2. Academic Validation
  3. Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models

Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models

  • EMBO Rep. 2024 Oct 24. doi: 10.1038/s44319-024-00292-6.
Chengfei Xu # 1 2,  Yahui Wang # 1,  Chaobo Ni 1,  Miao Xu 1,  Chengyu Yin 3,  Qiuli He 1,  Bing Ma 2,  Jie Fu 1,  Baoxia Zhao 1,  Liping Chen 1,  Tong Zhi 1,  Shirong Wei 1,  Liang Cheng 2,  Hui Xu 4,  Jiajun Xiao 5,  Lei Yang 1,  Qingqing Xu 1,  Jiao Kuang 1,  Boyi Liu 6,  Qinghe Zhou 1,  Xuewu Lin 7,  Ming Yao 8,  Huadong Ni 9
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, 314001, Jiaxing, China.
  • 2 Department of Anesthesiology, The Third People's Hospital of Bengbu, 38 Shengli Middle Road, 233000, Bengbu, China.
  • 3 Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.
  • 4 Department of Anesthesiology, The First People's Hospital of Bengbu, 233000, Bengbu, China.
  • 5 Bengbu Hospital of Traditional Chinese Medicine, 4339 Huai-Shang Road, 233000, Bengbu, China.
  • 6 Department of Neurobiology and Acupuncture Research, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
  • 7 Department of Pain Medicine, The First Affiliated Hospital of Bengbu Medical University, 233000, Bengbu, China. linxuewu@bbmc.edu.cn.
  • 8 Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, 314001, Jiaxing, China. jxyaoming@zjxu.edu.cn.
  • 9 Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, 314001, Jiaxing, China. huadongni@zjxu.edu.cn.
  • # Contributed equally.
PMID: 39448865 DOI: 10.1038/s44319-024-00292-6
Abstract

Bone Cancer pain (BCP) affects ~70% of patients in advanced stages, primarily due to bone metastasis, presenting a substantial therapeutic challenge. Here, we profile orphan G protein-coupled receptors in the dorsal root ganglia (DRG) following tumor infiltration, and observe a notable increase in GPR160 expression. Elevated Gpr160 mRNA and protein levels persist from postoperative day 6 for over 18 days in the affected DRG, predominantly in small-diameter C-fiber type neurons specific to the tibia. Targeted interventions, including DRG microinjection of siRNA or AAV delivery, mitigate mechanical allodynia, cold, and heat hyperalgesia induced by the tumor. Tumor infiltration increases DRG neuron excitability in wild-type mice, but not in Gpr160 gene knockout mice. Tumor infiltration results in reduced H3K27me3 and increased H3K27ac modifications, enhanced binding of the transcription activator Sp1 to the Gpr160 gene promoter region, and induction of GPR160 expression. Modulating histone-modifying Enzymes effectively alleviated pain behavior. Our study delineates a novel mechanism wherein elevated Sp1 levels facilitate Gpr160 gene transcription in nociceptive DRG neurons during BCP in rodents.

Keywords

Bone Cancer Pain; Dorsal Root Ganglia; GPR160; Histone Modification; Peripheral Sensitization.

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