RESUMEN
BACKGROUND: Conditioned pain modulation (CPM) is a potential predictor of treatment response that has not been studied in temporomandibular disorders (TMD). OBJECTIVES: We conducted a randomised, double-blind, placebo-controlled trial (RCT) of duloxetine in addition to self-management (SM) strategies to investigate its efficacy to reduce pain intensity in painful TMD patients. Moreover, we investigated whether baseline CPM would predict the duloxetine efficacy to reduce TMD pain intensity. METHODS: Eighty participants were randomised to duloxetine 60 mg or placebo for 12 weeks. The primary outcomes were the change in the pain intensity from baseline to week-12 and CPM-sequential paradigm at baseline. Safety, physical and emotional functioning outcomes were also evaluated. RESULTS: Of 80 participants randomised, 78 were included in intention-to-treat analysis. Pain intensity decreased for SM-duloxetine and SM-placebo but did not differ between groups (p = .82). A more efficient CPM was associated with a greater pain intensity reduction regardless of the treatment group (p = .035). Physical and emotional functioning did not differ between groups, but adverse events (p = .014), sleep impairment (p = .003) and catastrophizing symptoms (p = .001) were more prevalent in SM-duloxetine group. CONCLUSION: This study failed to provide evidence of a beneficial effect of adding duloxetine to SM strategies for treatment of painful TMD. Nonetheless, this RCT has shown the feasibility of applying pain modulation assessment to predict short-term treatment response in painful TMD patients, which confirms previous finds that CPM evaluation may serve a step forward in individualising pain treatment.
Asunto(s)
Automanejo , Trastornos de la Articulación Temporomandibular , Humanos , Método Doble Ciego , Clorhidrato de Duloxetina/uso terapéutico , Dolor/complicaciones , Trastornos de la Articulación Temporomandibular/tratamiento farmacológico , Trastornos de la Articulación Temporomandibular/complicaciones , Resultado del TratamientoRESUMEN
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.
RESUMEN
BACKGROUND: Previous evidence indicates significant association between genetic polymorphisms and phenotypes related to pain sensitivity in patients with temporomandibular disorders (TMD). Despite the important advances in cataloguing diverse factors such as sleep disorders, anxiety and depression, the interrelated mechanisms of painful TMD aetiopathogenesis still need investigation. OBJECTIVES: This case-control study aimed to evaluate the influence of genetic polymorphisms (rs6296, rs6295, rs1799971, rs4680, rs4633, rs4818) and psychosocial factors on the mechanical pain sensitivity and endogenous pain modulation in women with painful TMD and asymptomatic controls. METHODS: We evaluated six independent variables: anxiety levels, depression, stress, sleep quality, pain catastrophising and genetic polymorphisms, and four dependent variables: mechanical pain threshold (MPT), pressure pain threshold (PPT), wind-up ratio (WUR) and conditioned pain modulation (CPM) collected at masseter (trigeminal) and hand (spinal) areas in a sample of 95 painful TMD patients and 85 controls. A regression model was used to test the possible effect of the independent variables on dependent variables. RESULTS: The regression model was significant for MPT (F11,168 = 9.772; R2 = .390). Painful TMD diagnoses and sleep quality were associated with trigeminal MPT (B coefficient = -.499; and B coefficient = -.211, respectively). WUR was associated with rs6295 and rs6746030, respectively, for the spinal and the trigeminal area. CONCLUSION: Genetic polymorphisms had a slight contribution to endogenous pain modulation as indicated by the significant association with WUR but did not contribute to mechanical pain sensitivity. On the other hand, the presence of painful TMD and the sleep quality contributed significantly to mechanical pain sensitivity.