Non-Invasive Microstructural Assessment of Neuroinflammation in Chronic Pain
Abstract
The proposed search addresses the Chronification of pain Focus Area. Chronic pain affects the lives of more than 100 million in the United States alone. Unfortunately, available medications provide only limited pain relief, and can have significant side effects. A possible reason why existing drugs don’t work well is that they mostly try to reduce pain by lowering the activity of pain-transmitting neurons. Animal studies, however, suggest that treatments should also target so-called glial cells (i.e., the immune cells of the central nervous system). When a laboratory animal is injured, these cells become overactive, producing inflammation in the brain and/or the spinal cord. This is called neuroinflammation (or NI) and is thought to worsen and sustain the animal’s pain. Importantly, if the same animal is treated with a drug that reduces NI, its pain can be dramatically reduced. This suggests that treating NI might be a promising way to interrupt the vicious circle of pain chronification in humans. However, until recently our ability to see NI in humans suffering from chronic pain (i.e., how much, where, and when it can be found) has been limited. In turn, this has made it very difficult to develop medications that reduce NI. Using an advanced technique called positron emission tomography (PET), our group was the first to show that glial cells are overactive also in patients with chronic pain (back pain, fibromyalgia, migraine, and Gulf War Illness). While these studies are very informative, they have some limitations. For instance, they don’t tell us how the brain tissue changes during NI (an information that may give us important clues on what drugs could work best to reduce NI). Also, the technique used in these prior studies requires the injection of a special dye that is radioactive and can only be produced with very expensive machines available in a few highly specialized centers. Because large numbers of individuals need to be studied multiple times to be fully confident that chronic pain can be treated by reducing NI, we need a different method, one that can be widely available, less invasive, and less costly. Here we propose to develop a novel method to examine NI using a technique called diffusion magnetic resonance imaging (dMRI). dMRI provides insights into the properties of brain tissue by visualizing how water molecules move inside and outside our brain’s cells. As animal studies (including studies from our team) have shown, this principle can be used to infer in a sensitive manner how NI affects various properties of the brain tissue. For instance, when water molecules have more space to move inside cells, but less in the space between cells, we can infer that cells might have swollen, and/or increased in numbers (and these are phenomena that we know happen in overactive glial cells during NI in animals). In addition to providing access to detailed information about brain changes during NI, another advantage of dMRI is that it can be used in conventional MRI machines, and therefore could be widely adopted around the world, potentially allowing the study of very many people and illnesses. In our proposal, we will test our dMRI marker of NI by comparing chronic pain patients and healthy controls, as well as by evaluating its changes after surgery. We hypothesize that, in chronic pain patients, dMRI will allow us to visualize cell swelling, increase in cell numbers and other brain tissue alterations already observed in animals during NI. Moreover, we hypothesize that our dMRI marker of NI will predict the development of long-term pain (specifically, persistent post-surgical pain). Finally, we hypothesize using imaging and behavioral/psychological measures (such as depression and pain sensitivity) in combination rather than separately will be even better able to predict long-term pain, than the imaging marker alone. To this end, we will study patients with knee osteoarthritis, a very commo
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211003
Entities
People
- Marco L Loggia
Organizations
- Massachusetts General Hospital
- United States Army