Letter to the Editor |
Altered central excitability and analgesic treatment in patients with restless legs syndrome
1 Outpatient Department for the Treatment of Affective and Anxiety Disorders, Heinersreuth, 2 Department of Anesthesiology Mannheim, University of Heidelberg, Mannheim and 3 Department of Anesthesiology, Pain Clinic, University Hospital Erlangen, Erlangen, Germany
Correspondence to: Dr Wolfgang Koppert, Department of Anesthesiology, Pain Clinic, University Hospital Erlangen, Krankenhausstrasse 12, D-91054 Erlangen, Germany E-mail: Koppert{at}kfa.imed.uni-erlangen.de
Received October 1, 2004. Accepted January 18, 2005.
Sir,
Stiasny-Kolster et al. (2004)
found enhanced sensitivity to pinprick stimuli in patients with restless legs syndrome (RLS) compared with healthy controls. Interestingly, no dynamic mechanical hyperalgesia to light tactile stimuli (allodynia) was observed. The authors concluded there might be a close relationship of RLS and pain modulation disorders with altered excitability of central nociceptive pathways as seen in patients with neuropathic pain. Recent clinical data support their conclusion: in a sample of 243 consecutive patients with affective and anxiety disorders, 52 out of 65 patients with RLS also suffered from chronic recurrent pain (Leutgeb et al., 2002).
However, all but three of these 52 patients with chronic pain had a longstanding history of regular use or overuse of non-opioid analgesics before their RLS became manifest. The multivariate analysis of the sample confirmed a strong association of RLS with regular intake of non-opioid analgesics (odds ratio 25.5). Interestingly, the significant association between RLS and patients with chronic recurrent pain did not persist after adjusting for the regular intake of analgesics and age. These clinical findings may complement the experimental data obtained by Stiasny-Kolster et al. (2004) and raise the question of whether the regular intake of non-opioid analgesics in RLS-affected patients is the consequence of the enhanced pain sensitivity that led to overuse of analgesics, or if the regular intake of non-opioid analgesics enhances the risk of developing RLS.
Although the present studies do not allow conclusive answers, some of the following facts support the hypothesis that overuse of non-opioid analgesics enhances the risk of developing RLS. In a subsample of 172 patients described by Leutgeb and Martus (2002) who had only ever taken small amounts of non-opioid analgesics, the prevalence of RLS was 9%, which corresponds well to the frequency in the general population (Phillips et al., 2000). Since it is known that RLS symptoms may be triggered by antidepressant therapy, we cannot exclude an interaction between antidepressants and non-opioid analgesics. Therefore, an unbiased group of patients without concomitant diseases should be investigated in further studies. Despite this limitation, in RLS-affected patients with medication-overuse headache, the RLS improved along with the headache after they had stopped their overuse of non-opioid analgesics. The potential link between chronic pain conditions and RLS is supported by data from Young et al. (2003), who found that headache patients with RLS are at a greatly increased risk of developing drug-induced akathisia and proposed that RLS should be added to the list of disorders associated with migraine.
Supporting and extending the findings of Stiasny-Kolster and colleagues, we conclude that sensitization of central pain processing in RLS patients might be linked to chronic use of non-opioid analgesics, as observed in medication-overuse headache in predisposed patients (Diener and Limmroth, 2004). Therefore, it is tempting to propose a common pattern of central sensitization following non-opioid analgesic overuse in chronic pain and RLS, which awaits further clinical confirmation.
References
Diener HC, Limmroth V. Medication-overuse headache: a worldwide problem. Lancet Neurol 2004; 3: 475–83.[Medline]
Leutgeb U, Martus P. Regular intake of non-opioid analgesics is associated with an increased risk of restless legs syndrome in patients maintained on antidepressants. Eur J Med Res 2002; 7: 368–78.[Medline]
Phillips B, Young T, Finn L, Asher K, Hening WA, Purvis C. Epidemiology of restless legs symptoms in adults. Arch Intern Med 2000; 160: 2137–41.
Stiasny-Kolster K, Magerl W, Oertel WH, Möller JC, Treede RD. Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome. Brain 2004; 127: 773–82.
Young WB, Piovesan EJ, Biglan KM. Restless legs syndrome and drug-induced akathisia in headache patients. CNS Spectr 2003; 8: 450–6.[Medline]
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