Evidence map›Paper›PMID 31076578›Full record

ArticleScientific reports2019

Facilitation of neuropathic pain by the NPY Y1 receptor-expressing subpopulation of excitatory interneurons in the dorsal horn.

Tyler S Nelson, Weisi Fu, Renée R Donahue, Gregory F Corder, Tomas Hökfelt, Ronald G Wiley, Bradley K Taylor

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% of its field
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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
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  14. Neuropeptide Y and Pain: Insights from Brain Research.ACS pharmacology & translational science · 2024
    Review
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  19. Neuropeptide Y Signaling Regulates Recurrent Excitation in the Auditory Midbrain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 2 countries.

Tyler S NelsonDepartment of Anesthesiology, Center for Neuroscience at the University of Pittsburgh, Pittsburgh Center for Pain Research, and the Pittsburgh Project to end Opioid Misuse, University of Pittsburgh, Pittsburgh, PA, USA.
Weisi FuDepartment of Physiology, University of Kentucky Medical Center, Lexington, KY, USA.
Renée R DonahueDepartment of Physiology, University of Kentucky Medical Center, Lexington, KY, USA.
Gregory F CorderDepartment of Physiology, University of Kentucky Medical Center, Lexington, KY, USA.
Tomas HökfeltDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Ronald G WileyDepartment of Neurology, Vanderbilt University, Nashville, TN, USA.
Bradley K TaylorDepartment of Anesthesiology, Center for Neuroscience at the University of Pittsburgh, Pittsburgh Center for Pain Research, and the Pittsburgh Project to end Opioid Misuse, University of Pittsburgh, Pittsburgh, PA, USA. bkt@pitt.edu.
University of Kentucky · USKarolinska Institutet · SEUniversity of Pennsylvania · USUniversity of Pittsburgh · USVanderbilt University · US

Funding

NEUROPEPTIDERGIC INHIBITION OF SPINAL PAIN TRANSMISSIONR01NS045954 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BRADLEY K. TAYLOR · 2002 to 2026
$7.4M
PPAR Inhibition of Spinal Pain TransmissionR01NS062306 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, BRADLEY K. · 2009 to 2021
$4.0M
Long-term activation of spinal opioid analgesia after inflammationR01DA037621 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, BRADLEY K. · 2015 to 2019
$3.4M
NIDA NIH HHS R01 DA037621NINDS NIH HHS R01 NS045954NINDS NIH HHS R01 NS062306
6 · The paper itself

Abstract

Endogenous neuropeptide Y (NPY) exerts long-lasting spinal inhibitory control of neuropathic pain, but its mechanism of action is complicated by the expression of its receptors at multiple sites in the dorsal horn: NPY Y1 receptors (Y1Rs) on post-synaptic neurons and both Y1Rs and Y2Rs at the central terminals of primary afferents. We found that Y1R-expressing spinal neurons contain multiple markers of excitatory but not inhibitory interneurons in the rat superficial dorsal horn. To test the relevance of this spinal population to the development and/or maintenance of acute and neuropathic pain, we selectively ablated Y1R-expressing interneurons with intrathecal administration of an NPY-conjugated saporin ribosomal neurotoxin that spares the central terminals of primary afferents. NPY-saporin decreased spinal Y1R immunoreactivity but did not change the primary afferent terminal markers isolectin B4 or calcitonin-gene-related peptide immunoreactivity. In the spared nerve injury (SNI) model of neuropathic pain, NPY-saporin decreased mechanical and cold hypersensitivity, but disrupted neither normal mechanical or thermal thresholds, motor coordination, nor locomotor activity. We conclude that Y1R-expressing excitatory dorsal horn interneurons facilitate neuropathic pain hypersensitivity. Furthermore, this neuronal population remains sensitive to intrathecal NPY after nerve injury. This neuroanatomical and behavioral characterization of Y1R-expressing excitatory interneurons provides compelling evidence for the development of spinally-directed Y1R agonists to reduce chronic neuropathic pain.

Indexed as

AnimalsAxonsCalcitonin Gene-Related PeptideInjections, SpinalInterneuronsMaleNeuralgiaNeuronsPain MeasurementRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, NeuropeptideSpinal Cord Dorsal HornCalcitonin Gene-Related PeptideNpy1r protein, ratReceptors, G-Protein-CoupledReceptors, Neuropeptide

Identifiers

PMID31076578
PMCPMC6510760
OpenAlexW2943889767

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.