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Background: Many studies have shown effects of anodal transcranial direct current stimulation (a-tDCS) and high-frequency transcranial random noise stimulation (tRNS) on elevating cortical excitability. Moreover, tRNS with a direct current (DC)-offset is more likely to lead to increases in cortical excitability than solely tRNS. While a-tDCS over primary motor cortex (M1) has been shown to attenuate pain perception, tRNS + DC-offset may prove as an effective means for pain relief. Objective: This study aimed to examine effects of a-tDCS and high-frequency tRNS + DC-offset over M1 on pain expectation and perception, and assess whether these effects could be influenced by the certainty of pain expectation. Methods: Using a double-blinded and sham-controlled design, 150 healthy participants were recruited to receive a single-session a-tDCS, high-frequency tRNS + DC-offset, or sham stimulation over M1. The expectation and perception of electrical stimulation in certain and uncertain contexts were assessed at baseline, immediately after, and 30 min after stimulation. Results: Compared with sham stimulation, a-tDCS induced immediate analgesic effects that were greater when the stimulation outcome was expected with uncertainty; tRNS induced immediate and sustained analgesic effects that were mediated by decreasing pain expectation. Nevertheless, we found no strong evidence for tRNS being more effective for attenuating pain than a-tDCS. Conclusions: The analgesic effects of a-tDCS and tRNS showed different temporal courses, which could be related to the more sustained effectiveness of high-frequency tRNS + DC-offset in elevating cortical excitability. Moreover, expectations of pain intensity should be taken into consideration to maximize the benefits of neuromodulation.

Alterations of empathy for others’ pain among patients with chronic pain remained inconsistent. Here, applying a capsaicin-based ongoing pain model on healthy participants, this study investigated how ongoing first-hand pain influences empathic reactions to vicarious pain stimuli. Healthy participants were randomly treated with topical capsaicin cream (capsaicin group) or hand cream (control group) on the left forearm. Video clips showing limbs in painful and non-painful situations were used to induce empathic responses. The capsaicin group showed greater empathic neural responses in the right primary somatosensory cortex (S1) than the control group but smaller responses in the left anterior insula (AI) accompanied with smaller empathic pain-intensity ratings. Notably, the intensity of ongoing pain negatively correlated with empathy-related neural responses in the left AI. Inter-subject phase synchronization analysis was used to assess stimulus-dependent dynamic functional connectivity within or between brain regions engaged in pain empathy. The capsaicin group showed greater empathy-related neural synchronization within S1 and between S1 and AI, but less synchronization within AI and between AI and MCC. Behaviorally, the differential inter-subject pain-intensity rating alignment between painful and non-painful videos was more positive for the capsaicin group than for the control group, and this effect was partially mediated by the inter-subject neural synchronization between S1 and AI. These results suggest that ongoing first-hand pain facilitates neural activation and synchronization within brain regions associated with empathy-related somatosensory resonance at the cost of inhibiting activation and synchronization within brain regions engaged in empathy-related affective sharing.

Previous behavioral studies have shown that sharing painful experiences can strengthen social bonds and promote mutual prosociality, yet the neural mechanisms underlying this phenomenon remain unclear. We hypothesized that sharing a painful experience induces brain-to-brain synchronization and mutual empathy for each other's pain between pain-takers and pain-observers, which then leads to enhanced social bonding. To test this hypothesis, we adopted an electroencephalographic (EEG) hyper-scanning technique to assess neuronal and behavioral activity during a Pain-Sharing task in which high- or low-intensity pain stimulation was randomly delivered to one participant of a dyad on different experimental trials. Single-brain analysis showed that sensorimotor α-oscillation power was suppressed more when expecting high-intensity pain than when expecting low-intensity pain similarly for self-directed or partner-directed pain. Dual-brain analysis revealed that expecting high-intensity pain induced greater brain-to-brain synchronization of sensorimotor α-oscillation phases between pain-takers and pain-observers than did expecting low-intensity pain. Mediation analysis further revealed that brain-to-brain synchronization of sensorimotor α-oscillations mediated the effects of pain-stimulation intensity on mutual affective sharing for partner-directed pain. This mutual affective empathy during the task predicted the social bonding, as indexed by prosocial inclinations measured after the task. These results support the hypothesis that sharing a painful experience triggers emotional resonance between pairs of individuals through brain-to-brain synchronization of neuronal α-oscillations recorded over the sensorimotor cortex, and this emotional resonance further strengthens social bonds and motivates prosocial behavior within pairs of individuals.