Paracetamol reduces affective reactivity to other people’s positive experiences; & the experience of physical pain & positive empathy may have a more similar neurochemical basis than previously assumed

A Social Analgesic? Acetaminophen (Paracetamol) Reduces Positive Empathy
Dominik Mischkowski, Jennifer Crocker and Baldwin M. Way. Front. Psychol., March 29 2019. https://doi.org/10.3389/fpsyg.2019.00538

Abstract: Acetaminophen – a potent physical painkiller that also reduces empathy for other people’s suffering – blunts physical and social pain by reducing activation in brain areas (i.e. anterior insula and anterior cingulate) thought to be related to emotional awareness and motivation. Some neuroimaging research on positive empathy (i.e., the perception and sharing of positive affect in other people) suggests that the experience of positive empathy also recruits these paralimbic cortical brain areas. We thus hypothesized that acetaminophen may also impair affective processes related to the experience of positive empathy. We tested this hypothesis in a double-blind, placebo-controlled experiment. Specifically, we administered 1,000 mg acetaminophen or a placebo and measured effects on different measures of positive empathy while participants read scenarios about the uplifting experiences of other people. Results showed that acetaminophen reduced personal pleasure and other-directed empathic feelings in response to these scenarios. In contrast, effects on perceived positivity of the described experiences or perceived pleasure in scenario protagonists were not significant. These findings suggest that (1) acetaminophen reduces affective reactivity to other people’s positive experiences and (2) the experience of physical pain and positive empathy may have a more similar neurochemical basis than previously assumed. Because the experience of positive empathy is related to prosocial behavior, our findings also raise questions about the societal impact of excessive acetaminophen consumption.



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Experiencing and expressing positive empathy for other people’s good fortunes have striking personal and interpersonal benefits (Morelli et al., 2015). A substantial amount of research shows that understanding and sharing in other people’s pleasurable experiences foster psychological health, interpersonal trust, intimacy, and a prosocial orientation, both for the source and the recipient of positive empathy (Smith et al., 1989; Gable et al., 2006; Sallquist et al., 2009; Reis et al., 2010; Morelli et al., 2015; Andreychik and Lewis, 2017). Despite this host of findings on the psychological and relational benefits of positive empathy, however, our understanding of the physiological bases of positive empathy remains limited.

Most recent research on the biological underpinnings of positive empathy has focused on pinpointing its brain correlates using functional magnetic resonance imaging (fMRI; e.g., Immordino-Yang et al., 2009; Mobbs et al., 2009; Morelli et al., 2014; Lamm et al., 2015; Lockwood, 2016; Chiesa et al., 2017). Across fMRI studies, the experience of positive empathy seems to be represented in a complex neuronal network involved in emotional awareness, shared affect, and vicarious reward (e.g., Immordino-Yang et al., 2009; Ebisch et al., 2011; Braams et al., 2013; Apps and Ramnani, 2014; Lamm et al., 2015; Morelli et al., 2015). These studies have shown that positive empathy has a distinct neuronal signature compared to related psychosocial affective experiences, such as personal reward or negative empathy, which is generally defined as responsiveness to other people’s pain (Immordino-Yang et al., 2009; Ebisch et al., 2011; Morelli et al., 2014, 2015; Lamm et al., 2015; Lockwood, 2016). fMRI can contribute to our understanding of the component psychological processes of positive empathy but constitutes a correlational methodology, which limits our ability to make causal conclusions about the different processes underlying empathy (Decety, 2010; Zaki et al., 2016; Lamm et al., 2017).

Pharmacological experiments can supplement existing correlational findings about the nature of empathy, because such studies add a causal approach to the study of empathy’s psychological underpinnings (e.g., Rütgen et al., 2015, 2017; Mischkowski et al., 2016). Recent research suggests that the painkiller acetaminophen (or paracetamol, under its international designation) may be particularly well suited for studying the psychology of empathy, as acetaminophen reduces empathy for pain (Mischkowski et al., 2016). Acetaminophen is one of the most popular medicines in the USA (Kaufman et al., 2002) and easily accessible over the counter. Furthermore, acetaminophen is a potent analgesic, reducing pain in response to heat, electric shock, or cold (e.g., Bromm et al., 1992; Nielsen et al., 1992; Piguet et al., 1998; Yuan et al., 1998; Pickering et al., 2015). In addition to these effects on pain, acetaminophen also reduces psychological reactivity (e.g., DeWall et al., 2010; Randles et al., 2013, 2016; Durso et al., 2015; Roberts et al., 2017). Thus, acetaminophen affects a broad spectrum of psychological processes that are not limited to the processing of physical pain.

Neuroimaging evidence suggests that key brain areas involved in these psychological effects of acetaminophen are likely to be the anterior insula (AI) and anterior parts of the cingulate cortex (dACC). Acetaminophen reduces activation in these areas during physical and emotional pain (DeWall et al., 2010; Pickering et al., 2015). Some researchers have pointed out the centrality of these brain areas for positive empathy, as well (e.g., Immordino-Yang et al., 2009; Apps and Ramnani, 2014; Lockwood, 2016). This shared neural mechanism is plausible as the AI seems to be the core of a limbic cortical network related to emotional awareness, independent of emotional valence (Craig, 2009). Thus, both positive and negative empathy may rely on AI and ACC, even though these types of empathy are differentiable at other levels along the neuroaxis. Because acetaminophen appears to blunt responsiveness for one’s own pain and for the pain of others in brain areas overlapping with those involved in positive empathy, we hypothesize that acetaminophen may also impair people’s ability to experience empathy for others’ positive experiences.

To test this hypothesis, we used unpublished data from a previously published dataset (Study 2; Mischkowski et al., 2016). We administered acetaminophen or an inert placebo to healthy volunteers and tested participants’ empathic responses when reading written scenarios about different protagonists having uplifting, positive experiences. To further probe the effect of acetaminophen on positive empathy, we distinguished between empathic perceptions and empathic affect when measuring positive empathy (e.g., Davis, 1994; Decety and Jackson, 2004; Coll et al., 2017; de Waal and Preston, 2017); two of the core psychological processes of positive empathy are perspective taking and affect sharing – conceptual features of both positive empathy and empathy for pain (Morelli et al., 2015). To measure empathic perceptions, participants rated the perceived positivity of the uplifting experiences in the scenarios and the perceived pleasure in the scenario protagonists. To measure empathic affect, we focused on participants’ ability to affectively share in other people’s positive experiences. Specifically, participants rated personal pleasure for themselves and positive other-directed empathic feelings in response to scenario protagonists’ positive experiences. Finally, we explored a process model in which reductions in empathic perceptions statistically mediated the effects of acetaminophen consumption on reduced empathic affect to test whether the effects of acetaminophen on empathic affect are driven by respective impairments in empathic cognition, or not.