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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

Editor-in-Chief: Breivik, Harald


CiteScore 2018: 0.85

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The association between insomnia, c-reactive protein, and chronic low back pain: cross-sectional analysis of the HUNT study, Norway

Kevin Kwan Ngai Ho
  • Corresponding author
  • The University of Sydney, Musculoskeletal Research Group, Faculty of Health Sciences, Sydney, Australia
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/ Milena Simic
  • The University of Sydney, Musculoskeletal Research Group, Faculty of Health Sciences, Sydney, Australia
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/ Milada Cvancarova Småstuen
  • Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
  • Oslo Metropolitan University, Department of Health Science, Institute of Nursing Science, Oslo, Norway
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/ Marina de Barros Pinheiro
  • The University of Sydney, Musculoskeletal Research Group, Faculty of Health Sciences, Sydney, Australia
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/ Paulo Herrique Ferreira
  • The University of Sydney, Musculoskeletal Research Group, Faculty of Health Sciences, Sydney, Australia
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/ Marianne Bakke Johnsen
  • Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
  • Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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/ Ingrid Heuch
  • Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
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/ Margaret Grotle
  • Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
  • Oslo Metropolitan University, Department of Physiotherapy, Oslo, Norway
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/ John Anker Zwart
  • Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
  • Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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/ Kristian Bernhard Nilsen
  • Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway
  • NTNU, Department of Neuromedicine and Movement Science, Trondheim, Norway
  • Department of Neurology, Oslo University Hospital, Oslo, Norway
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Published Online: 2019-07-09 | DOI: https://doi.org/10.1515/sjpain-2019-0033

Abstract

Background and aims

Chronic low back pain (chronic LBP) is the number one cause for years lived with disability among 301 diseases and injuries analyzed by The Global Burden of Disease study 2013. Insomnia is highly prevalent among people with chronic LBP. To explain the sleep-pain relationship, theoretical models propose that insomnia symptoms may be associated with increased basal inflammation, operationalized as c-reactive protein (CRP) and lead to further pain and disrupted sleep. We aimed to determine the associations between insomnia, chronic LBP, and inflammation (operationalized as CRP), whilst controlling for age, body mass index, smoking, physical activity, depression, anxiety and osteoarthritis.

Methods

A cross-sectional analysis of the third Nord-Trøndelag Health Study (2006–2008), a rural population survey of 50,666 participants in Norway aged 20–96 years. Insomnia (dichotomous) was defined according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition, and chronic LBP (dichotomous) as low back pain or stiffness lasting at least 3 months. Data for CRP were obtained from non-fasting serum samples and assessed via latex immunoassay methodology. We excluded participants with the following self-reported chronic somatic diseases: chronic heart failure, chronic obstructive pulmonary disease, rheumatoid arthritis, fibromyalgia or ankylosing spondylosis. Possible associations between presence of insomnia and presence of chronic LBP (dependent), and the level of CRP and presence of chronic LBP (dependent), were assessed using logistic regression models. The possible association between insomnia and CRP (dependent) was assessed using linear regression. Multivariable analyses were conducted adjusting for confounders stated in our aim that achieved p ≤ 0.2 in univariate regressions. We performed stratified analyses for participants with “Normal” (<3 mg/L) “Elevated” (3–10 mg/L) and “Very High” (>10 mg/L) levels of CRP.

Results

In our total included sample (n = 30,669, median age 52.6, 54% female), 6.1% had insomnia (n = 1,871), 21.4% had chronic LBP (n = 6,559), and 2.4% had both (n = 719). Twenty four thousand two hundred eighty-eight (79%) participants had “Normal” CRP, 5,275 (17%) had “Elevated” CRP, and 1,136 (4%) had “Very High” CRP. For participants with “Normal” levels of CRP, insomnia was associated with higher levels of CRP (adjusted B = 0.04, 95%CI [0.00–0.08], p = 0.046), but not for people with “Elevated” or “Very High” levels of CRP. There was an association between CRP and presence of chronic LBP in the total sample (adjusted OR = 1.01, [1.00–1.01], p = 0.013) and for people with “Normal” CRP (1.05, [1.00–1.10, p = 0.034]. Insomnia was associated with the presence of chronic LBP in the total sample (adjusted OR = 1.99, 95%CI [1.79–2.21], <0.001) and for people with “Normal”, “Elevated” and “Very High”.

Conclusions

Individuals with insomnia have twice the odds of reporting chronic LBP. Insomnia, CRP and chronic LBP appear to be linked but the role of CRP appears to be limited. Longitudinal studies may help further explore the causal inference between insomnia chronic LBP, and inflammation.

Implications

Given the strong relationship between insomnia and chronic LBP, screening and management of comorbid insomnia and chronic LBP should be considered in clinical practice. Further longitudinal studies are required to explore whether the presence of insomnia and increased inflammation affects the development of chronic LBP.

Keywords: chronic low back pain; insomnia; c-reactive protein; inflammation; epidemiology

References

  • [1]

    Waddell G. The back pain revolution. London: Churchill Livingstone, 1998.Google Scholar

  • [2]

    Hagen KB, Kvien TK, Bjorndal A. Musculoskeletal pain and quality of life in patients with noninflammatory joint pain compared to rheumatoid arthritis: a population survey. J Rheumatol 1997;24:1703–9.PubMedGoogle Scholar

  • [3]

    Collaborators* GBoDS. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386:743–800.PubMedGoogle Scholar

  • [4]

    Alsaadi SM, McAuley JH, Hush JM, Maher CG. Prevalence of sleep disturbance in patients with low back pain. Eur Spine J 2011;20:737–43.PubMedCrossrefGoogle Scholar

  • [5]

    Kovacs FM, Seco J, Royuela A, Betegon JN, Sanchez-Herraez S, Meli M, Martinez Rodriguez ME, Nunez M, Alvarez-Galovich L, Moya J, Sanchez C, Luna S, Borrego P, Moix J, Rodriguez-Perez V, Torres-Unda J, Burgos-Alonso N, Gago-Fernandez I, Gonzalez-Rubio Y, Abraira V. The association between sleep quality, low back pain and disability: a prospective study in routine practice. Eur J Pain 2017;22:114–26.PubMedGoogle Scholar

  • [6]

    Marin R, Cyhan T, Miklos W. Sleep disturbance in patients with chronic low back pain. Am J Phys Med Rehabil 2006;85:430–5.PubMedCrossrefGoogle Scholar

  • [7]

    Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS, Bateson AN, Britton TC, Crowe C, Dijk DJ, Espie CA, Gringras P, Hajak G, Idzikowski C, Krystal AD, Nash JR, Selsick H, Sharpley AL, Wade AG. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol 2010;24:1577–601.PubMedCrossrefGoogle Scholar

  • [8]

    Kelly GA, Blake C, Power CK, O’Keeffe D, Fullen BM. The association between chronic low back pain and sleep: a systematic review. Clin J Pain 2011;27:169–81.CrossrefPubMedGoogle Scholar

  • [9]

    Bahouq H, Allali F, Rkain H, Hmamouchi I, Hajjaj-Hassouni N. Prevalence and severity of insomnia in chronic low back pain patients. Rheumatol Int 2013;33:1277–81.CrossrefPubMedGoogle Scholar

  • [10]

    Purushothaman B, Singh A, Lingutla K, Bhatia C, Pollock R, Krishna M. Prevalence of insomnia in patients with chronic back pain. J Orthop Surg (Hong Kong) 2013;21:68–70.CrossrefPubMedGoogle Scholar

  • [11]

    Sezgin M, Hasanefendioglu EZ, Sungur MA, Incel NA, Cimen OB, Kanik A, Sahin G. Sleep quality in patients with chronic low back pain: a cross-sectional study assesing its relations with pain, functional status and quality of life. J Back Musculoskelet Rehabil 2015;28:433–41.PubMedCrossrefGoogle Scholar

  • [12]

    Agmon M, Armon G. Increased insomnia symptoms predict the onset of back pain among employed adults. PLoS One 2014;9:e103591.CrossrefPubMedGoogle Scholar

  • [13]

    Smith MT, Quartana PJ, Okonkwo RM, Nasir A. Mechanisms by which sleep disturbance contributes to osteoarthritis pain: a conceptual model. Curr Pain Headache Rep 2009;13:447–54.CrossrefGoogle Scholar

  • [14]

    Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain 2013;14:1539–52.CrossrefGoogle Scholar

  • [15]

    Haack M, Sanchez E, Mullington JM. Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers. Sleep 2007;30:1145–52.PubMedCrossrefGoogle Scholar

  • [16]

    Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon 3rd RO, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith Jr. SC, Taubert K, Tracy RP, Vinicor F. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499–511.PubMedGoogle Scholar

  • [17]

    Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry 2016;80:40–52.CrossrefPubMedGoogle Scholar

  • [18]

    van den Berg R, Jongbloed EM, de Schepper EIT, Bierma-Zeinstra SMA, Koes BW, Luijsterburg PAJ. The association between pro-inflammatory biomarkers and nonspecific low back pain: a systematic review. Spine J 2018;18:2140–51.CrossrefPubMedGoogle Scholar

  • [19]

    Briggs MS, Givens DL, Schmitt LC, Taylor CA. Relations of C-reactive protein and obesity to the prevalence and the odds of reporting low back pain. Arch Phys Med Rehabil 2013;94:745–52.CrossrefPubMedGoogle Scholar

  • [20]

    Mork PJ, Vik KL, Moe B, Lier R, Bardal EM, Nilsen TI. Sleep problems, exercise and obesity and risk of chronic musculoskeletal pain: the Norwegian HUNT study. Eur J Public Health 2014;24:924–9.CrossrefPubMedGoogle Scholar

  • [21]

    Pinheiro MB, Ferreira ML, Refshauge K, Maher CG, Ordonana JR, Andrade TB, Tsathas A, Ferreira PH. Symptoms of depression as a prognostic factor for low back pain: a systematic review. Spine J 2016;16:105–16.PubMedCrossrefGoogle Scholar

  • [22]

    Pinheiro MB, Ferreira ML, Refshauge K, Ordonana JR, Machado GC, Prado LR, Maher CG, Ferreira PH. Symptoms of depression and risk of new episodes of low back pain: a systematic review and meta-analysis. Arthritis Care Res 2015;67:1591–603.CrossrefGoogle Scholar

  • [23]

    Pinheiro MB, Morosoli JJ, Colodro-Conde L, Ferreira PH, Ordonana JR. Genetic and environmental influences to low back pain and symptoms of depression and anxiety: a population-based twin study. J Psychosom Res 2018;105:92–8.PubMedCrossrefGoogle Scholar

  • [24]

    Fernandez M, Colodro-Conde L, Hartvigsen J, Ferreira ML, Refshauge KM, Pinheiro MB, Ordonana JR, Ferreira PH. Chronic low back pain and the risk of depression or anxiety symptoms: insights from a longitudinal twin study. Spine J 2017;17:905–12.PubMedCrossrefGoogle Scholar

  • [25]

    Parmelee PA, Tighe CA, Dautovich ND. Sleep disturbance in osteoarthritis: linkages with pain, disability and depressive symptoms. Arthritis Care Res 2015;67:358–65.CrossrefGoogle Scholar

  • [26]

    Suri P, Morgenroth DC, Kwoh CK, Bean JF, Kalichman L, Hunter DJ. Low back pain and other musculoskeletal pain comorbidities in individuals with symptomatic osteoarthritis of the knee: data from the osteoarthritis initiative. Arthritis Care Res 2010;62:1715–23.CrossrefGoogle Scholar

  • [27]

    Krokstad S, Langhammer A, Hveem K, Holmen TL, Midthjell K, Stene TR, Bratberg G, Heggland J, Holmen J. Cohort profile: the HUNT Study, Norway. Int J Epidemiol 2013;42:968–77.CrossrefGoogle Scholar

  • [28]

    Kuorinka I, Jonsson B, Kilbom A, Vinterberg H, Biering-Sorensen F, Andersson G, Jorgensen K. Standardised Nordic questionnaires for the analysis of musculoskeletal symptoms. Appl Ergon 1987;18:233–7.PubMedCrossrefGoogle Scholar

  • [29]

    Heuch I, Heuch I, Hagen K, Zwart JA. Is there a U-shaped relationship between physical activity in leisure time and risk of chronic low back pain? A follow-up in the HUNT Study. BMC Public Health 2016;16:306.CrossrefGoogle Scholar

  • [30]

    Hoy D, March L, Brooks P, Blyth F, Woolf A, Bain C, Williams G, Smith E, Vos T, Barendregt J, Murray C, Burstein R, Buchbinder R. The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 2014;73:968–74.PubMedCrossrefGoogle Scholar

  • [31]

    Dionne CE, Dunn KM, Croft PR, Nachemson AL, Buchbinder R, Walker BF, Wyatt M, Cassidy JD, Rossignol M, Leboeuf-Yde C, Hartvigsen J, Leino-Arjas P, Latza U, Reis S, Gil Del Real MT, Kovacs FM, Oberg B, Cedraschi C, Bouter LM, Koes BW, et al. A consensus approach toward the standardization of back pain definitions for use in prevalence studies. Spine (Phila Pa 1976) 2008;33:95–103.PubMedCrossrefGoogle Scholar

  • [32]

    Griffith LE, Hogg-Johnson S, Cole DC, Krause N, Hayden J, Burdorf A, Leclerc A, Coggon D, Bongers P, Walter SD, Shannon HS. Low-back pain definitions in occupational studies were categorized for a meta-analysis using Delphi consensus methods. J Clin Epidemiol 2007;60:625–33.PubMedGoogle Scholar

  • [33]

    American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed. Arlington, VA, USA: American Psychiatric Publishing, 2013.Google Scholar

  • [34]

    Engstrøm M, Ødegård SS, Sand T, Jacob Stovner L, Zwart J-A, Hagen K. The reliability of a New sleep screening questionnaire for large population-based studies: the third Nord-Trøndelag health study. Open Sleep J 2011;4:14–9.CrossrefGoogle Scholar

  • [35]

    Organization GWH. WHO/CDC. Assessing the iron status of populations, 2nd ed. Report of a joint World Health Organization/Centers for Disease Control and Prevention technical consultation on the assessment of iron status at the population level, 2007.Google Scholar

  • [36]

    Organization GWH. C-reactive protein concentrations as a marker of inflammation or infection for interpreting biomarkers of micronutrient status. Vitamin and Mineral Nutrition Information System. (WHO/NMH/NHD/EPG/14.7), 2014.Google Scholar

  • [37]

    Kurtze N, Rangul V, Hustvedt BE, Flanders WD. Reliability and validity of self-reported physical activity in the Nord-Trondelag Health Study: HUNT 1. Scand J Public Health 2008;36:52–61.PubMedCrossrefGoogle Scholar

  • [38]

    Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70.PubMedCrossrefGoogle Scholar

  • [39]

    Meier-Ewert HK, Ridker PM, Rifai N, Regan MM, Price NJ, Dinges DF, Mullington JM. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol 2004;43:678–83.CrossrefPubMedGoogle Scholar

  • [40]

    Haack M, Lee E, Cohen DA, Mullington JM. Activation of the prostaglandin system in response to sleep loss in healthy humans: potential mediator of increased spontaneous pain. Pain 2009;145:136–41.CrossrefPubMedGoogle Scholar

  • [41]

    Klyne DM, Barbe MF, Hodges PW. Systemic inflammatory profiles and their relationships with demographic, behavioural and clinical features in acute low back pain. Brain Behav Immun 2017;60:84–92.CrossrefPubMedGoogle Scholar

  • [42]

    Klyne DM, Barbe MF, van den Hoorn W, Hodges PW. ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode-the good, the bad, and the ugly. Eur Spine J 2018;27:763–77.CrossrefGoogle Scholar

  • [43]

    Sturmer T, Raum E, Buchner M, Gebhardt K, Schiltenwolf M, Richter W, Brenner H. Pain and high sensitivity C reactive protein in patients with chronic low back pain and acute sciatic pain. Ann Rheum Dis 2005;64:921–5.PubMedCrossrefGoogle Scholar

  • [44]

    Alsaadi SM, McAuley JH, Hush JM, Lo S, Bartlett DJ, Grunstein RR, Maher CG. The bidirectional relationship between pain intensity and sleep disturbance/quality in patients with low back pain. Clin J Pain 2014;30:755–65.CrossrefPubMedGoogle Scholar

  • [45]

    Uhlig BL, Sand T, Nilsen TI, Mork PJ, Hagen K. Insomnia and risk of chronic musculoskeletal complaints: longitudinal data from the HUNT study, Norway. BMC Musculoskelet Disord 2018;19:128.CrossrefGoogle Scholar

  • [46]

    Uhlig BL, Sand T, Odegard SS, Hagen K. Prevalence and associated factors of DSM-V insomnia in Norway: the Nord-Trondelag Health Study (HUNT 3). Sleep Med 2014;15:708–13.PubMedCrossrefGoogle Scholar

  • [47]

    Chung KF, Yeung WF, Ho FY, Yung KP, Yu YM, Kwok CW. Cross-cultural and comparative epidemiology of insomnia: the Diagnostic and statistical manual (DSM), International classification of diseases (ICD) and International classification of sleep disorders (ICSD). Sleep Med 2015;16:477–82.PubMedCrossrefGoogle Scholar

  • [48]

    Lee H, Herbert RD, McAuley JH. Mediation analysis. JAMA 2019;321:697–8.PubMedCrossrefGoogle Scholar

  • [49]

    Gore M, Sadosky A, Stacey BR, Tai KS, Leslie D. The burden of chronic low back pain: clinical comorbidities, treatment patterns, and health care costs in usual care settings. Spine (Phila Pa 1976) 2012;37:E668–77.PubMedCrossrefGoogle Scholar

  • [50]

    Foster NE, Anema JR, Cherkin D, Chou R, Cohen SP, Gross DP, Ferreira PH, Fritz JM, Koes BW, Peul W, Turner JA, Maher CG. Prevention and treatment of low back pain: evidence, challenges, and promising directions. Lancet 2018;391:2368–83.CrossrefPubMedGoogle Scholar

  • [51]

    Ho KKN, Ferreira PH, Pinheiro MB, Silva DA, Miller CB, GrunsteinR, Simic M. Sleep interventions for osteoarthritis and spinal pain: a systematic review and meta-analysis of randomized controlled trials. Osteoarthritis Cartilage 2019;27:196–218.CrossrefGoogle Scholar

  • [52]

    Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2016;165:125–33.PubMedCrossrefGoogle Scholar

  • [53]

    Morin CM, Vallieres A, Guay B, Ivers H, Savard J, Merette C, Bastien C, Baillargeon L. Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial. JAMA 2009;301:2005–15.PubMedCrossrefGoogle Scholar

  • [54]

    Schistad EI, Stubhaug A, Furberg AS, Engdahl BL, Nielsen CS. C-reactive protein and cold-pressor tolerance in the general population: the Tromso Study. Pain 2017;158:1280–8.CrossrefPubMedGoogle Scholar

  • [55]

    Afari N, Mostoufi S, Noonan C, Poeschla B, Succop A, Chopko L, Strachan E. C-reactive protein and pain sensitivity: findings from female twins. Ann Behav Med 2011;42:277–83.PubMedCrossrefGoogle Scholar

  • [56]

    Smith MT, Finan PH, Buenaver LF, Robinson M, Haque U, Quain A, McInrue E, Han D, Leoutsakis J, Haythornthwaite JA. Cognitive-behavioral therapy for insomnia in knee osteoarthritis: a randomized, double-blind, active placebo-controlled clinical trial. Arthritis Rheumatol 2015;67:1221–33.CrossrefPubMedGoogle Scholar

  • [57]

    Afolalu EF, Ramlee F, Tang NKY. Effects of sleep changes on pain-related health outcomes in the general population: a systematic review of longitudinal studies with exploratory meta-analysis. Sleep Med Rev 2018;39:82–97.PubMedCrossrefGoogle Scholar

About the article

Received: 2019-02-20

Revised: 2019-04-26

Accepted: 2019-06-06

Published Online: 2019-07-09


Authors’ statements

Research funding: The authors state there was no specific funding involved for this project. PHF is funded by an Australian National and Health Medical Research Council (NHMRC) fellowship. MS is funded by a Sydney University Research Accelerator Fellowship.

Conflict of interest: The authors state no conflict of interest.

Informed consent: Informed consent has been obtained from all individuals included in this study.

Ethical approval: The research related to human use complies with all the relevant national regulations, institutional policies and was performed in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.


Citation Information: Scandinavian Journal of Pain, 20190033, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2019-0033.

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