Duloxetine for Treatment of Painful Temporomandibular Joint Disorder

The proposed clinical trial will evaluate the analgesic and adverse effects of duloxetine, a serotonin and norepinephrine reuptake inhibitor, in comparison to placebo in patients with temporomandibular joint disorder (TMJD). Duloxetine is approved as an antidepressant and has been shown effective in the chronic pain conditions of fibromyalgia and diabetic neuropathy. Decrease in pain and dysfunction and improvement in quality of life and global satisfaction will be assessed over 6 weeks. Successful demonstration of a therapeutic effect may provide a basis for clinical use of duloxetine in patients with painful TMJD.

Background

TMJD is a heterogeneous family of musculoskeletal disorders associated with the temporomandibular joint, the periauricular region, and the muscles of the head and neck. TMJD has been identified as a major cause of nondental, chronic pain in the craniofacial region, second only to headache (NIH Technology Assessment Conference, 1997). Although few population-based epidemiological studies have been conducted, studies report the prevalence of TMJD as up to 20% in the adult population (Dworkin et al 1990, Schiffman et al 1990). Dworkin and colleagues conducted a series of studies of TMJD using valid and reliable examination and survey procedures (Von Korff et al 1988, Dworkin et al 1990, Carlsson and LeResche 1995) and identified 12.1% of the test population with painful TMJD with a female to male ratio of approximately 7:1. They also found the annual incidence of developing TMJD to be just over 2% with females tending to show a higher incidence rate than males (Von Korff et al 1993). Hence, TMJD is common in the general population, but it has also been reported that about 20% of patients with early signs and symptoms of TMJD will progress to a persistent pain state (Schiffman et al 1990).

Several studies of TMJD suggest that patients exhibit a state of CNS hypersensitivity similar to that reported in fibromyalgia (Maixner et al 1995, Maixner et al 1998, Sarlani and Greenspan 2003, Sarlani et al 2004) that contributes to the predicted widespread characteristics of the pain. Genetic factors that impact increased pain sensitivity, psychological traits and sex differences, and often coupled with environmental stress, may result in a phenotype that is vulnerable to musculoskeletal disease and susceptible to selective pharmacological treatment.

In addition to female gender, two other factors predict an elevated incidence of these disorders: a history of musculoskeletal pain at other body sites and quality of life symptoms typically associated with depression (Von Korff et al 1988, Raphael and Marbach 2001, John et al 2003). Patients diagnosed with fibromyalgia often exhibit concurrent orofacial symptomatology that mimics TMJD (Ta et al 2002, Sarlani and Greenspan 2003, Sarlani et al 2004). These observations and findings suggest that drugs useful for depression, affecting musculoskeletal systems, and effective in improving central monoaminergic neurotransmission, are prime candidates for the treatment of TMJD. For these reasons, we hypothesize that selective noradrenergic or combined noradrenergic and serotonin reuptake inhibitors should be effective for TMJD.