Chronic PainNCT05068908
Brain Connectivity Patterns in Chronic Temporomandibular Joint Disorders
An observational study of Chronic Pain and Temporomandibular Joint Disorders, run by University of Minnesota at 1 site in United States.
Trial summary
This study addresses the timely problem of painful temporomandibular disorders (TMD), the most common cause of orofacial pain second only to tooth pain. Findings from previous studies suggest that dysregulation of connectivity within specific brain circuits is part of chronic pain pathophysiology. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Chronic Pain, Temporomandibular Joint Disorders, Temporomandibular Joint Pain
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Mar 2022to 24 Jun 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Visits include a standardized clinical examination using the Diagnostic Criteria for TMD (DC/TMD) protocol, psychosocial questionnaires completion, quantitative sensory testing (QST) using a standard protocol, endogenous pain modulation (EPM) testing and a multi-modal Magnetic Resonance Imaging (MRI) data acquisition.
Who may be able to join
- Provide signed and dated informed consent form.
- Willing to comply with all study procedures and be available for the duration of study participation.
- All participants will be females (biological sex by self-report) between ages 18 to 65 years (inclusive), as this includes the majority of the patient population at risk for chronic TMD pain.
- Cases and controls will be matched for age within ±3 years, and all participants must be able to understand commands in English to follow study procedures (e.g., during sensory testing).
- Pain-free controls
- TMD-Pain screener score less than 3 out of 7 (Screener available as part of the DC/TMD)
Show all 23Show fewer
- No previous diagnosis for the most common pain-related TMD as defined in the DC/TMD criteria (myalgia, arthralgia, headache attributed to TMD)
- No significant orofacial pain (jaw pain, TMJ pain) in past 3 months ("significant" meaning 5 or more days in any month or any pain during the past month)
- 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
- Not meeting any of the most common pain-related TMD diagnosis as described in the DC/TMD criteria (myalgia, arthralgia, headache attributed to TMD) upon clinical examination following the DC/TMD protocol
- Chronic painful TMD cases
- TMD-pain screener score equal to or greater than 3
- Primary TMD caseness criteria: myalgia (masticatory muscle pain) based on clinical exam following the DC/TMD protocol
- Concurrent arthralgia (TMJ pain) and/or headache attributed to TMD allowed
- Myofascial pain must meet the following criteria:
- Onset >3 months, occurring >15 days/month on average for >3 months
- Minimum 10 jaw pain episodes since onset, each episode lasting at least 30 minutes and no less than 2 hours within the day, OR unremitting
- Low-impact TMD pain cases: Graded Chronic Pain Scale (GCPS) grade IIa or lower
- High-impact TMD pain cases: GCPS grade IIb or greater
- Be age 18-65 (inclusive)
- Provide a signed and dated informed consent form.
- Be willing to comply with all study procedures and be available for the duration of study participation.
- Be able to understand commands in English to follow study procedures.
Who cannot join
- Traumatic facial injury or surgery on the face/jaw, arms or hands
- Presence of pain related to dental or periodontal pathology
- Currently undergoing active orthodontic treatment
- Pregnant or nursing
- Has any of the following medical conditions by self-report:
- Renal failure or dialysis
Show all 30Show fewer
- Heart disease (examples: uncontrolled arrhythmia or hypertension, cardiomyopathy) or heart failure
- Non-allergic bronchospasm (chronic obstructive pulmonary disease and emphysema)
- Diabetes (Type I or II) that is not controlled with medication or diet
- Hyperthyroidism
- Uncontrolled seizures
- Used any injection therapy (i.e. tender or trigger point injections, steroid injections), acupuncture, biofeedback, or TENS for the management of facial pain within 2 weeks prior to the screening assessment
- If undergoing botulinum toxin injections in the head and neck areas, must be 3 months since last set of injections and refrain from this treatment until study has ended
- History of major depression or other major psychiatric disorder requiring hospitalization within the last 6 months prior to the screening assessments
- History of treatment for drug or alcohol abuse within the last 12 months
- Current pain medication use (e.g. opioids, ibuprofen, acetaminophen) that cannot be stopped <24 hours prior to each study visit
- Other conditions/diseases associated with altered pain perception: neurological or developmental disorders (dementia, autism spectrum disorder), neoplasm, multiple sclerosis, trigeminal neuralgia
- MRA contraindications including claustrophobia
- GCPS grade assigned at Visit 1 that does not match grade from screening GCPS (low-, high-impact pain) and it is not possible to assign the potential participant to the correct final group, due to the latter having met their recruitment quota
- Strictly left-handedness by self-report
- Thermal threshold for Pain-50 (determined at Visit 1) is outside the temperature range of 40-49 degrees Celsius
- Lack of access to electronic device with internet connection during the study
- Inability or unwillingness to receive daily text messages during the study
- Inability to complete at least four daily ratings between the Informed consent, Pre- visit 1 procedures and in-person visit 1
- Anything that would place the individual at increased risk or preclude the individual's full compliance with study procedures or completion of the study.
- Pregnant or nursing;
- MRI contraindications including claustrophobia;
- Adults lacking capacity to provide informed consent for themselves;
- Unable to understand instructions for sensory testing in English;
- Anything that would place the individual at increased risk or preclude the individual's full compliance with study procedures or completion of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
This study addresses the timely problem of painful temporomandibular disorders (TMD), the most common cause of orofacial pain second only to tooth pain. Findings from previous studies suggest that dysregulation of connectivity within specific brain circuits is part of chronic pain pathophysiology. This study will identify connectivity patterns within those brain circuits as potential signatures for pain- related disability in chronic TMD pain participants. New knowledge regarding these brain connectivity patterns is expected to be significant because it will support improved phenotyping of this heterogeneous participant population. It is also expected that this finding can potentially be extrapolated to other chronic pain conditions, such as back pain, migraine headache, and fibromyalgia that are frequently comorbid conditions in chronic TMD participants.
Read the detailed description
Evidence of dysregulation of brain circuits in chronic pain in general and in chronic temporomandibular disorder (TMD) pain specifically is well documented. Among putative brain circuits involved in chronic pain pathophysiology are thalamocortical brain pathways, which transmit nociceptive signals centrally from peripheral tissues. Pathways between the medial prefrontal cortex (mPFC) and the periaqueductal gray (PAG) are considered part of an antinociceptive brain circuit, since they are necessary to engage endogenous pain modulation. Dysfunction of endogenous pain modulation has been systematically reported in chronic pain patients, and a meta-analysis of clinical studies of TMD patients done by the Principal investigator and others showed increased pain facilitation and impaired pain inhibition in patients relative to pain-free controls.
Endogenous pain modulation can be assessed by psychophysical methods. For instance, pain facilitation can be assessed with temporal summation of pain (TSP) using brief noxious stimuli presented repeatedly over peripheral tissues at >0.3 Hz. Pain inhibition can be assessed with conditioned pain modulation (CPM) by presenting noxious stimuli over a body site during concurrent noxious stimuli elsewhere to induce pain inhibition. Neuroimaging studies in pain-free controls showed that functional connectivity within thalamocortical and antinociceptive brain circuits are related to increased TSP and reduced CPM responses, respectively. It is unknown if connectivity patterns within the thalamocortical and antinociceptive brain circuits are altered in chronic TMD patients, reflecting endogenous pain modulation dysfunction. Corticolimbic pathways connecting the mPFC, amygdala and nucleus accumbens are thought to play a key role in chronic pain and specifically, in emotion-driven modulation of nociceptive signals. Recently a longitudinal study showed that functional and structural connectivity patterns determined from neuroimaging data between these regions predict transition from acute to chronic back pain. A population study of TMD pain patients showed that approximately 64% of these patients also present with comorbid low back pain, thus it is possible that chronic TMD pain patients may display brain connectivity patterns that are similar to those identified in persistent back pain patients.
Functional brain connectivity is usually assessed from resting-state functional magnetic resonance imaging (fMRI), where participants lay at rest during fMRI scans to measure intrinsic functional connectivity (FC). Connectivity patterns within the thalamocortical, corticolimbic and antinociceptive circuits described above were determined using this traditional approach for FC assessment. Recent studies departed from this traditional approach and assessed FC during presentation of noxious stimuli during fMRI data acquisition and identified evoked FC changes. These studies' results suggest that noxious stimuli affect connectivity patterns in brain circuits involved in pain processing in pain-free participants and in fibromyalgia patients. Thus, it is reasonable that psychophysical testing for pain facilitation (e.g., TSP) and pain inhibition (e.g., CPM) could reflect changes in connectivity patterns within brain circuits associated with pain modulation. If confirmed, these evoked connectivity patterns identified from engaging endogenous pain modulation could serve as a "signature" for pain modulation in individuals, similar to a "functional connectome fingerprinting" demonstrated to predict fluid intelligence in healthy participants using data from the Human Connectome Project (HCP).
Taken together these results suggest new approaches to investigate dysregulation of brain circuits in chronic TMD pain with a focus on brain connectivity, that can serve as unique chronic pain "signatures" related to endogenous pain modulation function. There is a critical need to determine the potential of brain circuits' connectivity patterns to serve as signatures for pain- related disability. Addressing this critical need will provide novel ways to identify subgroups of chronic TMD pain patients who respond poorly to treatment. Closing this gap in our knowledge has reasonable potential to provide the opportunity for development of precise and valid brain imaging methods supporting refined phenotyping of chronic TMD pain patients leading to early identification of patients with poor prognosis.
Chronic pain causes suffering to more Americans than heart disease, diabetes and cancer combined, and TMD is the second most commonly occurring musculoskeletal condition resulting in pain and disability after chronic back pain. TMD affects approximately 5-12% of the population, with annual estimates of economic impact ranging between $4 billion per the NIDCR and $32 billion according to a study sponsored by the Agency for Healthcare Research and Quality . Pain-related disability significantly impacts patient's quality of life, and a subgroup of chronic TMD pain patients present with high pain-related disability, as identified by the Graded Chronic Pain Scale (GCPS), and these patients have poor prognoses - even with treatment - and greater health care costs.
About half to two-thirds of individuals with TMD seek treatment, and of those approximately 15% will develop chronic pain. Chronic TMD pain patients present with pain persisting ≥6 months, and it is well accepted that chronic TMD pain pathophysiology includes dysregulation of brain circuits. Recent evidence suggests that brain functional and anatomical characteristics, namely connectivity patterns within specific brain circuits, are related to processing, modulation and persistence of pain. Brain connectivity patterns within the thalamocortical circuit are associated with expression of endogenous pain facilitation, while connectivity patterns between prefrontal cortex and brainstem nuclei, an antinociceptive circuit, are related to endogenous pain inhibition. In addition, brain connectivity patterns within corticolimbic pathways involved in the emotion-driven modulation of nociceptive signals predict transition from acute to chronic back pain. These connectivity patterns within thalamocortical, antinociceptive, and corticolimbic brain circuits have not been described in chronic TMD patients, and it is unknown if connectivity patterns within these brain circuits can distinguish chronic TMD patients based on pain-related disability.
- Medical subject headings
- Chronic Pain, Temporomandibular Joint Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Low-impact chronic painful temporomandibular disorder (TMD) cases | Participants whose chronic painful TMD is determined to be low-impact. Visits include a standardized clinical examination using the Diagnostic Criteria for TMD (DC/TMD) protocol, psychosocial questionnaires completion, sensory and endogenous pain modulation (EPM) testing and a multi-modal Magnetic Resonance Imaging (MRI) data acquisition. | |
| High- impact chronic painful temporomandibular disorder (TMD) cases | Participants whose chronic painful TMD is determined to be high-impact. Visits include a standardized clinical examination using the Diagnostic Criteria for TMD (DC/TMD) protocol, psychosocial questionnaires completion, sensory and endogenous pain modulation (EPM) testing and a multi-modal Magnetic Resonance Imaging (MRI) data acquisition. | |
| Pain-free controls | Participants without chronic painful TMD. Visits include a standardized clinical examination using the Diagnostic Criteria for TMD (DC/TMD) protocol, psychosocial questionnaires completion, sensory and endogenous pain modulation (EPM) testing and a multi-modal Magnetic Resonance Imaging (MRI) data acquisition. | |
| Pilot study-MRI optimization group | A pilot study will be conducted separately from the "main project" for optimization of MRI parameters, where up to five participants will be recruited as a separate group to undergo only MRI sessions (single study visit). The goal is to optimize the parameters of the main project's MR imaging protocol in order to minimize imaging distortions related to the presence of the thermodes in close proximity to the field of view for the brain. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional connectivity (FC) for the thalamocortical brain circuit
Multi-modal MRI data will be used to assess functional connectivity patterns within the thalamocortical brain circuit in chronic TMD pain participants and pain free controls. Functional connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Measured: 2.5 hours
Functional connectivity (FC) for the antinociceptive brain circuit
Multi-modal MRI data will be used to assess functional connectivity patterns within the antinociceptive brain circuit in chronic TMD pain participants and pain free controls. Functional connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Measured: 2.5 hours
Functional connectivity (FC) for the corticolimbic brain circuit
Multi-modal MRI data will be used to assess functional connectivity patterns within the corticolimbic brain circuit in chronic TMD pain participants and pain free controls. Functional connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Measured: 2.5 hours
Anatomical connectivity (AC) for the thalamocortical brain circuit
Multi-modal MRI data will be used to assess anatomical connectivity patterns within the thalamocortical brain circuit in chronic TMD pain participants and pain free controls. Anatomical connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Measured: 2.5 hours
Anatomical connectivity (AC) for the antinociceptive brain circuit
Multi-modal MRI data will be used to assess anatomical connectivity patterns within the antinociceptive brain circuit in chronic TMD pain participants and pain free controls. Anatomical connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Measured: 2.5 hours
Change in anatomical connectivity of corticolimbic brain circuit
Multi-modal MRI data will be used to assess anatomical connectivity patterns within the corticolimbic brain circuit in chronic TMD pain participants and pain free controls. Anatomical connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Measured: 2.5 hours
Secondary outcomes (1)
Temporal Summation of Pain (TSP) and Conditioned Pain Modulation (CPM) responses
To assess correlations between functional connectivity and anatomical connectivity matrices and individual endogenous pain modulation responses, TSP and CPM testing will be conducted. TSP testing uses a thermal device and custom pressure algometers to deliver a single stimulus perceived as "slightly painful" by the participant, followed by 5- or 10-stimuli series repeated at 1 Hz. CPM testing uses a pressure algometer as test stimulus to deliver increasing pressure (50kPa/s rate) to the test site until the participant presses a switch signaling when the pressure sensation first becomes painful. The conditioning stimulus (CS) used to elicit pain inhibition for CPM testing is tonic noxious contact heat applied to the non-dominant volar forearm. CPM testing is also done in triplicate on two occasions: at baseline and during CS applied to the forearm. TSP and CPM responses will be assessed during Visit 2 of the study and reported as percentage values.
Measured: 3.5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2021
- Study start2 Mar 2022
- Primary completion24 Jun 2026
- Study completion24 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Estephan J Moana-Filho, DDS, MS, PhD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05068908
- Sponsor's protocol ID
- DENT-2020-29282
- Status last verified
- Jul 2026
- First submitted
- 25 Sep 2021
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Connectivity Patterns in Chronic Temporomandibular Joint Disorders
- ClinicalTrials.gov ID
- NCT05068908
- Acronym / sponsor ID
- DENT-2020-29282
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 2 Mar 2022 (actual)
- Primary completion
- 24 Jun 2026 (actual)
- Study completion
- 24 Jun 2026 (actual)
- First posted
- 6 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study addresses the timely problem of painful temporomandibular disorders (TMD), the most common cause of orofacial pain second only to tooth pain. Findings from previous studies suggest that dysregulation of connectivity within specific brain circuits is part of chronic pain pathophysiology. This study will identify connectivity patterns within those brain circuits as potential signatures for pain- related disability in chronic TMD pain participants. New knowledge regarding these brain connectivity patterns is expected to be significant because it will support improved phenotyping of this heterogeneous participant population. It is also expected that this finding can potentially be extrapolated to other chronic pain conditions, such as back pain, migraine headache, and fibromyalgia that are frequently comorbid conditions in chronic TMD participants.
Detailed description
Evidence of dysregulation of brain circuits in chronic pain in general and in chronic temporomandibular disorder (TMD) pain specifically is well documented. Among putative brain circuits involved in chronic pain pathophysiology are thalamocortical brain pathways, which transmit nociceptive signals centrally from peripheral tissues. Pathways between the medial prefrontal cortex (mPFC) and the periaqueductal gray (PAG) are considered part of an antinociceptive brain circuit, since they are necessary to engage endogenous pain modulation. Dysfunction of endogenous pain modulation has been systematically reported in chronic pain patients, and a meta-analysis of clinical studies of TMD patients done by the Principal investigator and others showed increased pain facilitation and impaired pain inhibition in patients relative to pain-free controls.
Endogenous pain modulation can be assessed by psychophysical methods. For instance, pain facilitation can be assessed with temporal summation of pain (TSP) using brief noxious stimuli presented repeatedly over peripheral tissues at >0.3 Hz. Pain inhibition can be assessed with conditioned pain modulation (CPM) by presenting noxious stimuli over a body site during concurrent noxious stimuli elsewhere to induce pain inhibition. Neuroimaging studies in pain-free controls showed that functional connectivity within thalamocortical and antinociceptive brain circuits are related to increased TSP and reduced CPM responses, respectively. It is unknown if connectivity patterns within the thalamocortical and antinociceptive brain circuits are altered in chronic TMD patients, reflecting endogenous pain modulation dysfunction. Corticolimbic pathways connecting the mPFC, amygdala and nucleus accumbens are thought to play a key role in chronic pain and specifically, in emotion-driven modulation of nociceptive signals. Recently a longitudinal study showed that functional and structural connectivity patterns determined from neuroimaging data between these regions predict transition from acute to chronic back pain. A population study of TMD pain patients showed that approximately 64% of these patients also present with comorbid low back pain, thus it is possible that chronic TMD pain patients may display brain connectivity patterns that are similar to those identified in persistent back pain patients.
Functional brain connectivity is usually assessed from resting-state functional magnetic resonance imaging (fMRI), where participants lay at rest during fMRI scans to measure intrinsic functional connectivity (FC). Connectivity patterns within the thalamocortical, corticolimbic and antinociceptive circuits described above were determined using this traditional approach for FC assessment. Recent studies departed from this traditional approach and assessed FC during presentation of noxious stimuli during fMRI data acquisition and identified evoked FC changes. These studies' results suggest that noxious stimuli affect connectivity patterns in brain circuits involved in pain processing in pain-free participants and in fibromyalgia patients. Thus, it is reasonable that psychophysical testing for pain facilitation (e.g., TSP) and pain inhibition (e.g., CPM) could reflect changes in connectivity patterns within brain circuits associated with pain modulation. If confirmed, these evoked connectivity patterns identified from engaging endogenous pain modulation could serve as a "signature" for pain modulation in individuals, similar to a "functional connectome fingerprinting" demonstrated to predict fluid intelligence in healthy participants using data from the Human Connectome Project (HCP).
Taken together these results suggest new approaches to investigate dysregulation of brain circuits in chronic TMD pain with a focus on brain connectivity, that can serve as unique chronic pain "signatures" related to endogenous pain modulation function. There is a critical need to determine the potential of brain circuits' connectivity patterns to serve as signatures for pain- related disability. Addressing this critical need will provide novel ways to identify subgroups of chronic TMD pain patients who respond poorly to treatment. Closing this gap in our knowledge has reasonable potential to provide the opportunity for development of precise and valid brain imaging methods supporting refined phenotyping of chronic TMD pain patients leading to early identification of patients with poor prognosis.
Chronic pain causes suffering to more Americans than heart disease, diabetes and cancer combined, and TMD is the second most commonly occurring musculoskeletal condition resulting in pain and disability after chronic back pain. TMD affects approximately 5-12% of the population, with annual estimates of economic impact ranging between $4 billion per the NIDCR and $32 billion according to a study sponsored by the Agency for Healthcare Research and Quality . Pain-related disability significantly impacts patient's quality of life, and a subgroup of chronic TMD pain patients present with high pain-related disability, as identified by the Graded Chronic Pain Scale (GCPS), and these patients have poor prognoses - even with treatment - and greater health care costs.
About half to two-thirds of individuals with TMD seek treatment, and of those approximately 15% will develop chronic pain. Chronic TMD pain patients present with pain persisting ≥6 months, and it is well accepted that chronic TMD pain pathophysiology includes dysregulation of brain circuits. Recent evidence suggests that brain functional and anatomical characteristics, namely connectivity patterns within specific brain circuits, are related to processing, modulation and persistence of pain. Brain connectivity patterns within the thalamocortical circuit are associated with expression of endogenous pain facilitation, while connectivity patterns between prefrontal cortex and brainstem nuclei, an antinociceptive circuit, are related to endogenous pain inhibition. In addition, brain connectivity patterns within corticolimbic pathways involved in the emotion-driven modulation of nociceptive signals predict transition from acute to chronic back pain. These connectivity patterns within thalamocortical, antinociceptive, and corticolimbic brain circuits have not been described in chronic TMD patients, and it is unknown if connectivity patterns within these brain circuits can distinguish chronic TMD patients based on pain-related disability.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low-impact chronic painful temporomandibular disorder (TMD) cases | – | –Participants whose chronic painful TMD is determined to be low-impact. Visits include a standardized clinical examination using the Diagnostic Criteria for TMD (DC/TMD) protocol, psychosocial questionnaires completion, sensory and endogenous pain modulation (EPM) testing and a multi-modal Magnetic Resonance Imaging (MRI) data acquisition. |
| High- impact chronic painful temporomandibular disorder (TMD) cases | – | –Participants whose chronic painful TMD is determined to be high-impact. Visits include a standardized clinical examination using the Diagnostic Criteria for TMD (DC/TMD) protocol, psychosocial questionnaires completion, sensory and endogenous pain modulation (EPM) testing and a multi-modal Magnetic Resonance Imaging (MRI) data acquisition. |
| Pain-free controls | – | –Participants without chronic painful TMD. Visits include a standardized clinical examination using the Diagnostic Criteria for TMD (DC/TMD) protocol, psychosocial questionnaires completion, sensory and endogenous pain modulation (EPM) testing and a multi-modal Magnetic Resonance Imaging (MRI) data acquisition. |
| Pilot study-MRI optimization group | – | –A pilot study will be conducted separately from the "main project" for optimization of MRI parameters, where up to five participants will be recruited as a separate group to undergo only MRI sessions (single study visit). The goal is to optimize the parameters of the main project's MR imaging protocol in order to minimize imaging distortions related to the presence of the thermodes in close proximity to the field of view for the brain. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Visits include a standardized clinical examination using the Diagnostic Criteria for TMD (DC/TMD) protocol, psychosocial questionnaires completion, quantitative sensory testing (QST) using a standard protocol, endogenous pain modulation (EPM) testing and a multi-modal Magnetic Resonance Imaging (MRI) data acquisition.
Key inclusion criteria (23 listed)
- Provide signed and dated informed consent form.
- Willing to comply with all study procedures and be available for the duration of study participation.
- All participants will be females (biological sex by self-report) between ages 18 to 65 years (inclusive), as this includes the majority of the patient population at risk for chronic TMD pain.
- Cases and controls will be matched for age within ±3 years, and all participants must be able to understand commands in English to follow study procedures (e.g., during sensory testing).
- Pain-free controls
Key exclusion criteria (30 listed)
- Traumatic facial injury or surgery on the face/jaw, arms or hands
- Presence of pain related to dental or periodontal pathology
- Currently undergoing active orthodontic treatment
- Pregnant or nursing
- Has any of the following medical conditions by self-report:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Functional connectivity (FC) for the thalamocortical brain circuit
Time frame: 2.5 hours
Multi-modal MRI data will be used to assess functional connectivity patterns within the thalamocortical brain circuit in chronic TMD pain participants and pain free controls. Functional connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Functional connectivity (FC) for the antinociceptive brain circuit
Time frame: 2.5 hours
Multi-modal MRI data will be used to assess functional connectivity patterns within the antinociceptive brain circuit in chronic TMD pain participants and pain free controls. Functional connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Functional connectivity (FC) for the corticolimbic brain circuit
Time frame: 2.5 hours
Multi-modal MRI data will be used to assess functional connectivity patterns within the corticolimbic brain circuit in chronic TMD pain participants and pain free controls. Functional connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Anatomical connectivity (AC) for the thalamocortical brain circuit
Time frame: 2.5 hours
Multi-modal MRI data will be used to assess anatomical connectivity patterns within the thalamocortical brain circuit in chronic TMD pain participants and pain free controls. Anatomical connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Anatomical connectivity (AC) for the antinociceptive brain circuit
Time frame: 2.5 hours
Multi-modal MRI data will be used to assess anatomical connectivity patterns within the antinociceptive brain circuit in chronic TMD pain participants and pain free controls. Anatomical connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
Change in anatomical connectivity of corticolimbic brain circuit
Time frame: 2.5 hours
Multi-modal MRI data will be used to assess anatomical connectivity patterns within the corticolimbic brain circuit in chronic TMD pain participants and pain free controls. Anatomical connectivity will be reported as a unitless value. Neuroimaging will be conducted during Visit 3.
1 secondary outcome
Temporal Summation of Pain (TSP) and Conditioned Pain Modulation (CPM) responses
Time frame: 3.5 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Estephan J Moana-Filho, DDS, MS, PhD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Pain and Temporomandibular Joint Disorders, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional connectivity (FC) for the thalamocortical brain circuit (time frame: 2.5 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.