Individual pain sensitivity is associated with resting-state cortical activities in healthy individuals but not in patients with migraine: a magnetoencephalography study

Abstract

Background Pain sensitivity may determine the risk, severity, prognosis, and efficacy of treatment of clinical pain. Magnetic resonance imaging studies have linked thermal pain sensitivity to changes in brain structure. However, the neural correlates of mechanical pain sensitivity remain to be clarified through investigation of direct neural activities on the resting-state cortical oscillation and synchrony. Methods We recorded the resting-state magnetoencephalographic (MEG) activities of 27 healthy individuals and 30 patients with episodic migraine (EM) and analyzed the source-based oscillatory powers and functional connectivity at 2 to 59 Hz in pain-related cortical regions, which are the bilateral anterior cingulate cortex (ACC), medial orbitofrontal (MOF) cortex, lateral orbitofrontal (LOF) cortex, insula cortex, primary somatosensory cortex (SI), primary motor cortex (MI), and posterior cingulate cortex (PCC). The mechanical punctate pain threshold (MPPT) was obtained at the supraorbital area (the first branch of the trigeminal nerve dermatome, V1) and the forearm (the first thoracic nerve dermatome, T1) and further correlated with MEG measures. Results The MPPT is inversely correlated with the resting-state relative powers of gamma oscillation in healthy individuals (all corrected P < 0.05). Specifically, inverse correlation was noted between the MPPT at V1 and gamma powers in the bilateral insula (r = − 0.592 [left] and − 0.529 [right]), PCC (r = − 0.619 and − 0.541) and MI (r = − 0.497 and − 0.549) and between the MPPT at T1 and powers in the left PCC (r = − 0.561) and bilateral MI (r = − 0.509 and − 0.520). Furthermore, resting-state functional connectivity at the delta to beta bands, especially between frontal (MOF, ACC, LOF, and MI), parietal (PCC), and sensorimotor (bilateral SI and MI) regions, showed a positive correlation with the MPPT at V1 and T1 (all corrected P < 0.05). By contrast, in patients with EM, the MPPT was not associated with resting-state cortical activities. Conclusions Pain sensitivity in healthy individuals is associated with the resting-state gamma oscillation and functional connectivity in pain-related cortical regions. Further studies must be conducted in a large population to confirm whether resting-state cortical activities can be an objective measurement of pain sensitivity in individuals without clinical pain.

Machine learning–based prediction of heat pain sensitivity by using resting-state EEG

“…In previous studies, during capsaicin-heat pain stimulation, peak alpha frequency over the sensorimotor region was inversely correlated with individual pain intensity [11,13]. In our recent study, we further confirmed that pain sensitivity is associated with the spontaneous regional oscillatory activities and intrinsic functional network [14]. Taken together, these findings suggest that cortical activation and functional network may reflect individual pain sensitivity and cause individual differences in pain perception.…”

“…As resting-state brain activities were associated with individual pain sensitivity in our recent study [14], spontaneous cortical oscillations and intrinsic functional networks might be pivotal mechanisms in the regulation of pain processes. Therefore, this study combined multimodal (neurophysiology and psychometrics) signatures, which might better represent pain complexity, and built a multivariate machine-learning model, which learns from the features of psychometric scores (from demography and questionnaires), spontaneous brain oscillatory powers (from within-electrode EEG analysis), and resting-state functional connectivity (FC, from between-electrode EEG analysis), to noticeably classify the training dataset and predict the testing dataset on individual heat pain sensitivity derived from the heat pain threshold (HPT).…”

“…EEG recording (Brain Products GmbH, Munich, Germany) was conducted for 5 min with a digitization rate of 1000 Hz; participants were instructed to close their eyes but remain awake and relaxed and perform no explicit task, which eliminated the artifacts of eye movement and revealed that the intrinsic cortical activities were associ-ated with pain sensitivity in our recent study [14]. The recording was stopped and then rerun if a participant fell asleep.…”

“…The principal components meeting the artifact's sensor topography were then manually excluded through orthogonal projection [23]. To obtain the electrodebased resting-state oscillations and FC, the spontaneous activities of each electrode were further analyzed as follows [14,[24][25][26]. First, oscillatory power in each electrode was estimated using the Welch method (window duration: 3 sec with 50% overlap) and defined as absolute power spectral density (PSD).…”

Pain-Related Brain Connectivity Changes in Migraine: A Narrative Review and Proof of Concept about Possible Novel Treatments Interference

“…A new era for migraine treatment was opened with the use of large molecules acting on CGRP, the main mediator of sterile inflammation. The CGRP-mAbs act at the peripheral level, with an improbable and weak effect on the CNS [ 82 ], which would reduce their long term efficacy on the complex migraine brain dysfunction. However, a very recent study reported that a single dose 70 mg of enerumab caused a relevant change of functional connectivity from the hypothalamus to the insula, temporal lobe, hippocampus and trigeminal nuclei.…”