Mechanisms Underlying Severe Chronic Pain in Schwannomatosis
Abstract
Patients with schwannomatosis suffer from chronic pain that cannot be treated using available pain medications or other interventions. Our laboratory found that cells – called Schwann cells – from the tumors of schwannomatosis patients release proteins that influence the numbers of nerve cells that respond to some types of painful signals. We saw similar results when examining Schwann cells with mutations in the SMARCB1 gene or the LZTR1 gene, which are often mutated in patients with schwannomatosis. A study of schwannomatosis patients suggests the patients with SMARCB1 mutations may experience different types or degrees of pain compared to patients with LZTR1 mutations. We characterized mice that lack SMARCB1 in their Schwann cells. These mice demonstrate increased pain sensitivity and express higher than normal levels of neurons that respond to certain pain stimuli. We identified several proteins that caused these changes and found that although they are elevated in SMARCB1-mutant Schwann cells they are not made to excess in LZTR1-mutant Schwann cells. In this study, we will compare pain sensitivity in mice whose Schwann cells have either SMARCB1 or LZTR1 mutations, identify the factors secreted by SMARCB1- and LZTR1-mutant Schwann cells, and test which of these factors are sufficient to induce changes in pain-sensing nerve cells and signaling. Then, we will test whether interfering with the proteins we identify in the mutant Schwann cells can reverse pain sensitivity in our mouse models. These studies have the potential to identify new approaches to treat the pain suffered by schwannomatosis patients. In addition, we hope that the mice in this study can be used by us and other investigators to screen new drugs that target schwannomatosis pain prior to clinical trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110280
Entities
People
- Steven Matsumoto
Organizations
- Oregon Health & Science University
- United States Army