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Dissection and Culture of Commissural Neurons from Embryonic Spinal Cord
Published on: May 25, 2010
The Ubiquitination of Spinal MrgC Alleviates Bone Cancer Pain and Reduces Intracellular Calcium Concentration in
Yu-E Sun1, Hua-Ye Xu2, Jing Hao2
1Department of Anesthesiology, Affiliated Drum Tower Hospital, Nanjing University Medical College, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu, People's Republic of China. annasun123@163.com.
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.
Insights
Mas-related G-protein-coupled receptor subtype C (MrgC) ubiquitination is crucial for bone cancer pain in mice. This process influences intracellular calcium levels in spinal neurons, offering potential therapeutic targets for pain management.
Area of Science:
- Neuroscience
- Oncology
- Pain Research
Background:
- Mas-related G-protein-coupled receptor subtype C (MrgC) is implicated in bone cancer pain.
- Ubiquitination is a known factor in pain signaling pathways.
- The specific role of MrgC ubiquitination in bone cancer pain requires investigation.
Purpose of the Study:
- To investigate the role of Mas-related G-protein-coupled receptor subtype C (MrgC) ubiquitination in the development and maintenance of bone cancer pain.
- To explore the relationship between MrgC ubiquitination, intracellular calcium concentration, and pain behaviors in a mouse model of osteosarcoma.
Main Methods:
- Osteosarcoma cells were implanted in mice to induce bone cancer pain.
- Intrathecal administration of an MrgC agonist (BAM 8-22) or antagonist (anti-MrgC antibody) was performed.
- Pain behaviors, MrgC ubiquitination levels, and spinal neuron intracellular calcium concentrations were measured.
Main Results:
- Tumor-bearing mice exhibited significant bone cancer pain, elevated MrgC ubiquitination, and increased spinal neuron intracellular calcium.
- MrgC agonist treatment alleviated pain, increased ubiquitination, and decreased calcium levels.
- The effects of the agonist were reversed by the antagonist.
Conclusions:
- MrgC ubiquitination plays a significant role in the generation and persistence of bone cancer pain in mice.
- This process may involve the modulation of intracellular calcium concentration in spinal neurons.
- Targeting MrgC ubiquitination presents a potential strategy for managing bone cancer pain.
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