Background & Aims

Hypersensitivity to painful and non-painful sensory stimuli, including light, is common among individuals with nociplastic pain. Since nociplastic pain is often superimposed upon nociceptive or neuropathic pain, we hypothesized that the degree of nociplastic pain would predict the amount of sensory hypersensitivity in multiple different chronic pain states. To assess this hypothesis, the present study investigated associations between evoked visual sensitivity, brain activation patterns, and clinical outcomes in participants with fibromyalgia – the prototypical nociplastic pain condition – as well as two nociceptive conditions (osteoarthritis and rheumatoid arthritis), one neuropathic condition (carpal tunnel syndrome), and healthy controls.

Methods

Study participants included those with fibromyalgia (FM, n=45), osteoarthritis of the hip (OA, n=41), rheumatoid arthritis (RA, n=32), carpal tunnel syndrome (CTS, n=17), and healthy controls (HC, n=35). Participants underwent a 3-minute dynamic visual stimulation task that consisted of alternating 20-second blocks of a flashing (8 Hz frequency) blue-yellow annulus checkerboard and a static fixation cross. The checkerboard was presented at six illumination levels in pseudorandom order ranging from 2.1 to 203.9 lux. Each illumination level was rated for sensory intensity (brightness) and unpleasantness on a 0-100 NRS with endpoints “not bright” and “not unpleasant” to “brightest image imaginable” and “most unpleasant image imaginable.” An abridged version (fixed at the highest brightness level) of the visual task was shown during fMRI.

Results

ANOVA identified significant main effects for visual brightness level (p<0.0001) and clinical cohort (p=0.0019), with a significant brightness by group interaction (p<0.0001). Increased visual unpleasantness ratings were correlated with increased self-reported pain intensity (r=0.383,p<0.0001) and fibromyalgia severity (r=0.310,p=0.0004). In a subset of these individuals (RA and HC), fMRI results during evoked visual stimuli showed that unpleasantness ratings were associated with greater activation in right superior frontal gyrus (peak: x=2,y=6,z=66; p=0.00011), right dorsolateral prefrontal cortex (peak: x=22,y=42,z=38; p=0.00045), and dorsal anterior cingulate cortex (peak: x=2,y=36,z=30;, p=0.045) in RAs as compared to HCs. Furthermore, the RAs also exhibited increased functional connectivity during the visual task from the right superior frontal gyrus to regions including the right intraparietal sulcus (peak: x=28,y=-58,z=40; p=0.011).

Conclusions

FMs and HCs reported the highest and lowest unpleasantness, respectively, while OAs, RAs, and CTSs reported intermediate unpleasantness on a continuum between FMs and HCs. Imaging results suggest regional hyperactivity in RAs as a possible underlying mechanism for increased visual sensitivity. As a whole, these findings suggest that centrally-mediated visual sensitivity may provide a transdiagnostic window into the nociplastic pain continuum, and that aberrant sensory processing within the regions including the prefrontal cortex and associated connectivity with regions including the intraparietal sulcus may represent key pathophysiological mechanisms of multisensory hypersensitivity in individuals with RA.

References

Harte SE, Ichesco E, Hampson JP, Peltier SJ, Schmidt-Wilcke T, Clauw DJ, Harris RE. Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula. Pain. 2016 Sep;157(9):1933-1945. doi: 10.1097/j.pain.0000000000000593. PMID: 27101425; PMCID: PMC4988086.

Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC): National Academies Press (US); 2011. PMID: 22553896.

Phillips K, Clauw DJ. Central pain mechanisms in the rheumatic diseases: future directions. Arthritis and rheumatism. Feb 2013;65(2):291-302.

Harte, SE, Harris, RE, Clauw, DJ. The neurobiology of central sensitization. J Appl Behav Res. 2018; 23:e12137. https://doi.org/10.1111/jabr.12137

Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014 Apr 16;311(15):1547-55. doi: 10.1001/jama.2014.3266. PMID: 24737367.

Presenting Author

Noah Waller

Poster Authors

Noah Waller BS

BS in Neuroscience

University of Michigan

Lead Author

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Chelsea Kaplan

PhD

University of Michigan

Lead Author

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Andrew Schrepf

University of Michigan

Lead Author

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Eric Ichesco BS

University of Michigan Chronic Pain and Fatigue Research Center

Lead Author

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Daniel Clauw

University of Michigan Chronic Pain and Fatigue Research Center

Lead Author

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Richard Harris PhD

University of California Irvine

Lead Author

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Steven Harte

PhD

University of Michigan Chronic Pain and Fatigue Research Center

Lead Author

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Topics

  • Pain Imaging