Role of Snf5 Mutations in Schwannomatosis Pain
Abstract
Patients with schwannomatosis suffer from chronic pain that cannot be treated using available pain medications or other interventions. Our laboratory has developed mice that lack one of the genes typically mutated in schwannomatosis patients, called Snf5, in their Schwann cells. These mice demonstrate increased pain sensitivity and express higher than normal levels of TRPV1, the so-called capsaicin receptor that detects a number of painful stimuli (such as high temperatures), and another mediator of pain, the calcitonin gene-related peptide (CGRP), in their sensory neurons. These data suggest that factors secreted by Schwann cells that have Snf5 mutations induce increased TRPV1 and CGRP in sensory neurons, contributing to increased pain sensitivity in schwannomatosis patients. Consistent with this idea, we found that schwannoma cells from a schwannomatosis patient also induced TRPV1 and CGRP in sensory neurons. In this study, we will identify the factors secreted by Snf5 mutant Schwann cells and test which ones are sufficient to induce TRPV1 and CGRP expression in sensory neurons. We will also test the relative contributions of TRPV1 and CGRP to pain in our novel mouse model of schwannomatosis pain. These studies have the potential to identify new approaches to treat the pain suffered by schwannomatosis patients. Because there are a number of drugs being developed to target the TRPV1 and CGRP pathways, it is possible that this research, if successful, could immediately lead to clinical trials aimed at relieving schwannomatosis pain.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510592
Entities
People
- Lawrence Sherman
Organizations
- Oregon Health & Science University
- United States Army