Suppression of KCNQ/M Potassium Channel in Dorsal Root Ganglia Neurons Contributes to the Development of Osteoarthritic Pain

被引:12
|
作者
Zhang, Fan [1 ]
Liu, Yani [2 ]
Zhang, Dandan [1 ]
Fan, Xizhenzi [1 ]
Shao, Decheng [3 ]
Li, Han [3 ]
机构
[1] Hebei Med Univ, Dept Biochem & Mol Biol, Shijiazhuang, Hebei, Peoples R China
[2] Qingdao Univ, Sch Pharm, Dept Pharmacol, Qingdao, Shandong, Peoples R China
[3] Hebei Med Univ, Hosp 3, Dept Orthopaed Surg, Biomech Key Lab Hebei Prov,Inst Biomech Sci, Shijiazhuang, Hebei, Peoples R China
基金
中国国家自然科学基金;
关键词
KCNQ/M channels; Osteoarthritic pain; Dorsal root ganglia; Modulators; RAT MODEL; RETIGABINE; OPENER; PERSISTENT;
D O I
10.1159/000496422
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Osteoarthritic pain has a strong impact on patients' quality of life. Understanding the pathogenic mechanisms underlying osteoarthritic pain will likely lead to the development of more effective treatments. In the present study of osteoarthritic model rats, we observed a reduction of M-current density and a remarkable decrease in the levels of KCNQ2 and KCNQ3 proteins and mRNAs in dorsal root ganglia (DRG) neurons, which were associated with hyperalgesic behaviors. The activation of KCNQ/M channels with flupirtine significantly increased the mechanical threshold and prolonged the withdrawal latency of osteoarthritic model rats at 3-14 days after model induction, and all effects of flupirtine were blocked by KCNQ/M-channel antagonist, XE-991. Together, these results indicate that suppression of KCNQ/M channels in primary DRG neurons plays a crucial role in the development of osteoarthritic pain. (c) 2019 S. Karger AG, Basel
引用
收藏
页码:257 / 262
页数:6
相关论文
共 37 条
  • [1] Suppression of KCNQ/M (Kv7) potassium channels in dorsal root ganglion neurons contributes to the development of bone cancer pain in a rat model
    Zheng, Qin
    Fang, Dong
    Liu, Min
    Cai, Jie
    Wan, You
    Han, Ji-Sheng
    Xing, Guo-Gang
    PAIN, 2013, 154 (03) : 434 - 448
  • [2] Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats
    Ito, Takaya
    Sakai, Atsushi
    Maruyama, Motoyo
    Miyagawa, Yoshitaka
    Okada, Takashi
    Fukayama, Haruhisa
    Suzuki, Hidenori
    MOLECULAR PAIN, 2020, 16
  • [3] Suppression of KCNQ/ME (Kv7) potassium channels in the spinal cord contributes to the sensitization of dorsal horn WDR neurons and pain hypersensitivity in a rat model of bone cancer pain
    Cai, Jie
    Fang, Dong
    Liu, Xiao-Dan
    Li, Song
    Ren, Juan
    Xing, Guo-Gang
    ONCOLOGY REPORTS, 2015, 33 (03) : 1540 - 1550
  • [4] Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain
    Berta, Temugin
    Qadri, Yawar
    Tan, Ping-Heng
    Ji, Ru-Rong
    EXPERT OPINION ON THERAPEUTIC TARGETS, 2017, 21 (07) : 695 - 703
  • [5] Functional Upregulation of Nav1.8 Sodium Channels on the Membrane of Dorsal Root Ganglia Neurons Contributes to the Development of Cancer-Induced Bone Pain
    Liu, Xiao-Dan
    Yang, Jing-Jing
    Fang, Dong
    Cai, Jie
    Wan, You
    Xing, Guo-Gang
    PLOS ONE, 2014, 9 (12):
  • [6] Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain: an update
    Berta, Temugin
    Strong, Judith A.
    Zhang, Jun-Ming
    Ji, Ru-Rong
    EXPERT OPINION ON THERAPEUTIC TARGETS, 2023, 27 (08) : 665 - 678
  • [7] Hedgehog signaling is directly required for the development of zebrafish dorsal root ganglia neurons
    Ungos, JM
    Karlstrom, RO
    Raible, DW
    DEVELOPMENT, 2003, 130 (22): : 5351 - 5362
  • [8] Defective branched-chain amino acid catabolism in dorsal root ganglia contributes to mechanical pain
    Xie, Huijing
    Li, Ju
    Lian, Nan
    Xie, Min
    Wu, Minming
    Tang, Kuo
    Kang, Yi
    Lu, Peilin
    Li, Tao
    EMBO REPORTS, 2023, 24 (11)
  • [9] α7-nAChR-mediated suppression of hyperexcitability of colonic dorsal root ganglia neurons in experimental colitis
    Abdrakhmanova, Galya R.
    AlSharari, Shakir
    Kang, Minho
    Damaj, M. Imad
    Akbarali, Hamid I.
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2010, 299 (03): : G761 - G768
  • [10] Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury
    Wu, Zizhen
    Li, Lin
    Xie, Fuhua
    Du, Junhui
    Zuo, Yan
    Frost, Jeffrey A.
    Carlton, Susan M.
    Walters, Edgar T.
    Yang, Qing
    JOURNAL OF NEUROTRAUMA, 2017, 34 (06) : 1260 - 1270