Grant: Project Grant

Chronic pain has a major impact on the life quality of ~30% of cancer survivors who had chemotherapy. Pain is part of chemotherapy-induced peripheral neuropathy, which is a major complication of chemotherapy. Cisplatin, a chemotherapeutic, enters and acts in the dorsal root ganglia that contains the cell bodies of pain sensing neurons. Despite its commonness, why cisplatin treatment leads to pain remains unclear. We think that cisplatin stimulates immune cells in the dorsal root ganglia to break down a structure called the extracellular matrix. The matrix provides structural support to the pain sensing neurons, and we are investigating how cisplatin causes the breakdown, and how this leads to pain. Using a mouse model of chemotherapy-induced peripheral neuropathy we will characterize the changes in the matrix. We will subsequently determine which molecules are breaking down the matrix, and whether blocking them is sufficient to prevent and reverse pain. Finally, we will determine which cell types are breaking down the matrix and assess if targeting these cells can protect mice from chemotherapy induced peripheral neuropathy. Our expected findings will identify new strategies to prevent or reduce chemotherapy-associated pain, thereby improving the life quality of cancer survivors.