Project 461574

Neuropathic pain (NP) is typically described as 'the worst pain imaginable' on patient rating scales. It is currently incurable, arising in response to injuries or diseases that directly affect the nervous system. While acute pain is often manageable with drugs like NSAIDs (i.e. aspirin) or opiates (i.e. morphine), NP is resistant to these medications. These currently available therapies to treat acute pain (including opioids) are often ineffective or result in unwanted side effects for people with NP. Over the past two decades, research has indicated that the cells of the immune system are intimately involved in the generation of NP. Historically, however, it was not possible to differentiate between certain immune cell types because they share many features (genes, surface proteins etc.). Our overall objectives are to 1) understand how immune cells contribute to the chronification of NP, 2) try to identify new biomarkers of NP and 3) develop a new, nonopioid treatment for NP. This project will capitalize on the most recent advances in genetic technology to assess the contributions made by specific immune cell types to the initiation and maintenance (i.e. chronification) of pain after injury to a peripheral nerve. By precisely identifying the specific cell type and genetic signature of the immune cells that invade injured nerves, we will be in a strong position to identify biomarkers for pain chronification and develop therapies to target the cells responsible for creating chronic pain. Insights generated from this work will also lead to treatments that will reverse established, chronic NP.