Evidence map›Paper›PMID 33846230›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021

Temporal Contribution of Myeloid-Lineage TLR4 to the Transition to Chronic Pain: A Focus on Sex Differences.

Nolan A Huck, Janelle Siliezar-Doyle, Elena S Haight, Ryosuke Ishida, Thomas E Forman, Shaogen Wu, Huaishuang Shen, Yoshinori Takemura, J David Clark, Vivianne L Tawfik

Open access · greenAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
4.7field-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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Sex differences in the transition to chronic pain.The Journal of clinical investigation · 2025
    Review
  11. Review
  12. Minocycline Abrogates Individual Differences in Nerve Injury-Evoked Affective Disturbances in Male Rats and Prevents Associated Supraspinal Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024
    Article
  13. Immune drivers of physiological and pathological pain.The Journal of experimental medicine · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Mechanisms of complex regional pain syndrome.Frontiers in pain research (Lausanne, Switzerland) · 2024
    Review
  18. Article
  19. Article
  20. Review
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

10 authors at 3 institutions in 3 countries.

Nolan A HuckDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.
Janelle Siliezar-DoyleDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.
Elena S HaightDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.ORCID 0000-0002-3463-0591
Ryosuke IshidaDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.
Thomas E FormanDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.
Shaogen WuDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.
Huaishuang ShenDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.
Yoshinori TakemuraDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.
J David ClarkDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305.
Vivianne L TawfikDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California 94305 vivianne@stanford.edu.ORCID 0000-0002-4422-2014
Stanford Medicine · USShimane University · JPSoochow University · CN

Funding

Training Program in Basic NeuroscienceT32MH020016 · NIMH · STANFORD UNIVERSITY · PI Justin L Gardner, Merritt C Maduke · 1997 to 2026
$16.2M
Neural Immunoregulation of Post-Traumatic AutoimmunityR01NS094438 · NINDS · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI DAVID J. CLARK, WADE S KINGERY · 2016 to 2026
$4.4M
Myeloid lineage targeting to improve recovery from injury and surgery: Cellular and molecular mechanismsR35GM137906 · NIGMS · STANFORD UNIVERSITY · PI Vivianne L Tawfik · 2020 to 2026
$3.0M
Peripheral and central immune contributions to pain chronificationK08NS094547 · NINDS · STANFORD UNIVERSITY · PI TAWFIK, VIVIANNE L · 2017 to 2020
$697k
Autonomic Regulation of the Immunological Response to Limb InjuryI01RX001475 · VA · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · PI CLARK, DAVID J. · 2015 to 2025
–
NIGMS NIH HHS R35 GM137906NIMH NIH HHS T32 MH020016NINDS NIH HHS K08 NS094547NINDS NIH HHS R01 NS094438RRD VA I01 RX001475
6 · The paper itself

Abstract

Complex regional pain syndrome (CRPS) is a chronic pain disorder with a clear acute-to-chronic transition. Preclinical studies demonstrate that toll-like receptor 4 (TLR4), expressed by myeloid-lineage cells, astrocytes, and neurons, mediates a sex-dependent transition to chronic pain; however, evidence is lacking on which exact TLR4-expressing cells are responsible. We used complementary pharmacologic and transgenic approaches in mice to more specifically manipulate myeloid-lineage TLR4 and outline its contribution to the transition from acute-to-chronic CRPS based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We demonstrate that systemic TLR4 antagonism is more effective at improving chronic allodynia trajectory when administered at the time of injury (early) in the tibial fracture model of CRPS in both sexes. In order to clarify the contribution of myeloid-lineage cells peripherally (macrophages) or centrally (microglia), we rigorously characterize a novel spatiotemporal transgenic mouse line,

Indexed as

AnimalsChronic PainComplex Regional Pain SyndromesFemaleHumansHyperalgesiaMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicrogliaMyeloid CellsPain MeasurementSex CharacteristicsSulfonamidesethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylateSulfonamidesTlr4 protein, mouseToll-Like Receptor 4CRPSmicrogliamyeloidpainsex differencesTLR4

Identifiers

PMID33846230
PMCPMC8143203
OpenAlexW3153099875

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.