Brain Consequences of Spinal Cord Injury with and without Neuropathic Pain: Translating Animal Models of Neuroinflammation Onto Human Neural Networks and Back
Abstract
Nerve pain is one of the most challenging medical problems after spinal cord injury (SCI). It is personally devastating, sometimes exceeding the impact of other consequences; it is difficult to treat successfully; and it impacts mood, rehabilitation, and life satisfaction. Gabapentin and tricyclic antidepressants are somewhat effective for nerve (or neuropathic) pain, but many patients still have no effective treatment options, pharmacological or behavioral. Current medications are focused on altering the functions of the nerves, and not cells called glial. Glia are the most common cells in the nervous system, and we now know that glia cells are important in brain metabolism and communication between neurons in health and in chronic pain. Animal studies indicate that a certain type of glia, called microglia, are overactive in neuropathic pain. This microglial activity is part of the body s defense, as microglia are involved in removing damaged nerve cells. A very recent study form our lab indicates that changing microglia activity in rats with SCI seems to reduce their nerve pain. A first step in translating these finding to clinical applications is to establish the role of microglia in human neuropathic pain after SCI. MRI (magnetic resonance imaging) and PET (positron emission tomography) are two imaging methods that have recently been combined into one PET-MR camera. With MRI, we will measure the activity and connections of the brains networks and the structure and connections of the spine. With PET, we will measure the activity of microglia. These measurements are safe and do not put patients at risk, and by doing the MRI and PET measures simultaneously, the images can be combined to look at how brain activity and microglial activity interact. This study aims at, for the first time, measuring microglia in the brain and spine of patients with SCI with and without neuropathic pain. We will measure how pain changes brain function and brain structure and how microglia may contribute to pain. We will also study rats with SCI using PET and MRI, and with detailed staining and microscopy. This will let us confirm the role of microglia in the animal model and also directly compare the results from humans with animal MRI, PET, and cell analyses. Many treatments that look promising in animals have not worked well when tested on humans. By directly defining the role of microglia in both humans and animals with similar methods, we hope to define microglia as a potential target for treatment. Methods to speed up the development of new treatment options, and also provide a more mechanistic understanding of the pathophysiology, are needed. The general framework that we propose to developed, going from human to animal models and back to humans, can be used to evaluate other new treatments. If successful, our approach will reduce the risk of running up blind alleys and putting patients at risk, and ultimately allow for a quicker and more cost-effective development of new treatments. This work will support future clinical trials in Veterans and others with SCI by allowing novel treatment to be evaluated in an objective manner with biological as well as behavioral endpoints.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510621
Entities
People
- Nils Linnman
Organizations
- United States Army