Neural Mechanisms of Light Driven Analgesia

Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

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 Design

Phase
N/A
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Intervention Model Description
The same sequence of light will be presented to all participants.
Primary Purpose
Other
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: 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.
  • 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.

Recruiting Locations

University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599
Contact:
Matthew Mauck, MD, PhD
919-966-5136
matt_mauck@med.unc.edu

More Details

Status
Recruiting
Sponsor
University of North Carolina, Chapel Hill

Study Contact

Matthew Mauck, MD, PhD
919-966-5136
matt_mauck@med.unc.edu

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.