Visual Quantitative Sensory Testing Provides Transdiagnostic Window into Behavioral and Functional Neural Correlates of Nociplastic Pain

Multisensory hypersensitivity to painful and non-painful stimuli, including light, is common among individuals with nociplastic pain. However, as nociplastic pain is often superimposed upon nociceptive and neuropathic pain, we hypothesized that the degree of nociplastic pain would predict the amount of sensory hypersensitivity in many 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 (FM,n=45) - the prototypical nociplastic pain condition - and osteoarthritis (OA,n=41), rheumatoid arthritis (RA,n=32), carpal tunnel syndrome (CTS,n=17), and healthy controls (HC,n=35). An aversive visual QST task was completed before and during fMRI. 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). 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. 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). The corresponding fMRI results showed that visual unpleasantness ratings were associated with greater activation in left anterior insula in FMs vs. HCs (peak: x=-50,y=28,z=5; z=6.03, p=0.00031). Similar findings were observed in right (peak: x=50,y=20,z=2; z=8.52, p<0.0001) and left (peak: x=-50,y=20,z=-4; z=6.58, p=0.00038) anterior insula in RAs vs. HCs. 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 insula may represent a key pathophysiological mechanism of nociplastic pain.