脊髓HDAC6通过神经元激活和神经炎症介导CCI诱导的伤害性行为。

IF 2.8 3区 医学 Q2 NEUROSCIENCES
Kai Sun, Hao Zhang, Ting Zhang, Nan Sun, Jingru Hao, Zhiping Wang, Can Gao
{"title":"脊髓HDAC6通过神经元激活和神经炎症介导CCI诱导的伤害性行为。","authors":"Kai Sun, Hao Zhang, Ting Zhang, Nan Sun, Jingru Hao, Zhiping Wang, Can Gao","doi":"10.1177/17448069231218352","DOIUrl":null,"url":null,"abstract":"<p><p>Neuropathic pain (NP) is often accompanied by psychiatric comorbidities and currently lacks effective treatment. Prior research has shown that HDAC6 plays a crucial role in pain sensitization, but the specific mechanisms remain unclear. HDAC6 inhibitors have been found to alleviate mechanical allodynia caused by inflammation and peripheral nerve damage. In this study, we investigated the cellular mechanisms of HDAC6 in the development and maintenance of neuropathic pain. Our findings indicate that HDAC6 expression in the spinal cord (SC) is upregulated in a time-dependent manner following chronic constriction injury (CCI). HDAC6 is primarily expressed in neurons and microglia in the spinal cord. CCI-induced HDAC6 production was abolished by intrathecal injection of a microglia inhibitor. ACY-1215, a specific HDAC6 inhibitor, significantly reduced CCI-induced mechanical allodynia, but not thermal hyperalgesia. ACY-1215 also inhibited neuron activation and suppressed CCI-induced pyroptosis and neuroinflammatory responses. In summary, our results suggest that HDAC6 contributes to the development and maintenance of NP through neuronal activation and neuroinflammation. HDAC6 may be a promising target for treating NP.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734332/pdf/","citationCount":"0","resultStr":"{\"title\":\"Spinal HDAC6 mediates nociceptive behaviors induced by chronic constriction injury via neuronal activation and neuroinflammation.\",\"authors\":\"Kai Sun, Hao Zhang, Ting Zhang, Nan Sun, Jingru Hao, Zhiping Wang, Can Gao\",\"doi\":\"10.1177/17448069231218352\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Neuropathic pain (NP) is often accompanied by psychiatric comorbidities and currently lacks effective treatment. Prior research has shown that HDAC6 plays a crucial role in pain sensitization, but the specific mechanisms remain unclear. HDAC6 inhibitors have been found to alleviate mechanical allodynia caused by inflammation and peripheral nerve damage. In this study, we investigated the cellular mechanisms of HDAC6 in the development and maintenance of neuropathic pain. Our findings indicate that HDAC6 expression in the spinal cord (SC) is upregulated in a time-dependent manner following chronic constriction injury (CCI). HDAC6 is primarily expressed in neurons and microglia in the spinal cord. CCI-induced HDAC6 production was abolished by intrathecal injection of a microglia inhibitor. ACY-1215, a specific HDAC6 inhibitor, significantly reduced CCI-induced mechanical allodynia, but not thermal hyperalgesia. ACY-1215 also inhibited neuron activation and suppressed CCI-induced pyroptosis and neuroinflammatory responses. In summary, our results suggest that HDAC6 contributes to the development and maintenance of NP through neuronal activation and neuroinflammation. HDAC6 may be a promising target for treating NP.</p>\",\"PeriodicalId\":19010,\"journal\":{\"name\":\"Molecular Pain\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734332/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Pain\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17448069231218352\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17448069231218352","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

神经性疼痛通常伴有精神疾病,目前缺乏有效的治疗方法。先前的研究表明,HDAC6在疼痛致敏中起着至关重要的作用,但具体的机制尚不清楚。已发现HDAC6抑制剂可减轻炎症和周围神经损伤引起的机械性异常痛。在这项研究中,我们研究了HDAC6在神经性疼痛发生和维持中的细胞机制。我们的研究结果表明,慢性收缩损伤(CCI)后,HDAC6在脊髓(SC)中的表达以时间依赖性的方式上调。HDAC6主要在脊髓的神经元和小胶质细胞中表达。鞘内注射小胶质细胞抑制剂可消除cci诱导的HDAC6生成。ACY-1215是一种特异性HDAC6抑制剂,可显著降低cci诱导的机械异常性痛,但对热痛觉过敏没有作用。ACY-1215还能抑制神经元激活,抑制cci诱导的焦亡和神经炎症反应。总之,我们的研究结果表明,HDAC6通过神经元激活和神经炎症参与NP的发展和维持。HDAC6可能是治疗NP的一个有希望的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Spinal HDAC6 mediates nociceptive behaviors induced by chronic constriction injury via neuronal activation and neuroinflammation.

Neuropathic pain (NP) is often accompanied by psychiatric comorbidities and currently lacks effective treatment. Prior research has shown that HDAC6 plays a crucial role in pain sensitization, but the specific mechanisms remain unclear. HDAC6 inhibitors have been found to alleviate mechanical allodynia caused by inflammation and peripheral nerve damage. In this study, we investigated the cellular mechanisms of HDAC6 in the development and maintenance of neuropathic pain. Our findings indicate that HDAC6 expression in the spinal cord (SC) is upregulated in a time-dependent manner following chronic constriction injury (CCI). HDAC6 is primarily expressed in neurons and microglia in the spinal cord. CCI-induced HDAC6 production was abolished by intrathecal injection of a microglia inhibitor. ACY-1215, a specific HDAC6 inhibitor, significantly reduced CCI-induced mechanical allodynia, but not thermal hyperalgesia. ACY-1215 also inhibited neuron activation and suppressed CCI-induced pyroptosis and neuroinflammatory responses. In summary, our results suggest that HDAC6 contributes to the development and maintenance of NP through neuronal activation and neuroinflammation. HDAC6 may be a promising target for treating NP.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Molecular Pain
Molecular Pain 医学-神经科学
CiteScore
5.60
自引率
3.00%
发文量
56
审稿时长
6-12 weeks
期刊介绍: Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信