ORIGINAL ARTICLE

High prevalence of restless legs syndrome among women with multi-site pain: A population-based study in Dalarna, Sweden R. Stehlik1,2, J. Ulfberg3, J. Hedner2, L. Grote2 1 Pain Center, Skonvik Medical Rehabilitation Clinic, Säter, Sweden 2 Center for Sleep and Vigilance Disorders, Sahlgrenska Academy, Gothenburg University, Sweden 3 Sleep Disorders Center, Capio Lakargruppen, Orebro, Sweden

Correspondence Romana Stehlik E-mail: [email protected] Funding sources Grants for Romana Stehlik: Centre for Clinical Research (CKF), in Dalarna, Sweden: 2010: € 18,000; 2012: € 12,000. Swedish Sleep Research Society: 2012: € 3500. Grants used for posting of the questionnaires to the population and for data management. Pain Rehabilitation Clinic, Säter, Sweden: 2011: € 10,000; 2012: € 20,000; 2013: € 5000. This amount was used for part-time salaries for personnel performing and evaluating the study. There are no other sources of funding. Conflicts of interest None declared. Accepted for publication 3 March 2014 doi:10.1002/ejp.504

Abstract Background: The chronic pain (CP) and chronic multi-site pain (CMP) condition is a highly prevalent health problem. Several studies have reported a high (31–64%) prevalence of co-morbid restless legs syndrome (RLS) in patients with fibromyalgia, one specifically defined form of chronic widespread pain. The current study explored the association between CMP and RLS. Method: The study included 4040 respondents to a postal questionnaire sent to 10,000 women in the age range of 18–64 years and randomly selected from the general population. Complete questionnaire data on type (acute/chronic), degree (mild to severe) and spreading (0–5 body zones) of pain, as well as RLS symptoms (validated questionnaire), were obtained from 3060 subjects. Information on lifestyle, anthropometrics, comorbidities and medication was collected. Results: RLS prevalence increased from 9.6% in subjects with no report of pain to 23,9%, 26.4%, 39.2%, 44.9% and 54.8% in those reporting one, two, three, four and five pain areas, respectively (p < 0.001). Further, RLS prevalence increased from 9.6% (no pain) to 27.9%, 37.9% and 42.4% in subjects with mild, moderate and severe chronic pain (p < 0.001). Multi-site pain, pain localized in the leg, extended pain duration and co-morbid psychiatric disorder were all independently associated with a RLS diagnosis in a multiple regression analysis. Conclusion: The prevalence of RLS increased progressively with pain severity and even more sharply with the degree of pain spreading in women recruited from the general population. Both acute and chronic pain was associated with RLS-related symptoms.

1. Background Non-specific regional, multiple and widespread pain disorders, here summarized as chronic multi-site pain (CMP), represent an increasing health problem that causes both individual suffering and high social costs (Woolf et al., 2004). The neurophysiological basis of CMP is complex. Several mechanisms including enhanced excitability, augmentation of sensory input and central sensitization are likely to contribute to the 1402 Eur J Pain 18 (2014) 1402–1409

development and maintenance of the condition (Yunus, 1992; Drewes, 1999). Biochemical abnormalities including central nervous serotonergic dysfunction (Marks et al., 2009) have also been identified in CMP. Development of chronic pain is further influenced by gender, age, and environmental as well as psychological factors (Pincus et al., 2002; Yunus, 2002; Bomholt et al., 2004; Buskila, 2007; Goffaux et al., 2008). Recent research also points to genetic factors in the pathogenesis of CMP (Buskila, 2007). © 2014 European Pain Federation - EFIC®

R. Stehlik et al.

High prevalence of restless legs syndrome among women with multi-site pain

What’s already known about this topic? • Restless legs syndrome is overrepresented by 43–56% in patients with known fibromyalgia, a specific condition frequently diagnosed in patients with chronic widespread pain. What does this study add? • This study has demonstrated, in a populationbased sample of middle-aged women, that different pain dimensions, such as pain intensity, pain duration and spreading pain, are linearly associated with the occurrence of restless legs symptoms.

Restless legs syndrome (RLS) is a highly prevalent condition characterized by sensorimotor disturbances preferentially in the extremities. RLS manifests as an unpleasant and sometimes painful crawling or creeping sensation and an urge to move the limbs. Symptoms are typically experienced during the late evening and early night period and may result in severe dyssomnia and corresponding daytime symptoms (Wetter and Pollmächer, 1997). The mechanisms behind RLS are incompletely understood, but a dysfunction of central nervous dopamine release has been proposed (Desautels et al., 2001; Trenkwalder et al., 2005). In addition, genetic factors and peripheral nervous system dysfunction may predispose to RLS (Gemignani et al., 2009; Winkelmann et al., 2011). Interestingly, biochemical, genetic and clinical intervention studies suggest that the dopaminergic system may also play an important role in the maintenance of CMP (Wood and Holman, 2009). Indeed, recent studies in fibromyalgia (FM), a specifically defined CMP condition, have reported a prevalence of co-morbid RLS symptoms ranging between 33% and 64% (Yunus and Aldag, 1996; Stehlik et al., 2009; Viola-Saltzman et al., 2010), which supports a possible common pathophysiological mechanisms in CMP and RLS. Female gender is overrepresented in both CMP and RLS. Previous studies on the association between CMP and RLS have addressed specific clinical cohorts with high burden of FM symptoms rather than the general population. We therefore decided to evaluate the relationship between type, localization and intensity of pain, and the occurrence of RLS symptoms in an unselected, middle-aged female population. We hypothesized that spreading of pain increases the likelihood of co-morbid RLS similar to what has been previously reported in patients with FM. © 2014 European Pain Federation - EFIC®

2. Method 2.1 Design and study population A survey using a multidimensional questionnaire was mailed to 10,000 women aged between 18 and 64 years in the Swedish county of Dalarna (approximately 81,000 female inhabitants in the targeted age range). The surveyed population, which is almost evenly distributed within the age range, was randomly selected from the population census. The selection process was automated and the investigators were not involved in the procedure. The questionnaire contained 138 items in the Swedish language. A random subgroup (n = 3000) of the 5960 non-responders received one reminder. A non-responder analysis was performed by telephone interview (n = 30) and by analysis of written information provided in returned but unanswered questionnaires (n = 70).

2.2 Questionnaire A study information letter with the heading ‘Study of the prevalence of CMP and RLS in females from the Dalarna region’ was attached to the mailed questionnaire. The questionnaire included items related to pain characteristics, anthropometrics [body mass index (BMI), smoking habits, alcohol use], socio-economic conditions, co-morbid disease/ complaints and ongoing medication. Localization and degree of pain were assessed by a validated screening questionnaire, which addresses intensity, timing and location of pain (Andersson, 2009). In detail, pain spreading was determined for five pain zones (neck, shoulders/arms, upper back region, lower back region and legs). The intensity of the average pain during the last 3 months was assessed using a validated 10-point visual analogue scale (VAS). Cut-off values used for pain classification, mild (VAS 0–4), moderate (VAS 5–6) or severe (VAS 7–10) pain, were retrospectively determined (Price et al., 1983). The history of pain was defined as short (

High prevalence of restless legs syndrome among women with multi-site pain: a population-based study in Dalarna, Sweden.

The chronic pain (CP) and chronic multi-site pain (CMP) condition is a highly prevalent health problem. Several studies have reported a high (31-64%) ...
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