Causal Mediation in the Development of Painful Temporomandibular Disorder

We explored causal mediation of sleep quality and perceived stress in development of painful temporomandibular disorder (TMD). Sleep quality and perceived stress were assessed at baseline and quarterly intervals thereafter in 2,737 initially TMD-free adults in the Orofacial Pain Prospective Evaluation and Risk Assessment study (OPPERA) prospective cohort study. During follow-up, incident TMD cases were classified using research diagnostic criteria. Mediation analysis was conducted using a weighted Cox proportional hazards regression model that estimated hazard ratios (HRs) and 95% confidence limits (CL) of first-onset TMD. Models determined whether: 1) poor sleep quality during follow-up mediated the effect of baseline perceived stress on first-onset TMD, and 2) perceived stress during follow-up mediated the effect of baseline poor sleep quality on first-onset TMD. In both analyses, the total effect was decomposed into natural direct and indirect effects. Poor baseline sleep quality led to heightened perceived stress that then contributed to TMD development. When the total effect of poor sleep quality (HR = 2.10, CL = 1.76, 2.50) was decomposed, 34% of its effect was mediated by perceived stress (indirect effect HR = 1.29, CL = 1.06, 1.58). The effect of perceived stress on first-onset TMD was not mediated by sleep quality. Improving sleep may avert escalation of stress, limiting effects of both factors on TMD development.

Causal mediation analysis highlights mechanisms by which poor sleep quality promotes development of TMD. First, poor sleep quality exerts a direct effect on pain. Second, it triggers a heightened perception of stress, which acts as an intermediate factor in the causal pathway between poor sleep quality and first-onset TMD pain.