Neural indices of multimodal sensory and autonomic hyperexcitability in fibromyalgia

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain and psychological distress. Research suggests people with FM experience increased somatosensory sensitization which generalizes to other sensory modalities and may indicate neural hyperexcitability. However, the available evidence is limited, and studies including measures of neural responsivity across sensory domains and both central and peripheral aspects of the neuraxis are lacking. Thirty-nine participants (51.5 ± 13.6 years of age) with no history of neurological disorders, psychosis, visual, auditory, or learning deficits, were recruited for this study. People with FM (N = 19) and control participants (CNT, N = 20) did not differ on demographic variables and cognitive capacity. Participants completed a task that combined innocuous auditory stimuli with electrocutaneous stimulation (ECS), delivered at individually-selected levels that were uncomfortable but not painful. Event-related potentials (ERPs) and electrodermal activity were analyzed to examine the central and sympathetic indices of neural responsivity. FM participants reported greater sensitivity to ECS and auditory stimulation, as well as higher levels of depression, anxiety, ADHD, and an array of pain-related experiences than CNT. In response to ECS, the P50 deflection was greater in FM than CNT participants, reflecting early somatosensory hyperexcitability. The P50 amplitude was positively correlated with the FM profile factor obtained with a principal component analysis. The N100 to innocuous tones and sympathetic reactivity to ECS were greater in FM participants, except in the subgroup treated with gabapentinoids, which aligns with previous evidence of symptomatic improvement with GABA-mimetic medications. These results support the principal tenet of generalized neural hyperexcitability in FM and provide preliminary mechanistic insight into the impact of GABA-mimetic pharmacological therapy on ameliorating the neural excitation dominance.