Engaging Motor Cortex Antinociceptive Circuits to Treat Chronic Pain Unpleasantness
Abstract
Many military personnel suffer from combat-related injuries and associated pain both during and after their service. For example, acute battlefield injuries commonly cause nerve damage and orthopedic trauma, which can lead to chronic pain that persists long after the wound has healed (>3 months). Over the last 20 years, it has become increasingly common to manage chronic pain with opioids, which are known to be dangerously addictive. Further, chronic pain and addiction can compound other conditions commonly suffered by Veterans, such as posttraumatic stress disorder (PTSD). Thus, safer, non-addictive alternatives to opioids could significantly improve the quality of life of many Veterans. One such alternative is transcranial magnetic stimulation (TMS) of the motor cortex, which can effectively alleviate pain in patients suffering from numerous chronic pain conditions, including stroke-related chronic pain and neuropathic pain. For many patients, TMS sessions can provide about 2 weeks of pain relief. It remains unclear why TMS is effective for many but not all patients with chronic pain, and how to achieve the longest possible period of pain relief. With some optimization, MCS could serve as a powerful, non-addictive and non-invasive tool to relieve chronic pain. This proposal aims to identify the neural circuits that contribute to TMS pain relief, and to use this mechanistic knowledge to optimize TMS protocols. To accomplish this, we will evaluate MCS in rodent models of two common types of battlefield injuries: nerve damage and orthopedic trauma. We will use neuronal activity markers and neuronal tracing strategies to identify the ideal stimulation site in motor cortex and determine how its neurons communicate with pain-relevant regions in the brain to relieve pain. Based on our previous work, we hypothesize that the connections between the motor cortex and amygdala are crucial for TMS analgesia. Thus, we will individually manipulate neural activity in the circuits connecting the motor cortex neurons to various pain areas, including the amygdala, to determine which pathways contribute to TMS-induced pain relief. Finally, we will evaluate neural activity in the motor cortex and in pain-related brain regions like the amygdala both before and after TMS to understand how activity in individual brain neurons changes as chronic pain develops and during TMS-induced analgesia. Thus far, the cutting-edge research strategies made possible by rodent models have been underutilized in the study of TMS. We will use rodent models of pain to reveal the basic mechanisms underlying TMS analgesia. Researchers and clinicians can use this knowledge to optimize TMS and expand its use as a non-addictive alternative to opioids for the treatment chronic pain. The availability of such a treatment could alleviate the suffering of millions of people in the United States alone, particularly Veterans and active-duty military personnel.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310634
Entities
People
- Gregory Scherrer
Organizations
- United States Army
- University of North Carolina at Chapel Hill