Expecting Pain

How expectations shape pain sensitivity. Disentangling pain-specific processes from supramodal coding. One of the most striking breakthroughs in pain research has been the discovery of expectancy modulations, according to which subjective experiences do not only reflect nociceptive input but also individuals' previous knowledge and beliefs. Expectancy modulations are noteworthy for their clinical implications, as convincing individuals of the effectiveness of an analgesic might induce a strong pain relief (placebo effect). Furthermore, expectancy effects have sparkled a major theoretical debate, with influential models suggesting that pain symptoms might be better explained through a Bayesian framework, where the brain estimates the (posterior) probability of body damage, based on the integration of sensory inputs and prior representations. However, pain is a multi-component experience, that has both sensory components and a strong unpleasantness, common with many other painless experiences (e.g., disgust). This raises the question about the nature of the predictive information at play during expectancy, and whether it relates to pain-specifically ("this will hurt"), or rather to an undistinctive negative event ("this will be bad").

Cross-modal Expectancy

Sharvit et al., 2015, Sci. Rep. 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.

Sharvit et al., 2018, Pain. 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 (e.g., unpleasantness), potentially common with other negative experiences. We used Functional Magnetic Resonance Imaging (fMRI) 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.

Sharvit et al., 2019, F1000Research. 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.

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