New Suspect in Gulf War Illness

Dr. Douglas FieldsChief of the Nervous System Development and Plasticity Section, National Institute of Child Health and Human Development

New Suspect In Gulf War Syndrome

Washington, D.C.– On February 26, 2010, the Veterans Affairs Department announced that it will re-examine the disability claims of thousands of Persian Gulf War veterans still suffering from the mysterious Gulf War illnesses two decades after the war ended. At a meeting of the Federal Advisory Committee on Gulf War Veteran’s Illnesses held yesterday in Washington, D.C., scientists from around the country presented their latest research to committee members searching for clues to this mysterious illness. Early in the meeting a new culprit emerged — “the other brain” — the non-electric portion of the brain composed of brain cells called glia.

“This is one of the best explanations I’ve heard,” commented distinguished neuroscientist Floyd Bloom, after a presentation by Dr. Linda Watkins of the University of Colorado speaking about her latest research showing that glial cells, called microglia, are the unsuspected agents in chronic pain and drug addiction. Previously neurons were thought to be the sole cause of chronic pain and morphine tolerance. However, the new insight into how these “immune cells” of the brain aggravate neurons after an injury by releasing substances that produce excruciating pain, a parallel with Gulf War Syndrome became apparent.

Gulf War syndrome is characterized by a collection of unexplained symptoms, many of them neurological, including chronic pain, chronic fatigue, depression, sleep disturbances, memory loss, as well as gastrointestinal and lung problems. A number of causes have been suspected, including exposure to low-level neurotoxins, including sarin gas, drugs taken to protect soldiers from biological and chemical warfare agents, pesticides used to treat tents and soldier’s uniforms stationed in the desert, depleted uranium from munitions, and the toxic mixture of fumes released for a year after the war ended from oil fields set ablaze by the retreating Iraq soldiers. The toxic fumes blotted out the sun at midday for miles.

Many people suffer chronic pain after an injury. Unlike normal pain, chronic pain does not end after the injury heals; in fact it often gets worse. The latest research shows that chronic pain results from an interaction between the immune system and the brain. When we are sick, substances are released by the body that tell the brain to initiate the familiar “sickness response,” which we have all experienced, for example when we catch the flu. Profound fatigue, headache, sensitivity to light and sound, and painful joints and muscles, drive us to bed. This sickness response forces us to rest and give the body the opportunity to fight the invading germ. This sounds a lot like the symptoms of many Gulf War veterans.

What Dr. Watkins suspects, based on her research on microglia in chronic pain, is that an initial exposure to some toxin “primes” the microglia in the brain to make them hyper alert. Then when a second infection, injury, or toxin is experienced, the brain’s immune cells over-react, releasing too much of the chemical signals that cause the “sickness response”, and they do not stop releasing the substances after the body heals. In the case of Gulf War veterans, the “initial trigger” could have been a reaction to an immunization, stress, or exposure to low-level toxins. Later a second insult to the body unleashes a run-away illness. Research from several labs on microglia in chronic pain has identified many steps in this neuro-immune signaling process that become disrupted and researchers have found specific drugs to restore the normal function of these pain circuits, thus ending the chronic pain. Most of this work is in laboratory animals but clinical studies are now under way.

In my overview to the committee on the four major kinds of glial cells in “the other brain”, several other ways in which glia could be involved in Gulf War illnesses were recognized. This includes the involvement of glial cells, called astrocytes, in processing toxins in the brain. Parkinson’s disease, for example can be caused by astrocytes acting on a foreign substance (a recreational drug), and converting it into a toxin that kills the neurons that die in Parkinson’s Disease. Astrocytes also release factors that protect neurons from damage caused by inflammation or oxidation, and they release growth factor proteins that stimulate the growth and repair of neurons.

The latest research on the myelin insulation on nerve fibers in the brain, which is essential for sending electrical signals, is revealing a previously unsuspected role of myelin in cognition and psychiatric illness. Myelin insulation is especially vulnerable to blast injuries and to autoimmune diseases in which the body’s immune system attacks the myelin sheath. The myelin sheath is made by a type of glial cell, called an oligodendrocyte. Prevously this insulation was of interest in diseases such as multiple sclerosis, but because the insulation speeds the rate of electrical transmission through nerve fibers (axons), myelin is now understood to have an important role in cognitive function, psychological illness, and learning.

One of the reasons the Gulf War Syndrome may have been so difficult to understand is that glia–the other brain–has itself been such a mystery until recently.

Related Articles

• The Other Brain
• New Culprits in Chronic Pain, Scientific American, November, 2009
• White Matter Matters, Scientific American, March, 2008