|Table of Contents|

Analgesic effect of sodium valproate on oxaliplatin chemotherapy-induced pain in rats and its mechanism

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 07
Page:
1181-1187
Research Field:
Publishing date:

Info

Title:
Analgesic effect of sodium valproate on oxaliplatin chemotherapy-induced pain in rats and its mechanism
Author(s):
CAO Yuanyuan1; YAN Ying2; YANG Heyu1; WU Ji3; XIE Min1; ZHANG Jun1; LU Hong1
1.School of Pharmacy,Medical College,Hubei University of Science and Technology,Hubei Xianning 437100,China;2.Xishui Hospital Affiliated to Hubei University of Science and Technology,Hubei Huanggang 438802,China;3.Clinical College of Youjiang Medical University for Nationalities,Guangxi Baise 533000,China.
Keywords:
sodium valproate; chemotherapy pain; neuroinflammation; histone deacetylase; Toll-like receptor 4/nuclear transcription factor-κB/interleukin-1β
PACS:
R730.5
DOI:
10.3969/j.issn.1672-4992.2023.07.001
Abstract:
Objective:To investigate the analgesic effect and mechanism of sodium valproate on oxaliplatin(OXA) chemotherapy-induced pain rats.Methods:A rat model of chemotherapy pain was established by five consecutive days of intraperitoneal injection of oxaliplatin.The rats were randomly divided into three groups（control group,model group and sodium valproate treatment group）.The behavioral tests and protein expression analysis were performed followed by intrathecal administration of sodium valproate.Changes in pain behavior and motor performance of rats were recorded.Molecular docking analyzed the binding of sodium valproate to histone deacetylase(HDAC6).Immunofluorescence and Western blot were used to detect the expression levels of HDAC6,astrocyte marker(GFAP),pro-inflammatory cytokine interleukin 1β,and components of Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor κB(NF-κB)/ Caspase-1 in the spinal cord from different group.In contrast to control group,Western blot and immunofluorescence analysis showed that expression levels of HDAC6,IL-1β,GFAP,TLR4,MyD88,NF-κB,and Caspase-1 (P<0.05) increased in spinal cord.Compared with the model group,intrathecal injection of sodium valproate significantly decreased the number of spontaneous flinches(P<0.05),increased mechanical pain threshold(P<0.05),increased the latency and distance on the rotarod(P<0.05).Moreover,sodium valproate administration reduced protein levels of HDAC6,IL-1β,GFAP,TLR4,MyD88,NF-κB and Caspase-1(P<0.05).Conclusion:Sodium valproate may inhibit spinal TLR4/NF-κB/IL-1β inflammatory signaling by targeting HDAC6 to alleviate chemotherapy-induced pain in rats.groups.Results:Behavioral testing showed that continuous intraperitoneal injection of OXA induced increased spontaneous flinches(P<0.05),decreased mechanical pain threshold(P<0.05),and impaired motor performance(P<0.05) compared with control group.In contrast to control group,Western blot and immunofluorescence analysis showed that expression levels of HDAC6,IL-1β,GFAP,TLR4,MyD88,NF-κB,and Caspase-1 (P<0.05) increased in spinal cord.Compared with the model group,intrathecal injection of sodium valproate significantly decreased the number of spontaneous flinches(P<0.05),increased mechanical pain threshold(P<0.05),increased the latency and distance on the rotarod(P<0.05).Moreover,sodium valproate administration reduced protein levels of HDAC6,IL-1β,GFAP,TLR4,MyD88,NF-κB and Caspase-1(P<0.05).Conclusion:Sodium valproate may inhibit spinal TLR4/NF-κB/IL-1β inflammatory signaling by targeting HDAC6 to alleviate chemotherapy-induced pain in rats.

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Memo

Memo:
National Natural Science Foundation of China（No.81901149）;国家自然科学基金资助项目（编号：81901149）；湖北省教育厅项目（编号：B2021230）；湖北科技学院校级团队项目（编号：2020TD02）
Last Update: 2023-02-28