文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

前扣带皮层中多巴胺能抑制锥体神经元减少导致慢性神经性疼痛。

Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain.

机构信息

Montréal Neurological Institute, Department of Neurology & Neurosurgery, Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC H3A 2B4, Canada.

Department of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, AZ 85721, USA.

出版信息

Cell Rep. 2021 Nov 30;37(9):109933. doi: 10.1016/j.celrep.2021.109933.

DOI:10.1016/j.celrep.2021.109933
PMID:34852233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8728690/
Abstract

Pyramidal neurons in the anterior cingulate cortex (ACC), a prefrontal region involved in processing the affective components of pain, display hyperexcitability in chronic neuropathic pain conditions, and their silencing abolishes hyperalgesia. We show that dopamine, through D1 receptor (D1R) signaling, inhibits pyramidal neurons of mouse ACC by modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Activation of G-coupled D1R by dopamine induces the opening of HCN channels at physiological membrane potentials, driving a significant decrease in input resistance and excitability. Systemic L-DOPA in chronic neuropathic mice rescues HCN channel activity, normalizes pyramidal excitability in ACC, and blocks mechanical and thermal allodynia. Moreover, microinjection of a selective D1R agonist in the ACC relieves the aversiveness of ongoing neuropathic pain, while an ACC D1R antagonist blocks gabapentin- and lidocaine-evoked antinociception. We conclude that dopaminergic inhibition via D1R in ACC plays an analgesic role in physiological conditions and is decreased in chronic pain.

摘要

扣带皮层前部（ACC）中的锥体神经元参与处理疼痛的情感成分，在慢性神经性疼痛情况下表现出过度兴奋，其沉默会消除痛觉过敏。我们表明，多巴胺通过 D1 受体（D1R）信号通过调制超极化激活环核苷酸门控（HCN）通道来抑制小鼠 ACC 的锥体神经元。多巴胺激活 G 蛋白偶联的 D1R 会在生理膜电位下打开 HCN 通道，导致输入电阻和兴奋性显著降低。慢性神经性疼痛小鼠中的系统 L-DOPA 可挽救 HCN 通道活性，使 ACC 中的锥体神经元兴奋性正常化，并阻断机械和热痛觉过敏。此外，在 ACC 中微注射选择性 D1R 激动剂可缓解持续性神经性疼痛的不适，而 ACC D1R 拮抗剂可阻断加巴喷丁和利多卡因引起的镇痛作用。我们得出的结论是，ACC 中的多巴胺能抑制通过 D1R 在生理条件下起镇痛作用，而在慢性疼痛中则降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/316995d537f0/nihms-1760953-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/bd641177c58c/nihms-1760953-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/73b00cd475dd/nihms-1760953-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/66c57ea5c03a/nihms-1760953-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/b11e99c28e16/nihms-1760953-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/034983049a73/nihms-1760953-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/8b89e564a91f/nihms-1760953-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/316995d537f0/nihms-1760953-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/bd641177c58c/nihms-1760953-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/73b00cd475dd/nihms-1760953-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/66c57ea5c03a/nihms-1760953-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/b11e99c28e16/nihms-1760953-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/034983049a73/nihms-1760953-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/8b89e564a91f/nihms-1760953-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7ca/8728690/316995d537f0/nihms-1760953-f0008.jpg

相似文献

[1]
Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain.

Cell Rep. 2021-11-30

[2]
Activation of mGluR1 contributes to neuronal hyperexcitability in the rat anterior cingulate cortex via inhibition of HCN channels.

Neuropharmacology. 2016-6

[3]
Peripheral Neuropathy Induces HCN Channel Dysfunction in Pyramidal Neurons of the Medial Prefrontal Cortex.

J Neurosci. 2015-9-23

[4]
Stress Impairs Prefrontal Cortical Function via D1 Dopamine Receptor Interactions With Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels.

Biol Psychiatry. 2015-12-15

[5]
The brain-penetrant 5-HT receptor agonist LP-211 reduces the sensory and affective components of neuropathic pain.

Neurobiol Dis. 2017-7-6

[6]
Upregulation of Beta4 subunit of BK channels in the anterior cingulate cortex contributes to mechanical allodynia associated anxiety-like behaviors.

Mol Brain. 2020-2-18

[7]
Optogenetic Activation of Dopamine Receptor D1 and D2 Neurons in Anterior Cingulate Cortex Differentially Modulates Trigeminal Neuropathic Pain.

Mol Neurobiol. 2020-10

[8]
Upregulation of tumor necrosis factor-alpha in the anterior cingulate cortex contributes to neuropathic pain and pain-associated aversion.

Neurobiol Dis. 2019-4-24

[9]
Pulsed Radiofrequency Treatment Enhances Dorsal Root Ganglion Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in a Rat Model of Neuropathic Pain.

J Mol Neurosci. 2015-9

[10]
Noradrenergic fiber sprouting and altered transduction in neuropathic prefrontal cortex.

Brain Struct Funct. 2017-11-1

引用本文的文献

[1]
Disruptions of morphological brain networks and their associations with multi-symptoms in children with spastic cerebral palsy.

Quant Imaging Med Surg. 2025-9-1

[2]
Brain compensation and volume alterations in patients with severe knee osteoarthritis: a cross-sectional neuroimaging study.

Rheumatol Int. 2025-8-13

[3]
Synergistic deficits in parvalbumin interneurons and dopamine signaling drive ACC dysfunction in chronic pain.

Proc Natl Acad Sci U S A. 2025-7

[4]
The relationship between abnormal glucose metabolism and chronic pain.

Cell Biosci. 2025-6-21

[5]
The analgesic mechanism of electroacupuncture at the central level for neuropathic pain: a review of studies based on animal experiments.

Front Neurol. 2025-5-29

[6]
Inhibitory effects of dopamine agonists on pain-responsive neurons in the central nucleus of the amygdala.

J Neurophysiol. 2025-6-1

[7]
Chronic silencing of Drd1a-Cre+ neurons impairs dopaminergic-driven cortical activation.

Front Neuroanat. 2025-4-28

[8]
Mechanism of the anterior cingulate cortex in sleep regulation.

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024-10-28

[9]
High-frequency terahertz stimulation alleviates neuropathic pain by inhibiting the pyramidal neuron activity in the anterior cingulate cortex of mice.

Elife. 2024-9-27

[10]
Targeting Prefrontal Cortex Dysfunction in Pain.

J Pharmacol Exp Ther. 2024-5-21

本文引用的文献

[1]
Sex-Specific Pharmacotherapy for Back Pain: A Proof-of-Concept Randomized Trial.

Pain Ther. 2021-12

[2]
Cognition in the Chronic Pain Experience: Preclinical Insights.

Trends Cogn Sci. 2021-5

[3]
Peripheral nerve injury-induced alterations in VTA neuron firing properties.

Mol Brain. 2019-11-4

[4]
The Role of Ventral Tegmental Area Gamma-Aminobutyric Acid in Chronic Neuropathic Pain after Spinal Cord Injury in Rats.

J Neurotrauma. 2018-4-20

[5]
Hyperactivity of Anterior Cingulate Cortex Areas 24a/24b Drives Chronic Pain-Induced Anxiodepressive-like Consequences.

J Neurosci. 2018-2-20

[6]
Brain-derived neurotrophic factor-mediated projection-specific regulation of depressive-like and nociceptive behaviors in the mesolimbic reward circuitry.

Pain. 2018-1

[7]
Chronic pain and pain processing in Parkinson's disease.

Prog Neuropsychopharmacol Biol Psychiatry. 2018-12-20

[8]
The brain-penetrant 5-HT receptor agonist LP-211 reduces the sensory and affective components of neuropathic pain.

Neurobiol Dis. 2017-7-6

[9]
D3 Receptors Regulate Excitability in a Unique Class of Prefrontal Pyramidal Cells.

J Neurosci. 2017-6-14

[10]
Levodopa prevents the reinstatement of cocaine self-administration in rats via potentiation of dopamine release in the medial prefrontal cortex.

Addict Biol. 2017-4-21

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索