Identification of Causes and Treatments for Chronic Pain in a Model of Gulf War Illness
Abstract
Over the past three decades, 25%-30% of 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 of GWI, and affects up to 17% of Veterans with GWI. Pain is not only a major quality of life burden for the patient, but exacts a substantial economic toll in terms of direct healthcare costs and absenteeism. Epidemiological studies have identified exposure to acetylcholinesterase inhibitors as a potential cause of GWI, as well as the stress of war as a sensitizing condition that might predispose soldiers to GWI. Rodent models have recapitulated the symptoms of GWI with exposure to these agents. With only one exception, pain has not been assessed in animal studies, despite being a principal symptom of GWI. Several mechanisms underlying GWI symptoms have been posited from animal studies, including neuroinflammatory signaling. However, no neuroimmune pharmacotherapies have been assessed in any model of GWI. Here, we aim to discover whether neuroinflammatory signaling is associated with musculoskeletal pain in a validated rodent model of GWI, and whether it can be treated with immunomodulatory agents that are either Food and Drug Administration (FDA)-approved or in the development pipeline. These immunomodulatory agents are explicitly chosen for study here, given their advanced preclinical development and FDA approval status, as this will greatly expedite translation of successes to the treatment of GWI Veterans. As these are all drugs that are appropriate for systemic dosing and are blood-brain barrier permeable (so they can reach sites of neuroinflammation within the brain and spinal cord), this provides a feasible and direct translation to patient-appropriate treatment with these or like compounds. By causally linking neuroinflammatory signaling to GWI pain, this study may provide a rationale to treat other GWI symptoms with these drugs, given the common underlying mechanisms. Taken together, positive results from the proposed studies would have enormous impact not only in spearheading the study of the causal role of brain and spinal cord neuroinflammation in GWI symptomatologies, but also in revealing a novel and clinical relevant approach for treating GWI Veterans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610717
Entities
People
- Peter M. Grace
Organizations
- United States Army
- University of Texas at Austin