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

Abstract

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.T here is widespread consensus that empathy recruits brain structures that are also involved in the first-hand experience of the emotion for which one is showing empathy. For example, in the domain of pain, recent image-based and coordinate-based meta-analyses of functional MRI (fMRI) studies have shown that sharing the pain of others consistently activates the bilateral anterior insular (AI) and anterior midcingulate cortex (aMCC) (1). The AI and aMCC are key areas of the network of areas activated by pain, and their activity has been directly related to the affective-motivational component of pain (2). The observation of such shared neural activations has therefore motivated simulationist models, such as the shared representations account of empathy (see refs. 3-5 for review), which propose that we come to understand the feelings of others by engaging the same mental representations as when directly experiencing the emotion with which we are empathizing.However, neuroimaging alone cannot provide sufficient empirical support for such claims because fMRI activation of the same brain area does not necessarily imply equivalence of mental representations and neural functions (see ref. 6 for review). Areas such as the aMCC and AI, for example, are not only activated by pain, but also by phenomena as distinct as cognitive control and responding to salient events in general (see refs. 7-9 for review). This ambiguity is a result of inherent methodological limitations. First, fMRI has mostly been used as a correlational method that identifies neural responses co-occurring with certain c...

Neurocomputational mechanisms of prosocial learning and links to empathy

“…29 and 30), and for pleasant touch (63). Other studies have also supported a simulationist view of empathy by exploiting the placebo analgesia effect, showing that placebo analgesia changes self pain as well as vicarious pain (64,65). Although these studies are consistent with a simulationist account, it remains possible that there exist additional processes that do not operate through self-other overlap that participate in the experience of empathy (15,30).…”

What’s in a word? How instructions, suggestions, and social information change pain and emotion

“…For example, studies could directly compare hypnosis, placebo effects, observational learning and/or social information effects in the same subjects. Future studies could also investigate transfer and interactions between those different types of effects, and between different affective target states (see e.g., Rütgen et al, 2015). Another important aspect of comparison across modulatory effects will be to test similarity of brain pathways using fine-grained brain imaging methods such as multivariate pattern analysis (MVPA) and connectivity analyses.…”

“…Parallel to placebo studies on pain, these studies suggest reductions in areas associated with emotional experience such as ACC and AI (Petrovic et al, 2005; Rütgen et al, 2015; Schienle et al, 2014), and often associated increased activations in prefrontal regions including OFC and dlPFC (Benedetti, 2014; Koban et al, in revision; Mayberg et al, 2002; Petrovic et al, 2005). …”

“…While still less studied, progress has been made for placebo effects on other modalities such as depression (Leuchter et al, 2002; Mayberg et al, 2002), negative (Koban et al, in revision; Meyer et al, 2015; Petrovic et al, 2005; Rütgen et al, 2015; Schienle et al, 2014), and positive emotions (Ellingsen et al, 2013) as well. Parallel to placebo studies on pain, these studies suggest reductions in areas associated with emotional experience such as ACC and AI (Petrovic et al, 2005; Rütgen et al, 2015; Schienle et al, 2014), and often associated increased activations in prefrontal regions including OFC and dlPFC (Benedetti, 2014; Koban et al, in revision; Mayberg et al, 2002; Petrovic et al, 2005).…”

Functional MRI examination of empathy for pain in people with schizophrenia reveals abnormal activation related to cognitive perspective-taking but typical activation linked to affective sharing

“…3,4 The relative importance of each set of processes in the experience of pain empathy has been recently debated. Some authors propose that empathy for pain is based mainly on processes "functionally equivalent to those engaged by first-hand experience of pain" (i.e., shared representations between self and others), 5 whereas others argue that empathy relies instead on our capacity to adopt others' perspectives and infer their emotional states. 6 Previous questionnaire-based research in schizophrenia has suggested abnormalities both in the cognitive and the affective processes, as evidenced respectively by lower perspective taking and increased personal distress scores compared with controls on the Interpersonal Reactivity Index (IRI 7 ).…”