Dopamine and the spinal cord in restless legs syndrome: does spinal cord physiology reveal a basis for augmentation?

The pathophysiology of restless legs syndrome (RLS) is incompletely understood. L-DOPA, as the precursor of dopamine, as well as dopamine agonists, plays an essential role in the treatment of RLS leading to the assumption of a key role of dopamine function in the pathophysiology of RLS. Periodic limb movements in sleep are a key feature of RLS. They are generated in the spinal cord. Here we review RLS phenomenology on the basis of known dopaminergic influence on spinal control, which has been studied a great deal in recent decades in animals. In particular, we propose that the differential effects of l-DOPA and opioids on early and late flexor reflexes may be linked to the phenomenon of augmentation.