Corticospinal pain processing and modulation in fibromyalgia: a combined brain-cord fMRI study
Poster No:
1328
Submission Type:
Abstract Submission
Authors:
Dario Pfyffer1, Merve Kaptan1, Christine Law1, Kenneth Weber1, Valeria Oliva1, Sandrine Bédard1, Tara Maronesy1, Gary Glover1, Sean Mackey1
Institutions:
1Stanford University, Palo Alto, CA
First Author:
Co-Author(s):
Introduction:
Chronic widespread pain represents the cardinal symptom of fibromyalgia (FM)1. While physical therapy was found to relieve pain2, its modulatory mechanisms in the central nervous system remain understudied. Brain and more recently spinal cord (SC) functional magnetic resonance imaging (fMRI) have advanced knowledge of neural correlates of pain processing3,4. Regions showing increased pain-related activity in FM include the thalamus, insula, somatosensory cortices, and SC dorsal horn5. Moreover, dysfunctions in cerebral pain-modulatory systems were reported6, but their link to the SC is missing. We currently lack understanding of the intricate interplay between spinal and supraspinal networks during pain perception as brain and SC fMRI are conventionally performed separately. Here, we characterize corticospinal mechanisms of aberrant nociceptive processing in FM, by means of combined brain-SC fMRI, and explore descending pain-modulatory effects related to physical activity.
Methods:
This preliminary study includes 6 female FM patients (age range: 22-62) and 4 female healthy volunteers (HV, age range: 33-62 years). The imaging protocol consisted of the combined brain-SC sequence7 (EPI pulse sequence, dynamic per slice shimming; 3T GE SIGNA 750 scanner; 16-channel neurovascular array coil; TR=2.5s, TE=30ms, GRAPPA=2), 30 brain slices (3.4x3.4x5.0mm3) and 13 cervical SC slices (1.25x1.25x5.0mm3) centered at C5 vertebral level, axial (FOV=22cm, matrix size=128x128, ΔTE=1ms) and sagittal (FOV=30cm, matrix size=256x64, ΔTE=1ms) field maps for shimming, and anatomical scans (brain: T1w 3DFSPGR (1.0x1.0x1.0mm3); SC: T2w reduced-FOV 3D turbo spin-echo (0.7x0.5x0.5mm3)). The experimental design included four conditions (8x each, 13s) in randomized order: stimulation ON/OFF paired with motor task ON/OFF. Thermal stimuli were applied at the right volar forearm (C6 dermatome) at individual temperatures producing a 6 on the Numeric Rating Scale (0-10), using an ATS thermode (Medoc, 3x3cm2 surface). The motor task consisted of repetitive isometric right-hand gripping with visual feedback (60% of maximal voluntary contraction) using a Dynamometer (BIOPAC). Blocks were followed by 5s pain rating and 6s rest periods. SC and brain images were processed (slice-time correction, motion correction, spatial normalization, smoothing) using FSL and Spinal Cord Toolbox. Preprocessing included RETROICOR8 correction and cerebrospinal fluid regression to account for the physiological noise. Activation maps (fixed effects) were cluster-corrected (z>2.3) for the brain and uncorrected for the SC, with a threshold of p=0.05.
Results:
While average pain ratings decreased by 0.6 points for stimulations during motor task vs. stimulations at rest for HV, they only dropped by 0.2 points for FM. Upon stimulation during motor task, greater activity was found within regions implicated in sensory pain aspects (S1, ACC, insula) in FM compared to HV (Fig. 1, red). Enhanced activity was demonstrated in regions implicated in pain regulation (PFC, PAG, pgACC, PCC, motor cortices) in HV compared to FM (Fig. 1, green). SC dorsal horns exhibited higher and more widespread activity at the level corresponding to the site of stimulation (C6) in FM (red) than HV (green) during the motor task (Fig. 2A). This is supported by the greater activity observed in the same region when contrasting FM > HV (Fig. 2B, red).
Conclusions:
Our findings expand previous work detecting elevated activity in pain-related brain regions upon noxious thermal stimulation by showing the same pattern in the SC. Crucially, executing a motor task during stimulation reduced pain ratings and engaged brain regions implicated in descending pain modulation in HV9. FM, in contrast, exhibited greater activity in brain regions processing sensory pain and SC dorsal horns. Using combined brain-SC fMRI, we identified neural correlates of aberrant pain modulation in FM which can advance development of objective biomarkers of chronic pain.
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 1
Motor Behavior:
Motor Planning and Execution
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Novel Imaging Acquisition Methods:
BOLD fMRI
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 2
Keywords:
FUNCTIONAL MRI
Motor
MRI
Pain
Physical Therapy
Somatosensory
Spinal Cord
Other - corticospinal fMRI; fibromyalgia; pain modulation
1|2Indicates the priority used for review
Provide references using author date format
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