NCT07245303

Neural Mechanisms of Light Driven Analgesia

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: University of North Carolina, Chapel Hill · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

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.

Conditions

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

Interventions

Type	Name	Description
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	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.
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.

Timeline

• Start date: 2026-02-01
• Primary completion: 2030-01-31
• Completion: 2030-01-31
• First posted: 2025-11-24
• Last updated: 2026-01-13

Locations

1 site across 1 country: United States