Evidence map›Paper›PMID 25716835›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015

Peripheral nerve injury induces persistent vascular dysfunction and endoneurial hypoxia, contributing to the genesis of neuropathic pain.

Tony K Y Lim, Xiang Q Shi, Julia M Johnson, Malena B Rone, Jack P Antel, Samuel David, Ji Zhang

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

72 citing papers in PubMed, 127 citations in OpenAlex.

  1. Article
  2. Macrophage Dab1 Links Early Hypoxia to Adaptive Angiogenesis to Drive Peripheral Nerve Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  17. Article
  18. Fibromyalgia: Chronic Pain Due to a Blood Dysfunction?International journal of molecular sciences · 2025
    Review
  19. Article
  20. Effectiveness ofToxins · 2025
    Review

12 more citing papers are in PubMed but not listed here.

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 2 institutions in 2 countries.

Tony K Y LimNeurology and Neurosurgery, Alan Edwards Centre for Research on Pain, and.
Xiang Q ShiAlan Edwards Centre for Research on Pain, and.
Julia M JohnsonAlan Edwards Centre for Research on Pain, and.
Malena B RoneNeurology and Neurosurgery.
Jack P AntelNeurology and Neurosurgery.
Samuel DavidNeurology and Neurosurgery, Centre for Research in Neuroscience, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada, H3G 1A4.
Ji ZhangNeurology and Neurosurgery, Alan Edwards Centre for Research on Pain, and Faculty of Dentistry, McGill University, Montreal Quebec, Canada H3A 0G4, and ji.zhang@mcgill.ca.
Edwards (United Kingdom) · GBNeurology, Inc · US

Funding

Canadian Institutes of Health Research MOP-111129
6 · The paper itself

Abstract

Nerve injury is associated with microvascular disturbance; however, the role of the vascular system has not been well characterized in the context of neuropathic pain. Furthermore, ischemia is thought to play a role in a number of neuropathic pain conditions, and yet the role of hypoxia has also not been characterized in neuropathic pain conditions. In this study, we observed the presence of persistent endoneurial hypoxia in a mouse model of traumatic peripheral nerve injury, causing painful mononeuropathy. We attribute the ongoing hypoxia to microvascular dysfunction, endoneurial fibrosis, and increased metabolic requirements within the injured nerve. Increased lactate levels were observed in injured nerves, as well as increased oxygen consumption and extracellular acidification rates, suggesting that anaerobic glycolysis is required to maintain cellular ATP levels. Hypoxia causes a reduction in levels of the Na(+)/K(+) ATPase ion transporter in both cultured primary dorsal root ganglion neurons and injured peripheral nerve. A reduction of Na(+)/K(+) ATPase ion transporter levels likely contributes to the hyperexcitability of injured nerves. Physiological antagonism of hypoxia with hyperbaric oxygen alleviated mechanical allodynia in nerve-injured animals. These results suggest that hypoxia and the Na(+)/K(+) ATPase ion transporter may be a novel mechanistic target for the treatment of neuropathic pain. In addition, the findings support the possibility of using hypoxia activated pro-drugs to localize treatments for neuropathic pain and nerve injury to injured nerves.

Indexed as

Adenosine TriphosphateAnimalsCell HypoxiaEndothelium, VascularGlycolysisMaleMiceMice, Inbred C57BLNeuralgiaOxygenOxygen ConsumptionPeripheral Nerve InjuriesSciatic NerveSodium-Potassium-Exchanging ATPaseAdenosine TriphosphateOxygenSodium-Potassium-Exchanging ATPasedrug developmenthypoxiaNa+/K+ ATPase ion transporternerve injuryneuropathic painvascular dysfunction

Identifiers

PMID25716835
PMCPMC6605560
OpenAlexW1978797498

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.