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Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety.

作者信息

Wang Guo-Qiang, Cen Cheng, Li Chong, Cao Shuai, Wang Ning, Zhou Zheng, Liu Xue-Mei, Xu Yu, Tian Na-Xi, Zhang Ying, Wang Jun, Wang Li-Ping, Wang Yun

机构信息

Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.

Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

出版信息

Nat Commun. 2015 Jul 16;6:7660. doi: 10.1038/ncomms8660.

DOI:10.1038/ncomms8660
PMID:26179626
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4518290/
Abstract

The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/770249dca44a/ncomms8660-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/e8bea31a33b0/ncomms8660-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/af8ed0e7c6f9/ncomms8660-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/0fcd63a60d37/ncomms8660-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/8431040fec29/ncomms8660-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/bd1d01018e05/ncomms8660-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/b35e31489e20/ncomms8660-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/2076050d16e3/ncomms8660-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/770249dca44a/ncomms8660-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/e8bea31a33b0/ncomms8660-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/af8ed0e7c6f9/ncomms8660-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/0fcd63a60d37/ncomms8660-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/8431040fec29/ncomms8660-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/bd1d01018e05/ncomms8660-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/b35e31489e20/ncomms8660-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/2076050d16e3/ncomms8660-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc46/4518290/770249dca44a/ncomms8660-f8.jpg

相似文献

[1]
Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety.

Nat Commun. 2015-7-16

[2]
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[3]
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[4]
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[6]
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[7]
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[8]
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[9]
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引用本文的文献

[1]
Distinct neural circuits processing pleasant and unpleasant sounds: an fMRI-based approach.

BMC Neurosci. 2025-8-26

[2]
Disruptions in cortical circuit connectivity distinguish widespread hyperalgesia from localized pain.

Front Pain Res (Lausanne). 2025-6-20

[3]
Chronic unpredictable stress produces hyperalgesia and promotes inhibitory drive in medial prefrontal cortex.

J Pain. 2025-8

[4]
Excitatory projections from the nucleus reuniens to the medial prefrontal cortex modulate pain and depression-like behaviors in mice.

PLoS Biol. 2025-5-20

[5]
The Burning Pain Transcriptome in the Mouse Primary Somatosensory Cortex.

Int J Mol Sci. 2025-4-9

[6]
Zingerone alleviates inflammatory pain by reducing the intrinsic excitability of anterior cingulate cortex neurons in a mice model.

Front Pharmacol. 2025-3-11

[7]
A systematic review of the pain-related emotional and cognitive impairments in chronic inflammatory pain induced by CFA injection and its mechanism.

IBRO Neurosci Rep. 2025-2-27

[8]
Stress-induced GHS-R1a expression in medial prefrontal cortical neurons promotes vulnerability to anxiety in mice.

Commun Biol. 2025-3-13

[9]
Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit.

Nat Commun. 2025-1-22

[10]
Action potential-independent spontaneous microdomain Ca transients-mediated continuous neurotransmission regulates hyperalgesia.

Proc Natl Acad Sci U S A. 2025-1-21

本文引用的文献

[1]
Activation of corticostriatal circuitry relieves chronic neuropathic pain.

J Neurosci. 2015-4-1

[2]
Coexistence of two forms of LTP in ACC provides a synaptic mechanism for the interactions between anxiety and chronic pain.

Neuron. 2014-12-31

[3]
Brain signature of chronic orofacial pain: a systematic review and meta-analysis on neuroimaging research of trigeminal neuropathic pain and temporomandibular joint disorders.

PLoS One. 2014-4-23

[4]
Prefrontal cortical circuit for depression- and anxiety-related behaviors mediated by cholecystokinin: role of ΔFosB.

J Neurosci. 2014-3-12

[5]
Psychological processing in chronic pain: a neural systems approach.

Neurosci Biobehav Rev. 2013-12-27

[6]
Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression.

Nature. 2013-11-20

[7]
Upregulation of presynaptic proteins and protein kinases associated with enhanced glutamate release from axonal terminals (synaptosomes) of the medial prefrontal cortex in rats with neuropathic pain.

Pain. 2014-2

[8]
Surgical incision-induced nociception causes cognitive impairment and reduction in synaptic NMDA receptor 2B in mice.

J Neurosci. 2013-11-6

[9]
Distinct behavioural and network correlates of two interneuron types in prefrontal cortex.

Nature. 2013-5-26

[10]
Enhanced excitability in the infralimbic cortex produces anxiety-like behaviors.

Neuropharmacology. 2013-5-3

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