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Sodium butyrate restored TRESK current controlling neuronal hyperexcitability in a mouse model of oxaliplatin-induced peripheral neuropathic pain
被引:0
|作者:
Ho, Idy H. T.
[1
,2
]
Zou, Yidan
[1
,2
]
Luo, Kele
[3
]
Qin, Fenfen
[1
,2
]
Jiang, Yanjun
[1
,2
]
Li, Qian
[1
,2
]
Jin, Tingting
[1
,2
]
Zhang, Xinyi
[1
,2
]
Chen, Huarong
[1
,2
,4
,5
]
Tan, Likai
[1
,2
]
Zhang, Lin
[5
,6
,7
]
Gin, Tony
[1
,2
]
Wu, William K. K.
[1
,2
,3
,5
]
Chan, Matthew T. V.
[1
,2
]
Jiang, Changyu
[8
,9
]
Liu, Xiaodong
[1
,2
]
机构:
[1] Chinese Univ Hong Kong, Fac Med, Dept Anaesthesia & Intens Care, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Peter Hung Pain Res Inst, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Shenzhen, Peoples R China
[4] Chinese Univ Hong Kong, Inst Digest Dis, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China
[5] Chinese Univ Hong Kong, State Key Lab Digest Dis, Hong Kong, Peoples R China
[6] Chinese Univ Hong Kong, Microbiota I Ctr MagIC, Hong Kong, Peoples R China
[7] Chinese Univ Hong Kong, Fac Med, Dept Med & Therapeut, Hong Kong, Peoples R China
[8] Shenzhen Univ, Affiliated Hosp 6, Med Sch, Dept Pain Med, Shenzhen, Peoples R China
[9] Shenzhen Univ, Affiliated Hosp 6, Med Sch, Shenzhen Municipal Key Lab Pain Med, Shenzhen, Peoples R China
基金:
中国国家自然科学基金;
关键词:
Chemotherapy-induced peripheral neuropathy;
Butyrate;
Epigenetics;
Histone deacetylase inhibition;
Dorsal root ganglion;
HISTONE DEACETYLASES;
K+ CHANNELS;
SPINAL-CORD;
EXPRESSION;
HYPERSENSITIVITY;
INHIBITORS;
BEHAVIORS;
RECEPTORS;
HDACS;
D O I:
10.1016/j.neurot.2024.e00481
中图分类号:
R74 [神经病学与精神病学];
学科分类号:
摘要:
Chemotherapy-induced peripheral neuropathy (CIPN) and its related pain are common challenges for patients receiving oxaliplatin chemotherapy. Oxaliplatin accumulation in dorsal root ganglion (DRGs) is known to impair gene transcription by epigenetic dysregulation. We hypothesized that sodium butyrate, a pro-resolution shortchain fatty acid, inhibited histone acetylation in DRGs and abolished K+ channel dysregulation-induced neuronal hyperexcitability after oxaliplatin treatment. Mechanical allodynia and cold hyperalgesia of mice receiving an accumulation of 15 mg/kg oxaliplatin, with or without intraperitoneal sodium butyrate supplementation, were assessed using von Frey test and acetone evaporation test. Differential expressions of histone deacetylases (HDACs) and pain-related K+ channels were quantified with rt-qPCR and protein assays. Immunofluorescence assays of histone acetylation at H3K9/14 were performed in primary DRG cultures treated with sodium butyrate. Current clamp recording of action potentials and persistent outward current of Twik-related-spinal cord K+ (TRESK) channel were recorded in DRG neurons with small diameters extract. Accompanied by mechanical allodynia and cold hyperalgesia, HDAC1 was upregulated in mice receiving oxaliplatin treatment. Sodium butyrate enhanced global histone acetylation at H3K9/14 in DRG neurons. In vivo sodium butyrate supplementation restored oxaliplatin-induced Kcnj9 and Kcnk18 expression and pain-related behaviors in mice for at least 14 days. Oxaliplatin-induced increase in action potentials frequencies and decrease in magnitudes of KCNK18-related current were reversed in mice receiving sodium butyrate supplementation. This study suggests that sodium butyrate was a useful agent to relieve oxaliplatin-mediated neuropathic pain.
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