Chronic pain afflicts ~100 million Americans, and the current therapies - that target only neurons - are minimally effective.
The mission of the Grace Lab is to understand the neuroinflammatory mechanisms that drive chronic pain so that new treatment strategies can be developed.
Current Research Projects
Neuroinflammatory mechanisms underlying the transition from acute to chronic pain
Reciprocal signaling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning chronic pain mechanisms. Immune mediators released by CNS-resident microglia and astrocytes, and by infiltrating immune cells, can powerfully enhance neuronal excitability. This line of research has recently turned to the question of why acute pain becomes chronic in only a subset of patients.
Our work has shown that an immune challenge sensitizes glia to each subsequent challenge, leading to an exaggerated neuroinflammatory response and consequently pain that is increased in magnitude and duration. Intriguingly, the Watkins Lab has discovered that opioid analgesics such as morphine can also act as an “immune challenge”. Despite their status as gold-standard therapeutic analgesics, we have discovered that opioids also initiate microgliosis and proinflammatory cytokine release via activation of Toll Like Receptor 4 (TLR4). A short course of opioids paradoxically exacerbates peripheral and central neuropathic pain, inflammatory pain and postoperative pain for weeks to months after opioid administration is concluded.
This work is now being extended into models of sleep disruption, aging, and Gulf War Illness.
The insights gained from these investigations may lead to novel therapeutics for mechanism-based treatment of pain, and strategies to prevent the transition to chronic pain.
Funded by Department of Defense Grant 14001001 (co-PI)
Identification of causes and treatments for chronic pain in a model of Gulf War Illness
Veterans from the 1990-1991 Gulf War have consistently reported numerous unexplained chronic health symptoms affecting their quality of life, which has been termed Gulf War Illness (GWI). Musculoskeletal pain is a principal symptom, affecting up to 17% of veterans with GWI.
This project aims to discover whether neuroinflammatory signaling is associated with musculoskeletal pain in a model of GWI, and whether it can be treated with immuno-modulatory agents that are either FDA-approved, or in the development pipeline.
Funded by Department of Defense Grant GWI150187 (PI)