Healthcare experience affects pain-specific responses to others' suffering in the anterior insula.

Medical students and professional healthcare providers often underestimate patients' pain, together with decreased neural responses to pain information in the anterior insula (AI), a brain region implicated in self-pain processing and negative affect. However, the functional significance and specificity of these neural changes remains debated. Across two experiments, we recruited university medical students and emergency nurses to test the role of healthcare experience on the brain reactivity to other's pain, emotions, and beliefs, using both pictorial and verbal cues. Brain responses to self-pain was also assessed and compared with those to observed pain. Our results confirmed that healthcare experience decreased the activity in AI in response to others' suffering. This effect was independent from stimulus modality (pictures or texts), but specific for pain, as it did not generalize to inferences about other mental or affective states. Furthermore, representational similarity and multivariate pattern analysis revealed that healthcare experience impacted specifically a component of the neural representation of others' pain that is shared with that of first-hand nociception, and related more to AI than to other pain-responsive regions. Taken together, our study suggests a decreased propensity to appraise others' suffering as one's own, associated with a reduced recruitment of pain-specific information in AI. These findings provide new insights into neural mechanisms leading to pain underestimation by caregivers in clinical settings.

The influence of social signals on the self-experience of pain: A neuroimaging review.

Researchers in cognitive neuroscience have investigated extensively how psychological factors shape the processing and perception of pain using behavioral, physiological, and neuroimaging methods. However, social influences of pain, an essential part of biopsychosocial pain models, have received relatively little attention. This is particularly true for the neurobiological mechanisms underlying social modulations on pain. Therefore, this review discusses the findings of recent neuroimaging studies measuring the effects of social manipulations on pain perception (e.g., verbal and non-verbal social signals, social interaction style, conformity, social support, and sociocultural mediators). Finally, a schematic summary of the different social modulatory themes is presented.

Sensory-specific predictive models in the human anterior insula.

Expectations affect the subjective experience of pain by increasing sensitivity to noxious events, an effect underlain by brain regions such as the insula. However, it has been debated whether these neural processes operate on pain-specific information or on more general signals encoding expectation of unpleasant events. To dissociate these possibilities, two independent studies ( Sharvit et al., 2018, Pain; Fazeli and Büchel, 2018, J. Neurosci) implemented a cross-modal expectancy paradigm, testing whether responses to pain could also be modulated by the expectation of similarly unpleasant, but painless, events. Despite their differences, the two studies report remarkably convergent (and in some cases complementary) findings. First, the middle-anterior insula response to noxious stimuli is modulated only by expectancy of pain but not of painless adverse events, suggesting coding of pain-specific information. Second, sub-portions of the middle-anterior insula mediate different aspects of pain predictive coding, related to expectancy and prediction error. Third, complementary expectancy effects are also observed for other negative experiences (i.e., disgust), suggesting that the insular cortex holds prospective models of a wide range of events concerning their sensory-specific features. Taken together, these studies have strong theoretical implications on the functional properties of the insular cortex.

Modality-specific effects of aversive expectancy in the anterior insula and medial prefrontal cortex.

Expectations modulate the subjective experience of pain by increasing sensitivity to nociceptive inputs, an effect mediated by brain regions such as the insula. However, it is still unknown whether the neural structures underlying pain expectancy hold sensory-specific information or, alternatively, code for modality-independent features (eg, unpleasantness), potentially common with other negative experiences. We used functional magnetic resonance imaging to investigate neural activity underlying the expectation of different, but comparably unpleasant, pain and disgust. We presented participants with visual cues predicting either a painful heat or disgusting odor, and assessed how they affected the subsequent subjective experience of stimuli from the same (within-modality) or opposite (cross-modal) modality. We found a reliable influence of expectancy on the subjective experience of stimuli whose modality matched that of the previous cue. At the brain level, this effect was mediated by the intermediate dysgranular section of the insula, whereas it was suppressed by more anterior agranular portions of the same region. Instead, no expectancy modulation was observed when the modality of the cue differed from that of the subsequent stimulus. Our data suggest that the insular cortex encodes prospective aversive events in terms of their modality-specific features, and whether they match with subsequent stimulations.

Cross-modal and modality-specific expectancy effects between pain and disgust.

Pain sensitivity increases when a noxious stimulus is preceded by cues predicting higher intensity. However, it is unclear whether the modulation of nociception by expectancy is sensory-specific ("modality based") or reflects the aversive-affective consequence of the upcoming event ("unpleasantness"), potentially common with other negative events. Here we compared expectancy effects for pain and disgust by using different, but equally unpleasant, nociceptive (thermal) and olfactory stimulations. Indeed both pain and disgust are aversive, associated with threat to the organism, and processed in partly overlapping brain networks. Participants saw cues predicting the unpleasantness (high/low) and the modality (pain/disgust) of upcoming thermal or olfactory stimulations, and rated the associated unpleasantness after stimuli delivery. Results showed that identical thermal stimuli were perceived as more unpleasant when preceded by cues threatening about high (as opposed to low) pain. A similar expectancy effect was found for olfactory disgust. Critically, cross-modal expectancy effects were observed on inconsistent trials when thermal stimuli were preceded by high-disgust cues or olfactory stimuli preceded by high-pain cues. However, these effects were stronger in consistent than inconsistent conditions. Taken together, our results suggest that expectation of an unpleasant event elicits representations of both its modality-specific properties and its aversive consequences.

'Pain inhibits pain' mechanisms: Is pain modulation simply due to distraction?

'Diffuse noxious inhibitory controls' (DNIC), a form of supraspinal descending endogenous analgesia, requires a noxious conditioning stimulus for pain attenuation. This may be partly dependent on a distraction effect. The term "conditioned pain modulation" (CPM) has recently been introduced to describe the psychophysical paradigm to test DNIC. The present study aimed to determine whether distraction and tonic heat stimulation inhibit pain through the same or different mechanisms by looking at whether there is a similar or even an additive effect on pain attenuation. Test pain was brief heat stimulation applied to the left volar of 34 healthy volunteers. For conditioning, the right hand was immersed in 46.5 degrees C water. Distraction was provided by three different difficulty levels of continuous cognitive visual tasks. Experimental blocks consisted of test pain: (1) alone; 'baseline', (2) with conditioning pain; 'CPM', (3) with distraction; 'distraction' and (4) with conditioning pain and distraction; 'combined'. They were randomized and repeated three times and pain intensity and unpleasantness rated. Results showed an overall effect of experimental block on test pain intensity (P=0.0125). Post-hoc tests revealed a significant reduction in pain intensity ratings under Combined (21.2+/-2.3; mean+/-SEM) compared to CPM alone (16.0+/-2.3) (P<0.05). Furthermore, at all levels of distraction there were always a few subjects who were not distracted despite expressing CPM. Based on the additive effect of CPM and distraction on pain inhibition, and the cases of no distraction despite CPM, we suggest that CPM acts independently from distraction.