Unraveling the neuroimmune mechanisms in cancer- induced bone pain: New horizons for therapeutic intervention of the two- phase paradigm

• 成果类型: Article
• 署名作者: Wang, Changming; Ji, Haiwang; Wang, Hanwen; Chen, Ziyun; Zhou, Lan; Yang, Yan; Jiang, Yucui; Yu, Guang; Jiang, Ling; Tang, Zongxiang
• 署名单位: Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing Medical University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10313
• DOI: 10.1073/pnas.2503779122
• 发表日期: 2025-08-26
• 关键词: substance-p; matrix metalloproteinases; protein; activation; release

摘要

Cancer- induced bone pain (CIBP) is a severely painful condition that profoundly impacts patients' quality of life. However, the neuroimmune mechanisms underlying CIBP remain largely elusive. Substance P (SP), which is known to play a pivotal role in pain perception, became the focal point of our study. To this end, we adopted a comprehensive approach combining behavioral and physiological methods to investigate its role in neuroimmune interactions in CIBP. The results showed that SP released by dorsal root ganglion (DRG) neurons via exocytosis initiates CIBP, with its release peaking on the 14th day and correlating with pain behavior. Macrophages were found to infiltrate the DRGs and the sciatic nerves. Notably, in mice with CIBP, the population of macrophage type I was significantly augmented. Significantly, we found that the deletion of macrophages led to a notable alleviation of CIBP, while the blockade of the tration in the primary phase and chemokine- mediated macrophage recruitment in the with cancer development.