Evidence map›Paper›PMID 42582843›Full record

ArticlePNAS nexus2026

Painful neuromas exhibit axonal phenotypic shift via nociceptive and mechanosensitive marker up-regulation.

Vlad Tereshenko, Floris V Raasveld, Charles D Hwang, Madison R Hussey, Benjamin Johnston, Ian L Valerio, William G Austen, Brian J Wainger, William Renthal, Kyle R Eberlin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PNAS nexus, 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

10 authors.

Vlad TereshenkoDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.ORCID https://orcid.org/0000-0001-7761-5191
Floris V RaasveldDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.ORCID https://orcid.org/0000-0002-7566-1159
Charles D HwangDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Madison R HusseyDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.ORCID https://orcid.org/0009-0003-5589-7695
Benjamin JohnstonDepartment of Plastic, Reconstructive and Aesthetic Surgery, Vienna General Hospital, Medical University of Vienna, Vienna 1090, Austria.
Ian L ValerioDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
William G AustenDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Brian J WaingerDepartments of Anesthesia, Critical Care and Pain Medicine and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.ORCID https://orcid.org/0000-0002-3664-7231
William RenthalDepartment of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Kyle R EberlinDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.ORCID https://orcid.org/0000-0003-4427-2588

Funding

Spatial Core (Moffit)U19NS130617 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI Jeffrey Moffitt · 2022 to 2026
$15.5M
NINDS NIH HHS U19 NS130617
6 · The paper itself

Abstract

Neuropathic pain encompasses a spectrum of conditions that significantly impact quality of life. In case of nerve injuries, when regenerating axons fail to reach their target organs, they can form painful neuromas, yet the mechanisms underlying their formation remain unclear. In this exploratory study, we analyzed the neural components of painful neuromas by examining the expression patterns of key nociceptor markers. Neural components within neuromas exhibited up-regulated growth-associated protein 43, indicating their regenerative potential. Calcitonin gene-related peptide was expressed in 84% of axons, versus 3% in healthy nerves, suggesting a phenotypic shift toward a nociceptive profile. We also observed increased expression of the mechanosensitive channel Piezo2 in 78% of axons and up-regulation of the low-threshold sodium channel Nav1.3, consistent with heightened mechanosensitivity and hyperexcitability. These observations identify candidate molecular alterations in painful neuromas and may provide a guide for future development of targeted therapies for neuroma-related pain.

Indexed as

nerve surgeryneuromanociceptionperipheral nervePiezo2

Identifiers

PMID42582843
PMCPMC13459132

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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 OpenQuestion graph.