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  2. Sex Differences in Pain Contagion Determined by the Balance of Oxytocin and Corticosterone in the Anterior Cingulate Cortex in Rodents

Sex Differences in Pain Contagion Determined by the Balance of Oxytocin and Corticosterone in the Anterior Cingulate Cortex in Rodents

  • Neurosci Bull. 2025 Aug 6. doi: 10.1007/s12264-025-01473-6.
Zhiyuan Xie # 1 Wenxi Yuan # 1 Lingbo Zhou 1 Jie Xiao 1 2 Huabao Liao 1 2 Jiang-Jian Hu 1 2 Xue-Jun Song 3 4
Affiliations

Affiliations

  • 1 Department of Medical Neuroscience, Southern University of Science and Technology School of Medicine, Shenzhen, 518055, China.
  • 2 SUSTech Center for Pain Medicine, Southern University of Science and Technology School of Medicine, Shenzhen, 518055, China.
  • 3 Department of Medical Neuroscience, Southern University of Science and Technology School of Medicine, Shenzhen, 518055, China. songxuejun@sustech.edu.cn.
  • 4 SUSTech Center for Pain Medicine, Southern University of Science and Technology School of Medicine, Shenzhen, 518055, China. songxuejun@sustech.edu.cn.
  • # Contributed equally.
Abstract

Empathy is crucial for communication and survival for individuals. Whether empathy in pain contagion shows sex differences and its underlying mechanisms remain unclear. Here, we report that pain contagion can occur in stranger female rats, but not in stranger males. Blocking oxytocin receptors in the anterior cingulate cortex (ACC) suppressed pain contagion in female strangers, while oxytocin administration induced pain contagion in male strangers. In vitro, corticosterone reduces neuronal activation by oxytocin. During male stranger interactions, higher corticosterone decreased oxytocin receptor-positive neuronal activity in the ACC, suppressing pain contagion. These findings highlight the role of oxytocin in pain contagion and suggest that sex differences in empathy may be determined by the balance of oxytocin and corticosterone in the ACC. This study suggests an approach for the treatment of certain mental disorders associated with abnormal empathy, such as autism and depression.

Keywords

Corticosterone; Empathic behavior; Empathy; Oxytocin; Pain; Sex difference.

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