Promoting Recovery by Inhibiting PDE10A-Mediated Inflammation
Abstract
This proposal aligns with two Focus Areas: (1) solutions to accelerate recovery and restore Warfighter performance and (2) pain management strategies following acute and/or chronic neuromusculoskeletal injury. This proposal will investigate specific inflammatory pathways that link peripheral nerve injury-mediated motor dysfunction and neuropathic pain. Preliminary data showed that phosphodiesterase 10A expression was highly induced in sciatic nerve and blood vessels following injury and was strongly associated with inflammation. We will use mouse peripheral nerve injury models to understand, at the molecular level, how phosphodiesterase 10A signaling affects nerve and muscle functional recovery. We will develop a new pharmacological treatment (Phosphodiesterase 10A inhibition by specific inhibitor, TP-10) capable of eliciting specific anti-inflammatory responses in the peripheral nervous system to improve nerve and muscle function. Furthermore, we will study the combined effects of exercise training and TP-10 administration to reduce chronic pain. TP-10 has been used systemically in clinical trials and proven to be safe in humans. Successful accomplishment of this project will provide a powerful strategy to enhance motor functional recovery, reduce chronic pain, and thereby improve life quality after peripheral nerve injury.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110125
Entities
People
- Bradford C. Berk
Organizations
- United States Army
- University of Rochester