Role of Snf5 Mutations in Schwannomatosis Pain

Abstract

The overarching goal of this proposal is to test the hypothesis that mutations in the Snf5gene (also called SMARCB1) contribute to the intractable pain experienced by patients with schwannomatosis. We previously found that Schwann cells with Snf5 mutations secrete factors the induce the TRPV1 capsaicin receptor in sensory neurons. During the second year of the project, we have confirmed that Schwann cells with Snf5 mutations secrete the chemokine CCL2,and that CCL2 induces TRPV1 expression in sensory neurons linked to pain signaling. We have also found that TRPV1 becomes elevated in sensory neurons through a mechanism that does not involve increased TRPV1 gene transcription. These findings have resulted in a refocusing of the project to confirm the roles of CCL2 in schwannomatosis pain and in the induction of the calcitonin gene-related peptide (CGRP) in the pain phenotypes of SNf5-mutant mice.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2017
Accession Number
AD1050003

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  • Larry S Sherman

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  • Oregon Health & Science University

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