Evidence map›Paper›PMID 40411263›Full record

ArticleEuropean journal of pain (London, England)2025

Astrocytic Inducible Nitric Oxide Synthase Upregulation Contributes to Chronic Below-Level Neuropathic Pain Following Spinal Cord Injury in Male Rats.

Youngkyung Kim, Hyunggoo Kang, Young Wook Yoon

Abstract read
In one paragraph

Article in European journal of pain (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. 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

3 authors.

Youngkyung KimDepartment of Physiology, Korea University College of Medicine, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0002-8797-8073
Hyunggoo KangDepartment of Emergency Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0002-9522-2532
Young Wook YoonDepartment of Physiology, Korea University College of Medicine, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0001-5701-6204

Funding

Korea Science and Engineering Foundation KOSEFKorea University K2509181Ministry of Science and ICT GrantMinistry of Science and ICT MSITMinistry of Science and ICT NRF-2022R1F1A1073548
6 · The paper itself

Abstract

backgroundSpinal cord injury (SCI) leads to persistent inflammation, contributing to chronic neuropathic pain. However, current treatments show limited efficacy. Three types of nitric oxide synthase (NOS) play different roles in inflammation and neuronal hyperexcitation. Therefore, this study aimed to determine the predominant NOS subtype involved in neuropathic pain after spinal contusion.

methodsWe investigated the effects of intrathecal NOS inhibitors on mechanical sensitivity following a moderate spinal contusion injury in male Sprague-Dawley rats. These NOS inhibitors were N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME; non-selective NOS inhibitor), 1400W (iNOS inhibitor), Nω-propyl-L-arginine hydrochloride (NPLA; nNOS inhibitor) and N5-(1-iminoethyl)-L-ornithine (L-NIO; eNOS inhibitor). Additionally, we analysed protein expression and cellular localisation of spinal NOS subtypes in rats that underwent SCI or sham procedures.

resultsTreatment with L-NAME significantly reduced paw withdrawal threshold in a dose-dependent manner, although motor deficits appeared at the highest dose (30 μM), while 1400W effectively alleviated mechanical hypersensitivity without motor side effects. NPLA showed limited efficacy, and L-NIO had no effect. Protein expression of iNOS increased two-fold in the L4-5 spinal segment of SCI rats compared with sham controls. After SCI, iNOS-immunoreactivity colocalized with GFAP in the superficial laminae of the L4-5 spinal segment. Treatment with 1400W reduced the hyper-reactivity of both iNOS and GFAP.

conclusionsThese findings indicate that iNOS plays a significant role in below-level neuropathic pain following thoracic spinal cord contusion in rats. Specific blockade of iNOS activity may have potential as a therapeutic intervention for spinal-contusion-induced neuropathic pain with reduced risk of side effects. SIGNIFICANCE STATEMENT: iNOS inhibition effectively alleviated pain without motor side effects, unlike non-selective NOS, nNOS and eNOS inhibitors. The colocalization of iNOS with astrocytes in the spinal cord suggests a key mechanism in pain maintenance. These findings highlight the potential of targeting iNOS as a therapeutic strategy for SCI-induced neuropathic pain with reduced risks of side effects.

Indexed as

AstrocytesNeuralgiaNitric Oxide Synthase Type IISpinal Cord InjuriesAnimalsEnzyme InhibitorsHyperalgesiaMaleNG-Nitroarginine Methyl EsterRatsRats, Sprague-DawleySpinal CordUp-RegulationEnzyme InhibitorsNG-Nitroarginine Methyl EsterNitric Oxide Synthase Type II

Identifiers

PMID40411263
PMCPMC12102686

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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.