The Ubiquitination of Spinal MrgC Alleviates Bone Cancer Pain and Reduces Intracellular Calcium Concentration in Spinal Neurons in Mice

  • Yu-E SunEmail author
  • Hua-Ye Xu
  • Jing Hao
  • Wen-Wen Huo
  • Yue Qian
  • Bai-Ling Hou
Original Paper


Mas-related G-protein-coupled receptor subtype C (MrgC) has been shown to play an important role in the development of bone cancer pain. Ubiquitination is reported to participate in pain. However, whether MrgC ubiquitination plays a role in bone cancer pain remains unclear. To answer this question, we designed and performed this study. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer pain. MrgC agonist bovine adrenal medulla 8–22 (BAM 8–22) or MrgC antagonist anti-MrgC antibody were injected intrathecally on day 14 after bone cancer pain was successfully induced. The pain behaviors, the MrgC ubiquitination levels and intracellular calcium concentration in spinal neurons were measured before and after injection, respectively. With comparison to normal and sham group, mice in tumor group exhibited serious bone cancer pain on day 14, and the level of MrgC ubiquitination and intracellular calcium concentration in spinal neurons was significantly higher. Intrathecal injection of BAM 8–22 significantly alleviated bone cancer pain, increased the MrgC ubiquitination level and decreased intracellular calcium concentration in spinal neurons; however, these effects were reversed by administration of anti-MrgC antibody. Our study reveals that MrgC ubiquitination participates in the production and maintenance of bone cancer pain in mice, possibly through the regulation of intracellular calcium concentration in mice spinal neurons.


Bone cancer pain Mas-related G-protein-coupled receptor subtype C (MrgC) Ubiquitination Calcium concentration 



This work was supported by National Natural Science Foundation of China (Nos. 81870871, 81400914) and Key Project supported by Medical Science and Technology Development Foundation, Nanjing Department of Health (QRX17138, ZKX18018).

Compliance with Ethical Standards

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical Approval

This experiment was approved by the Institution of Animal Care and Usage Committee at the Medical School of Nanjing University.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Anesthesiology, Affiliated Drum Tower HospitalNanjing University Medical CollegeNanjingPeople’s Republic of China

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