BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury DOI Creative Commons
Lianyan Huang, Jianhua Jin, Kai Chen

et al.

PLoS Biology, Journal Year: 2021, Volume and Issue: 19(7), P. e3001337 - e3001337

Published: July 22, 2021

Peripheral nerve injury–induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet mechanisms underlying such maladaptive plasticity remain unclear. Here, we show that male mice, structural and functional changes primary somatosensory cortex (S1) caused peripheral injury require neuron-microglial signaling within local circuit. Following injury, microglia S1 maintain ramified morphology normal density but up-regulate mRNA expression of brain-derived neurotrophic factor (BDNF). Using vivo two-photon imaging Cx3cr1 CreER ; Bdnf flox conditional knockout BDNF from prevents synaptic remodeling pyramidal neuron hyperactivity S1, as well pain hypersensitivity mice. Importantly, S1-targeted removal microglial largely recapitulates beneficial effects systemic depletion on allodynia. Together, these findings reveal a pivotal role cerebral hypersensitivity.

Language: Английский

Neuropathic Pain: From Mechanisms to Treatment DOI
Nanna Brix Finnerup, Rohini Kuner, Troels S. Jensen

et al.

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(1), P. 259 - 301

Published: June 25, 2020

Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is common chronic condition with major impact on quality life. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic and central poststroke pain. Most patients complain an ongoing intermittent spontaneous of, for example, burning, pricking, squeezing quality, which may be accompanied evoked pain, particular to light touch cold. Ectopic activity in, nerve-end neuroma, compressed nerves nerve roots, dorsal root ganglia, thalamus in different conditions underlie Evoked spread neighboring areas, underlying pathophysiology involves peripheral sensitization. Maladaptive structural changes number cell-cell interactions molecular signaling sensitization nociceptive pathways. These alteration ion channels, activation immune cells, glial-derived mediators, epigenetic regulation. The classes therapeutics drugs acting α 2 δ subunits calcium sodium descending modulatory inhibitory

Language: Английский

Citations

1032
A neuronal circuit for activating descending modulation of neuropathic pain DOI
Junting Huang, Vinícius M. Gadotti, Lina Chen

et al.

Nature Neuroscience, Journal Year: 2019, Volume and Issue: 22(10), P. 1659 - 1668

Published: Sept. 9, 2019

Language: Английский

Citations

260
Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment DOI Creative Commons
Irene Tracey, Clifford J. Woolf, Nick Andrews

et al.

Neuron, Journal Year: 2019, Volume and Issue: 101(5), P. 783 - 800

Published: March 1, 2019

Language: Английский

Citations

201
A harmonized atlas of mouse spinal cord cell types and their spatial organization DOI Creative Commons
D. Russ, Ryan B. Patterson Cross, Li Li

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 29, 2021

Abstract Single-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases mouse spinal cord have been published in recent years but not integrated together. Here, we generate an atlas types based on single-cell transcriptomic data, unifying available datasets into a common reference framework. We report hierarchical structure postnatal relationships, with location providing highest level organization, then neurotransmitter status, family, and finally, dozens refined populations. validate combinatorial marker code for each neuronal map their spatial distributions adult cord. also show complex lineage relationships among Additionally, develop open-source classifier, SeqSeek, to facilitate standardization identification. This work provides view types, gene expression signatures, organization.

Language: Английский

Citations

183
Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury DOI Creative Commons
Cédric Peirs, Sean-Paul G. Williams, Xinyi Zhao

et al.

Neuron, Journal Year: 2020, Volume and Issue: 109(1), P. 73 - 90.e7

Published: Nov. 11, 2020

Language: Английский

Citations

153
Brain circuits for pain and its treatment DOI
Nicole Mercer Lindsay, Chong Chen, Gadi Gilam

et al.

Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(619)

Published: Nov. 10, 2021

Understanding the organization of brain’s pain circuits is critical for developing effective treatments patients suffering from chronic pain.

Language: Английский

Citations

149
Neocortical circuits in pain and pain relief DOI
Linette Liqi Tan, Rohini Kuner

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(8), P. 458 - 471

Published: June 14, 2021

Language: Английский

Citations

115
Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states DOI
Xia Zhu,

Hao-Di Tang,

Wanying Dong

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(4), P. 542 - 553

Published: March 8, 2021

Language: Английский

Citations

108
Neuropathic pain caused by miswiring and abnormal end organ targeting DOI Creative Commons
Vijayan Gangadharan, Hongwei Zheng, Francisco J. Taberner

et al.

Nature, Journal Year: 2022, Volume and Issue: 606(7912), P. 137 - 145

Published: May 25, 2022

Abstract Nerve injury leads to chronic pain and exaggerated sensitivity gentle touch (allodynia) as well a loss of sensation in the areas which injured non-injured nerves come together 1–3 . The mechanisms that disambiguate these mixed paradoxical symptoms are unknown. Here we longitudinally non-invasively imaged genetically labelled populations fibres sense noxious stimuli (nociceptors) (low-threshold afferents) peripherally skin for longer than 10 months after nerve injury, while simultaneously tracking pain-related behaviour same mice. Fully denervated initially lost sensation, gradually recovered normal developed marked allodynia aversion several injury. This reinnervation-induced neuropathic involved nociceptors sprouted into territories precisely reproducing initial pattern innervation, were guided by blood vessels showed irregular terminal connectivity lowered activation thresholds mimicking low-threshold afferents. By contrast, afferents—which normally mediate intact 4–7 —did not reinnervate, leading an aberrant innervation tactile end organs such Meissner corpuscles with alone. Genetic ablation fully abrogated reinnervation allodynia. Our results thus reveal emergence form is driven structural plasticity, abnormal malfunction during reinnervation, provide mechanistic framework sensory manifestations observed clinically can impose heavy burden on patients.

Language: Английский

Citations

103
Sound induces analgesia through corticothalamic circuits DOI Open Access
Wenjie Zhou, Chonghuan Ye, Haitao Wang

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6602), P. 198 - 204

Published: July 7, 2022

Sound-including music and noise-can relieve pain in humans, but the underlying neural mechanisms remain unknown. We discovered that analgesic effects of sound depended on a low (5-decibel) signal-to-noise ratio (SNR) relative to ambient noise mice. Viral tracing, microendoscopic calcium imaging, multitetrode recordings freely moving mice showed low-SNR sounds inhibited glutamatergic inputs from auditory cortex (ACxGlu) thalamic posterior (PO) ventral (VP) nuclei. Optogenetic or chemogenetic inhibition ACxGlu→PO ACxGlu→VP circuits mimicked sound-induced analgesia inflamed hindpaws forepaws, respectively. Artificial activation these two abolished analgesia. Our study reveals corticothalamic sound-promoted by deciphering role system processing.

Language: Английский

Citations

75