Gulf War Illness (GWI) is a chronic disorder characterized by a wide range of symptoms, including muscle pain, fatigue, and cognitive problems. It is thought to affect approximately 30% of the ~700,000 veterans who served in the 1991 Gulf War. Although the causes of this disorder remain undetermined, some of the GWI symptoms are thought to reflect a process of "brain inflammation," possibly due to the exposure to chemical substances during the war. Many scientists now believe that new advances in the study of the interaction between brain and immune system may provide important new clues to the physical cause of GWI and eventually lead to specific avenues of targeted treatment strategies. Only recently has the importance of brain-immune system cross-talk been recognized and it appears to work through the microglia. Microglia are the immune cells of the brain. That is, they are specialized cells able to detect foreign invaders to the brain, such as bacteria that can cause infection. They also work by identifying damaged or dying cells inside us that release bits of blood or break down products (called "alarmins") that microglia see as dangerous to our survival. Microglia react to these foreign invaders, or "alarmins," by causing inflammation and other "sickness" symptoms, such as feeling tired and achy, and having an upset stomach or not being able to concentrate. This type of response is helpful when we have an infection and our body needs rest to get better. However, there appear to be times when this system gets caught in a loop of continuous activation resulting in long-lasting or chronic "sickness" symptoms. It appears that GWI could be one of those types of chronic activation between the brain and the immune system. This might happen by "alarmins" from damaged brain cells (neurons) causing microglia to be continually activated and become over-sensitive (creating chronic activation loops). While this hypothesis is supported by initial research, no study to date has been able to directly test whether veterans suffering from GWI do in fact have brain inflammation and microglial activation, because of the prior limitations of brain imaging techniques.

In this study, we will use a new type of brain imaging technique that will now, for the first time, allow us to compare the degree of brain inflammation/microglial activation in GW veterans with GWI, and in healthy GW veteran controls. As a second comparison group, we will also study individuals with fibromyalgia (FM), a chronic disorder that has many similarities with GWI, including persistent, widespread body pain, fatigue, sleep, and cognitive problems. In this study we will determine whether veterans with GWI have brain inflammation, whether this inflammation is similar and in the same brain pathways as FM patients, and whether this inflammation is associated with increased rates of pain, fatigue, and cognitive symptoms experienced by GW veterans.

The results from this study may help veterans with GWI, as well as related disorders, in multiple ways. First, our study may change the way GWI and other, similar disorders are diagnosed by using specialized neuroimaging techniques, which allow us to visualize the microglial activation that causes brain inflammation as never before. Second, the results from our study may change the way that GWI and other similar disorders are treated because identifying microglial activation in GWI could result in using currently available medicines that reduce microglial activation and brain inflammation to treat the symptoms of GWI.