Affective dimensions of pain and region -specific involvement of nitric oxide in the development of empathic hyperalgesia

Fatemeh Mohammadi,Kristi Anne Kohlmeier,Meysam Ahmadi-Zeidabadi,Sajad Jeddi,Mohammad Shabani

doi:10.1038/s41598-020-66930-w

Abstract

Empathy for pain depends on the ability to feel, recognize, comprehend and share painful emotional conditions of others. In this study, we investigated the role of NO in a rat model of empathic pain. Pain was socially transferred from the sibling demonstrator (SD) who experienced five formalin injection to the naïve sibling observer (SO) through observation. SO rats received L-NAME (a nonspecific NO synthase inhibitor) or L-arginine (a precursor of NO) prior to observing the SD. Nociception, and concentrations of NO metabolites (NOx) in the serum, left and right hippocampus, prefrontal cortex, and cerebellum were evaluated. Nociceptive responses were significantly increased in the pain-observing groups. NOx levels measured 24 h after the last pain observation using the Griess method, were indicative of NOx concentration decreases and increases in the left hippocampus and cerebellum, respectively. There was an increase in tissue concentration of NOx in cerebellum and prefrontal cortex in both pain and observer groups 7 days after the fifth formalin injection. Our results suggest that NO is involved in development of empathic hyperalgesia, and observation of sibling’s pain can change NO metabolites in different brain regions in observer rats.

Highlights

Empathy for pain depends on the ability to feel, recognize, comprehend and share painful emotional conditions of others
We have shown that alterations in nitric oxide (NO) synthesis altered nociception in observers of conspecifics receiving pain[42]
Since NO plays an important role in pain[43] and we have shown a role for NO in empathic pain[42], the aim of this study was to further explore this role in brain regions involved in empathic pain

Summary

Introduction

Empathy for pain depends on the ability to feel, recognize, comprehend and share painful emotional conditions of others. As the hippocampus is crucial in learning and memory, and a major player in the emotion-controlling limbic system, and alterations in its functioning have been seen upon the pain experience and in those exhibiting deficits in empathetic responding[30], it could play a role in empathetic pain. While the molecular mechanisms of empathetic pain have not been elucidated, NO is a free radical[37] synthesized from L-arginine (L-Arg; a precursor of NO) by three known NO synthases (neuronal (nNOS), endothelial (eNOS) and inducible (iNOS)[38,39,40], and the gene for nNOS (nitric oxide synthesis 1) has been shown to play an essential role in social behavior such as empathy[41]

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