Neural Mechanisms of Light Driven Analgesia

NCT07245303 | Recruiting

• 2 other identifiers: 24-2288RM1NS140200-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Musculoskeletal Pain; Fibromyalgia; Healthy Controls Group - Age and Sex-matched

Keywords

functional connectivity; colored light analgesia; functional magnetic resonance imaging; quantitative sensory testing

Outcome Measures

Primary Outcomes (3)

• Resting State Functional Connectivity-seed Voxel Analysis in Participants with cMSP and Healthy Controls

  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

  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

  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 Outcomes (3)

• Pressure Pain Threshold

  Within ~2 hours pre-scan

• Temporal Summation

  Within ~2 hours pre-scan

• Conditioned Pain Modulation

  Within ~2 hours pre-scan

Study Arms (6)

Light Sequence 1

EXPERIMENTAL

The sequence of stimulus presentation for resting state scans will be Static Green for 8 minutes then Equal Energy White for 8 minutes then S-cone modulating stimuli for 8 minutes.

Other: S-cone modulating visual stimulus; Other: Equal Energy White Visual Stimulus; Other: Green light visual stimulus (S-OFF); Other: Evoked Pressure Pain Stimulus

Light Sequence 2

EXPERIMENTAL

The sequence of stimulus presentation for resting state scans will be Equal Energy White for 8 minutes then Static Green for 8 minutes then S-cone modulating stimuli for 8 minutes.

Other: S-cone modulating visual stimulus; Other: Equal Energy White Visual Stimulus; Other: Green light visual stimulus (S-OFF); Other: Evoked Pressure Pain Stimulus

Light sequence 3

EXPERIMENTAL

The sequence of stimulus presentation for resting state scans will be Equal Energy White for 8 minutes then S-cone modulating for 8 minutes then Static Green stimuli for 8 minutes

Other: S-cone modulating visual stimulus; Other: Equal Energy White Visual Stimulus; Other: Green light visual stimulus (S-OFF); Other: Evoked Pressure Pain Stimulus

Light Sequence 4

EXPERIMENTAL

The sequence of stimulus presentation for resting state scans will be Equal Energy White for 8 minutes then S-cone modulating for 8 minutes then Static Green for 8 minutes

Other: S-cone modulating visual stimulus; Other: Equal Energy White Visual Stimulus; Other: Green light visual stimulus (S-OFF); Other: Evoked Pressure Pain Stimulus

Light Sequence 5

EXPERIMENTAL

The sequence of stimulus presentation for resting state scans will be S-cone modulating for 8 minutes then Static Green for 8 minutes then Equal Energy White stimuli for 8 minutes

Other: S-cone modulating visual stimulus; Other: Equal Energy White Visual Stimulus; Other: Green light visual stimulus (S-OFF); Other: Evoked Pressure Pain Stimulus

Light Sequence 6

EXPERIMENTAL

The sequence of stimulus presentation for resting state scans will be Static Green for 8 minutes, S-cone modulating for 8 minutes, then Equal Energy White for 8 minutes

Other: S-cone modulating visual stimulus; Other: Equal Energy White Visual Stimulus; Other: Green light visual stimulus (S-OFF); Other: Evoked Pressure Pain Stimulus

Interventions

S-cone modulating visual stimulus OTHER

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.

Light Sequence 1; Light Sequence 2; Light Sequence 4; Light Sequence 5; Light Sequence 6; Light sequence 3

Equal Energy White Visual Stimulus OTHER

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.

Light Sequence 1; Light Sequence 2; Light Sequence 4; Light Sequence 5; Light Sequence 6; Light sequence 3

Green light visual stimulus (S-OFF) OTHER

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.

Light Sequence 1; Light Sequence 2; Light Sequence 4; Light Sequence 5; Light Sequence 6; Light sequence 3

Evoked Pressure Pain Stimulus OTHER

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.

Light Sequence 1; Light Sequence 2; Light Sequence 4; Light Sequence 5; Light Sequence 6; Light sequence 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• additional participants without chronic MSP will be recruited with diagnosed congenital stationary night blindness

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

Musculoskeletal Pain; Fibromyalgia

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Matthew Mauck, MD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Mauck, MD, PhD

CONTACT

919-966-5136; matt_mauck@med.unc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Light stimuli will be presented in random sequence

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): January 31, 2030
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: At the time of manuscript publication or within 1 year of study completion.
• Access Criteria: The data will be made available on an NIH approved repository.

Locations

US (1)