Hang Xu, Hongtao Lu, Lu Lu, Zhenghao Li, Zhisheng Piao, Yi Jia, Xiaoyan Meng, Feixiang Wu
{"title":"表达：纳米颗粒MgH 2抑制trpm2介导的NLRP3炎性体缓解骨癌疼痛。","authors":"Hang Xu, Hongtao Lu, Lu Lu, Zhenghao Li, Zhisheng Piao, Yi Jia, Xiaoyan Meng, Feixiang Wu","doi":"10.1177/17448069251348770","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Bone cancer metastases are the third most common site of cancer spread after lungs and liver. This condition often causes severe pain that impairs patients' physical, psychological, and social well-being. We aimed to explore the potential therapeutic benefits of magnesium hydride (MgH<sub>2</sub>) on bone cancer pain (BCP).</p><p><strong>Methods: </strong>A BCP model was established in Wistar rats. Daily oral dosing of 0.5% w/w MgH<sub>2</sub> was administered. Assessment included pain sensitivity, motor coordination, and emotional behaviors. Hippocampal samples underwent RNA sequencing, Western blotting, immunofluorescence, and quantitative RT-PCR.</p><p><strong>Results: </strong>MgH<sub>2</sub> markedly reduced mechanical hypersensitivity and depressive behaviors in rats with BCP. These effects were linked to suppression of the TRPM2-NLRP3 signaling axis in hippocampal microglia. Additionally, MgH<sub>2</sub> served as an adjuvant to reduce opioid tolerance during fentanyl co-treatment, enabling lower opioid dosages. Collectively, MgH<sub>2</sub> inhibited TRPM2 activation, microglial activation, oxidative stress, and NLRP3 inflammasome formation, which together reduced neuroinflammation and improved therapeutic outcomes.</p><p><strong>Conclusion: </strong>MgH<sub>2</sub> nanoparticles may relieve BCP and comorbid depressive symptoms by inhibiting TRPM2-mediated NLRP3 inflammasome activation in hippocampal microglia.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251348770"},"PeriodicalIF":2.8000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185947/pdf/","citationCount":"0","resultStr":"{\"title\":\"Nanoparticulate MgH<sub>2</sub> suppresses TRPM2-mediated NLRP3 inflammasome to relieve bone cancer pain.\",\"authors\":\"Hang Xu, Hongtao Lu, Lu Lu, Zhenghao Li, Zhisheng Piao, Yi Jia, Xiaoyan Meng, Feixiang Wu\",\"doi\":\"10.1177/17448069251348770\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Bone cancer metastases are the third most common site of cancer spread after lungs and liver. This condition often causes severe pain that impairs patients' physical, psychological, and social well-being. We aimed to explore the potential therapeutic benefits of magnesium hydride (MgH<sub>2</sub>) on bone cancer pain (BCP).</p><p><strong>Methods: </strong>A BCP model was established in Wistar rats. Daily oral dosing of 0.5% w/w MgH<sub>2</sub> was administered. Assessment included pain sensitivity, motor coordination, and emotional behaviors. Hippocampal samples underwent RNA sequencing, Western blotting, immunofluorescence, and quantitative RT-PCR.</p><p><strong>Results: </strong>MgH<sub>2</sub> markedly reduced mechanical hypersensitivity and depressive behaviors in rats with BCP. These effects were linked to suppression of the TRPM2-NLRP3 signaling axis in hippocampal microglia. Additionally, MgH<sub>2</sub> served as an adjuvant to reduce opioid tolerance during fentanyl co-treatment, enabling lower opioid dosages. Collectively, MgH<sub>2</sub> inhibited TRPM2 activation, microglial activation, oxidative stress, and NLRP3 inflammasome formation, which together reduced neuroinflammation and improved therapeutic outcomes.</p><p><strong>Conclusion: </strong>MgH<sub>2</sub> nanoparticles may relieve BCP and comorbid depressive symptoms by inhibiting TRPM2-mediated NLRP3 inflammasome activation in hippocampal microglia.</p>\",\"PeriodicalId\":19010,\"journal\":{\"name\":\"Molecular Pain\",\"volume\":\" \",\"pages\":\"17448069251348770\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185947/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Pain\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17448069251348770\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17448069251348770","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Nanoparticulate MgH2 suppresses TRPM2-mediated NLRP3 inflammasome to relieve bone cancer pain.
Background: Bone cancer metastases are the third most common site of cancer spread after lungs and liver. This condition often causes severe pain that impairs patients' physical, psychological, and social well-being. We aimed to explore the potential therapeutic benefits of magnesium hydride (MgH2) on bone cancer pain (BCP).
Methods: A BCP model was established in Wistar rats. Daily oral dosing of 0.5% w/w MgH2 was administered. Assessment included pain sensitivity, motor coordination, and emotional behaviors. Hippocampal samples underwent RNA sequencing, Western blotting, immunofluorescence, and quantitative RT-PCR.
Results: MgH2 markedly reduced mechanical hypersensitivity and depressive behaviors in rats with BCP. These effects were linked to suppression of the TRPM2-NLRP3 signaling axis in hippocampal microglia. Additionally, MgH2 served as an adjuvant to reduce opioid tolerance during fentanyl co-treatment, enabling lower opioid dosages. Collectively, MgH2 inhibited TRPM2 activation, microglial activation, oxidative stress, and NLRP3 inflammasome formation, which together reduced neuroinflammation and improved therapeutic outcomes.
Conclusion: MgH2 nanoparticles may relieve BCP and comorbid depressive symptoms by inhibiting TRPM2-mediated NLRP3 inflammasome activation in hippocampal microglia.
期刊介绍：
Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.
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