2. Academic Validation
  3. Earlier onset of chemotherapy-induced neuropathic pain in females by ICAM-1-mediated accumulation of perivascular macrophages

Earlier onset of chemotherapy-induced neuropathic pain in females by ICAM-1-mediated accumulation of perivascular macrophages

  • Sci Adv. 2025 Apr 18;11(16):eadu2159. doi: 10.1126/sciadv.adu2159.
Li Chen 1,  Xin Zou 1,  Cui-Cui Liu 2,  Pu Yan 3,  Jie Deng 4,  Chen Wang 4,  Mu-Yang Chen 1,  Xiao-Qing Tang 5,  Jing-Ming Shi 6,  Wen-Jun Xin 1 6,  Xiang-Zhong Zhang 7,  Xia Feng 4,  Ting Xu 1,  Jing-Dun Xie 8
Affiliations

Affiliations

  • 1 Guangdong Province Key Laboratory of Brain Function and Disease, Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, China.
  • 2 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China.
  • 3 Department of Hematology, Shenzhen Longgang District People's Hospital, Shenzhen, Guangdong 518172, China.
  • 4 Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • 5 Department of Neurology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 6 Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xian Yang, Shaanxi Province 712082, China.
  • 7 Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510010, China.
  • 8 Department of Anesthesiology, State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
PMID: 40238872 DOI: 10.1126/sciadv.adu2159
Abstract

Sex differences in the pathogenesis of a variety of diseases have drawn increasing attention. However, it remains unclear whether such differences exist in chemotherapy-induced neuropathic pain. Here, we conducted a retrospective analysis of clinical case data and found that peripheral sensory disorders occurred earlier in females than in males following bortezomib (BTZ) treatment in patients with multiple myeloma. BTZ treatment led to an early elevation of intercellular adhesion molecule-1, which triggered the infiltration of peripheral monocytes into the perivascular region of the spinal cord in female mice. The CC-chemokine ligand 1 released by infiltrating macrophages directly activated neurons or indirectly activated neurons by enhancing the astrocyte activity, ultimately leading to the earlier onset of BTZ-induced neuropathic pain in females. Together, clarifying the mechanism underlying the earlier onset of BTZ-induced neuropathic pain will contribute to the precise treatment of multiple myeloma in females.

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