Single-cell atlas of neuroma-induced DRG remodeling reveals intervention-specific glial and immune programs.

Authors

Casey L Stewart, Michael M Morris, Alexandra E Halevi, Amy M Moore, Valeria Cavalli, Oshri Avraham

Published in

Disease models & mechanisms. Oct 19, 2026. Epub Oct 19, 2026.

Abstract

Peripheral nerve injury caused by cut, crush, or excessive stretch can lead to disordered regeneration and painful neuroma formation. Regrowing axons may terminate in a swollen, hypersensitive nerve stump, producing pain that can outweigh sensory or motor deficits. Despite the frequency of neuromas, treatment outcomes remain inconsistent, and the mechanisms that initiate and sustain neuroma-associated pain are poorly understood. A proximal nerve crush performed upstream of a neuroma or transection may reshape axonal growth and interrupt retrograde injury signaling, potentially promoting a regenerative, pain-resolving state. However, its long-term effects on dorsal root ganglion (DRG) programs remain unclear. Here, we use single-cell RNA sequencing to build an atlas of DRG remodeling after neuroma-forming injury and compare it with two interventions: proximal nerve crush and nerve resection. By resolving transcriptional responses across sensory neurons, satellite glial cells, Schwann cells, and macrophages, we identify intervention-specific glial, neuronal, and immune programs that distinguish regenerative from persistent injury-associated states and nominate pathways that may guide mechanism-based therapies for painful neuromas.

PMID:
42894959
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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