Evidence map›Paper›PMID 42491735›Full record

ArticleiScience2026

Keratinocytes and PDGF-B/PDGFRβ signaling modulate peripheral opioid tolerance.

Luca Posa, Angelique J Buton, Anita M Khasnavis, Sophia A Miracle, Kathryn M Albers, Matthew J Fanelli, Timmy Le, Mackenzie Gamble, Ashley K McDonald, Gilles Martin and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2026. 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

14 authors.

Luca PosaDepartment of Pharmacology, Physiology and Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
Angelique J ButonDepartment of Psychiatry and Behavioral Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Anita M KhasnavisDepartment of Psychiatry and Behavioral Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Sophia A MiracleDepartment of Pharmacology, Physiology and Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
Kathryn M AlbersDepartment of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA.
Matthew J FanelliDepartment of Psychiatry and Behavioral Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Timmy LeDepartment of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Mackenzie GambleDepartment of Psychiatry and Behavioral Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Ashley K McDonaldDepartment of Pharmacology, Physiology and Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
Gilles MartinDepartment of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Salome Fabri-RuizDECOD, L'Institut Agro, IFREMER, INRAE, Nantes 44311, France.
Zachary FreybergDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Ryan W LoganDepartment of Psychiatry and Behavioral Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Stephanie PuigDepartment of Psychiatry and Behavioral Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

Funding

ONGOING STUDIES OF TREATMENT FOR HIGH RISK DRUG USERSR37DA006124 · NIDA · UNIVERSITY OF DELAWARE · PI INCIARDI, JAMES A · 1994 to 2003
$5.3M
Novel roles of VGLUT in sex differences in dopamine neuron vulnerability to environmental toxicant-induced neurodegenerationR01ES034037 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZACHARY FREYBERG · 2023 to 2026
$2.3M
Molecular rhythm alterations in human post-mortem brain associated with opioid use disorderR01DA051390 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOGAN, RYAN W, SENEY, MARIANNE L · 2020 to 2023
$1.9M
Cross-talk between the colon epithelium, colon afferents and sympathetic neurons regulate pain in the normal and inflamed colonR01DK124955 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALBERS, KATHRYN MARIE, DAVIS, BRIAN M · 2020 to 2023
$1.8M
Novel roles for the circadian transcription factor NPAS2 and striatal dopamine D3 receptor signaling in diurnal fentanyl craving and relapseR01DA061243 · NIDA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ZACHARY FREYBERG, Ryan W Logan · 2024 to 2026
$1.4M
A novel role for midbrain glutamate co-transmitting neurons in alcohol drinking and motivated behaviorsR21AA028800 · NIAAA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREYBERG, ZACHARY, LOGAN, RYAN W · 2021 to 2022
$446k
Targeting PDGFRβ to treat peripheral opioid toleranceR21DA051636 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PUIG, STEPHANIE, ZACHARIOU, VENETIA · 2021 to 2022
$419k
NIAAA NIH HHS R21 AA028800NIDA NIH HHS R01 DA051390NIDA NIH HHS R01 DA061243NIDA NIH HHS R21 DA051636NIDA NIH HHS R37 DA006124NIDDK NIH HHS R01 DK124955NIEHS NIH HHS R01 ES034037
6 · The paper itself

Abstract

Peripheral opioids are safer than systemic opioids by avoiding central side effects. However, peripheral tolerance hampers their clinical use. We highlight an epithelial-neuronal communication mechanism for peripheral opioid tolerance. We discovered that both repeated intraplantar (i.pl.) morphine injections or repeated keratinocyte photostimulation in mice cause peripheral tolerance in a platelet-derived growth factor type B (PDGF-B) and PDGF receptor beta (PDGFRβ)-dependent manner. We also find that morphine i.pl. increases PDGF-B in mu-opioid receptor-expressing keratinocytes and alters the electrophysiological properties of keratinocytes. This underscores the importance of keratinocytes and the necessity for PDGF-B release for peripheral tolerance, though the source of PDGF-B remains undetermined. Nevertheless, we show that PDGFRβ inhibition completely blocks peripheral tolerance in peripheral chronic pain models, highlighting the translational relevance of our findings. Overall, we highlight that keratinocytes and PDGFRβ are promising targets to reduce peripheral tolerance, which could allow shifting from systemic to peripheral opioid delivery and increase opioid safety.

Indexed as

growth factorsKeratinocytesopioid analgesiaPeripheral opioid tolerance

Identifiers

PMID42491735
PMCPMC13378143

What Socratic holds

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Registered trials

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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.