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
机构:
Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Neurobiol, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Cai, Jie
;
Fang, Dong
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Fang, Dong
;
Liu, Xiao-Dan
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Liu, Xiao-Dan
;
Li, Song
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Li, Song
;
Ren, Juan
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Xi An Jiao Tong Univ, Hosp 1, Ctr Canc, Xian 710061, Shaanxi, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Ren, Juan
;
Xing, Guo-Gang
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Neurobiol, Beijing 100191, Peoples R China
Minist Educ, Key Lab Neurosci, Beijing 100191, Peoples R China
Minist Hlth, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
机构:
Univ Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Hebei Med Univ, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R ChinaUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Gao, Haixia
;
Boillat, Aurelien
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Univ Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, EnglandUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Boillat, Aurelien
;
Huang, Dongyang
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Hebei Med Univ, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R ChinaUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Huang, Dongyang
;
Liang, Ce
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Hebei Med Univ, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R ChinaUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Liang, Ce
;
Peers, Chris
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Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Fac Med & Hlth, Leeds LS2 9JT, W Yorkshire, EnglandUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Peers, Chris
;
Gamper, Nikita
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Univ Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Hebei Med Univ, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R ChinaUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
机构:
Takeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, JapanTakeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, Japan
Hayashi, Hiroki
;
Iwata, Masashi
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Takeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, JapanTakeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, Japan
Iwata, Masashi
;
Tsuchimori, Noboru
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Takeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, JapanTakeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, Japan
Tsuchimori, Noboru
;
Matsumoto, Tatsumi
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Takeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, JapanTakeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, Japan
机构:
Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Neurobiol, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Cai, Jie
;
Fang, Dong
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Fang, Dong
;
Liu, Xiao-Dan
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Liu, Xiao-Dan
;
Li, Song
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机构:
Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Li, Song
;
Ren, Juan
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机构:
Xi An Jiao Tong Univ, Hosp 1, Ctr Canc, Xian 710061, Shaanxi, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Ren, Juan
;
Xing, Guo-Gang
论文数: 0引用数: 0
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机构:
Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Neurobiol, Beijing 100191, Peoples R China
Minist Educ, Key Lab Neurosci, Beijing 100191, Peoples R China
Minist Hlth, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
机构:
Univ Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Hebei Med Univ, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R ChinaUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Gao, Haixia
;
Boillat, Aurelien
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Univ Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, EnglandUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Boillat, Aurelien
;
Huang, Dongyang
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Hebei Med Univ, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R ChinaUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Huang, Dongyang
;
Liang, Ce
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Hebei Med Univ, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R ChinaUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Liang, Ce
;
Peers, Chris
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机构:
Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Fac Med & Hlth, Leeds LS2 9JT, W Yorkshire, EnglandUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Peers, Chris
;
Gamper, Nikita
论文数: 0引用数: 0
h-index: 0
机构:
Univ Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
Hebei Med Univ, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R ChinaUniv Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
机构:
Takeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, JapanTakeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, Japan
Hayashi, Hiroki
;
Iwata, Masashi
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机构:
Takeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, JapanTakeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, Japan
Iwata, Masashi
;
Tsuchimori, Noboru
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机构:
Takeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, JapanTakeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, Japan
Tsuchimori, Noboru
;
Matsumoto, Tatsumi
论文数: 0引用数: 0
h-index: 0
机构:
Takeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, JapanTakeda Pharmaceut Co Ltd, Inflammat Drug Discovery Unit, Div Pharmaceut Res, Fujisawa, Kanagawa, Japan