Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have repeatedly been shown to improve cognitive empathy (e.g. mind reading and emotion recognition). However, OXT has not yet been shown to increase neural empathic responses to pain in others, a core aspect of affective empathy. Effects of OXT on empathy for pain are difficult to predict, because OXT evidently has pain-reducing properties. Accordingly, OXT might paradoxically decrease empathy for pain. Here, using functional neuroimaging we show robust activation in the neural circuitry of pain (insula and sensorimotor regions) when subjects observe pain in others. Crucially, this empathy-related activation in the neural circuitry of pain is strongly reduced after intranasal OXT, specifically in the left insula. OXT on the basis of our neuroimaging data thus remarkably decreases empathy for pain, but further research including behavioral measures is necessary to draw definite conclusions.

[1]  J. Panksepp Affective Neuroscience: The Foundations of Human and Animal Emotions , 1998 .

[2]  Christian Keysers,et al.  Empathy for positive and negative emotions in the gustatory cortex , 2007, NeuroImage.

[3]  Christian Unkelbach,et al.  Oxytocin Selectively Facilitates Recognition of Positive Sex and Relationship Words , 2008, Psychological science.

[4]  P. Zak,et al.  Oxytocin Increases Generosity in Humans , 2007, PloS one.

[5]  Aldo Aguirre-Camacho,et al.  Oxytocin and Pain: A Systematic Review and Synthesis of Findings , 2013, The Clinical journal of pain.

[6]  C. R. Snyder,et al.  Positive Psychological Assessment: A Handbook of Models and Measures , 2003 .

[7]  Jaak Panksepp,et al.  Oxytocin sharpens self-other perceptual boundary , 2013, Psychoneuroendocrinology.

[8]  J. Zubieta,et al.  Placebo effects on human μ-opioid activity during pain , 2007, Proceedings of the National Academy of Sciences.

[9]  Jean Decety,et al.  Giving peace a chance: Oxytocin increases empathy to pain in the context of the Israeli–Palestinian conflict , 2013, Psychoneuroendocrinology.

[10]  Jamil Zaki,et al.  Oxytocin Selectively Improves Empathic Accuracy , 2010, Psychological science.

[11]  S Baron-Cohen,et al.  Theory of mind and psychopathy: can psychopathic individuals read the ‘language of the eyes’? , 2003, Neuropsychologia.

[12]  Simone G. Shamay-Tsoory,et al.  Intranasal Administration of Oxytocin Increases Envy and Schadenfreude (Gloating) , 2009, Biological Psychiatry.

[13]  Marius V Peelen,et al.  The sight of others' pain modulates motor processing in human cingulate cortex. , 2007, Cerebral cortex.

[14]  Angela C. Rowe,et al.  Men perform comparably to women in a perspective taking task after administration of intranasal oxytocin but not after placebo , 2013, Front. Hum. Neurosci..

[15]  Till Sprenger,et al.  Opioidergic activation in the medial pain system after heat pain , 2006, PAIN.

[16]  S. Preston,et al.  Empathy: Its ultimate and proximate bases. , 2001, The Behavioral and brain sciences.

[17]  Jean Decety,et al.  Oxytocin increases empathy to pain when adopting the other- but not the self-perspective , 2015, Social neuroscience.

[18]  N. Bolger,et al.  Social effects of oxytocin in humans: context and person matter , 2011, Trends in Cognitive Sciences.

[19]  Michael X. Cohen,et al.  Oxytocin Enhances Amygdala-Dependent, Socially Reinforced Learning and Emotional Empathy in Humans , 2010, The Journal of Neuroscience.

[20]  Julia Schikora,et al.  Empathy and social desirability: a comparison of delinquent and non-delinquent participants using direct and indirect measures , 2009 .

[21]  J. Panksepp,et al.  Toward a cross-species understanding of empathy , 2013, Trends in Neurosciences.

[22]  Steven M. Gillespie,et al.  Spontaneous versus deliberate vicarious representations: different routes to empathy in psychopathy and autism. , 2014, Brain : a journal of neurology.

[23]  C. Kirschbaum,et al.  Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress , 2003, Biological Psychiatry.

[24]  Nancy Eisenberg,et al.  Empathy and its measurement. , 2003 .

[25]  T. Campbell,et al.  The Effect of Intranasal Oxytocin Administration on Acute Cold Pressor Pain: A Placebo-Controlled, Double-Blind, Within-Participants Crossover Investigation , 2014, Psychosomatic medicine.

[26]  Ana C. Barceló,et al.  The Striatum and Pain Modulation , 2011, Cellular and Molecular Neurobiology.

[27]  Jean Decety,et al.  Brain response to empathy-eliciting scenarios involving pain in incarcerated individuals with psychopathy. , 2013, JAMA psychiatry.

[28]  A. Craig,et al.  How do you feel — now? The anterior insula and human awareness , 2009, Nature Reviews Neuroscience.

[29]  W. Young,et al.  Oxytocin: The great facilitator of life , 2009, Progress in Neurobiology.

[30]  Peng Li,et al.  Oxytocin in the periaqueductal gray participates in pain modulation in the rat by influencing endogenous opiate peptides , 2011, Peptides.

[31]  Shaul Shalvi,et al.  References and Notes Supporting Online Material Materials and Methods Som Text Figs. S1 to S16 References the Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict among Humans , 2022 .

[32]  Claus Lamm,et al.  Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain , 2011, NeuroImage.

[33]  M. Dadds,et al.  Are We There Yet? The Clinical Potential of Intranasal Oxytocin in Psychiatry , 2012 .

[34]  A. Campbell,et al.  Attachment, aggression and affiliation: The role of oxytocin in female social behavior , 2008, Biological Psychology.

[35]  Larry J. Young,et al.  Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior , 2009, Frontiers in Neuroendocrinology.

[36]  R. Meli,et al.  Central administration of oxytocin reduces hyperalgesia in mice: Implication for cannabinoid and opioid systems , 2012, Peptides.

[37]  Ian B. Hickie,et al.  Intranasal Oxytocin Improves Emotion Recognition for Youth with Autism Spectrum Disorders , 2010, Biological Psychiatry.

[38]  Xiaoying Wang,et al.  Do You Feel My Pain? Racial Group Membership Modulates Empathic Neural Responses , 2009, The Journal of Neuroscience.

[39]  Christian Keysers,et al.  Reply: Spontaneous versus deliberate vicarious representations: different routes to empathy in psychopathy and autism. , 2014, Brain : a journal of neurology.

[40]  G. Northoff,et al.  Common brain activations for painful and non-painful aversive stimuli , 2012, BMC Neuroscience.

[41]  Geoffrey Bird,et al.  Effects of Oxytocin and Prosocial Behavior on Brain Responses to Direct and Vicariously Experienced Pain , 2008, Emotion.

[42]  Baldwin M. Way,et al.  Variation in the μ-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection , 2009, Proceedings of the National Academy of Sciences.

[43]  Christian Keysers,et al.  Somatosensation in social perception , 2010, Nature Reviews Neuroscience.

[44]  Long-chuan Yu,et al.  Involvement of opioid receptors in oxytocin-induced antinociception in the nucleus accumbens of rats. , 2007, The journal of pain : official journal of the American Pain Society.

[45]  M. Bakermans-Kranenburg,et al.  Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy , 2013, Translational Psychiatry.

[46]  S. Herpertz,et al.  Oxytocin Improves “Mind-Reading” in Humans , 2007, Biological Psychiatry.

[47]  Greg Miller,et al.  Neuroscience. The promise and perils of oxytocin. , 2013, Science.

[48]  Christian Keysers,et al.  Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy , 2013, Brain : a journal of neurology.

[49]  A. Sirigu,et al.  Racial Bias Reduces Empathic Sensorimotor Resonance with Other-Race Pain , 2010, Current Biology.

[50]  Matthew D. Lieberman,et al.  A Picture's Worth , 2009, Psychological science.

[51]  J. O'Doherty,et al.  Empathy for Pain Involves the Affective but not Sensory Components of Pain , 2004, Science.

[52]  Jean Decety,et al.  Annals of the New York Academy of Sciences the Neuroevolution of Empathy , 2022 .

[53]  Peter A. Bos,et al.  Acute effects of steroid hormones and neuropeptides on human social–emotional behavior: A review of single administration studies , 2012, Frontiers in Neuroendocrinology.

[54]  Shaul Shalvi,et al.  Oxytocin promotes human ethnocentrism , 2011, Proceedings of the National Academy of Sciences.

[55]  Christian Keysers,et al.  Dissociating the ability and propensity for empathy , 2014, Trends in Cognitive Sciences.

[56]  Emiliano Macaluso,et al.  Their pain is not our pain: Brain and autonomic correlates of empathic resonance with the pain of same and different race individuals , 2013, Human brain mapping.

[57]  Simon B. Eickhoff,et al.  Assignment of functional activations to probabilistic cytoarchitectonic areas revisited , 2007, NeuroImage.

[58]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[59]  Richard J. Davidson,et al.  PSYCHOLOGICAL SCIENCE Research Article Lending a Hand Social Regulation of the Neural Response to Threat , 2022 .

[60]  Jaak Panksepp,et al.  Primary Process Affects and Brain Oxytocin , 2009, Biological Psychiatry.