Pain sensitivity may determine the risk, severity, prognosis, and treatment efficacy of clinical pain [1, 2]. Reduced pain sensitivity may delay recognition and undermine treatment efficacy in acute pain , whereas elevated pain sensitivity may increase health care costs and susceptibility to chronic pain conditions . In the era of precision medicine, objective assessment of pain sensitivity at the individual level is an unmet need. Pain sensitivity is highly variable across individuals. Notably, genetic [5, 6], environmental [7, 8], and psychological [9, 10] factors influence individual pain perception .
Some studies have explored the neural correlates of pain sensitivity. Studies involving structural magnetic resonance imaging (MRI) have identified that cortical thickness or volume density change in the pain-related cortical network may contribute to varying pain sensitivity across healthy individuals. More specifically, high pain sensitivity was associated with cortical thickening in the primary somatosensory cortex (SI), posterior cingulate cortex (PCC), and orbitofrontal cortex . Additionally, the intensity rating of thermal pain was negatively correlated with grey matter density in the SI, PCC, precuneus, intraparietal sulcus, and inferior parietal cortex . In line with the aforementioned MRI studies, neurophysiological studies obtaining direct neural signals showed that noxious stimuli activated a widely distributed brain network related to pain processing, including the SI, primary motor cortex (MI), insula, anterior cingulate cortex (ACC), medial frontal cortex, and PCC . Moreover, activations among some of these regions were greater in pain-sensitive individuals than in pain-insensitive ones , and the magnitude increased with increasing stimulus intensity or perceived magnitude of pain intensity . The aforementioned findings suggest the pain-related cortical network as the structural correlate of individual thermal pain sensitivity, and noxious-evoked neural oscillations and synchronizations in these regions may cause the intersubject variability in pain perception. However, how the neural correlates of spontaneous cortical activities with the mechanical pain sensitivity and in clinical pain remains elusive.
The rating of individual pain in response to noxious stimulus has been coded from cortical activation [16–19], and pain intensity during heat stimulation was related to gamma oscillation in the medial frontal cortex . In another study, during capsaicin-heat pain, peak alpha frequency over the sensorimotor region was inversely correlated with individual pain intensity . The inconsistent findings regarding cortical regions and oscillations may be attributable to the influence of the pain modalities and the involvement of cognitive processes, such as the salience or attention effect. Therefore, some studies have investigated prestimulus functional connectivity instead of stimulus-evoked responses and found that the connectivity of the anterior insula cortex  and frontocentral network  determined the pain perception of the subsequent noxious stimulus. Thus, brain activities or synchrony might involve the neurophysiological mechanisms for individual pain perception. Moreover, brain oscillations and synchrony serve integrative functions through flexibly regulating information flow among the cortical regions [22–24]. Thus, exploring oscillation and synchrony during the resting-state condition might yield promising insights into how functionally diverse processes relevantly reflect the intersubject variability of pain sensitivity.
This study investigates the hypothesis that resting-state cortical activities at the pain-related cortical network underpin interindividual pain variability. To characterize temporal–spatial features of cortical oscillations and cortico-cortical synchronization within this pain-related network, the present study used magnetoencephalography (MEG) to record brain activities during the resting-state condition. Moreover, this study assessed individual pain sensitivity with the mechanical punctate pain threshold (MPPT) instead of the thermal pain threshold used in most of the earlier pertinent studies. Furthermore, we recruited patients with episodic migraine (EM) to determine whether the study findings are exclusive to patients with pain disorder. We selected EM here because patients with EM have been characterized as having an aberrant pain sensitivity threshold , heightened cortical excitability [26, 27], and altered resting-state cortical oscillations and connectivity in pain-related regions [28–30]. Moreover, whether the underlying pain sensitivity mechanism is reshaped for pain disorder remains uncertain. The specific aims of this study were to (1) elucidate the relationship between cortical oscillations and pain sensitivity, (2) investigate the correlation of cortical synchronization with pain sensitivity, and (3) examine the effect of pain disorder in patients with EM on the cortical mechanism of pain sensitivity.