Endogenous Pain Inhibition Deficiency in Chronic TMD Pain (TMD-CPM)

The Role of Endogenous Pain Inhibition Deficiency in Chronic TMD Pain Pathophysiology

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Temporomandibular Disorders (TMD)
• Intervention / Treatment: Other: Pain modulation testing

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Carla Campbell; Phone Number: (612-625-6976; Email: camp2757@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • University of Minnesota
      • Contact: Carla Campbell

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

"1- Chronic Temporomandibular disorder (TMD) pain group 2- Age- and sex-matched pain-free controls"

Description

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. "

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chronic Temporomandibular disorder (TMD) pain group	Other: Pain modulation testing; During the visit, noxious heat stimuli will be applied bilaterally to the face and distant body sites as part of conditioned pain modulation (CPM) testing. The test stimuli will be individually tailored to be moderately painful, while the conditioning stimulus will vary in intensity: moderately painful, non-painful, and sham heat. Participants will also record daily TMD pain intensity ratings for seven days before and after the visit.
Age- and sex-matched pain-free controls	Other: Pain modulation testing; During the visit, noxious heat stimuli will be applied bilaterally to the face and distant body sites as part of conditioned pain modulation (CPM) testing. The test stimuli will be individually tailored to be moderately painful, while the conditioning stimulus will vary in intensity: moderately painful, non-painful, and sham heat. Participants will also record daily TMD pain intensity ratings for seven days before and after the visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conditioned pain modulation (CPM) effect	The CPM effect is manifested as a reduction of pain intensity evoked by a test stimulus (Ts) presented concurrently or right after a painful conditioning stimulus (Cs) applied to a distant body site.	3.5 hours single in-person visit
The relationship between daily pain intensity fluctuation and endogenous pain modulation (EPM) efficiency	The daily presentation of chronic TMD pain is variable, especially in those presenting with pain that affects their daily activities. This variability could be partially attributed to the varying efficiency of EPM in this patient population.	14 days: 7 days before and 7 days after the in-person visit

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Estephan Moana-Filho, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2024
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): December 15, 2026

Study Registration Dates

• First Submitted: September 24, 2024
• First Submitted That Met QC Criteria: September 24, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Healthy volunteers; Chronic pain; Temporomandibular disorders (TMD)
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Stomatognathic Diseases; Muscular Diseases; Joint Diseases; Jaw Diseases; Mandibular Diseases; Craniomandibular Disorders; Myofascial Pain Syndromes; Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome
• Other Study ID Numbers: STUDY00022663

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No