Evidence map›Paper›PMID 31921220›Full record

ReviewFrontiers in immunology2019

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management.

Arden G Vanderwall, Erin D Milligan

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 3 pooled it
6.6field-weighted citation impact, top 2% 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

124 citing papers in PubMed, 3 syntheses or guidelines pooled it, 200 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Glial cells in neuropathic pain.Physiological reviews · 2026
    Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Sex-specific effects of surgical duration on peak pain after pediatric adenotonsillectomy.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

64 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

2 authors at 1 institution in 1 country.

Arden G VanderwallDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, United States.
Erin D MilliganDepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM, United States.
University of New Mexico · US

Funding

Understanding neurophysiological deficits in response inhibition in children with FASDP50AA022534 · NIAAA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Carlos Fernando Valenzuela · 2014 to 2026
$21.5M
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
Alcohol Research Training in NeurosciencesT32AA014127 · NIAAA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Jonathan L Brigman · 2003 to 2026
$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
Chronic neuropathic pain, glial-immune responses and fetal alcohol exposureR21AA023051 · NIAAA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI MILLIGAN, ERIN DAMITA, NORENBERG, JEFFREY PAUL · 2015 to 2016
$400k
NIAAA NIH HHS P50 AA022534NIAAA NIH HHS R01 AA025967NIAAA NIH HHS R21 AA023051NIAAA NIH HHS T32 AA014127NIDA NIH HHS R01 DA018156
6 · The paper itself

Abstract

Current pain therapeutics offer inadequate relief to patients with chronic pain. A growing literature supports that pro-inflammatory cytokine signaling between immune, glial, and neural cells is integral to the development of pathological pain. Modulation of these communications may hold the key to improved pain management. In this review we first offer an overview of the relationships between pro-inflammatory cytokine and chemokine signaling and pathological pain, with a focus on the actions of cytokines and chemokines in communication between glia (astrocytes and microglia), immune cells (macrophages and T cells), and neurons. These interactions will be discussed in relation to both peripheral and central nervous system locations. Several novel non-neuronal drug targets for controlling pain are emerging as highly promising, including non-viral IL-10 gene therapy, which offer the potential for substantial pain relief through localized modulation of targeted cytokine pathways. Preclinical investigation of the mechanisms underlying the success of IL-10 gene therapy revealed the unexpected discovery of the powerful anti-nociceptive anti-inflammatory properties of D-mannose, an adjuvant in the non-viral gene therapeutic formulation. This review will include gene therapeutic approaches showing the most promise in controlling pro-inflammatory signaling via increased expression of anti-inflammatory cytokines like interleukin-10 (IL-10) or IL-4, or by directly limiting the bioavailability of specific pro-inflammatory cytokines, as with tumor necrosis factor (TNF) by the TNF soluble receptor (TNFSR). Approaches that increase endogenous anti-inflammatory signaling may offer additional opportunities for pain therapeutic development in patients not candidates for gene therapy. Promising novel avenues discussed here include the disruption of lymphocyte function-associated antigen (LFA-1) activity, antagonism at the cannabinoid 2 receptor (CB2R), and toll-like receptor 4 (TLR4) antagonism. Given the partial efficacy of current drugs, new strategies to manipulate neuroimmune and cytokine interactions hold considerable promise.

Indexed as

AnimalsChronic DiseaseCytokinesDisease SusceptibilityGenetic TherapyHumansImmunityInflammation MediatorsPainPain ManagementSignal TransductionCytokinesInflammation MediatorsCCL2chemokineschronic paincytokinesgene therapyIL-10IL-4TNF-α

Identifiers

PMID31921220
PMCPMC6935995
OpenAlexW2998373951

What Socratic 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 Socratic graph.