Evidence map›Paper›PMID 24884664›Full record

ArticleJournal of neuroinflammation2014

Improvement of spinal non-viral IL-10 gene delivery by D-mannose as a transgene adjuvant to control chronic neuropathic pain.

Ellen C Dengler, Lauren A Alberti, Brandi N Bowman, Audra A Kerwin, Jenny L Wilkerson, Daniel R Moezzi, Eugene Limanovich, James A Wallace, Erin D Milligan

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

31 citing papers in PubMed, 56 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Emerging role of macrophages in neuropathic pain.Journal of orthopaedic translation · 2025
    Review
  5. Review
  6. Review
  7. Article
  8. Evolving techniques for reducing phantom limb pain.Experimental biology and medicine (Maywood, N.J.) · 2023
    Review
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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

9 authors at 1 institution in 1 country.

Ellen C Dengler
Lauren A Alberti
Brandi N Bowman
Audra A Kerwin
Jenny L Wilkerson
Daniel R Moezzi
Eugene Limanovich
James A Wallace
Erin D MilliganDepartment of Neurosciences, UNM School of Medicine, University of New Mexico Health Sciences Center, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA. EMilligan@salud.unm.edu.
University of New Mexico · US

Funding

Spinal Neuroimmune Mechanisms Underlying IL-10 Gene Therapy for Pain ControlR01DA018156 · NIDA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI MILLIGAN, ERIN DAMITA · 2004 to 2014
$3.3M
Prenatal Alcohol Exposure Potentiates Pain via Lifelong Spinal-immune ChangesR01AA025967 · NIAAA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI MILLIGAN, ERIN DAMITA · 2017 to 2021
$1.5M
NIAAA NIH HHS R01 AA025967NIDA NIH HHS R01 DA018156
6 · The paper itself

Abstract

backgroundPeri-spinal subarachnoid (intrathecal; i.t.) injection of non-viral naked plasmid DNA encoding the anti-inflammatory cytokine, IL-10 (pDNA-IL-10) suppresses chronic neuropathic pain in animal models. However, two sequential i.t. pDNA injections are required within a discrete 5 to 72-hour period for prolonged efficacy. Previous reports identified phagocytic immune cells present in the peri-spinal milieu surrounding the i.t injection site that may play a role in transgene uptake resulting in subsequent IL-10 transgene expression.

methodsIn the present study, we aimed to examine whether factors known to induce pro-phagocytic anti-inflammatory properties of immune cells improve i.t. IL-10 transgene uptake using reduced naked pDNA-IL-10 doses previously determined ineffective. Both the synthetic glucocorticoid, dexamethasone, and the hexose sugar, D-mannose, were factors examined that could optimize i.t. pDNA-IL-10 uptake leading to enduring suppression of neuropathic pain as assessed by light touch sensitivity of the rat hindpaw (allodynia).

resultsCompared to dexamethasone, i.t. mannose pretreatment significantly and dose-dependently prolonged pDNA-IL-10 pain suppressive effects, reduced spinal IL-1β and enhanced spinal and dorsal root ganglia IL-10 immunoreactivity. Macrophages exposed to D-mannose revealed reduced proinflammatory TNF-α, IL-1β, and nitric oxide, and increased IL-10 protein release, while IL-4 revealed no improvement in transgene uptake. Separately, D-mannose dramatically increased pDNA-derived IL-10 protein release in culture supernatants. Lastly, a single i.t. co-injection of mannose with a 25-fold lower pDNA-IL-10 dose produced prolonged pain suppression in neuropathic rats.

conclusionsPeri-spinal treatment with D-mannose may optimize naked pDNA-IL-10 transgene uptake for suppression of allodynia, and is a novel approach to tune spinal immune cells toward pro-phagocytic phenotype for improved non-viral gene therapy.

Indexed as

Genetic TherapyAnimalsAnti-Inflammatory AgentsCells, CulturedChronic DiseaseConstriction, PathologicCytokinesDexamethasoneDisease Models, AnimalInterleukin-10MaleMannoseMiceMicrophthalmosNeuralgiaNitric OxideAnti-Inflammatory AgentsCytokinesDexamethasoneInterleukin-10MannoseNitric Oxide

Identifiers

PMID24884664
PMCPMC4046049
OpenAlexW2131962374

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.