Neural Mechanisms of Light Driven Analgesia

NCT ID: NCT07245303

Last Updated: 2026-01-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-01

Study Completion Date

2030-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Light stimuli will be presented in random sequence
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Light Sequence 1

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.

Group Type EXPERIMENTAL

S-cone modulating visual stimulus

Intervention Type 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.

Equal Energy White Visual Stimulus

Intervention Type 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.

Green light visual stimulus (S-OFF)

Intervention Type 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.

Evoked Pressure Pain Stimulus

Intervention Type 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 2

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.

Group Type EXPERIMENTAL

S-cone modulating visual stimulus

Intervention Type 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.

Equal Energy White Visual Stimulus

Intervention Type 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.

Green light visual stimulus (S-OFF)

Intervention Type 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.

Evoked Pressure Pain Stimulus

Intervention Type 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 3

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

Group Type EXPERIMENTAL

S-cone modulating visual stimulus

Intervention Type 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.

Equal Energy White Visual Stimulus

Intervention Type 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.

Green light visual stimulus (S-OFF)

Intervention Type 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.

Evoked Pressure Pain Stimulus

Intervention Type 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 4

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

Group Type EXPERIMENTAL

S-cone modulating visual stimulus

Intervention Type 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.

Equal Energy White Visual Stimulus

Intervention Type 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.

Green light visual stimulus (S-OFF)

Intervention Type 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.

Evoked Pressure Pain Stimulus

Intervention Type 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 5

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

Group Type EXPERIMENTAL

S-cone modulating visual stimulus

Intervention Type 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.

Equal Energy White Visual Stimulus

Intervention Type 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.

Green light visual stimulus (S-OFF)

Intervention Type 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.

Evoked Pressure Pain Stimulus

Intervention Type 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 6

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

Group Type EXPERIMENTAL

S-cone modulating visual stimulus

Intervention Type 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.

Equal Energy White Visual Stimulus

Intervention Type 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.

Green light visual stimulus (S-OFF)

Intervention Type 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.

Evoked Pressure Pain Stimulus

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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.


-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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthew Mauck, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Matthew Mauck, MD, PhD

Role: CONTACT

919-966-5136

Facility Contacts

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Matthew Mauck, MD, PhD

Role: primary

919-966-5136

Other Identifiers

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RM1NS140200-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

24-2288

Identifier Type: -

Identifier Source: org_study_id

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