(Vienna, 12 August 2026) Painful neuromas can develop following injuries to peripheral nerves or amputations and can significantly impair the quality of life of those affected. An international research team, including researchers from MedUni Vienna, has now identified characteristic molecular changes in these misdirected nerve structures. The findings provide new insights into the development of neuroma pain and point to potential targets for future therapies. The study was published in the journal PNAS Nexus.
Peripheral nerves possess a remarkable capacity for regeneration. Following an injury, severed nerve fibres – known as axons – begin to regrow. However, if they fail to reach their original target tissue, a neuroma may form at the end of the damaged nerve. These changes can be associated, particularly following nerve injuries and amputations, with severe chronic pain as well as a high sensitivity to touch or pressure.
The international research team, led by Kyle Eberlin of Massachusetts General Hospital and with Vlad Tereshenko of the Department of Plastic, Reconstructive and Aesthetic Surgery of the Medical University of Vienna as first author, investigated the molecular characteristics of painful neuromas. To this end, surgically removed neuromas were compared with healthy nerve samples from amputated lower legs. Using specific molecular markers, the scientists analysed the composition and properties of the nerve fibres contained within them.
Significantly altered profile of the nerve fibres
The analyses revealed fundamental differences between painful neuromas and healthy nerves. The axons in the neuromas exhibited a disorganised structure and strong activation of markers associated with nerve fibre regeneration. At the same time, the researchers found significantly more sympathetic nerve fibres.
The difference was particularly pronounced in the case of calcitonin gene-related peptide (CGRP), a neuropeptide that plays a key role in pain perception: whilst CGRP was detectable in 84 per cent of the axons examined in the painful neuromas, the proportion in healthy nerves was just three per cent.
Furthermore, the researchers observed increased expression of the mechanosensitive ion channel Piezo2, as well as upregulation of the sodium channel Nav1.3. These changes suggest that the nerve fibres in painful neuromas are particularly easily excited and react more strongly to mechanical stimuli such as touch or pressure.
Starting points for new therapies
The results thus paint a detailed molecular picture of the changes that distinguish painful neuromas from healthy nerves. In particular, the increased activity of pain-related and mechanosensitive signalling pathways could explain why even minor mechanical stimuli can trigger severe pain in those affected.
At the same time, the identified molecular differences open up potential new therapeutic targets. Future treatment strategies could specifically target those signalling pathways involved in the increased pain sensitivity and excitability of the nerve fibres.
The study was conducted as part of a collaboration between the Medical University of Vienna, Harvard Medical School and Massachusetts General Hospital, and was supported by the Global Nerve Foundation Young Investigator Award (https://professional.globalnervefoundation.org/young-investigator-award/).
Publication: PNAS Nexus
“Painful neuromas exhibit axonal phenotypic shift via nociceptive and mechanosensitive marker upregulation,” by Vlad Tereshenko, Floris V. Raasveld, Charles D. Hwang, Madison R. Hussey, Benjamin Johnston, Ian L. Valerio, William G. Austen Jr., Brian J Wainger, William Renthal, and Kyle R. Eberlin.
https://academic.oup.com/pnasnexus/article-lookup/doi/10.1093/pnasnexus/pgag257