Evidence map›Paper›PMID 38712022›Full record

ArticlebioRxiv : the preprint server for biology2024

The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States.

Aman Upadhyay, Mark A Gradwell, Thomas J Vajtay, James Conner, Arnab A Sanyal, Chloe Azadegan, Komal R Patel, Joshua K Thackray, Manon Bohic, Fumiyasu Imai and 5 more

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In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Aman UpadhyayW.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA; Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.ORCID 0000-0001-6447-0368
Mark A GradwellW.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA; Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.ORCID 0000-0003-3308-8005
Thomas J VajtayW.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA; Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.
James ConnerMolecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID 0000-0002-0731-8746
Arnab A SanyalW.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA; Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.
Chloe AzadeganW.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA; Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.ORCID 0000-0002-1266-1637
Komal R PatelW.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA; Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.
Joshua K ThackrayHuman Genetics Institute of New Jersey, Rutgers University, The State University of New Jersey, Piscataway, New Jersey, USA.ORCID 0000-0003-2828-452X
Manon BohicW.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA; Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.ORCID 0000-0003-4400-8314
Fumiyasu ImaiBurke Neurological Institute, White Plains, New York City, New York, USA.ORCID 0000-0003-1364-1846
Simon O OgundareZuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA; Department of Biological Sciences, Columbia University, New York City, New York, USA.
Yutaka YoshidaBurke Neurological Institute, White Plains, New York City, New York, USA.ORCID 0000-0003-0664-0888
Ishmail Abdus-SaboorZuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA; Department of Biological Sciences, Columbia University, New York City, New York, USA.ORCID 0000-0003-2120-0063
Eiman AzimMolecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID 0000-0002-1015-1772
Victoria E AbrairaW.M. Keck Center for Collaborative Neuroscience, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA; Cell Biology and Neuroscience Department, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.ORCID 0000-0001-9936-9921

Funding

Using Mouse Pain Scales to Discover Unusual Pain Sensitivity and New Pain TargetsDP2NS130454 · NINDS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI ABDUS-SABOOR, ISHMAIL JOHN · 2022 to 2023
$2.5M
Touching on locomotion: Olise Oputa Diversity Supplement_Nov 15R01NS119268 · NINDS · RUTGERS, THE STATE UNIV OF N.J. · PI ABRAIRA, VICTORIA EUGENIA GUADALUPE · 2020 to 2024
$2.5M
Refining Oxytocin Therapy for Pain: Context is KeyR01NS124799 · NINDS · RUTGERS, THE STATE UNIV OF N.J. · PI Victoria Eugenia Guadalupe Abraira · 2023 to 2026
$2.0M
A new mechanistic and technological framework for uncovering the spinal cord neural systems important for functional recovery after injuryK01NS116224 · NINDS · RUTGERS, THE STATE UNIV OF N.J. · PI ABRAIRA, VICTORIA EUGENIA GUADALUPE · 2020 to 2024
$1.2M
NINDS NIH HHS DP2 NS130454NINDS NIH HHS K01 NS116224NINDS NIH HHS R01 NS119268NINDS NIH HHS R01 NS124799
6 · The paper itself

Abstract

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. Two main drivers of peripheral tactile information, low-threshold mechanoreceptors (LTMRs) and postsynaptic dorsal column neurons (PSDCs), terminate in the brainstem dorsal column nuclei (DCN). Activity within the DRG, spinal cord, and DCN have all been implicated in mediating allodynia, yet the DCN remains understudied at the cellular, circuit, and functional levels compared to the other two. Here, we show that the gracile nucleus (Gr) of the DCN mediates tactile sensitivity for low-threshold stimuli and contributes to mechanical allodynia during neuropathic pain in mice. We found that the Gr contains local inhibitory interneurons in addition to thalamus-projecting neurons, which are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations resulted in bidirectional changes to tactile sensitivity, but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, silencing Gr projection neurons or activating Gr inhibitory neurons was able to reduce tactile hypersensitivity, and enhancing inhibition was able to ameliorate paw withdrawal signatures of neuropathic pain, like shaking. Collectively, these results suggest that the Gr plays a specific role in mediating hypersensitivity to low-threshold, innocuous mechanical stimuli during neuropathic pain, and that Gr activity contributes to affective, pain-associated phenotypes of mechanical allodynia. Therefore, these brainstem circuits work in tandem with traditional spinal circuits underlying allodynia, resulting in enhanced signaling of tactile stimuli in the brain during neuropathic pain.

Identifiers

PMID38712022
PMCPMC11071288

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.