An Open Label Study Assessing REN Treatment in Headache Management in Temporomandibular Disorders

Temporomandibular disorders (TMD) encompass a group of conditions involving the masticatory muscles, temporomandibular joint (TMJ), and associated structures. TMD is the most common cause of non-odontogenic orofacial pain and is the second most commonly occurring musculoskeletal condition. Up to 70% of the general population experiences signs and/or symptoms of TMD, with headache presenting as one of the most common manifestations. Recent studies highlight the comorbid presence of headache and TMD, hypothesizing that a relationship likely exists between the two conditions. Headache severity has also been associated with the number of TMD symptoms such that the prevalence of headache in TMD patients. A key mechanism underlying both TMD and migraine is the deficiency in Conditioned Pain Modulation (CPM), a descending inhibitory pathway that regulates pain processing. CPM impairment has been implicated in chronic pain states, including both migraine and TMD, contributing to their frequent co-occurrence and shared pathophysiology. Remote Electrical Neuromodulation (REN) is an emerging non-pharmacological intervention that exerts its analgesic effects by activating the CPM system, which is deficient in individuals with TMD and migraine. The Nerivio REN wearable device is FDA-cleared for acute and/or migraine prevention, in patients 8 years of age or older. Given the evidence linking CPM dysfunction to TMD pathogenesis, REN presents a promising therapeutic approach to addressing both the underlying pain dysregulation and symptom burden in affected patients.

Inclusion Criteria: 1. Is of 12 years of age and older (inclusive; of any gender, race, or ethnicity) 2. Meets diagnostic criteria for chronic TMD (Myalgia and/or Arthralgia) based on the Diagnostic Criteria for TMD (DC/TMD) 3. Has experienced TMD pain for at least 6 months 4. Has experienced TMD pain at level ≥4 on a 0-10 scale for at least 10 days of the last 30 days 5. Commits to not making any changes to TMD treatment regime (medication and/or non-medication), including not adding or removing treatment, and if on any existing treatment then maintaining the same treatment type, dosage, and frequency from 3 months prior to enrollment to study completion 6. Naïve to REN treatment 7. Willing and able to understand and comply with all study procedures and be available for the duration of the study 8. Has their own smartphone or tablet device that is connected to the internet 9. Provides a signed and dated informed consent form Exclusion Criteria: 1. Has any of the following medical conditions: 1.1 Uncontrolled seizures/epilepsy 1.2 Benign and malignant TMJ and masticatory muscle tumors 1.3 Presence of implanted electrical device 2. Has experienced facial trauma or orofacial surgery within 6 weeks prior to the Screening and Baseline Visit 3. Is undergoing current active orthodontic treatment 4. Currently being treated with chemotherapy or radiation therapy 5. Meets the ICHD-3 diagnostic criteria for migraine with or without aura, either chronic or non-chronic migraine 6. Currently taking an opioid medication, whether episodically or daily, within 30 days prior to the Screening and Baseline Visit 7. Has been treated with another investigational drug or treatment within 30 days prior to the Enrollment Visit 8. Taking more than one prescription drug for the treatment of pain (including all types of drugs and modalities, e.g. pill, spray, injection) Note that this criterion does not refer to drug-free based treatments (including split therapy, physical therapy, acupuncture, massage therapy, biofeedback, CBT, or transcutaneous electrical nerve stimulation) for the treatment of pain, which may be used (single or multiple treatments) as long as not changed throughout the study. 9. Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study