Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Abstract

Individual differences in pain perception are of key interest in basic and clinical research as altered pain sensitivity is both a characteristic and a risk factor for many pain conditions. It is, however, unclear how individual susceptibility to pain is reflected in the pain-free resting-state brain activity and functional connectivity. Here, we identified and validated a network pattern in the pain-free resting-state functional brain connectome that is predictive of interindividual differences in pain sensitivity. Our predictive network signature (https://spisakt.github.io/RPN-signature) allows assessing the individual susceptibility to pain without applying any painful stimulation, as might be valuable in patients where reliable behavioural pain reports cannot be obtained. Additionally, as a direct, non-invasive readout of the supraspinal neural contribution to pain sensitivity, it may have broad implications for translational research and the development and assessment of analgesic treatment strategies.

Baseline Resting-State Functional Connectivity Determines Subsequent Pain Ratings to a Tonic Ecologically Valid Experimental Model of Orofacial Pain

“…Analogous to the current findings, a recent study demonstrated that data-driven, multivariate analyses of rsFC in a pain-free state predicted individual differences in pain sensitivity during later testing [84].…”

“…pain anticipation [15,56] and following nociceptive stimulation [64]. Analogous to the current findings, a recent study demonstrated that data-driven, multivariate analyses of rsFC in a pain-free state predicted individual differences in pain sensitivity during later testing [73]. Their measure of pain sensitivity was a ‘composite’ based on a weighted average of heat, cold and mechanical pain thresholds delivered 1-3 days from the time of resting-state functional imaging.…”

“…Greater insight into these individual differences has been provided by structural and functional brain imaging studies [23,31,40,43,[59][60][61]. Notably, structural grey matter differences [30,31] and resting-state functional connectivity (rsFC) [21,84] are related to individual differences in pain sensitivity in laboratory-based studies. However, laboratory-based studies of experimental pain are limited in their ecological validity in evaluating a realistic painful experience.…”

“…However, laboratory-based studies of experimental pain are limited in their ecological validity in evaluating a realistic painful experience. Recent studies of brain-based predictors of pain have relied on multivariate machine learning approaches, which provide limited insight into neural mechanisms [73,75,79]. Here, we investigate whether baseline brain structure and function can predict pain induced by an ecologically valid and clinically relevant tonic orofacial pain stimulus—orthodontic elastomeric separator insertion.…”

Functional and diffusion MRI reveal the functional and structural basis of infants’ noxious-evoked brain activity

“…A high degree of correspondence between resting-state and task-related brain activities has been observed in adult fMRI studies 26,27 . In adults, fMRI-recorded resting-state activity is a distinguishing feature of an individual's brain functionality 28 , predicts individuals' task-related brain activity under both experimental 29 and clinical conditions 30 , as well as adults' individual pain sensitivities 31 . While analogous studies have not been conducted in neonatal populations, large-scale resting-state networks are detectable using fMRI from birth and correspond to adult canonical resting-state and task-response networks 32,33 , suggesting a similar functional coupling could exist at this early developmental stage.…”