Johns Hopkins Researchers at Neuroscience 2008 - People with restless leg syndrome often have found that sleep-inducing allergy drugs worsen their symptoms. Now, researchers at the Johns Hopkins University School of Medicine have discovered a possible reason for that and help explain why RLS in general interferes with sleep but doesn't seem to result in daytime drowsiness. The common thread, the researchers say, is that histamine receptors - proteins found on the surface of some cells that are triggered by histamine - in the brain work to modulate nerve responses. When activated, histamine receptors stimulate alertness or wakefulness.

To sort out the relationship they suspected, the researchers first gave 12 RLS patients either a true sedative or diphenhydramine, the active ingredient in many allergy medications that tames histamine and induces sleepiness. They found that while sedatives had little to no effect on RLS, diphenhydramine made the RLS as much as three to four times worse. The team then looked at autopsied brains from RLS patients for possible differences in histamine receptor location and found that the substantia nigra, the part of the brain implicated in RLS, contained a higher number of histamine-3 receptor proteins, suggesting that this molecular pathway is more active in people with RLS.

"Five out of six patients in our study showed this elevated number of histamine receptor proteins," says Richard Allen, Ph.D., a research associate in neurology at Hopkins. "The histamine system appears to alter the balance of the nervous system so that one is not sleepy in the daytime, even with sleep loss, which might explain why RLS patients can get by on so little sleep. This also suggests that histamine receptors might be a new target for study and therapy of RLS."

Johns Hopkins Medicine