First-hand Pain Research Articles

Autistic and Non-autistic Children's Pain Perception is Modulated by Their First-Hand Pain Sensitivity and Theory of Mind.

The current study examined whether autistic children's perception of others' pain could be modulated by their first-hand pain sensitivity and theory of mind (ToM). We measured the first-hand pain sensitivity, the rating of others' pain intensity, and the performance in the ToM tasks in 43 5- to 8-year-old autistic and 30 neurotypical children. Our results revealed hyposensitivity to first-hand pain, underestimation of others' pain intensity, as well as difficulties in the False Belief subtasks of ToM in autistic children. Furthermore, we detected an interaction between children's first-hand pain sensitivity and ToM in predicting their perception of others' pain. To be specific, for autistic and NT children with normal or hyper-sensitivity to first-hand pain, better performance on ToM predicted higher ratings for others' pain intensity; while for autistic and NT children with hyposensitivity to first-hand pain, ToM did not predict ratings for others' pain intensity. Our study contributes to the understanding of pain perception in young children and provides implications for clinical practices to improve social understanding in autistic children.

The relationship between oxytocin and empathy for others’ pain: Testing the mediating effect of first-hand pain sensitivity

Although previous studies have shown that oxytocin attenuates first-hand pain sensitivity, studies of its effects on empathetic reactions to the observation of others’ pain have yielded inconsistent and controversial results. Given the link between first-hand pain and empathy for others’ pain, we hypothesized that oxytocin affects empathy for others’ pain by modulating first-hand pain sensitivity. Using a double-blind, placebo-controlled, between-participant experimental design, healthy participants (n = 112) were randomly assigned to either an intranasal oxytocin or placebo group. Pain sensitivity was evaluated by pressure pain threshold, and empathetic responses were assessed by ratings in response to viewing video clips depicting others in physically painful scenarios. Results showed that pressure pain thresholds decreased over time in both groups, indicating increased sensitivity to first-hand pain after repeated measurements. However, this decrease was smaller for participants who received intranasal oxytocin, indicative of oxytocin-induced attenuation of first-hand pain sensitivity. In addition, although empathetic ratings were comparable between oxytocin and placebo groups, first-hand pain sensitivity fully mediated the impact of oxytocin on pain empathetic ratings. Thus, intranasal oxytocin can indirectly affect pain empathetic ratings by reducing first-hand pain sensitivity. These findings expand our understanding of the relationship among oxytocin, pain, and empathy.

Ongoing first-hand pain facilitates somatosensory resonance but inhibits affective sharing in empathy for pain

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.

The influence of EEG oscillations, heart rate variability changes, and personality on self-pain and empathy for pain under placebo analgesia

We induced placebo analgesia (PA), a phenomenon explicitly attenuating the self-pain feeling, to assess whether this resulted in reduced empathy pain when witnessing a confederate undergoing such pain experience. We recorded EEG and electrocardiogram during a painful Control and PA treatment in healthy adults who rated their experienced pain and empathy for pain. We derived HRV changes and, using wavelet analysis of non-phase-locked event-related EEG oscillations, EEG spectral power differences for self-pain and other-pain conditions. First-hand PA reduced self-pain and self-unpleasantness, whereas we observed only a slight decrease in other unpleasantness. We derived linear combinations of HRV and EEG band power changes significantly associated with self-pain and empathy for pain changes using PCAs. Lower Behavioral Inhibition System scores predicted self-pain reduction through the mediating effect of a relative HR-slowing and a decreased midline ϑ-band (4–8 Hz) power factor moderated by lower Fight-Flight-Freeze System trait scores. In the other-pain condition, we detected a direct positive influence of Total Empathic Ability on the other-pain decline with a mediating role of the midline β2-band (22–30 Hz) power reduction. These findings suggest that PA modulation of first-hand versus other pain relies on functionally different physiological processes involving different personality traits.

Autistic Traits and Empathy for Others' Pain Among the General Population: Test of the Mediating Effects of First-Hand Pain Sensitivity.

Autism spectrum disorders (ASD) are characterized by reduced pain empathy-a process that is grounded in first-hand pain perception. Because autistic traits are continuously distributed in the general population, we hypothesized that first-hand pain sensitivity would mediate the link between autistic traits and pain empathy. After controlling for alexithymia, higher autistic traits were associated with lower cognitive and emotional empathy in response to others' pain, as well as lower sensitivity to cold and heat pain (higher cold pain tolerance and lower laser heat pain-intensity ratings). Importantly, pain sensitivity fully mediated the link between autistic traits and pain empathy. These findings highlight the role of atypical first-hand pain sensitivity in the lack of pain empathy observed in people with high autistic traits or ASD.

Different priming effects of empathy on neural processing associated with firsthand pain and nonpain perception.

The shared-representation model of empathy is still debated. One of the major questions is whether empathy-eliciting stimuli depicting others' pain selectively activate the representations of self-pain. To address this issue, we assessed the priming effects of empathy-eliciting pictures on firsthand pain and nonpain perception, as well as its associated neural processing. In Experiment 1, when compared with nonpainful pictures depicting individuals' body parts with no injury, participants primed by painful pictures showing individuals' body parts with injury reported higher ratings for perceived intensity, unpleasantness, and salience of nociceptive and auditory stimuli, but they only exhibited increased N2 amplitude in response to nociceptive stimuli. In Experiment 2, the results from another group of participants replicated the observations of Experiment 1 and validated the findings in the non-nociceptive somatosensory modality. Importantly, participants' concern ratings for priming pictures predicted their unpleasantness ratings for subsequent nociceptive stimuli, while participants' attention ratings predicted their unpleasantness ratings for subsequent auditory and tactile stimuli. This finding implies that empathy for pain might influence pain and nonpain perception via different psychological mechanisms. In summary, our findings highlight the existence of pain-selective representations in empathy for pain and contribute to a better understanding of the shared-representation model of empathy.

Placebo Analgesia Does Not Reduce Empathy for Naturalistic Depictions of Others' Pain in a Somatosensory Specific Way.

The shared representations account postulates that sharing another’s pain recruits underlying brain functions also engaged during first-hand pain. Critically, direct causal evidence for this was mainly shown for affective pain processing, while the contribution of somatosensory processes to empathy remains controversial. This controversy may be explained, however, by experimental paradigms that did not direct attention towards a specific body part, or that did not employ naturalistic depictions of others’ pain. In this preregistered functional magnetic resonance imaging study, we aimed to test whether causal manipulation of first-hand pain affects empathy for naturalistic depictions of pain in a somatosensory-matched manner. Forty-five participants underwent a placebo analgesia induction in their right hand and observed pictures of other people’s right and left hands in pain. We found neither behavioral nor neural evidence for somatosensory-specific modulation of pain empathy. However, exploratory analyses revealed a general effect of the placebo on empathy, and higher brain activity in bilateral anterior insula when viewing others’ right hands in pain (i.e., corresponding to one’s own placebo hand). These results refine our knowledge regarding the neural mechanisms of pain empathy, and imply that the sharing of somatosensory representations seems to play less of a causal role than the one of affective representations.

Observation of others' painful heat stimulation involves responses in the spinal cord.

Observing others' aversive experiences is central to know what is dangerous for ourselves. Hence, observation often elicits behavioral and physiological responses comparable to first-hand aversive experiences and engages overlapping brain activation. While brain activation to first-hand aversive experiences relies on connections to the spinal cord, it is unresolved whether merely observing aversive stimulation also involves responses in the spinal cord. Here, we show that observation of others receiving painful heat stimulation involves neural responses in the spinal cord, located in the same cervical segment as first-hand heat pain. However, while first-hand painful experiences are coded within dorsolateral regions of the spinal cord, observation of others' painful heat stimulation involves medial regions. Dorsolateral areas that process first-hand pain exhibit negative responses when observing pain in others. Our results suggest a distinct processing between self and others' pain in the spinal cord when integrating social information.

Beyond Sharing Unpleasant Affect-Evidence for Pain-Specific Opioidergic Modulation of Empathy for Pain.

It is not known how specific the neural mechanisms underpinning empathy for different domains are. In the present study, we set out to test whether shared neural representations between first-hand pain and empathy for pain are pain-specific or extend to empathy for unpleasant affective touch as well. Using functional magnetic resonance imaging and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them with the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiates the role of shared representations in empathy.

Another's pain in my brain: No evidence that placebo analgesia affects the sensory-discriminative component in empathy for pain

The shared representations account of empathy suggests that sharing other people's emotions relies on neural processes similar to those engaged when directly experiencing such emotions. Recent research corroborated this by showing that placebo analgesia induced for first-hand pain resulted in reduced pain empathy and decreased activation in shared neural networks. However, those studies did not report any placebo-related variation of somatosensory engagement during pain empathy. The experimental paradigms used in these studies did not direct attention towards a specific body part in pain, which may explain the absence of effects for somatosensation. The main objective of this preregistered study was to implement a paradigm overcoming this limitation, and to investigate whether placebo analgesia may also modulate the sensory-discriminative component of empathy for pain. We induced a localized, first-hand placebo analgesia effect in the right hand of 45 participants by means of a placebo gel and conditioning techniques, and compared this to the left hand as a control condition. Participants underwent a pain task in the MRI scanner, receiving painful or non-painful electrical stimulation on their left or right hand, or witnessing another person receiving such stimulation. In contrast to a robust localized placebo analgesia effect for self-experienced pain, the empathy condition showed no differences between the two hands, neither for behavioral nor neural responses. We thus report no evidence for somatosensory sharing in empathy, while replicating previous studies showing overlapping brain activity in the affective-motivational component for first-hand and empathy for pain. Hence, in a more rigorous test aiming to overcome limitations of previous work, we again find no causal evidence for the engagement of somatosensory sharing in empathy. Our study refines the understanding of the neural underpinnings of empathy for pain, and the use of placebo analgesia in investigating such models.

The linkage between first-hand pain sensitivity and empathy for others' pain: Attention matters.

Many studies suggested shared psychological and neural representations for first‐hand physical pain and empathy for others' pain, both of which depend strongly upon top–down controlled mechanisms such as attention. This study aimed to assess the interindividual variation in first‐hand physical pain and empathy for pain, and whether their relationship is dependent upon attention. We recruited participants exhibiting high and low sensitivity to first‐hand pain (HPS and LPS), and adopted pain empathy paradigms involving attention directed toward or withdrawn from pain of another. Relative to the LPS group, participants in the HPS group estimated greater pain intensity experienced by others, felt greater unpleasantness when viewing others in pain, and exhibited greater sensitivity in discriminating others' pain. Electroencephalographic data showed that when attention was directed toward others' pain, only participants in the HPS group exhibited significant pain empathic effects on the N1 component of event‐related potentials and on the α‐oscillation response. These empathic neural responses mediated the linkage between first‐hand pain sensitivity and empathic behavioral responses. Nevertheless, empathic responses were comparable between two groups when attention was withdrawn from others' pain. These results demonstrate a shared sensitivity to first‐hand pain and empathy for pain provided that attention is directed toward pain.

Pattern similarity and connectivity of hippocampal-neocortical regions support empathy for pain.

Empathy is thought to engage mental simulation, which in turn is known to rely on hippocampal-neocortical processing. Here, we tested how hippocampal-neocortical pattern similarity and connectivity contributed to pain empathy. Using this approach, we analyzed a data set of 102 human participants who underwent functional MRI while painful and non-painful electrical stimulation was delivered to themselves or to a confederate. As hypothesized, results revealed increased pattern similarity between first-hand pain and pain empathy (compared to non-painful control conditions) within the hippocampus, retrosplenial cortex, the temporo-parietal junction and anterior insula. While representations in these regions were unaffected by confederate similarity, pattern similarity in the dorsal medial prefrontal cortex was increased the more dissimilar the other individual was perceived. Hippocampal-neocortical connectivity during first-hand pain and pain empathy engaged largely distinct but neighboring primary motor regions, and empathy-related hippocampal coupling with the fusiform gyrus positively scaled with trait measures of perspective taking. These findings suggest that shared representations and mental simulation might contribute to pain empathy via hippocampal-neocortical pattern similarity and connectivity, partially affected by personality traits and the similarity of the observed individual.

Others' Pain Appraisals Modulate the Anticipation and Experience of Subsequent Pain

The present study investigated how pain appraisals from other individuals modulated self-pain anticipation and perception. Appraisals of pain intensity from 10 other individuals were presented before the participants received identical electrical pain stimulation themselves. In reality, the presented other's pain appraisals, with either low or high in mean and variance, were generated by the experimenter, and were randomly paired with the subsequent electrical stimulation at either low or high intensity. Specifically, the mean and variance of others' pain appraisals were manipulated to induce participants' expectation and certainty to the upcoming pain. Subjective ratings of pain intensity and electroencephalographic (EEG) responses to the electrical stimulation, as well as anticipatory EEG activities measured prior to the onset of electrical stimulation, were compared. Results showed that the mean and variance of others' pain appraisal modulated the subjective pain ratings and the affective-motivational P2 responses elicited by the electrical stimulation, as well as anticipatory sensorimotor α-oscillation measured before the onset of pain stimulation. When the mean of others' pain appraisal was low, higher variance suppressed the sensorimotor α-oscillations and enhanced subsequent pain perception. In contrast, when the mean was high, the higher variance enhanced sensorimotor α-oscillations and suppressed subsequent pain perception. These results demonstrated that others' pain appraisals can modulate both of the anticipation and perception of first-hand pain. It also suggested that the top-down modulation of others' pain appraisals on pain perception could be partially driven by the different brain states during the anticipation stage, as captured by the prestimulus sensorimotor α-oscillations.

Does my pain affect your disgust? Cross-modal influence of first-hand aversive experiences in the appraisal of others' facial expressions.

Embodied models of social cognition argue that others' affective states are processed by re-enacting a sensory-specific representation of the same state in the observer. However, neuroimaging studies suggest that a reliable part of the representation shared between self and others is supramodal and relates to dimensions such as Unpleasantness or arousal, common to qualitatively different experiences. Here we investigated whether representations of first-hand pain and disgust influenced the subsequent evaluation of facial expressions in Modality-specific fashion, or in terms of Unpleasantness or arousal. Thirty volunteers were subjected to thermal painful and olfactory disgusting events, and subsequently were asked to classify computer-generated faces expressing pain (characterized by high Unpleasantness and arousal), disgust (high Unpleasantness and low arousal), surprise (low Unpleasantness and high arousal) and hybrid combinations thereof. Thermal and olfactory events were associated with comparable Unpleasantness ratings and heart rate (but stronger galvanic response was found for painful temperatures). Furthermore, we found that the appraisal of facial expressions was biased by the prior stimulus, with more frequent pain classifications following thermal stimuli, and more frequent disgust classifications following olfactory stimuli. Critically, this modulation was cross-modal in nature, as each first-hand stimulation influenced in comparable fashion facial traits diagnostic of both pain and disgust, without instead generalizing to features of surprise. Overall, these data support the presence of shared coding between one's aversive experiences and the appraisal of others' facial responses, which is best describable as supramodal representation of the Unpleasantness of the experience. These results extend previous findings about common representational coding between the experience of first-hand and others' pain. In particular, they highlight that reliable part of the information shared is supramodal in nature and relates to a broad dimension of Unpleasantness common also to painless aversive states such as disgust.

Emotional Mirror Neurons in the Rat’s Anterior Cingulate Cortex

SummaryHow do the emotions of others affect us? The human anterior cingulate cortex (ACC) responds while experiencing pain in the self and witnessing pain in others, but the underlying cellular mechanisms remain poorly understood. Here we show the rat ACC (area 24) contains neurons responding when a rat experiences pain as triggered by a laser and while witnessing another rat receive footshocks. Most of these neurons do not respond to a fear-conditioned sound (CS). Deactivating this region reduces freezing while witnessing footshocks to others but not while hearing the CS. A decoder trained on spike counts while witnessing footshocks to another rat can decode stimulus intensity both while witnessing pain in another and while experiencing the pain first-hand. Mirror-like neurons thus exist in the ACC that encode the pain of others in a code shared with first-hand pain experience. A smaller population of neurons responded to witnessing footshocks to others and while hearing the CS but not while experiencing laser-triggered pain. These differential responses suggest that the ACC may contain channels that map the distress of another animal onto a mosaic of pain- and fear-sensitive channels in the observer. More experiments are necessary to determine whether painfulness and fearfulness in particular or differences in arousal or salience are responsible for these differential responses.

Extraordinary Altruists Exhibit Enhanced Self–Other Overlap in Neural Responses to Distress

Shared neural representations during experienced and observed distress are hypothesized to reflect empathic neural simulation, which may support altruism. But the correspondence between real-world altruism and shared neural representations has not been directly tested, and empathy’s role in promoting altruism toward strangers has been questioned. Here, we show that individuals who have performed costly altruism (donating a kidney to a stranger; n = 25) exhibit greater self–other overlap than matched control participants (n = 27) in neural representations of pain and threat (fearful anticipation) in anterior insula (AI) during an empathic-pain paradigm. Altruists exhibited greater self–other correspondence in pain-related activation in left AI, highlighting that group-level overlap was supported by individual-level associations between empathic pain and firsthand pain. Altruists exhibited enhanced functional coupling of left AI with left midinsula during empathic pain and threat. Results show that heightened neural instantiations of empathy correspond to real-world altruism and highlight limitations of self-report.

The good, the bad, and the suffering. Transient emotional episodes modulate the neural circuits of pain and empathy

People's sensitivity to first-hand pain is affected by their ongoing emotions, with positive states (joy, amusement) exerting analgesic-like effects, and negative states (sadness, fear) often enhancing the subjective experience. It is however less clear how empathetic responses to others’ pain are affected by one's own emotional state. Following embodied accounts that posit a shared representational code between self and others’ states, it is plausible that pain empathy might be influenced by emotions in the same way as first-hand pain. Alternatively, other theories in psychology suggest that social resources (including empathetic reactions) might be enhanced by positive states, but inhibited by negative states, as only in the former case, one's mindset is sufficiently broad to take into consideration others’ needs. To disambiguate between these opposing predictions, we conducted two experiments in which volunteers observed positive, neutral, or negative video clips, and subsequently either received painful thermal stimuli on their own body (first-hand pain), or observed images of wounded hands (others’ pain). We measured subjective pain ratings as well as physiological responses and brain activity using fMRI. We found that, contrary to the case of first-hand pain, others’ pain produced weaker galvanic responses and lower neural activity in anterior insula and middle cingulate cortex following negative (relative to neutral and positive) videos. Such inhibition was partially counteracted by personal empathy traits, as individuals with higher scores retained greater sensitivity to others’ pain after negative emotion induction, in both behavioral and neural responses in medial prefrontal cortex. Furthermore, multivoxel pattern analysis confirmed similar neural representation for first-hand and others’ pain in anterior insula, with representation similarity increasing the more the video preceding the observation of others’ suffering was positive. These findings speak against the idea that emotion induction affects first-hand and others’ pain in an isomorphic way, but rather supports the idea that contrary to negative emotions, positive emotions favors a broader access to social resources.

Dissociable Roles of Cerebral μ-Opioid and Type 2 Dopamine Receptors in Vicarious Pain: A Combined PET-fMRI Study.

Neuroimaging studies have shown that seeing others in pain activates brain regions that are involved in first-hand pain, suggesting that shared neuromolecular pathways support processing of first-hand and vicarious pain. We tested whether the dopamine and opioid neurotransmitter systems involved in nociceptive processing also contribute to vicarious pain experience. We used in vivo positron emission tomography to quantify type 2 dopamine and μ-opioid receptor (D2R and MOR, respectively) availabilities in brains of 35 subjects. During functional magnetic resonance imaging, the subjects watched short movie clips depicting persons in painful and painless situations. Painful scenes activated pain-responsive brain regions including anterior insulae, thalamus and secondary somatosensory cortices, as well as posterior superior temporal sulci. MOR availability correlated negatively with the haemodynamic responses during painful scenes in anterior and posterior insulae, thalamus, secondary and primary somatosensory cortices, primary motor cortex, and superior temporal sulci. MOR availability correlated positively with orbitofrontal haemodynamic responses during painful scenes. D2R availability was not correlated with the haemodynamic responses in any brain region. These results suggest that the opioid system contributes to neural processing of vicarious pain, and that interindividual differences in opioidergic system could explain why some individuals react more strongly than others to seeing pain.

Psychopharmacological modulation of event-related potentials suggests that first-hand pain and empathy for pain rely on similar opioidergic processes

Accumulating evidence suggests that empathy for pain recruits similar neural processes as the first-hand experience of pain. The pain-related P2, an event-related potential component, has been suggested as a reliable indicator of neural processes associated with first-hand pain. Recent evidence indicates that placebo analgesia modulates this component for both first-hand pain and empathy for pain. Moreover, a psychopharmacological study showed that administration of an opioid antagonist blocked the effects of placebo analgesia on self-report of both first-hand pain and empathy for pain. Together, these findings suggest that the opioid system plays a similar role during first-hand pain and empathy for pain. However, such a conclusion requires evidence showing that neural activity during both experiences is similarly affected by psychopharmacological blockage of opioid receptors. Here, we measured pain-related P2 amplitudes and self-report in a group of participants who first underwent a placebo analgesia induction procedure. Then, they received an opioid receptor antagonist known to block the previously induced analgesic effects. Self-report showed that blocking opioid receptors after the induction of placebo analgesia increased both first-hand pain and empathy for pain, replicating previous findings. Importantly, P2 amplitudes were also increased during both experiences. Thus, the present findings extend models proposing that empathy for pain is partially grounded in first-hand pain by suggesting that this also applies to the underlying opioidergic neurochemical processes.

Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain

Empathy for pain activates brain areas partially overlapping with those underpinning the first-hand experience of pain. It remains unclear, however, whether such shared activations imply that pain empathy engages similar neural functions as first-hand pain experiences. To overcome the limitations of previous neuroimaging research, we pursued a conceptually novel approach: we used the phenomenon of placebo analgesia to experimentally reduce the first-hand experience of pain, and assessed whether this results in a concomitant reduction of empathy for pain. We first carried out a functional MRI experiment (n = 102) that yielded results in the expected direction: participants experiencing placebo analgesia also reported decreased empathy for pain, and this was associated with reduced engagement of anterior insular and midcingulate cortex: that is, areas previously associated with shared activations in pain and empathy for pain. In a second step, we used a psychopharmacological manipulation (n = 50) to determine whether these effects can be blocked via an opioid antagonist. The administration of the opioid antagonist naltrexone blocked placebo analgesia and also resulted in a corresponding "normalization" of empathy for pain. Taken together, these findings suggest that pain empathy may be associated with neural responses and neurotransmitter activity engaged during first-hand pain, and thus might indeed be grounded in our own pain experiences.