Patients with de novo restless legs syndrome present a unique type of central sensitization accompanied by tactile hypoesthesia. Somatosensory changes were reversed by dopaminergic treatment.
Pain and other sensory signs in patients with restless legs syndrome (RLS) are still poorly understood, as most investigations focus on motor system dysfunctions. This study aimed to investigate somatosensory changes in patients with primary RLS and the restoration of somatosensory function by guideline-based treatment. Forty previously untreated RLS patients were investigated unilaterally over hand and foot using quantitative sensory testing (QST) and were compared with 40 age- and gender-matched healthy subjects. The predominant finding in RLS patients was 3- to 4-fold increase of sensitivity to pinprick stimuli in both extremities (hand: P < .05; foot: P < .001), a sensory pathway involved in withdrawal reflexes. Pinprick hyperalgesia was not paralleled by dynamic mechanical allodynia. Additional significant sensory changes were tactile hypoesthesia in both extremities (hand: P < .05; foot P < .01) and dysesthesia to non-noxious cold stimuli (paradoxical heat sensation), which was present in the foot in an unusually high proportion (14 of 40 patients; P < .01). In 8 patients, follow-up QST 2 to 20 months after treatment with l-DOPA (L-3,4-dihydroxyphenylalanine) revealed a significant reduction of pinprick hyperalgesia (−60%, P < .001), improved tactile detection (+50%, P < .05), and disappearance of paradoxical heat sensation in half of the patients. QST suggested a type of spinal or supraspinal central sensitization differing from neuropathic pain or human experimental models of central sensitization by the absence of dynamic mechanical allodynia. Reversal of pinprick hyperalgesia by l-DOPA may be explained by impaired descending inhibitory dopaminergic control on spinal nociceptive neurons. Restoration of tactile sensitivity and paradoxical heat sensations suggest that they were functional disturbances resulting from central disinhibition.
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aDepartment of Neurology, Philipps-University, Marburg, Germany
bSomnomar, Institute for Medical Research and Sleep Medicine, Marburg, Germany
cDepartment of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany
*Corresponding author. Address: Department of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany. Tel.: +49 621 383 3861; fax: +49 621 383 9921.
1These authors contributed equally to this article, and both should be considered first author.
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Submitted December 31, 2012; revised April 19, 2013; accepted May 3, 2013.