.118) after the onset of in-office tooth bleaching. Conclusion: The use of desensitizers containing potassium nitrate and sodium fluoride or potassium nitrate and arginine associated with dentifrices containing arginine and calcium carbonate or potassium nitrate showed a significant reduction of sensitivity during the clinical sessions, without affecting the result of in-office tooth bleaching.

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INTRODUCTION

Sensitivity is the main adverse effect of tooth bleaching,1-3 it is reported by at least two thirds of patients,4,5 and it occurs mainly in the first weeks of the treatment.6,7 The etiology of this symptom has been attributed to the amount of hydrogen peroxide free radicals that reach the pulp.4,5,8,9

Some clinical techniques may be used to eliminate or minimize this adverse effect, such as decreasing the concentration and application time of hydrogen peroxide and the frequency of bleaching gel application,4,5 administering analgesics/anti-inflammatories,10 and using desensitizers.1,6,7,11

Desensitizing agents work by two action mechanisms. First, through the obliteration of the dentinal tubules, preventing the movement of dentinal fluids and assisting in dentin remineralization with agents such as fluoride and arginine.1,5,12 The second mechanism works by blocking the nerve pulp activity, decreasing the sensory excitability of nociceptors,1,5 using agents such as potassium nitrate.

These desensitizing agents may be applied professionally in-office before or after the bleaching treatment or they may be self-administered by the patient at home using specific dentifrices and fluoride gels.13 The literature shows that the topical application of 5% potassium nitrate with 2% sodium fluoride before applying the bleaching gel was effective in reducing sensitivity during the bleaching procedure, but it was not effective in the interval between the sessions.13,14,15 Thus, the use of such products could not yet eliminate the sensitivity related to bleaching.16 In addition, there is a lack of studies in the literature assessing potassium nitrate associated with other desensitizing products, such as bioglass and arginine, which have been used in desensitizing dentifrices and could potentiate the effects of potassium nitrate when used as desensitizing agents.13,14,17

Vieira-Junior et al. (2018) assessed in vitro dentifrices containing bioglass or arginine prior to tooth bleaching and they were effective in protecting enamel against the mineral loss promoted by bleaching, but without interfering with the result of the treatment. Pintado-Palomino et al. (2015) assessed the effect of desensitizing dentifrices application on tooth sensitivity due to bleaching. However, there are no studies in the literature formulating and assessing the effect of desensitizers containing arginine on dentin sensitivity.18,19 Therefore, the

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developments of desensitizers containing arginine and potassium nitrate that act on tooth sensitivity caused by tooth bleaching, as well as their longitudinal clinical assessment, are required.

Based on the above, an experimental desensitizer containing arginine and potassium nitrate was formulated. The objective this study was to evaluate the clinical performance regarding pain sensitivity reduction and color variation during in-office tooth bleaching of the desensitizer developed and other commercial desensitizing dentifrices were assessed longitudinally through a double-blind controlled clinical trial. The hypothesis was that the use of experimental and commercial desensitizers associated with desensitizing dentifrices could reduce tooth sensitivity, but without interfering with color variation.

MATERIAL AND METHODS ETHICAL ASPECTS

The project of this study was submitted to and approved by the Research Ethics Committee affiliated to the National Commission of Research Ethics (CONEP) under protocol number 104/2015, and registered in the Clinical Trials Records and Results Database (ClinicalTrials.gov) under protocol NCT03019224. All the volunteers signed an informed consent form. The clinical trial was reported according to the standard protocol of the CONSORT Statement.

MATERIAL

Three types of desensitizing gels and three types of dentifrices were used to assess the desensitizing products (Table 1).

Table 1:Description of the desensitizing products used and their composition and manufacturers.

Material Composition Manufacturer

Control Desensitizing

(DSP) Glycerin, carbopol, 2% deionized water, and neutralizing agent (GT)

Compounding pharmacy Proderma (Piracicaba, SP,

Brazil) Desensibilize KF 2%

(DK) associated with 2% Sodium 5% Potassium Nitrate Fluoride (NF)

FGM (Joinville, SC, Brazil)

Experimental 5% potassium nitrate associated

with 8% arginine (NA) Proderma (Piracicaba, SP, Compounding pharmacy Brazil)

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Desensitizing (DE)

Control Dentifrice (DTP) Sucralose (S) Compounding pharmacy Proderma (Piracicaba, SP,

Brazil) Colgate Sensitive

Pro-Relief (CS) Arginine and calcium carbonate associated with sodium monofluorophosphate (1450ppm

fluorine) (AC)

Colgate-Palmolive (Sao Paulo, SP, Brazil)

Sensodyne Pronamel (SP)

5% potassium nitrate associated with sodium

monofluorophosphate (1450ppm fluorine) (PN)

Glaxosmithkline Brazil (Rio de Janeiro, RJ Brazil)

EXPERIMENTAL DESIGN

A longitudinal double-blind controlled clinical trial with 108 volunteers was performed. The objects of the study were a desensitizing gel in three levels (two levels of treatment and one level of control) and a desensitizing dentifrice in three levels (two levels of treatment and one level of control). The response variables included pain sensitivity and color variation (ΔE).

EXPERIMENTAL GROUPS

The interaction between the desensitizer and the dentifrice resulted in nine experimental groups (Table 2).

Table 2: Groups and their active ingredients used in the experiment.

Groups Active ingredients

GT/S Glycerin and thickener / Sucralose

NF/S Potassium nitrate and sodium fluoride / Sucralose NA/S Potassium nitrate and arginine / Sucralose GT/AC Glycerin and thickener / Arginine and calcium carbonate

NF/AC Potassium nitrate and sodium fluoride / Arginine and calcium carbonate NA/AC Potassium nitrate and arginine / Arginine and calcium carbonate GT/PN Glycerin and thickener / Potassium nitrate

NF/PN Potassium nitrate and sodium fluoride / Potassium nitrate NA/PN Potassium nitrate and arginine / Potassium nitrate CLINICAL PROCEDURES

Selection and preparation of volunteers

Patients who attended an undergraduate clinic for a bleaching treatment were invited to participate in the study. The researcher (who did not participate in

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the randomization process) informed the volunteers about all aspects of the study and that they would be free to refuse to participate, remove their consent, or quit participating at any time during the treatment. In addition, it was explained that their participation was voluntary and refusal to participate would not result in any penalty or loss of benefits related to the treatment.

The volunteers who chose to participate in the study signed an informed consent form and, after reading the study carefully, the initial clinical assessment was applied.

Inclusion criteria were age between 18 and 30 years, good oral and general health, healthy anterior teeth with chroma superior to A2 in the Vita Classical color scale (VITA Zahnfabrink, Bad Säckingen, Germany), signing the informed consent form, and availability for all dental visits.

The exclusion criteria were smokers, pregnant or lactating women, previous tooth bleaching, use of desensitizers or orthodontic appliances, parafunctional habits, dentin sensitivity, gingival recession, non-carious cervical lesions, anterior teeth with restorations and carious lesions, non-vital tooth darkening and unsatisfactory posterior restorations.

The volunteers were assessed through anamnesis and clinical examination with clinical mirror and dental explorer. Interproximal and periapical radiographs were performed for the radiographic examination. This assessment allowed analyzing whether the patients met the inclusion criteria of the research, which resulted in a sample of 108 volunteers.

After the selection of volunteers, oral conditioning was performed by supragingival scaling with periodontal curettes, and prophylaxis was performed with rubber cups at low rotation using water/pumice paste.

One week before starting the experiment, a specific toothpaste (Colgate Total 12, Colgate-Palmolive, Sao Paulo, Brazil) and toothbrush (Slim Soft, Colgate-Palmolive, Sao Paulo, Brazil) were given to the volunteers, followed by the recommendation of using only such dentifrice and toothbrush for oral hygiene until starting the bleaching sessions.

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After the selection of volunteers, the groups were randomized. A researcher (responsible for steps 1, 2, and 3) and a dentist (responsible for step 4 and clinical stages) performed the randomization of the study. Step 1 consisted of removing desensitizers and dentifrices from the original packaging. Step 2 consisted of associating the products. Step 3 consisted of drawing the code of the respective association. Step 4 consisted of the dentist applying the desensitizer on the volunteers and distributing the dentifrices to them, as shown in Figure 1.

Figure 1: Randomization of the study.

GT: glycerin and thickener, NF: potassium nitrate and sodium fluoride, NA: potassium nitrate and arginine, S: sucralose, AC: arginine and calcium carbonate, PN: potassium nitrate. 1: GT/S, 2: NF/S, 3: NA/S, 4: GT/AC, 5: NF/AC, 6: NA/AC, 7: GT/PN, 8: NF/PN, 9: NA/PN.

Use of desensitizing dentifrices

Between the clinical bleaching sessions, each volunteer used an unidentified dentifrice corresponding to the experimental group, which was defined previously by means of a draw performed by a professional who did not participate in the study. Thus, the researcher (dentist) who provided the dentifrice and the volunteer were not aware to which experimental group the volunteer belonged (double blind).

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After the first in-office bleaching session, each volunteer was instructed on how to use the dentifrice. They were instructed to use only the specific dentifrice provided to their experimental group, which should be used for oral hygiene three times a day (after breakfast, after lunch, and after dinner).

Color assessment

An objective assessment was performed using a spectrophotometer (Vita Easyshade Advance, Vident, Brea, CA, USA) before the first bleaching session, one week after the end of bleaching, and 24 weeks after the onset of the bleaching treatment.

Color was assessed always in the same position through a silicone guide on hydrated teeth. For the preparation of the guide, the impression of the upper incisors was performed using addition silicone (Express XT Pasta Densa Soft, 3M ESPE, Sumaré, SP, Brazil). Tooth color was assessed through an opening compatible with the tip size of the spectrophotometer, in the middle third on the buccal surface of the right upper central incisor of the guide.

Color was determined using the parameters of the EasyShade device, which indicate the following values: L*, a*, and b*. The L* represents the tooth value on a scale from 0 (black) to 100 (white) and a* and b* represent the shadow, in which a* is the measure along the red (a* positive) and green (a* negative) axes, and b* is the measure along the yellow (b* positive) and blue (b* negative) axes. Color was compared using color variation (ΔE), which was calculated with equation ΔE = [(ΔL*)2+(Δa*)2+(Δb*)2]1/2. This evaluation was performed to verify the effectiveness of the bleaching treatment and whether the dentifrices used would affect the quality of the treatment.

Isolation of the surgical field

The clinical procedures were performed under relative isolation using a lip retractor (Arcflex, FGM, Joinville, SC, Brazil) and cotton rolls for applying gingival barrier, desensitizing agent, and bleaching agent from the right first molar to the left first molar of upper and lower arches.

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The gingival barrier (Top Dam, FGM, Joinville, SC, Brazil) with approximately 3 mm of height was inserted on the gingival margins and papillae of the teeth that received the bleaching gel. Groups with three teeth each were then photopolymerized for 20 seconds using high power LEDs (irradiance = 600 mw/cm²) (RadiiCal, Sao Paulo, SP, Brazil).

Application of desensitizing agent

As mentioned above, the choice of the specific desensitizing gel was defined previously by means of a draw performed by a professional who did not participate in the study. Thus, the researcher (dentist) who provided the dentifrice and the volunteer were not aware to which experimental group the patient belonged (double blind).

The desensitizing gel was applied with a microbrush applicator. The product remained for 10 minutes on the buccal surface of all teeth from the right first molar to the left first molar of upper and lower arches. Then, the desensitizer was removed with water jet and a disposable plastic suction cannula.

Application of bleaching agent

The preparation of the 35% hydrogen peroxide (Whiteness HP, FGM, Joinville, SC, Brazil) followed the manufacturer's recommendations, which consisted of mixing 24 drops of 35% hydrogen peroxide with 8 drops of thickener. The gel remained in contact with the buccal surface of the teeth for 15 minutes and it was removed with a suction cannula and water jet. This procedure was performed three times per clinical session. The volunteers underwent three clinical bleaching sessions, with a one-week interval between them.

Assessment of pain sensitivity

Sensitivity was assessed at seven times, as follows: S1: immediately after the first session, S2: 24 hours after the first session; S3: immediately after the second session; S4: 24 hours after the second session; S5: immediately after the third session; S6: 24 hours after the third session; and S7: 24 weeks after the first bleaching session. In order to assess pain sensitivity, the numerical rating scale, with scores from 0 to 10, was applied.

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STATISTICAL ANALYSIS

The pain sensitivity data were submitted to the multivariate analysis of variance (MANOVA) with repeated measures and Lambda Wilks test (p<0.05). For the color variation analysis, the completely random variance analysis was applied (p<0.05).

RESULTS

At the end of four weeks, 108 participants completed the study (50 men and 58 women), while at the end of 24 weeks, 104 participants completed the study (50 men and 54 women) (Figure 2).

Figure 2: CONSORT flow chart.

GT/S: glycerin and thickener/sucralose, NF/S: potassium nitrate and sodium fluoride/sucralose, NA/S: potassium nitrate and arginine/sucralose, GT/AC: glycerin and thickener/arginine and calcium carbonate, NF/AC: potassium nitrate and sodium fluoride/arginine and calcium carbonate, NA/AC: potassium nitrate and arginine/arginine and calcium carbonate, GT/PN: glycerin and thickener/potassium nitrate, NF/PN: potassium nitrate and sodium fluoride/potassium nitrate, NA/PN: potassium nitrate and arginine/potassium nitrate.

After four weeks, the means of sensitivity among the groups were compared two by two by the Lambda Wilks test and the result showed a statistical difference (p<0.05) between the groups (Graph 1). In addition, none of the groups showed sensitivity at the 24-week assessment. The comparison among the groups after 24 weeks of the onset of the bleaching treatment showed (p=1) no statistical differences (p≥0.05).

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Graph 1 shows the pain sensitivity of each group in the seven assessments. Groups NF/AC (2.02), NA/AC (1.88), NF/PN (1.82), and NA/PN (2.05) showed the lowest sensitivity levels when compared to the other groups (GT/S (3.90), NF/S (3.79), NA/S (3.78), GT/AC (3.78), and GT/PN (3.37)), which showed higher levels of sensitivity.

Graph 1 shows that, for the analysis of sensitivity regarding time, the same groups that presented lower levels of sensitivity (NF/AC, NA/AC, NF/PN, and NA/PN) also presented a sensitivity reduction throughout the clinical bleaching sessions. In addition, all groups showed no sensitivity at the 24-week assessment.

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Graph 1: Mean, standard deviation, and Lambda Wilks test for pain sensitivity

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*Mean (standard deviation) and Lambda Wilks test (Capital letters compare the rows). GT/S: glycerin and thickener/sucralose, NF/S: potassium nitrate and sodium fluoride/sucralose, NA/S: potassium nitrate and arginine/sucralose, GT/AC: glycerin and thickener/arginine and calcium carbonate, NF/AC: potassium nitrate and sodium fluoride/arginine and calcium carbonate, NA/AC: potassium nitrate and arginine/arginine and calcium carbonate, GT/PN: glycerin and thickener/potassium nitrate, NF/PN: potassium nitrate and sodium fluoride/potassium nitrate, NA/PN: potassium nitrate and arginine/potassium nitrate. S1: sensitivity immediately after the first session, S2: sensitivity 24 hours after the first session, S3: sensitivity immediately after the second session, S4: sensitivity 24 hours after the second session, S5: sensitivity immediately after the third session; S6: sensitivity 24 hours after the third session; S7: sensitivity 24 weeks after the first bleaching session.

Color variation was visually perceptible after four weeks (ΔE> 3.3)18 and after 24 weeks (Table 3).

The completely random variance analysis was applied for color variation and the values after 24 weeks were lower than the values after four weeks, even though there was no statistical difference between them (p=0.074) (Table 3). In addition, the comparison among groups showed statistical similarity at the four-week (p=0.084) and 24-four-week (p=0.118) assessments after in-office tooth bleaching (Table 3).

Table 3: Tukey’s test results for ΔE values and their parameters after four and

twenty four weeks.

Groups ΔE ΔL Δa Δb

ΔE 4w

Mean (SD) Mean (SD) ΔE 24w Mean (SD) ΔL 4w Mean (SD) ΔL 24w Mean (SD) Δa 4w Mean (SD) Δa 24w Mean (SD) Δb 4w Mean (SD) Δb 24w GT/S 4.91 (1.06)aA 3.40 (0.94)aA 1.21 (0.06)bB 1.82 (0.08)bB 0.91 (0.06)cC 0.88 (0.06)cC -0.62 (0.06)dD -0.83 (0.06)dD NF/S 4.61 (1.19)aA 3.56 (1.02)aA 0.91 (0.19)bB 1.16 (0.19)bB 0.61 (0.19)cC 0.72 (0.15)cC -0.81 (0.19)dD -0.74 (0.20)dD NA/S 4.51 (1.20)aA 3.37 (0.83)aA 0.71 (0.20)bB 1.42 (0.31)bB 0.51 (0.10)cC 0.62 (0.13)cC -0.83 (0.20)dD -0.63 (0.10)dD GT/AC 4.42 (1.49)aA 3.39 (1.05)aA 1.02 (0.49)bB 1.02 (0.49)bB 0.82 (0.49)cC 0.74 (0.41)cC -0.62 (0.49)dD -0.42 (0.09)dD NF/AC 4.57 (1.31)aA 3.64 (1.02)aA 0.90 (0.31)bB 1.07 (0.31)bB 0.57 (0.21)cC 0.68 (0.24)cC -0.86 (0.31)dD -0.76 (0.09)dD NA/AC 4.81 (1.81)aA 3.41 (1.02)aA 1.01 (0.61)bB 1.09 (0.91)bB 0.81 (0.12)cC 0.92 (0.32)cC -0.81 (0.21)dD -0.64 (0.13)dD GT/PN 4.69 (1.81)aA 3.79 (0.98)aA 0.87 (0.49)bB 1.89 (0.82)bB 0.69 (0.31)cC 0.92 (0.41)cC -0.73 (0.44)dD -0.84 (0.24)dD NF/PN 4.87 (1.79)aA 3.54 (1.02)aA 1.07 (0.29)bB 1.88 (0.49)bB 0.87 (0.19)cC 0.99 (0.21)cC -0.97 (0.16)dD -0.77 (0.26)dD NA/PN 4.52 (1.81)aA 3.41 (0.98)aA 0.91 (0.81)bB 1.52 (0.70)cB 0.52 (0.21)cC 0.92 (0.32)cC -0.42 (0.09)dD -0.52 (0.09)dD *GT/S: glycerin and thickener/sucralose, NF/S: potassium nitrate and sodium fluoride/sucralose, NA/S: potassium nitrate and arginine/sucralose, GT/AC: glycerin and thickener/arginine and calcium carbonate, NF/AC: potassium nitrate and sodium fluoride/arginine and calcium carbonate, NA/AC: potassium nitrate and arginine/arginine and calcium carbonate, GT/PN: glycerin and thickener/potassium nitrate, NF/PN: potassium nitrate and sodium fluoride/potassium nitrate, NA/PN: potassium nitrate and arginine/potassium nitrate.*Coefficients with the same letter show no statistical difference among the means of color variation. *Lower-case letters compare the rows. *Capital letters compare the columns.

DISCUSSION

The hypothesis that the use of experimental and commercial desensitizers associated with desensitizing dentifrices could reduce tooth sensitivity, but without interfering with color variation was confirmed.

The sensitivity values showed that the group containing glycerin and thickener or sucralose (GT/S) had no statistical difference compared to groups

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NF/S, NA/S, GT/AC, and GT/PN. These groups have in common the same glycerin and thickener or sucralose with the addition of potassium nitrate and arginine or calcium carbonate. In turn, groups lacking glycerin and thickener or sucralose (NF/AC, NA/AC, NF/PN, and NA/PN) presented a significant reduction in sensitivity when compared to the other groups.

Glycerin is the commercial form of glycerol which is nothing more than a colorless, viscous, and sweet-tasting liquid organic compound that has been used because its viscosity is similar to commercial desensitizers and it does not affect sensitivity.19 Sucralose is made of and tastes like sugar, but the body does not recognize it as a carbohydrate, and it has zero calories. Moreover, it is not used as a substrate for the oral bacteria that cause caries and it does not affect sensitivity, which represented a good reason for using it in the control dentifrice.20 These two compounds were used as placebo (control) for the double-blind design of the study.

The desensitizers NF and NA associated with the control dentifrice S did not induce a reduction in sensitivity (NF/S and NA/S). This result may be explained because such compounds require more time in enamel to show an effective action. Thus, the application with desensitizing gel may not have been sufficient for NF and NA to diffuse into enamel, obliterate the dentinal tubules, and smooth the movement of fluids through enamel and dentin.20 This agrees with authors who state that products containing potassium nitrate associated with fluoride or arginine at small concentrations are only able to reduce dentin sensitivity near the fourth week of use.20,21 The action of NF and NA was even more limited in enamel, as shown in the present study.

Regarding the experimental desensitizer NA, even with the presence of potassium nitrate in its composition, the obliteration of dentinal tubules by arginine did not allow reducing the excitability of the nervous fibers through the inhibition of movement of sodium and potassium ions around sensory fibers, which is usually promoted by potassium nitrate.22-23

The NF/AC, NA/AC, NF/PN, and NA/PN groups showed a significant reduction in pain sensitivity in combinations of desensitizers containing NF or NA with dentifrices containing AC or PN. This result is justified by the synergic action

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of arginine and potassium nitrate when associated with desensitizing dentifrices.22,23

The NA desensitizer and the AC dentifrice can diffuse through enamel and they are deposited on dentin surfaces to physically block and seal the dentinal tubules.22-23 This technology, based on arginine-containing products, promotes the diffusion through prisms of bleached enamel, physically obliterating and forming a plug in the dentinal tubules, thus allowing to relieve pain sensitivity.22-24 This new technology provides clinically proven benefits over rapid and long-lasting sensitivity relief. It also shows that arginine works alongside to accelerate the natural mechanisms of tubular occlusion with a protective layer deposit on the surface of the dentin adjacent to the bleached enamel.25 Clinical findings show that arginine-containing products provide significant sensitivity relief.22,23

The NF desensitizers and PN dentifrices work by blocking the sensory activity of the nerve fibers of the pulp and decreasing the sensory excitability of nociceptors.4,25,26,27 Potassium nitrate diffuses through enamel and dentin into the nerve endings of sensory fibers, reducing the excitability of nerve fibers by inhibiting the movement of sodium and potassium ions around the sensory fibers. This action results in modulation or suppression of painful sensation.21,28,29 Because of this mechanism, potassium salts have been suggested as effective treatment for pain sensitivity caused by tooth bleaching.4,21 Our study shows that the use of products with nitrate may be more effective than fluoride in reducing pain after tooth bleaching, agreeing with results described in the studies of Sowinski et al. (2001) and Thiesen et al. (2013).

The reduction of sensitivity during tooth bleaching is beneficial because it improves comfort and facilitates the patient's commitment to treatment.4,15 The association of dentifrice and desensitizer in our study proved to be an efficient procedure for reducing the pain sensitivity caused by in-office tooth bleaching.

The sensitivity assessment over time showed that sensitivity values 24 hours after applying the bleaching agent in the last two sessions decreased significantly in the AC or PN containing groups (NF/AC, NA/AC, NF/PN, and NA/PN). This occurred due to the continued use of the dentifrice, which allowed a longer contact time between the toothpaste and the dental surface, inhibiting the painful symptomatology.15,21,29

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The association of desensitizers with dentifrices did not affect the results of the bleaching treatment, considering there was no significant difference in tooth shades among the groups evaluated. Desensitizers containing NA and dentifrices containing AC were expected to affect the diffusion of the bleaching gel due to their action mechanism, which is similar to that of fluoride, as both promote the reduction of enamel permeability and obliteration of dentinal tubules. Nevertheless, the hydrogen peroxide molecule has a reduced size and can penetrate the spaces between the enamel prisms.11,30,31 This probably explains the similar results of color variation after bleaching obtained for different groups.

The present study showed that the association of desensitizers containing NF or NA with dentifrices containing AC or PN might be an efficient alternative to reduce pain sensitivity due to in-office tooth bleaching. However, the limitations of this study are related to the need of a long-standing follow-up of the volunteers to analyze color stability after the end of the bleaching treatment. Consequently, further studies with longer follow-up periods are required.

CONCLUSION

The use of desensitizers containing potassium nitrate and sodium fluoride or potassium nitrate and arginine associated with dentifrices containing arginine and carbonate or potassium nitrate showed a significant reduction of pain sensitivity during in-office tooth bleaching sessions, without affecting the final treatment result and representing a viable technique for clinical use.

Acknowledgements

The authors would like to thank the Coordination for the Improvement of Higher Education Personnel (CAPES) for granting the scholarship as financial support.

Conflicts of interest

The authors declare no potential conflicts of interest related to the publication of this article.

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22. Ayad F, Ayad N, Zhang YP, DeVizio W, Cummins D, Mateo LR. Comparing the efficacy in reducing dentin hypersensitivity of a new toothpaste containing 8.0% arginine, calcium carbonate, and 1450 ppm fluoride to a commercial sensitive toothpaste containing 2% potassium ion: an eight-week clinical study on Canadian adults. The Journal of Clinical Dentistry 2009;20(1):10-6.

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relief of dentin hypersensitivity. The Journal of Clinical Dentistry 2009;20(4):109-14.

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3. CONCLUSÃO

O uso de dessensibilizantes contendo nitrato de potássio e fluoreto de sódio ou nitrato de potássio e arginina associados a dentifrícios contento arginina e carbonato ou nitrato de potássio apresentaram redução significativa da sensibilidade dolorosa ao longo das sessões clínicas de clareamento dental em consultório, sem influenciar no resultado final do tratamento e mostrando-se uma técnica viável para uso clínico.

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