PROJECT SUMMARY (Project 2) We propose a plan for the development of a biobank of human neuroma and intact nerve tissues, accompanied by a comprehensive set of transcriptomic, proteomic, and histological analyses, to generate correlations and testable hypotheses on the mechanistic basis for the pain in painful neuromas and the active biochemical and signaling pathways that may contribute to this phenotype that will be an important tool for the pain community to identify the exact composition and spatial architecture of painful neuromas and the identification of those features that uniquely are present only in the presence of pain. Given that painful neuromas are a major source of peripheral neuropathic pain, and that recent data increasingly points to immune and glial cells as drivers of the pain by virtue of the signaling molecules that they produce to act on injured neurons, the data generated may realistically provide important and novel insight into the pathophysiology of neuropathic pain in patients which in turn could lead to the development of new therapeutic strategies. It is conceivable that the data may reveal that the drivers of pain may change with time and may be linked to the genotype of patients or coexisting diseases, features which preclinical studies will not reveal.