Evidence map›Paper›PMID 27355182›Full record

ArticlePain2016

Prior voluntary wheel running attenuates neuropathic pain.

Peter M Grace, Timothy J Fabisiak, Suzanne M Green-Fulgham, Nathan D Anderson, Keith A Strand, Andrew J Kwilasz, Erika L Galer, Frederick Rohan Walker, Benjamin N Greenwood, Steven F Maier and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 5 pooled it
15.4field-weighted citation impact, top 1% 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

74 citing papers in PubMed, 5 syntheses or guidelines pooled it, 133 citations in OpenAlex.

  1. Pooled it
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  6. Trial
  7. Article
  8. Article
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  10. Article
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  12. [Mechanisms of spinal microglia and astrocytes in exercise-induced analgesia].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Review
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  14. Article
  15. Article
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  18. Emerging role of macrophages in neuropathic pain.Journal of orthopaedic translation · 2025
    Review
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14 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

12 authors at 3 institutions in 2 countries.

Peter M GraceaDepartment of Psychology and Neuroscience, University of Colorado, Boulder, CO, USA bThe Center for Neuroscience, University of Colorado, Boulder, CO, USA cDiscipline of Pharmacology, School of Medicine, University of Adelaide, Adelaide, Australia dSchool of Biomedical Sciences and Pharmacy, Centre for Translational Neuroscience and Mental Health Research, Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia eDepartment of Integrative Physiology, University of Colorado, Boulder, CO, USA.
Timothy J Fabisiak
Suzanne M Green-Fulgham
Nathan D Anderson
Keith A Strand
Andrew J Kwilasz
Erika L Galer
Frederick Rohan Walker
Benjamin N Greenwood
Steven F Maier
Monika Fleshner
Linda R Watkins
University of Colorado Boulder · USHunter Medical Research Institute · AUUniversity of Adelaide · AU

Funding

Preventing Transition of Acute-to-Chronic Neuropathic Pain: Models, Mechanisms &R01DE021966 · NIDCR · UNIVERSITY OF COLORADO · PI BARTH, DANIEL S., FLESHNER, MONIKA · 2011 to 2015
$2.0M
Exploring the Potential of Glia for Regulating Clinically Relevant Opiod ActionsR01DA023132 · NIDA · UNIVERSITY OF COLORADO · PI WATKINS, LINDA · 2008 to 2012
$1.9M
NIDA NIH HHS R01 DA023132NIDCR NIH HHS R01 DE021966
6 · The paper itself

Abstract

Exercise is known to exert a systemic anti-inflammatory influence, but whether its effects are sufficient to protect against subsequent neuropathic pain is underinvestigated. We report that 6 weeks of voluntary wheel running terminating before chronic constriction injury (CCI) prevented the full development of allodynia for the ∼3-month duration of the injury. Neuroimmune signaling was assessed at 3 and 14 days after CCI. Prior exercise normalized ipsilateral dorsal spinal cord expression of neuroexcitatory interleukin (IL)-1β production and the attendant glutamate transporter GLT-1 decrease, as well as expression of the disinhibitory P2X4R-BDNF axis. The expression of the macrophage marker Iba1 and the chemokine CCL2 (MCP-1), and a neuronal injury marker (activating transcription factor 3), was attenuated by prior running in the ipsilateral lumbar dorsal root ganglia. Prior exercise suppressed macrophage infiltration and/or injury site proliferation, given decreased presence of macrophage markers Iba1, iNOS (M1), and Arg-1 (M2; expression was time dependent). Chronic constriction injury-driven increases in serum proinflammatory chemokines were suppressed by prior running, whereas IL-10 was increased. Peripheral blood mononuclear cells were also stimulated with lipopolysaccharide ex vivo, wherein CCI-induced increases in IL-1β, nitrite, and IL-10 were suppressed by prior exercise. Last, unrestricted voluntary wheel running, beginning either the day of, or 2 weeks after, CCI, progressively reversed neuropathic pain. This study is the first to investigate the behavioral and neuroimmune consequences of regular exercise terminating before nerve injury. This study suggests that chronic pain should be considered a component of "the diseasome of physical inactivity," and that an active lifestyle may prevent neuropathic pain.

Indexed as

Activating Transcription Factor 3AnimalsCalcium-Binding ProteinsConstriction, PathologicCytokinesDisease Models, AnimalExcitatory Amino Acid Transporter 2Exercise Movement TechniquesFunctional LateralityGanglia, SpinalHyperalgesiaLeukocytes, MononuclearMaleMicrofilament ProteinsNeuralgiaNitritesActivating Transcription Factor 3Aif1 protein, ratAtf3 protein, ratCalcium-Binding ProteinsCytokinesExcitatory Amino Acid Transporter 2Microfilament ProteinsNitritesNLR Family, Pyrin Domain-Containing 3 Proteinp21-Activated Kinasesp38 Mitogen-Activated Protein KinasesReceptors, Purinergic P2X5Slc1a2 protein, rat

Identifiers

PMID27355182
PMCPMC4988888
OpenAlexW2474105214

What OpenQuestion holds

Textmetadata
LicenceTDM
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.