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, Dept Neurobiol, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Zheng, Qin
Fang, Dong
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Dept Neurobiol, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Fang, Dong
Liu, Min
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Dept Neurobiol, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Liu, Min
Cai, Jie
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Dept Neurobiol, Beijing 100191, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Cai, Jie
Wan, You
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Minist Educ, Key Lab Neurosci, Beijing, Peoples R China
Minist Publ Hlth, Beijing, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Wan, You
Han, Ji-Sheng
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Dept Neurobiol, Beijing 100191, Peoples R China
Minist Educ, Key Lab Neurosci, Beijing, Peoples R China
Minist Publ Hlth, Beijing, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Han, Ji-Sheng
Xing, Guo-Gang
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Peking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
Peking Univ, Dept Neurobiol, Beijing 100191, Peoples R China
Minist Educ, Key Lab Neurosci, Beijing, Peoples R China
Minist Publ Hlth, Beijing, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100191, Peoples R China
机构:
Tokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, Japan
Nippon Med Sch, Dept Pharmacol, Tokyo, JapanTokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, Japan
Ito, Takaya
Sakai, Atsushi
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Nippon Med Sch, Dept Pharmacol, Tokyo, JapanTokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, Japan
Sakai, Atsushi
Maruyama, Motoyo
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Nippon Med Sch, Dept Pharmacol, Tokyo, Japan
Nippon Med Sch, Div Lab Anim Sci, Tokyo, JapanTokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, Japan
Maruyama, Motoyo
Miyagawa, Yoshitaka
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Nippon Med Sch, Dept Mol & Med Genet, Tokyo, JapanTokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, Japan
Miyagawa, Yoshitaka
Okada, Takashi
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Nippon Med Sch, Dept Mol & Med Genet, Tokyo, JapanTokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, Japan
Okada, Takashi
Fukayama, Haruhisa
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Tokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, JapanTokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, Japan
Fukayama, Haruhisa
Suzuki, Hidenori
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Nippon Med Sch, Dept Pharmacol, Tokyo, JapanTokyo Med & Dent Univ, Grad Sch, Anesthesiol & Clin Physiol, Tokyo, Japan
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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 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:
Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USAUniv Cincinnati, Med Ctr, Dept Anesthesiol, Pain Res Ctr, Cincinnati, OH 45267 USA
Qadri, Yawar
Tan, Ping-Heng
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I Shou Univ, Sch Med, E Da Hosp, Dept Anesthesiol, Kaohsiung, TaiwanUniv Cincinnati, Med Ctr, Dept Anesthesiol, Pain Res Ctr, Cincinnati, OH 45267 USA
Tan, Ping-Heng
Ji, Ru-Rong
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Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA
Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USAUniv Cincinnati, Med Ctr, Dept Anesthesiol, Pain Res Ctr, Cincinnati, OH 45267 USA
机构:
Peking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China
Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Neurobiol, Beijing 100871, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China
Liu, Xiao-Dan
Yang, Jing-Jing
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Peking Univ, Neurosci Res Inst, Beijing 100871, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China
Yang, Jing-Jing
Fang, Dong
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Peking Univ, Neurosci Res Inst, Beijing 100871, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China
Fang, Dong
Cai, Jie
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Peking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China
Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Neurobiol, Beijing 100871, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China
Cai, Jie
Wan, You
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Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Neurobiol, Beijing 100871, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China
Wan, You
Xing, Guo-Gang
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Peking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China
Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Neurobiol, Beijing 100871, Peoples R China
Minist Educ, Key Lab Neurosci, Beijing, Peoples R China
Minist Hlth, Beijing, Peoples R ChinaPeking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China