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

The Ubiquitination of Spinal MrgC Alleviates Bone Cancer Pain and Reduces Intracellular Calcium Concentration in Spinal Neurons in Mice. Neurochem Res. 2019 Sep 12;: Authors: Sun YE, Xu HY, Hao J, Huo WW, Qian Y, Hou BL 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...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research

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Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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Source: Pediatric Blood and Cancer - Category: Cancer & Oncology Authors: Tags: RESEARCH ARTICLE Source Type: research
AbstractStereotactic body radiotherapy (SBRT) for spinal metastases is very effective for pain relief and local tumor control. However, high-level evidence is limited to lesions in a single vertebra or in 2 contiguous vertebrae. To clarify the toxicities, we report herein the results of treatment for 4 patients who received SBRT to large-volume spinal tumors. The lesions comprised bone metastasis from renal cancer, local recurrence of rectal cancer invading the spine, osteosarcoma, and giant cell tumor of bone in 1 case each. Tumor volumes ranged from 738 to 1,766  ml. Doses ranging from 24 Gy in 2 fraction to 35...
Source: International Cancer Conference Journal - Category: Cancer & Oncology Source Type: research
In the United States, bone tumors (Osteosarcoma and Ewing ’s sarcoma) account for nearly 800 new cases of pediatric cancer per year. These solid bone tumors typically occur in long bones and are treated with systemic chemotherapy and surgery which causes increased morbidity with long term consequences. Over the years, surgical procedures have evolved fro m amputation to limb-salvage procedures in an attempt to maintain the anatomical structures and functionality of the affected structure. Adequate pain control in the acute post-operatory setting and the recovery are a fundamental key to bringing the patient back func...
Source: The Journal of Pain - Category: Materials Science Authors: Source Type: research
This study builds on preliminary findings from the first phase of the INTERSTROKE study, which identified ten modifiable risk factors for stroke in 6,000 participants from 22 countries. The full-scale INTERSTROKE study included an additional 20,000 individuals from 32 countries in Europe, Asia, America, Africa and Australia, and sought to identify the main causes of stroke in diverse populations, young and old, men and women, and within subtypes of stroke. To estimate the proportion of strokes caused by specific risk factors, the investigators calculated the population attributable risk for each factor (PAR; an esti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Current Osteoporosis Reports - Category: Orthopaedics Source Type: research
Conclusions Upregulation of CRTC1 enhancing CREB-dependent gene transcription in spinal cord may play an important role in bone cancer pain. Inhibition of spinal CRTC1 expression reduced bone cancer pain. Interruption to the positive feedback circuit between CREB/CRTC1 and its targets may contribute to the analgesic effects. These findings may provide further insight into the mechanisms and treatment of bone cancer pain.
Source: Molecular Pain - Category: Molecular Biology Authors: Tags: Research Article Source Type: research
ConclusionsThese findings suggest that activation of spinal CREB/CRTC1 signalling may play an important role in bone cancer pain. Interruption to the positive feedback regulation between CREB/CRTC1 and its target gene miR‐132 can effectively relieved the bone cancer‐induced mechanical allodynia and spontaneous pain. What does this study add?The positive feedback regulation between CREB/CRTC1 and its target gene miR‐132 in spinal cord plays an important role in bone cancer pain.
Source: European Journal of Pain - Category: Anesthesiology Authors: Tags: Original Article Source Type: research
ConclusionsThese findings suggest that activation of spinal CREB/CRTC1 signalling may play an important role in bone cancer pain. Interruption to the positive feedback regulation between CREB/CRTC1 and its target gene miR‐132 can effectively relieved the bone cancer‐induced mechanical allodynia and spontaneous pain. What does this study add?The positive feedback regulation between CREB/CRTC1 and its target gene miR‐132 in spinal cord plays an important role in bone cancer pain.
Source: European Journal of Pain - Category: Anesthesiology Authors: Tags: Original Article Source Type: research
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Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
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