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Proteomic analysis of isolated nerve terminals from NaV1.9 knockout mice reveals pathways relevant for pain signaling

ABSTRACT: Chronic pain substantially affects the mental and physical well-being of patients and magnifies the socio-economic burden on the healthcare system. It is important to understand the molecular mechanisms underlying chronic pain to effectively target it. To investigate peripheral mechanisms relevant to pain signaling, we isolated nerve terminals from mouse footpads. The isolated peripheral terminals contain both pre- and post-synaptic proteins and are deficient in keratin and histone in both mice and humans. We detected the protein translational machinery and mitochondria in nerve terminals and observed that they were capable of endocytosis. An unbiased proteomic analysis of nerve terminals from footpads of NaV1.9 knockout mice shows dysregulation of the p38 mitogen-activated protein kinase (MAPK) and extracellular regulated kinase 1/2 (ERK1/2) pathways, and of protein components involved in translation and energy metabolism. Our study thus reveals peripheral signaling mechanisms implicated in pain perception.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD055516 | Pride | 2025-11-24

REPOSITORIES: Pride

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Proteomic analysis of isolated nerve terminals from NaV1.9 knockout mice reveals pathways relevant for pain perception.

Rawat Ankita A Vu Duc Tung DT Erbacher Christoph C Stigloher Christian C Üçeyler Nurcan N Metousis Andreas A Mann Matthias M Briese Michael M Sendtner Michael M

Pain 20250729

<h4>Abstract</h4>Neuropathic pain substantially affects the mental and physical well-being of patients and magnifies the socio-economic burden on the healthcare system. It is important to understand the molecular mechanisms underlying chronic pain to effectively target it. To investigate peripheral mechanisms relevant to pain signalling, we isolated nerve terminals from mouse footpads of wild type and NaV1.9-deficient mice, which exhibit impaired pain sensation and chronification. The isolated p ...[more]

PMID: 40719881

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