Abstract Aim To identify the phenotypic characteristics of individuals with temporomandibular disorders (TMD) who may benefit from adding duloxetine to self-management (SM) strategies. Methodology This was a post hoc exploratory analysis of a randomized, placebo-controlled clinical trial with SM-duloxetine (duloxetine 60 mg/day plus SM strategies for 12 weeks) in adult participants with painful TMD. The primary outcome was the proportion of responders to treatment (individuals with ≥ 30% reduction in pain intensity) in SM-duloxetine and SM-placebo group at week 12. For responder analysis, five phenotyping domains recommended by Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials were assessed: pain, psychological, sleep, quantitative sensory testing, and conditioned pain modulation. Relative risk (RR), 95% confidence intervals (CI), and absolute risk reduction were calculated. Results Among participants treated with SM-duloxetine, severe pain intensity (RR 1.33, 95% CI: 0.56, 3.17), pain disability (RR 1.30, 95% CI: 0.63, 2.67), ≥ 1 painful comorbidity (RR 1.48, 95% CI: 0.57, 3.79), and anxiety symptoms (RR 1.80, 95% CI: 0.75, 4.34) were associated with greater likelihood of response to treatment. Among individuals treated with SM-placebo, only temporal summation of pain was associated with greater likelihood of response to treatment. Conclusion Personalized medicine may be implemented in painful TMD management, and phenotype characteristics related to pain and psychological domains may predict which individuals with painful TMD are more likely to respond to the addition of serotonin and norepinephrine reuptake inhibitors to SM strategies to clinically and significantly reduce pain intensity. (TMD selfmanagement self management (SM randomized placebocontrolled placebo controlled SMduloxetine 6 mgday mg day weeks 30 SMplacebo Methods Measurement assessed sleep testing modulation RR, RR , (RR) 95 CI, CI (CI) calculated SMduloxetine, duloxetine, 133 33 1.33 056 0 56 0.56 3.17, 317 3.17 3 17 3.17) 130 1.30 063 63 0.63 2.67, 267 2.67 2 67 2.67) 148 48 1.48 057 57 0.57 3.79, 379 3.79 79 3.79) 180 80 1.80 075 75 0.75 4.34 434 4 34 SMplacebo, placebo, 9 (CI 13 1.3 05 5 0.5 31 3.1 06 0.6 26 2.6 14 1.4 37 3.7 7 18 8 1.8 07 0.7 4.3 43 1. 0. 3. 2. 4.

Abstract Stress is a contributing factor to painful temporomandibular disorders (TMD). Nevertheless, the underpinnings of this relationship are not fully understood. Objective To investigate the effects of acute mental stress on conditioned pain modulation (CPM) in TMD patients compared with healthy individuals. Methodology Twenty women with chronic myofascial TMD diagnosed according to the RDC/TMD and 20 age-matched healthy women had the CPM assessed before and after a stressful task using the Paced Auditory Serial Addition Task (PASAT) in a single session. Subjective stress response was assessed with the aid of visual analog scale (VAS). Pressure pain threshold (PPT) on masseter muscle was the test stimulus (TS) and immersion of the participant’s hand on hot water was the conditioning stimulus (CS) - CPM-sequential paradigm. Results Healthy individuals reported PASAT are more stressful when compared with TMD patients and the stress task did not affect the CPM in neither group. Nonetheless, a negative correlation was observed between change in CPM and change in TS from baseline to post-stress session, which indicates that the greater the increase in PPT after the stress task, the greater was the decrease in CPM magnitude. The correlation was strong for healthy controls (r=- 0.72, p<0.001) and moderate for TMD patients (r=- 0.44, p=0.047). Conclusions The correlation between the change in CPM and the TS change following the stress task may possibly indicate an overlapping pathway between stress-induced analgesia/hyperalgesia and descending pain inhibition.

RESUMO JUSTIFICATIVA E OBJETIVOS: Transtorno de estresse pós-traumático é um transtorno incapacitante que pode se desenvolver após exposição ou testemunho de um evento traumático. Evidências demonstram a coexistência entre transtorno de estresse pós-traumático e condições dolorosas crônicas como a disfunção temporomandibular. Este estudo teve como objetivo revisar a literatura para descrever a relação de coexistência entre transtorno de estresse pós-traumático e disfunção temporomandibular. CONTEÚDO: Foi realizada uma busca não sistemática nas bases de dados Pubmed, BVS e LILACS para estudos avaliando a relação entre transtorno de estresse pós-traumático e disfunção temporomandibular. Foram selecionados estudos clínicos publicados nos últimos 10 anos e que apresentassem critério diagnóstico validado para a disfunção temporomandibular e transtorno de estresse pós-traumático. Seis trabalhos foram incluídos na revisão. Os resultados demonstraram que o transtorno de estresse pós-traumático ocorre frequentemente em pacientes com disfunção temporomandibular e ao mesmo tempo, uma maior prevalência de disfunção temporomandibular é encontrada em indivíduos com transtorno de estresse pós-traumático. Há uma tendência indicando uma associação maior entre transtorno de estresse pós-traumático e dor muscular que dor na articulação temporomandibular. Presença do transtorno de estresse pós-traumático modula o nível de comprometimento físico, psicológico e comportamental em indivíduos com disfunção temporomandibular e pode predizer início desta condição dolorosa. CONCLUSÃO: A revisão demonstra uma relação de coexistência complexa entre transtorno de estresse pós-traumático e disfunção temporomandibular dolorosa.

ABSTRACT BACKGROUND AND OBJECTIVES: Post-traumatic stress disorder is a disabling disorder that can be developed after a person has experienced or exposed to a traumatic event. The evidence shows the coexistence between post-traumatic stress disorder and chronic painful conditions as the temporomandibular dysfunction. This study aimed to review the literature to describe the coexistence relation between post-traumatic stress disorder and temporomandibular dysfunction. CONTENTS: A non-systematic search was carried on the Pubmed, BVS and LILACS databases on studies evaluating the relationship between post-traumatic stress disorder and temporomandibular dysfunction. Clinical studies published in the last 10 years that presented a diagnostic criterion validated for temporomandibular dysfunction and the post-traumatic stress disorder were selected. Six studies were included in the review. The results showed that the post-traumatic stress disorder often occurs in patients with temporomandibular dysfunction and, at the same time, a higher prevalence of temporomandibular dysfunction is found in individuals with post-traumatic stress disorder. There is a trend for a larger connection between post-traumatic stress disorder and muscular pain than pain in the temporomandibular joint. The presence of post-traumatic stress disorder modulates the level of physical, psychological and behavioral involvement in individuals with temporomandibular dysfunction, and can predict the onset of this painful conditions. CONCLUSION: The review shows a complex coexistence between post-traumatic stress disorder and painful temporomandibular dysfunction.