Neural Mechanisms of Light Driven Analgesia

May 8, 2026 updated by: University of North Carolina, Chapel Hill
The goal of this study will be to understand the biological mechanisms that are responsible to light-driven analgesia. Light presented to the retina has been shown to have pain relieving properties in pre-clinical and clinical studies. In this study the investigators will evaluate the functional connectivity between subcortical visual areas and non-image forming brain areas that are involved in pain sensation. The investigators will also evaluate how three colored light stimuli presented to the retina results in changes in whole brain evoked activation patterns in participants with chronic musculoskeletal pain and in healthy controls. The investigators will also assess while brain evoked activation patterns in response to a pressure pain stimulus in the presence of three light stimuli in individuals with chronic musculoskeletal pain and healthy controls.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The investigators will recruit 30 participants with chronic musculoskeletal pain (cMSP) and 30 healthy, matched controls. Participants will undergo a comprehensive assessment of important covariates that influence pain experience. Individuals will then undergo quantitative sensory testing that will be used to psychophysically assess pain sensitivity and conditioned pain modulation (CPM) immediately prior to the scanning session. Individuals will then undergo fitting of a rapid inflation pressure cuff on the left calf to achieve the same level of pain among each participant (who may have different pain sensitivity). Once these settings are established, participants undergo MRI scanning per the protocol described below. Following each scan block, a brief pain assessment will be performed to determine pain severity (0-100 visual analog scale) to serve as a covariate for our proposed analyses (as pain can change over the course of imaging) and will enable correlation of BOLD signal change to pain in exploratory analyses designed to validate our mechanistic discoveries. The imaging data will then be pre-processed to ensure data quality and assurance and then analyzed to determine the functional connectivity and the evoked brain activation patterns.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina at Chapel Hill
        • Contact:
        • Principal Investigator:
          • Matthew Mauck, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria for participants with cMSP and healthy controls (n=30)

  • Adults ≥18 years of age.
  • Individuals who do not have any plans for medication or treatment changes for the next 3 months.
  • Participants must be willing and able to undergo an MRI.
  • Participants must not be claustrophobic
  • Participants must be alert and oriented and able to provide informed consent.
  • Individuals must be able to speak and read English.

Inclusion Criteria for participants with cMSP only (n=30)

  • To be eligible, participants must have a score of ≥7 on the Widespread pain index (WPI) and ≥5 on the symptom severity scale (SSS), or 4-6 on the WPI and ≥9 on the SSS in the 2016 Fibromyalgia Questionnaire.
  • Pain symptoms must have been present for 3 months or longer.
  • Pain must be present in 4 out of 5 body regions.
  • Individuals enrolled will have an average pain severity ≥4 on the 0-10 NRS over the month prior to enrollment to recruit individuals with moderate to severe chronic MSP.

Inclusion Criteria for Participants with Congenital Stationary Night Blindness (n=2)

-2 additional participants without chronic MSP will be recruited with diagnosed congenital stationary night blindness

Exclusion Criteria:

  • Presence of retinal vision disorders or conditions resulting in vision impairment.
  • Patient-reported photosensitivity, photophobia, or aversion (as may occur in autoimmune diseases such as systematic lupus erythematosus).
  • Disorders including uveitis, cataracts, color-blindness, history of seizure disorder.
  • Plans for analgesic treatment plan changes in next 3 months (surgery, analgesic medication changes, injections, pain procedures, etc).
  • Prisoner Status.
  • Pregnancy.
  • Contraindications to MRI imaging. These include the presence of implanted/embedded ferromagnetic materials, implanted medical devices that are not MRI compatible, and claustrophobia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Light sequence during imaging
The sequence of stimulus presentation for resting state scans will be Equal Energy White (with luminance modulation) for 8 minutes then Static Green for 8 minutes, followed by an anatomical scan, then S-cone modulating stimuli for 8 minutes.
Other: S-cone modulating visual stimulus
The investigators will deliver a uniform wide-field, S-cone modulating stimulus via a fiberoptic, MRI-safe visual stimulator. This stimulus approximates the appearance of white but modulates the S-cone, driving the S-ON and S-OFF pathways by alternating two lights at 19 Hz using a mixture of light emitting diodes (LEDs), including those embedded in our stimulus with spectral peaks of 405, 565, and 660 nm. This stimulus will differentially activate the S-cones where, between the two phases the ratio of S-cone activity is 100. The frequency alternating between the two lights, 19 Hz, was chosen because retinal ganglion cells in the retina still respond robustly but above the cortical perceptual flicker detection threshold.
Other: Green light visual stimulus (S-OFF)
The investigators will deliver a uniform wide-field, green light modulating stimulus via a fiberoptic, MRI-safe visual stimulator. Static Green (565 nm) Light presented via MRI compatible light guides.
Other: Evoked Pressure Pain Stimulus
The pressure in which a rapid inflation cuff positioned over the left gastrocnemius achieves a pain severity of 40 where 0 is "no pain" and 100 is the "worst pain imaginable will be determined pre-scan and applied during the entire functional imaging acquisition to evoke a deep pressure pain.
Other: Equal Energy White Visual Stimulus
The investigators will deliver a uniform wide-field, equal-energy light stimulus via a fiberoptic, MRI-safe visual stimulator. This will serve as a reference condition in which chromatic opponency has been eliminated. This stimulus ensures that the quantal catch of each cone photoreceptor (S-, M- and L-) is held constant using a mixture of LEDs, including those embedded in our stimulus with spectral peaks of 405, 565, and 660 nm. The stimulus will modulate to nearly approximate the appearance of the S-cone modulating light.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Resting State Functional Connectivity-seed Voxel Analysis in Participants with cMSP and Healthy Controls
Time Frame: During 8 minute resting state scan as part of the ~1 hour scanning session
Functional connectivity assessed under three lighting conditions will be assessed with a seed voxel analysis with the seed region of interest set as the pregeniculate nucleus. A map of connectivity will be generated and displayed over inflated brain space. This map will be constructed by calculating the Fisher-transformed correlation coefficients between each voxel with the BOLD times series for the Pregeniculate nucleus. The higher the correlation coefficient, the stronger connectivity of each voxel to the pregeniculate. The correlation coefficient will be plotted as an map.
During 8 minute resting state scan as part of the ~1 hour scanning session
Whole Brain Evoked Activation Patterns in Response to Chromatic Stimuli Contrasted with Achromatic Stimuli in Participants with cMSP and Healthy Controls
Time Frame: During 6 minute functional imaging scan within the ~1 hour scanning protocol
A generalized linear model (GLM) using Statistical Parametric Mapping (SPM) version 12 will be constructed. Blood oxygenation level dependent (BOLD) activation signal time series collected under the dynamic S-cone modulating stimulus condition will be contrasted to those collected during the equal energy stimulus condition. SPM will be used to create a contrast vector between the two conditions and a T-map will be created where the T-statistic for the contrast at each voxel will be plotted. The larger the t-statistic for each voxel the larger the contrast between the two light conditions.
During 6 minute functional imaging scan within the ~1 hour scanning protocol
Whole Brain Evoked Activation Patterns in Response to Chromatic Stimuli Contrasted with Achromatic Stimuli in Patients with cMSP and Healthy Controls Exposed to a Pressure Pain Stimulus
Time Frame: During 6 minute functional imaging scan within the 1 hour scanning protocol
A generalized linear model (GLM) using Statistical Parametric Mapping (SPM) version 12 will be constructed. Blood oxygenation level dependent (BOLD) activation signal time series collected under the dynamic S-cone modulating stimulus condition will be contrasted to those collected during the equal energy stimulus condition in context of an evoked pressure pain stimulus. SPM will be used to create a contrast vector between the two conditions and a T-map will be created where the T-statistic for the contrast at each voxel will be plotted. The larger the t-statistic for each voxel the larger the contrast between the two light conditions.
During 6 minute functional imaging scan within the 1 hour scanning protocol

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pressure Pain Threshold
Time Frame: Within ~2 hours pre-scan
Pressure Pain Threshold is the threshold in which pain is experienced in response to increasing force applied to the trapezius measured by a pressure algometer in kilograms of force per square centimeter (kgf/cm^2). The higher the value, the higher the threshold. The maximum is 10 kgf/cm^2 and minimum is 0.
Within ~2 hours pre-scan
Temporal Summation
Time Frame: Within ~2 hours pre-scan
The investigators will evaluate temporal summation using a 40g Neuropen applied to the skin of the volar forearm and lumbar region, following a train of 10 identical stimuli (1 Hz). Participants will report retrospectively, the pain intensity of the 1st and 10th pinprick using a 0-10 numerical rating scale (NRS). 0 is the minimum and 10 is the maximum pain intensity that will be reported.
Within ~2 hours pre-scan
Conditioned Pain Modulation
Time Frame: Within ~2 hours pre-scan
Conditioned Pain modulation magnitude will be calculated as the difference in mean pressure pain threshold (kgf/cm^2) measured prior to and during the conditioning stimulus (cold water bath), with increases in pressure pain threshold during conditioning interpreted as evidence of efficient endogenous pain inhibition.
Within ~2 hours pre-scan

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of North Carolina, Chapel Hill

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Matthew Mauck, MD, PhD, University of North Carolina, Chapel Hill

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 24, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 17, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 24, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 24-2288
  • RM1NS140200-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified individual data that supports the results will be shared at the time of manuscript publication at the end of the study within 1 year of completion. The data will be shared via the NIH HEAL Ecosystem. After the data is shared, there are no plans to stop sharing the data.

IPD Sharing Time Frame

At the time of manuscript publication or within 1 year of study completion.

IPD Sharing Access Criteria

The data will be made available on an NIH approved repository.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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