Evidence map›Paper›PMID 40753003›Full record

ArticleBritish journal of anaesthesia2026

Neuronal toxicity and recovery from early bortezomib-induced neuropathy: blood-nerve barrier dysfunction without dorsal root ganglion damage.

Mariam Sobhy Atalla, Anna-Lena Bettenhausen, Julius M Verse, Nadine Cebulla, Susanne M Krug, Reine-Solange Sauer, Mugdha Srivastava, Thorsten Bischler, Jeremy T C Chen, K Martin Kortüm and 3 more

Abstract read
In one paragraph

Article in British journal of anaesthesia, 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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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

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5 · Who and what money

Authors and funding

13 authors.

Mariam Sobhy AtallaDepartment of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Centre for Interdisciplinary Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
Anna-Lena BettenhausenDepartment of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Centre for Interdisciplinary Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
Julius M VerseDepartment of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Centre for Interdisciplinary Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
Nadine CebullaDepartment of Neurology, University Hospital Würzburg, Würzburg, Germany.
Susanne M KrugCharité - Universitätsmedizin Berlin, Clinical Physiology/Nutritional Medicine, Berlin, Germany.
Reine-Solange SauerDepartment of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Centre for Interdisciplinary Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
Mugdha SrivastavaCore Unit Systems Medicine, University of Würzburg, Würzburg, Germany.
Thorsten BischlerCore Unit Systems Medicine, University of Würzburg, Würzburg, Germany.
Jeremy T C ChenDepartment of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Centre for Interdisciplinary Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
K Martin KortümDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Robert J KittelDepartment of Animal Physiology, Institute of Biology, Leipzig University, Leipzig, Germany.
Claudia SommerDepartment of Neurology, University Hospital Würzburg, Würzburg, Germany.
Heike L RittnerDepartment of Anesthesiology, Intensive Care, Emergency and Pain Medicine, Centre for Interdisciplinary Pain Medicine, University Hospital Würzburg, Würzburg, Germany. Electronic address: rittner_h@ukw.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUse of the first in class proteasome inhibitor bortezomib (BTZ) is highly effective in the treatment of multiple myeloma. However, its long-term use is limited by the fact that most treated patients develop painful polyneuropathy. In some of the treated patients, pain resolves with time; in others, it persists, with the underlying mechanisms poorly understood. One prerequisite for neural toxicity is the ability of a drug to penetrate the blood-nerve barrier.

methodsWe analysed the pathways involved in early BTZ-induced polyneuropathy development and its resolution in rats and in patients with myeloma using pain behaviour, barrier analysis, transcriptomics, immunohistochemistry, and clinical data.

resultsOne cycle of BTZ elicited transient tactile and cold allodynia in rats. Transcriptomic signature and network analysis revealed regulation of circadian, extracellular matrix, and immune genes within the nerve and modest changes in the dorsal root ganglia. Recovery processes resealed the small molecule leakiness of the perineurial barrier, reversed axonal swelling, and normalised fibre density in the skin. Expression of the microtubule-associated cytoskeletal protein cortactin matched this process in the perineurium. Netrin-1 as a known barrier sealer was also upregulated in pain resolution in nerve and skin. In patients with painful BTZ-induced polyneuropathy, skin innervation was reduced and netrin-1 was unchanged, compatible with the persistence of pain.

conclusionsIn summary, our data demonstrate that early bortezomib toxicity targets mainly peripheral nerves and indicate that pain resolution could be supported by protective growth factors such as netrin-1 for remodelling of the extracellular matrix and neuronal barriers. CLINICAL

trial registrationDRKS00025422.

Indexed as

Antineoplastic AgentsBortezomibGanglia, SpinalPolyneuropathiesAgedAnimalsFemaleHumansHyperalgesiaMaleMiddle AgedMultiple MyelomaRatsRats, Sprague-DawleyAntineoplastic AgentsBortezomibblood-nerve barrierbortezomibimmune systemneuronal barrierpolyneuropathySchwann cell

Identifiers

PMID40753003
PMCPMC13014509

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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.