Endogenous Pain Inhibition Deficiency in Chronic TMD Pain

Temporomandibular disorders (TMDs) involve a range of conditions with varied causes, affecting a large portion of the U.S. population and posing challenges for diagnosis and management, especially in chronic cases. Despite advances in understanding TMD pathophysiology, the role of central sensitization, particularly deficient endogenous pain inhibition, remains unclear. The conditioned pain modulation (CPM) test, used to assess pain inhibition in chronic TMD pain, has produced inconsistent results due to varying testing parameters. The proposed cross-sectional study will investigate the efficiency of endogenous pain inhibition in individuals with chronic TMD pain compared to controls by applying noxious and non-noxious stimuli to facial and non-facial sites. The findings aim to clarify the impact of weaker pain inhibition over the face, how the conditioning stimulus' painfulness affects inhibition and the relationship between pain inhibition and fluctuations in TMD pain intensity.


Eligibility Criteria:
Inclusion Criteria:

To be eligible to participate in this study, an individual must meet all the following criteria:

1. Provide informed consent, documented in a signed and dated form.
2. Will comply with all study procedures, including daily ratings filling before and after the in-person study visit, and be available for the study duration.
3. All participants of both genders between ages 18 to 74 years.
4. Cases and controls will be matched for age within ±5 years, and all participants must understand English commands to follow study procedures (e.g., during CPM testing).

Pain-free controls:

1. Age matching (within ±5 years)
2. No previous diagnosis for the most common pain-related TMD as defined in the DC/TMD criteria (myalgia, arthralgia, headache attributed to TMD)
3. No significant orofacial pain (jaw pain, TMJ pain) in the past 3 months (""significant"" meaning 5 or more days in any month or any pain during the past month)
4. No report of significant pain in the last 3 months elsewhere in the body (""significant"" meaning 5 or more days in any month or any pain during the past month), e.g., low back pain, fibromyalgia, migraine headaches
5. Not meeting any of the most common pain-related TMD diagnoses as described in the DC/TMD criteria (myalgia, arthralgia, headache attributed to TMD) upon clinical exam following the DC/TMD protocol

Chronic painful TMD cases:

1. Primary TMD case criteria: Myalgia (masticatory muscle pain) based on clinical exam following the DC/TMD protocol
2. Concurrent arthralgia (TMJ pain) and/or headache attributed to TMD allowed
3. Myofascial pain must meet the following criteria:

   1. Onset \>3 months, occurring \>15 days/month on average for \>3 months
   2. Minimum of 10 jaw pain episodes since onset, each lasting at least 30 minutes and no less than 2 hours within the day, OR unremitting."

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Traumatic facial injury or surgery on the face/jaw, arms, or hands
2. Presence of pain related to dental and periodontal pathology
3. Pregnant
4. Has any of the following medical conditions by self-report:

   1. Renal failure or dialysis
   2. Heart disease (examples: uncontrolled arrhythmia or hypertension, cardiomyopathy) or heart failure
   3. Non-allergic bronchospasm (chronic obstructive pulmonary disease and emphysema)
   4. Diabetes (type I or II) that is not controlled with medication or diet
   5. Hyperthyroidism
   6. Uncontrolled seizures
5. Used any injection therapy (e.g., tender or trigger point injections, steroid injections), acupuncture, biofeedback, or TENS for managing facial/jaw pain within 2 weeks before the screening assessment.
6. If undergoing botulinum toxin injections in the head and neck area, must be 3 months since the last set of injections, and refrain from this treatment until study participation has ended
7. History of major depression or other major psychiatric disorder requiring inpatient hospitalization within the last 6 months before the screening assessment
8. History of treatment for drug or alcohol abuse within the last 12 months
9. Current pain medication use (e.g., opioids, ibuprofen, acetaminophen) that cannot be stopped \<24 hours before each study visit
10. Other conditions/diseases associated with altered pain perception: neurological or development disorders (dementia, autism spectrum disorder), neoplasm, multiple sclerosis, trigeminal neuralgia
11. Adults lacking the capacity to provide informed consent for themselves
12. Unable to understand instructions for sensory testing in English.
13. Thermal threshold for Pain-50 (pre-determined at the beginning of visit 1) is outside the temperature range of 40ºC to 49ºC
14. Inability to complete at least four daily ratings between the Informed consent, Pre-visit 1 procedures, and in-person visit 1
15. Lack of access to electronic devices with internet connection during the study participation
16. Anything that would place the individual at increased risk or preclude the individual's full compliance with study procedures or completion of the study. "