Proceedings of The Physiological Society
University College London December 2005 (2006) Proc Physiol Soc 1, C2
Contribution of the spinal flexor reflex (FRA) system to the Restless Legs Syndrome (RLS). A comparative analysis
Schomburg, Eike; Paulus, Walter;
1. Institute of Physiology, University of Goettingen, Goettingen, Germany. 2. Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany.
RLS is characterized by urged periodic movements preferentially of the lower limb (often accompanied by sensory symptoms) during sleep or at rest. Active movements may cause temporary and partial relief of the discomfort. With a prevalence of 3-9% in the general population RLS is not a rare disease. A comparative analysis of the occurrence and the therapeutical responsiveness of RLS to L-DOPA and opioids in humans and the findings obtained from animal experiments suggest that a disturbance of the spinal FRA system and its supra-spinal control may play an essential role in the development of the RLS. All animal data were obtained from anaemically decapitated high spinal (at C1) cats. Until complete anaemic decapitation (permanent bilateral ligation of the carotids and their branches and of the vertebral arteries) the cats were anaesthetised with a mix of O2-N2O (1:2) and halothane initially at 2.5%, then increasingly replaced by ether, as required for full anaesthesia, judged from absence of any reflexes and non-reactive pupils. Subsequently, neuromuscular blockade was established with pancuronium bromide and the cats were artificially ventilated (for full details of the safeguards taken to ensure insentience at all stages see Schomburg et al. 2001). (1) RLS is characterized by involuntary, partly rhythmic movements. The spinal FRA system may generate complex movements up to locomotor activity. Flexor reflexes are enhanced in RLS patient particularly during sleep (Bara-Jimenez et al. 2000). (2) RLS may be suppressed by active movements. The FRA system is under strong supraspinal control with distinct descending inhibition. If this descending inhibition, which is probably particularly active during special active movements (thus suppressing an unspecific FRA activity), is reduced e.g. during rest or sleep, the FRA system may develop an overactivity with the generation of complex movements. (3) RLS can effectively be treated by L-DOPA. The transmission in early FRA reflex pathways (nociceptive and non-nociceptive) is suppressed by L-DOPA. (4) RLS may partly develop a delayed augmentation after L-DOPA application. In addition to the depression of the short latency FRA pathways, L-DOPA facilitates late, long-lasting FRA reflex pathways, which form the neuronal basis of the spinal locomotor generator. (5) RLS is most effectively suppressed by opioids, which are also effective to suppress the augmentation after L-DOPA therapy. Opioids non-selectively suppress the transmission in non-nociceptive and nociceptive short-latency spinal FRA, but in addition the transmission in the long-latency FRA pathways and the generation of spinal locomotor activity. (For references on FRA see Schomburg, 1990 and 1997). The aspect of an engagement of the spinal FRA system in the development of RLS would allow for an experimental testing of the therapeutic effectiveness of different compounds for RLS.
Where applicable, experiments conform with Society ethical requirements