Evidence mapPaperPMID 41588097Full record

ArticleDiabetologia2026

Dermal fibroblast mitochondrial profiles in painful diabetic neuropathy.

Julie Mie Mølgaard Bentzen, Peter Kolind Brask-Thomsen, Maiken Krogsbæk, Xiaoli Hu, Jens Randel Nyengaard, Sandra Sif Gylfadottir, Pall Karlsson, Nanna Brix Finnerup, Rikke Katrine Jentoft Olsen, Zahra Nochi

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Article in Diabetologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Julie Mie Mølgaard BentzenResearch Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0009-0004-7677-4210
Peter Kolind Brask-ThomsenDanish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-8323-1394
Maiken KrogsbækDanish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-9893-237X
Xiaoli HuDanish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-9770-6517
Jens Randel NyengaardCore Centre for Molecular Morphology, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0002-8084-4646
Sandra Sif GylfadottirDanish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-0411-4403
Pall KarlssonDanish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-7082-9576
Nanna Brix FinnerupDanish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-5541-0240
Rikke Katrine Jentoft OlsenResearch Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-3470-5589
Zahra NochiResearch Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. z.nochi@clin.au.dk.ORCID http://orcid.org/0000-0002-8088-1666

Funding

Lundbeck Foundation R359-2020-2620Novo Nordisk Fonden NNF14SA0006Novo Nordisk Fonden NNF18OC0052301
6 · The paper itself

Abstract

aims/hypothesisDermal fibroblasts have emerged as potential contributors to chronic pain, yet their role in diabetic polyneuropathy (DPN) and neuropathic pain remains poorly defined. Mitochondrial dysfunction and low-grade inflammation have been implicated in different pain conditions, but whether fibroblast mitochondrial health and cytokine secretion contribute to painful DPN is unknown.

methodsWe conducted an integrated cellular and molecular profiling of dermal fibroblasts and skin biopsies from 30 participants, grouped into control participants (n=5), diabetes without DPN (n=7), pain-free DPN (n=7) and painful DPN (n=11). Fibroblast cultures (n=24) were evaluated for morphology, growth rate, phenotype, inflammatory mediator secretion and mitochondrial function. Immunohistochemistry of skin biopsies was used to assess fibroblast density, mitochondrial markers and immune cell infiltration.

resultsFibroblast morphology and proliferation did not differ significantly between groups. Flow cytometric profiling revealed no significant differences in fibroblast subtype distributions across groups. Inflammatory mediator secretion was limited. Mitochondrial mass, membrane potential, reactive oxygen species production and bioenergetic parameters were not different across groups. Skin biopsy analyses confirmed comparable fibroblast density and mitochondrial profiles across groups, regardless of neuropathy or pain. Notably, dermal macrophage infiltration was significantly elevated in the painful DPN group (mean ~8%; ANOVA p=0.02; painful DPN vs control participants p=0.02; painful DPN vs pain-free DPN p=0.07), consistent with prior findings from the same cohort, while Langerhans cell area fraction did not differ between groups. CONCLUSIONS/

interpretationFibroblasts from participants with painful DPN did not differ in inflammatory and mitochondrial profiles compared with those from pain-free DPN. However, persistent dermal macrophage infiltration in painful DPN suggests a stable immune-activated microenvironment, potentially contributing to pain maintenance. Our results suggest that immune-related, rather than fibroblast-intrinsic, mechanisms could play a role in sustaining neuropathic pain in painful DPN.

Indexed as

Diabetic NeuropathiesFibroblastsMitochondriaNeuralgiaSkinAdultAgedCells, CulturedFemaleHumansMaleMiddle AgedBioenergeticsCytokine secretionDermal fibroblastsDiabetic polyneuropathyFibroblast phenotypingImmunohistochemistryMacrophage infiltrationMitochondrial functionNeuropathic painSkin biopsy

Identifiers

PMID41588097
PMCPMC13005869

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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.