The local molecular signature of human peripheral neuropathic pain

作者：Oliver Sandy-Hindmarch, Pao-Sheng Chang, Paulina S. Scheuren, Iara De Schoenmacker, Michèle Hubli, Constantinos Loizou, Stephan Wirth, Devendra Mahadevan, Akira Wiberg, Dominic Furniss, Margarita Calvo, David Bennett, Franziska Denk, Georgios Baskozos, Annina B. Schmid · 发表于：Pain · 年份：2024 · DOI：10.1097/j.pain.0000000000003472 · 被引用次数：20 · 研究领域：Pain Mechanisms and Treatments、Nerve injury and regeneration、Spine and Intervertebral Disc Pathology

ABSTRACT: Focal nerve injuries are often associated with neuropathic pain. Preclinical research suggests altered neuroimmune signalling underlies such neuropathic pain; however, its cause remains poorly understood in humans. In this multicentre cohort study, we describe the local cellular and molecular signature of neuropathic pain at the lesion site, using Morton's neuroma as a human model system of neuropathic pain (n = 22; 18 women) compared with nerves from participants without nerve injury (n = 11; 4 women). Immunofluorescent staining revealed demyelination and chronic infiltration of immune cells in Morton's neuroma. RNA bulk sequencing identified 3349 differentially expressed genes between Morton's neuroma and controls. Gene ontology enrichment analysis and weighted gene co-expression network analyses revealed modules specific for host defence and neurogenesis. Deconvolution analysis confirmed higher densities of macrophages and B cells in Morton's neuroma than control samples. Modules associated with defence response, neurogenesis, and muscle system development as well as macrophage cell populations identified by deconvolution correlated with patients' paroxysmal or evoked pain. Of note, we identified a consistently differentially expressed gene signature ( MARCO, CD163, STAB1 ) , indicating the presence of a specific M(GC) subset of macrophages. MARCO gene expression correlated with paroxysmal pain. Targeted immunofluorescent analyses confirmed higher densities of in...