Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome

• Published in: Brain (London, England : 1878) England : 1878), 2004-04, Vol.127 (4), p.773-782
• Main Authors: Stiasny‐Kolster, K., Magerl, W., Oertel, W. H., Möller, J. C., Treede, R.‐D.
• Format: Article
• Language: English
• Subjects: Adult; Aged; ANCOVA = analysis of covariance; Biological and medical sciences; Dopamine Agents - therapeutic use; Drug Administration Schedule; Female; Foot - innervation; Hand - innervation; Humans; Hyperalgesia - drug therapy; Hyperalgesia - physiopathology; IRLS = International RLS study Group severity scale; IRLSSG = International RLS Study Group; LSD = least squares differences; Male; Mechanoreceptors - physiology; Medical sciences; Middle Aged; Neurology; NMDA = N‐methyl‐d‐aspartate; nociceptive processing; pain; Pain Measurement; pathophysiology; Physical Stimulation - methods; PLM = periodic leg movements; PLMS = periodic leg movements in sleep; PLMW = periodic leg movements during wakefulness; REM = rapid eye movement; restless legs syndrome; Restless Legs Syndrome - drug therapy; Restless Legs Syndrome - physiopathology; RLS = restless legs syndrome
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/awh079

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 Aδ‐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 Aδ‐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.