Neurostimulation in Temporomandibular Disorders (TMD) Patients

Temporomandibular disorders (TMD) are musculoskeletal pain conditions characterized by pain
in the temporomandibular joint and/or the masticatory muscles. TMD are amongst the most
common chronic musculoskeletal conditions affecting 6 to 12% of the general population yet
there are no medicines approved specifically for its treatment. TMD cause substantial
suffering and TMD pain is the most common symptom that compels patients to seek therapy. One
study found average ratings of pain intensity due to TMD of 4.3 on a 10-point scale, similar
to the averages reported for chest pain and back pain. Studies consistently find that TMD
has a pronounced impact on quality of life. Thus, a new successful approach to TMD therapy
would have a significant clinical and economic impact.

Caloric vestibular stimulation (CVS) is a routine diagnostic test for the assessment of
vestibular function and Central nervous system pathology. It is usually conducted by
instilling cold or warm water into the external ear canal and has been shown to activate
anterior cingulate, temporoparietal and insular cortices. In addition to its use as a
diagnostic test, CVS has also been shown to reduce pain in several chronic conditions
including migraine, phantom limb pain, spinal cord injury, thalamic pain, and complex
regional pain syndrome.

Central sensitization is a common feature of the pain conditions shown to be alleviated by
CVS. It is a dysfunctional state of the central nervous system in which pain is no longer
coupled to a noxious peripheral stimulus. In the presence of central sensitization the
response to a noxious stimulus is exaggerated and prolonged (hyperalgesia) and may involve
areas outside the site of injury (secondary hyperalgesia). Pain can also arise spontaneously
and can be elicited by innocuous stimuli (allodynia). While the neural mechanisms underlying
the development of TMD are poorly understood, there is accumulating evidence that central
sensitization plays a critical role in TMD pathogenesis. It has been proposed that there is
a cyclical process in which TMD pain results in central sensitization that in turn
predisposes patients to more pain. Thus any treatment that reverses central sensitization
should in turn result in a decrease in pain.

Caloric vestibular stimulation (CVS) is a safe and effective procedure used for the
diagnosis of brainstem injury and for balance assessment. As noted already, there have been
intriguing observations in the literature suggesting that caloric vestibular stimulation can
lead to the abatement of pain. When a caloric stimulation (warm or cool relative to body
temperature) is applied to the ear canal, conduction (primarily via dense bone) to the inner
ear, and in particular the prominence of the lateral semicircular canal (SCC), sets up
convection currents in the endolymph. The resultant deformation of the cupula (membrane
spanning the ampula of the SCC) leads to a phasic change in the tonic firing rate of hair
cells at the base of the cupula, thereby altering the firing rate of the afferents of the
vestibular nerve (thus a device delivering CVS may be viewed as a class of neurostimulator).
The afferents map to nuclei in the brainstem (as well as some phylogenetically ancient,
direct connections, e.g. to the thalamus and hippocampus) and then to the fastigial nuclei
in the cerebellum. It is hypothesized that the method of action of CVS on pain relates to
alteration of the phasic firing rate in the vestibular nerve afferents, which in turn alters
the activation of the receiving areas (brainstem and cerebellum).

The primary impediment to therapeutic applications of CVS has been the lack of a clinical
device that provides controlled, prolonged, and repeatable caloric stimulation. The use of
"ice water" irrigation using syringes or even the water/air irrigators used in balance
studies are not practical for treatment regimens that extend up to 10 minutes. Further, the
applicants believe that a controlled, time-varying thermal waveform is essential to avoid
the effects of adaptation of the cupula, which then attenuates control of the phasic firing
rate of the hair cells.

Inclusion Criteria:

- Aged 18-65 years

- English speaking

- Females with chronic TMD

Exclusion Criteria:

- History of any of the following: Terminal, progressive and /or unstable medical
illness; Previous head or neck surgery for neoplasm; current chemotherapy or
radiation therapy; facial trauma or orofacial surgery within the last 6 weeks;
seizures, history of drug or alcohol abuse; Otologic disorders including chronic
vertigo, chronic tinnitus, otitis external, otitis media, mastoiditis and tympanic
membrane perforation; Stroke, transient ischemia attacks or Arnold- Chiari
malformation; significant cardiac or respiratory disease; epilepsy or neurological
disorders such as dementia, brain injury, and brain tumor

- Subjects who score ≥ 31 on the Becks depression inventory (performed at first
appointment)

- History of or current destructive nerve therapies, defibrillator, pacemakers, deep
brain stimulator, or Implantable nerve stimulators

- Utilization of other alternative or complementary therapies during the study period

- Participation in a clinical trial involving the use of a clinical devise in the last
30 days

- Women who are currently pregnant or nursing.

- Patients who are left handed.

- Current orthodontic treatment.

- Use of an opiate in the 48 hour period preceding the baseline study visit

- The use of anti-histamines 6 hours before, during or immediately after the treatment
period

- The use of anti-nausea or anti-vertigo drugs 6 hours before or during the treatment
period