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

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Abstract

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.

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Funding

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).

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  1. Yu-E Sun, Hua-Ye Xu, Jing Hao have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Affiliated Drum Tower Hospital, Nanjing University Medical College, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, People’s Republic of China

    Yu-E Sun, Hua-Ye Xu, Jing Hao, Wen-Wen Huo, Yue Qian & Bai-Ling Hou

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  1. Yu-E Sun
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  2. Hua-Ye Xu
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Sun, YE., Xu, HY., Hao, J. et al. The Ubiquitination of Spinal MrgC Alleviates Bone Cancer Pain and Reduces Intracellular Calcium Concentration in Spinal Neurons in Mice. Neurochem Res 44, 2527–2535 (2019). https://doi.org/10.1007/s11064-019-02869-3

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