Evidence map›Paper›PMID 38798460›Full record

ArticlebioRxiv : the preprint server for biology2024

Regulatory T cell-derived enkephalin gates nociception.

Élora Midavaine, Beatriz C Moraes, Jorge Benitez, Sian R Rodriguez, Joao M Braz, Nathan P Kochhar, Walter L Eckalbar, Ana I Domingos, John E Pintar, Allan I Basbaum and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Élora MidavaineDepartment of Anatomy, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0002-0364-8975
Beatriz C MoraesDepartment of Anatomy, University of California San Francisco, San Francisco, California, USA.
Jorge BenitezDepartment of Anatomy, University of California San Francisco, San Francisco, California, USA.
Sian R RodriguezDepartment of Anatomy, University of California San Francisco, San Francisco, California, USA.
Joao M BrazDepartment of Anatomy, University of California San Francisco, San Francisco, California, USA.
Nathan P KochharDepartment of Anatomy, University of California San Francisco, San Francisco, California, USA.
Walter L EckalbarDepartment of Anatomy, University of California San Francisco, San Francisco, California, USA.
Ana I DomingosDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
John E PintarDepartment of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Allan I BasbaumDepartment of Anatomy, University of California San Francisco, San Francisco, California, USA.
Sakeen W KashemDepartment of Dermatology, University of California San Francisco, San Francisco, CA, USA.

Funding

From the spinal cord to the brain: Neurology of the pain and itch neuronsR35NS097306 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASBAUM, ALLAN I. · 2017 to 2024
$7.2M
UCSF Dermatology Training GrantT32AR007175 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Wilson Liao, Michael David Rosenblum · 1986 to 2026
$6.1M
Cutaneous opioid circuitry in skin inflammation and sensationK08AR085766 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Sakeen W Kashem · 2025 to 2026
$372k
NIAMS NIH HHS K08 AR085766NIAMS NIH HHS T32 AR007175NINDS NIH HHS R35 NS097306
6 · The paper itself

Abstract

T cells have emerged as sex-dependent orchestrators of pain chronification but the sexually dimorphic mechanisms by which T cells control pain sensitivity is not resolved. Here, we demonstrate an influence of regulatory T cells (Tregs) on pain processing that is distinct from their canonical functions of immune regulation and tissue repair. Specifically, meningeal Tregs (mTregs) express the endogenous opioid, enkephalin, and mTreg-derived enkephalin exerts an antinociceptive action through a presynaptic opioid receptor signaling mechanism that is dispensable for immunosuppression. We demonstrate that mTregs are both necessary and sufficient to suppress mechanical pain sensitivity in female, but not male, mice, with this modulation reliant on sex hormones. These results uncover a fundamental sex-specific, and immunologically-derived endogenous opioid circuit for nociceptive regulation with critical implications for pain biology.

Indexed as

enkephalinmeningesneuroimmunologyopioidPainregulatory T cellssensory neuronssex dimorphism

Identifiers

PMID38798460
PMCPMC11118376

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.