Treatment and Management of  Augmentation in Restless Legs SyndromeCase # 1601

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Technology Contact

A. Carlyle Rogers, PhD
Phone: 252-737-1648

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Restless Legs Syndrome (RLS) is a chronic neurological sensorimotor disorder characterized by an irritable urge to move the affected body part (usually the legs). These sensations range from "creepy-crawling" feelings to pain-like symptoms that severely disrupt sleep and that usually require life-long treatment. The classical and initially highly effective RLS treatment with dopamine agonists usually fails over time, leading to a worsening of the symptoms with the treatment (augmentation). There are currently no available treatments that specifically target this dopamine-associated augmentation in RLS.


Stefan Clemens, PhD, of the Department of Physiology at the Brody School of Medicine at East Carolina University, discovered in an animal model that treatment of RLS with a dopamine 3 receptor agonist switches pain reflexes from analgesic effects (early) to hyperalgesic states (with long-term treatment), mimicking the switch in sensory effects observed in patients with augmentation. His lab found in the animal model that, by blocking dopamine 1 receptor activation in animals previously treated with dopamine 3 receptor agonist, animal behavior returned from hyperalgesic to normal behavioral ranges. If these findings can be translated to RLS patients, this will allow for the patient's pain sensitivity to return to normal.


  • RLS affects up to 10% of the United States Population
  • 82% of RLS patients will experience augmentation
  • New treatment can be combined with conventional dopamine 3 receptor agonists

Selected Publications

Keeler B.E., Lallemand P., Patel M.M, de Castro Bràs L.E., Clemens S "Opposing aging-related shift of excitatory dopamine D1 and inhibitory D3 receptor protein expression in striatum and spinal cord", Journal of Neurophysiology doi: 10.1152/jn.00390.2015, PMID: 26561599

Brewer K.L., Baran C.A., Whitfield B.R., Jensen, A.M., Clemens S. "Dopamine D3 receptor dysfunction prevents anti-nociceptive effects of morphine in the spinal cord", Frontiers in Neural Circuits, doi:10.3389/fncir.2014.00062 PMID:24966815

Clemens S., Rye, D.R., and Hochman S. "Restless Legs Syndrome: A new perspective from the spinal cord", Neurology, 67:125-133, PMID: 16832090

Inventor Profile

Dr. Stefan Clemens is a Associate Professor in the Department of Physiology at East Carolina University. Dr. Clemens lab is interested in understanding the organization and the functioning of the spinal cord, and the neural networks that drive and modulate this integral part of the nervous system.  Click to learn more...