Overcoming Pain

Why people experience chronic pain, and the power they have to de-intensify it

This Is Your Brain On Restless Leg Syndrome

RLS patients sleep little, but many do not experience excessive sleepiness.

Neurologists have long wondered why so-called “dopaminergic” (dopamine being a brain neurotransmitter) treatments help restless leg syndrome (RLS), but not the sleep loss associated with that disorder; even as, at least from the patient’s perspective, this lack of sleep may just be no big deal: While research has shown that RLS patients sleep on average a little over five hours each night, the typical RLS patients does not report excessive sleepiness during the day. It may be that this apparent arousal component of RLS is due to the effects of “glutamatergic” (glutamate and glutamine being two other brain neurotransmitters) activity.

This month’s issue of the journal “Neurology” discusses the results of an investigation into brain glutamatergic activity. The researchers studied the ratio of total glutamate and glutamine concentration to the total creatine, their hypotheses being that the ratio would be higher for RLS patients, and the ratio would directly correlate with insomnia during the sleep period.

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The use of MR spectroscopy examined the brains of the RLS patients, comparing this image to a control group. Some patients underwent a sleep study also, and researchers found a positive correlation between brain glutamatergic activity and arousal, and/or the amount of time awake during what should have been a sleep period. In fact, glutamatergic activity also correlated with things such as waking after the patient finally began to sleep, and just how long it takes for that patient to fall asleep.

Interestingly, glutamatergic activity showed no association with the leg movements of RLS, although, the higher glutamate levels did result in a more sleep-disturbed RLS patient.

And the control group with no sleep problems had stable glutamate levels, and proved to be resistant to the other findings that can be observed in the course of a sleep study.

There are glutamate-reducing drugs already on the market (including Neurontin, and Lyrica), and in the future it would be interesting to see whether these drugs play a role in improving sleep. In the clinic, perhaps a cocktail of glutamate reduction to help sleep, in combination with dopamine agents to help the leg movements of RLS would be helpful.

As always, one must consider the hypothesis also, and not just what is being studied that might validate or reject the hypothesis: Perhaps this glutamatergic activity is not causing the sleep problems of RLS patients. Perhaps the sleep difficulties of RLS simply trigger the brain to produce more glutamate. Making things more confusing is that not every RLS patient has elevated glutamate levels.

There is a significant amount of chronic pain associated with RLS and the sleeplessness that accompanies this disorder. Many patients await the studies that are sure to follow.

Mark Borigini, M.D., is a board-certified rheumatologist who has devoted his career to treating illnesses that cause chronic pain and disability.


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