Brain Advance Access originally published online on February 25, 2004
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Brain, Vol. 127, No. 4, 773-782, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh079
Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome
1 Department of Neurology, Center of Nervous Diseases, Philipps-University, Marburg, and 2 Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, Mainz, Germany
Correspondence to: Karin Stiasny-Kolster, Department of Neurology, Center of Nervous Diseases, Rudolf-Bultmann-Strasse 8, D-35033 Marburg, GermanyE-mail: stiasny{at}staff.uni-marburg.de
*These authors contributed equally to this study
Pain sensitivity was assessed in 11 patients (age 60 ± 10 years) with ‘primary’ restless leg syndrome (RLS) (disease duration 18 ± 15 years) and 11 age- and gender-matched healthy control subjects. Stimulus-response functions for pricking pain were obtained with seven calibrated punctate mechanical stimulators activating A
-high threshold mechano-nociceptors. Stimuli at the foot were significantly more painful than at the hand in both patients and healthy control subjects both in the morning and evening. Generally, pin-prick pain ratings in RLS patients were significantly elevated, by a factor of 5.3 in the upper limb and by a factor of 6.4 in the lower limb indicating a significant generalized static hyperalgesia more pronounced in the lower limb. In contrast, pain to light touch (allodynia = dynamic mechanical hyperalgesia) as tested by a battery of three gentle tactile stimuli was never reported. Acute single-dose dopaminergic treatment with 100 mg levodopa + 25 mg benserazide, 90 min prior to the evening measurements, largely resolved patients’ RLS symptoms, but had no effect on pin-prick pain. Static hyperalgesia to pin-prick, however, was significantly reversed (median reduction –74%) by long-term individually tailored dopaminergic treatment. Our study shows that patients with RLS exhibit a profound static mechanical hyperalgesia to pin-prick stimuli, but no dynamic mechanical hyperalgesia (allodynia). This type of hyperalgesia is probably mediated by central sensitization to A-fibre high-threshold mechanoreceptor input, a hallmark sign of the hyperalgesia type of neuropathic pain. The reduction of hyperalgesia in RLS patients by long-term dopaminergic treatment suggests that the pathophysiology of RLS includes disturbed supraspinal pain modulation involving the basal ganglia and/or descending dopaminergic pathways.
Key Words: restless legs syndrome; pathophysiology; pain; nociceptive processing
Abbreviations: ANCOVA = analysis of covariance; IRLS = International RLS study Group severity scale; IRLSSG = International RLS Study Group; LSD = least squares differences; NMDA = N-methyl-D-aspartate; PLM = periodic leg movements; PLMS = periodic leg movements in sleep; PLMW = periodic leg movements during wakefulness; REM = rapid eye movement; RLS = restless legs syndrome
Received September 2, 2003. Revised November 19, 2003. Accepted November 23, 2003.
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