Skip to content
Licensed Unlicensed Requires Authentication Published online by De Gruyter April 14, 2022

A bidirectional study of the association between insomnia, high-sensitivity C-reactive protein, and comorbid low back pain and lower limb pain

Kevin K. N. Ho, Eivind S. Skarpsno, Kristian B. Nilsen, Paulo H. Ferreira, Marina B. Pinheiro, Laila A. Hopstock, Marianne Bakke Johnsen, Ólöf A. Steingrímsdóttir, Christopher S. Nielsen, Audun Stubhaug and Milena Simic

Abstract

Objectives

To examine the possible bidirectional association between insomnia and comorbid chronic low back pain (LBP) and lower limb pain and to explore whether high-sensitivity C-reactive protein (hsCRP) amplifies these associations.

Methods

We calculated adjusted risk ratios (RR) with 95% confidence intervals (CI) for the development of insomnia and mild-to-severe chronic LBP and lower limb pain at 11 years follow-up in participants aged ≥32 years and with hsCRP ≤10 mg/L at baseline in 2007–2008: 3,714 without chronic LBP or lower limb pain (sample 1) and 7,892 without insomnia (sample 2).

Results

Compared to participants without chronic pain, participants with comorbid chronic LBP and lower limb pain had a RR of insomnia of 1.37 (95% CI 1.12–1.66). Compared with participants without insomnia, participants with insomnia did not have an increased risk of comorbid chronic LBP and lower limb pain (RR: 1.06, 95% CI 0.76–1.46); however, participants with insomnia had a RR of chronic LBP of 1.20 (95% CI 1.02–1.42). There was no strong amplifying effect of elevated hsCRP (3.00–10.0 mg/L) on these associations.

Conclusions

These findings suggest that elevated hsCRP does not amplify the associations between insomnia and mild-to-severe chronic LBP and lower limb pain. Further research using data on the temporal relation between insomnia, chronic pain, and inflammatory responses are required to fully understand the causal pathways.


Corresponding author: Kevin K. N. Ho, Faculty of Medicine and Health, Sydney School of Health Sciences, The University of Sydney, Level 7 East, Susan Wakil Health Building, Western Ave, Camperdown, Sydney, 2050, NSW, Australia, Phone: +61 2 9351 9010, E-mail:
Dr Ho and Dr Skarpsno share first authorship.

Acknowledgements

We acknowledge the participants and staff of the Tromsø Study.

  1. 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. MBP is funded by an Australian National and Health Medical Research Council (NHMRC) early career fellowship. ESS is funded by a grant from the Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU) (grant number: 90502200).

  2. Author Contribution: Author contributions in reference to (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted, are: Dr Kevin Kwan Ngai HO: 1, 2 and 3; Dr Eivind S SKARPSNO: 1, 2 and 3; Dr Kristian Bernhard NILSEN: 1, 2 and 3; Professor Paulo FERREIRA: 1, 2 and 3; Dr Marina De Barros PINHEIRO: 1, 2 and 3; Dr Laila Arnesdatter HOPSTOCK: 1, 2 and 3; Dr Marianne Bakke JOHNSEN: 1, 2 and 3; Dr Olöf Anna STEINGRIMSDOTTIR: 1, 2 and 3; Dr Christopher Sivert NIELSEN: 1, 2 and 3; Professor Audun STUBHAUG: 1, 2 and 3; Associate Professor Milena SIMIC: 1, 2 and 3

  3. Conflict of interest: Authors state no conflict of interest.

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

  5. 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.

References

1. Meucci, RD, Fassa, AG, Faria, NM. Prevalence of chronic low back pain: systematic review. Rev Saude Publica 2015;49:1. https://doi.org/10.1590/S0034-8910.2015049005874.Search in Google Scholar PubMed PubMed Central

2. Peat, G, McCarney, R, Croft, P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. Ann Rheum Dis 2001;60:91–7. https://doi.org/10.1136/ard.60.2.91.Search in Google Scholar PubMed PubMed Central

3. Damen, J, van Rijn, RM, Emans, PJ, Hilberdink, W, Wesseling, J, Oei, EHG, et al.. Prevalence and development of hip and knee osteoarthritis according to American College of Rheumatology criteria in the CHECK cohort. Arthritis Res Ther 2019;21:4. https://doi.org/10.1186/s13075-018-1785-7.Search in Google Scholar PubMed PubMed Central

4. Skou, ST, Koes, BW, Gronne, DT, Young, J, Roos, EM. Comparison of three sets of clinical classification criteria for knee osteoarthritis: a cross-sectional study of 13,459 patients treated in primary care. Osteoarthritis Cartilage 2020;28:167–72. https://doi.org/10.1016/j.joca.2019.09.003.Search in Google Scholar PubMed

5. 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. https://doi.org/10.1002/acr.20324.Search in Google Scholar PubMed PubMed Central

6. Stupar, M, Cote, P, French, MR, Hawker, GA. The association between low back pain and osteoarthritis of the hip and knee: a population-based cohort study. J Manipulative Physiol Therapeut 2010;33:349–54. https://doi.org/10.1016/j.jmpt.2010.05.008.Search in Google Scholar PubMed

7. 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. https://doi.org/10.1016/j.smrv.2017.08.001.Search in Google Scholar PubMed PubMed Central

8. Finan, PH, Goodin, BR, Smith, MT. The association of sleep and pain: an update and a path forward. J Pain 2013;14:1539–52. https://doi.org/10.1016/j.jpain.2013.08.007.Search in Google Scholar PubMed PubMed Central

9. Whibley, D, AlKandari, N, Kristensen, K, Barnish, M, Rzewuska, M, Druce, KL, et al.. Sleep and pain: a systematic review of studies of mediation. Clin J Pain 2019;35:544–58. https://doi.org/10.1097/ajp.0000000000000697.Search in Google Scholar

10. 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 Muscoskel Disord 2018;19:128. https://doi.org/10.1186/s12891-018-2035-5.Search in Google Scholar PubMed PubMed Central

11. Tang, NK, McBeth, J, Jordan, KP, Blagojevic-Bucknall, M, Croft, P, Wilkie, R. Impact of musculoskeletal pain on insomnia onset: a prospective cohort study. Rheumatology 2015;54:248–56. https://doi.org/10.1093/rheumatology/keu283.Search in Google Scholar PubMed PubMed Central

12. Skarpsno, ES, Mork, PJ, Nilsen, TIL, Steingrimsdottir, OA, Zwart, JA, Nilsen, KB. The interplay between sleeplessness and high-sensitivity C-reactive protein on risk of chronic musculoskeletal pain: longitudinal data from the Tromso Study. Sleep 2019;42. https://doi.org/10.1093/sleep/zsz127.Search in Google Scholar PubMed

13. Agmon, M, Armon, G. Increased insomnia symptoms predict the onset of back pain among employed adults. PLoS One 2014;9: e103591. https://doi.org/10.1371/journal.pone.0103591.Search in Google Scholar PubMed PubMed Central

14. Staud, R. Evidence for shared pain mechanisms in osteoarthritis, low back pain, and fibromyalgia. Curr Rheumatol Rep 2011;13:513–20. https://doi.org/10.1007/s11926-011-0206-6.Search in Google Scholar PubMed

15. Bernstein, IA, Malik, Q, Carville, S, Ward, S. Low back pain and sciatica: summary of NICE guidance. BMJ 2017;356. https://doi.org/10.1136/bmj.i6748.Search in Google Scholar PubMed

16. National Clinical Guideline C. National Institute for Health and Clinical Excellence: Guidance. Osteoarthritis: Care and Management in Adults. London: UK. National Clinical Guideline Centre; 2014.Search in Google Scholar

17. Koes, BW, van Tulder, MW, Peul, WC. Diagnosis and treatment of sciatica. Br Med J 2007;334:1313–7. https://doi.org/10.1136/bmj.39223.428495.be.Search in Google Scholar

18. Nijs, J, Mairesse, O, Neu, D, Leysen, L, Danneels, L, Cagnie, B, et al.. Sleep disturbances in chronic pain: neurobiology, assessment, and treatment in physical therapist practice. Phys Ther 2018;98:325–35. https://doi.org/10.1093/ptj/pzy020.Search in Google Scholar PubMed

19. 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. https://doi.org/10.1007/s11916-009-0073-2.Search in Google Scholar PubMed

20. 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. https://doi.org/10.1093/sleep/30.9.1145.Search in Google Scholar PubMed PubMed Central

21. Haack, M, Simpson, N, Sethna, N, Kaur, S, Mullington, J. Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Neuropsychopharmacology 2020;45:205–16. https://doi.org/10.1038/s41386-019-0439-z.Search in Google Scholar PubMed PubMed Central

22. 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. https://doi.org/10.1097/j.pain.0000000000000912.Search in Google Scholar PubMed

23. Ho Kevin Kwan, N, Simic, M, Cvancarova Småstuen, M, de Barros Pinheiro, M, Ferreira Paulo, H, Bakke Johnsen, M, et al.. The association between insomnia, C-reactive protein, and chronic low back pain: cross-sectional analysis of the HUNT study, Norway. Scand J Pain 2019;19:765–77. https://doi.org/10.1515/sjpain-2019-0033.Search in Google Scholar PubMed

24. Eggen, AE, Mathiesen, EB, Wilsgaard, T, Jacobsen, BK, Njolstad, I. The sixth survey of the Tromso Study (Tromso 6) in 2007-08: collaborative research in the interface between clinical medicine and epidemiology: study objectives, design, data collection procedures, and attendance in a multipurpose population-based health survey. Scand J Publ Health 2013;41:65–80. https://doi.org/10.1177/1403494812469851.Search in Google Scholar PubMed

25. von Elm, E, Altman, DG, Egger, M, Pocock, SJ, Gotzsche, PC, Vandenbroucke, JP, et al.. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61:344–9. https://doi.org/10.1016/j.jclinepi.2007.11.008.Search in Google Scholar PubMed

26. Pearson, TA, Mensah, GA, Alexander, RW, Anderson, JL, Cannon, RO3rd, Criqui, M, et al.. 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. https://doi.org/10.1161/01.cir.0000052939.59093.45.Search in Google Scholar PubMed

27. Sivertsen, B, Lallukka, T, Petrie, KJ, Steingrimsdottir, OA, Stubhaug, A, Nielsen, CS. Sleep and pain sensitivity in adults. Pain 2015;156:1433–9. https://doi.org/10.1097/j.pain.0000000000000131.Search in Google Scholar PubMed

28. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA, USA: American Psychiatric Publishing; 2013.10.1176/appi.books.9780890425596Search in Google Scholar

29. Pallesen, S, Bjorvatn, B, Nordhus, IH, Sivertsen, B, Hjornevik, M, Morin, CM. A new scale for measuring insomnia: the Bergen Insomnia Scale. Percept Mot Skills 2008;107:691–706. https://doi.org/10.2466/pms.107.3.691-706.Search in Google Scholar PubMed

30. Geneva: World Health Organization. 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.Search in Google Scholar

31. Prieto-Alhambra, D, Judge, A, Javaid, MK, Cooper, C, Diez-Perez, A, Arden, NK. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Ann Rheum Dis 2014;73:1659–64. https://doi.org/10.1136/annrheumdis-2013-203355.Search in Google Scholar PubMed PubMed Central

32. Shiri, R, Falah-Hassani, K. Does leisure time physical activity protect against low back pain? Systematic review and meta-analysis of 36 prospective cohort studies. Br J Sports Med 2017;51:1410–8. https://doi.org/10.1136/bjsports-2016-097352.Search in Google Scholar PubMed

33. Zhang, TT, Liu, Z, Liu, YL, Zhao, JJ, Liu, DW, Tian, QB. Obesity as a risk factor for low back pain: a meta-analysis. Clin Spine Surg 2018;31:22–7. https://doi.org/10.1097/bsd.0000000000000468.Search in Google Scholar

34. Silverwood, V, Blagojevic-Bucknall, M, Jinks, C, Jordan, JL, Protheroe, J, Jordan, KP. Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage 2015;23:507–15. https://doi.org/10.1016/j.joca.2014.11.019.Search in Google Scholar PubMed

35. Ferreira, PH, Pinheiro, MB, Machado, GC, Ferreira, ML. Is alcohol intake associated with low back pain? a systematic review of observational studies. Man Ther 2013;18:183–90. https://doi.org/10.1016/j.math.2012.10.007.Search in Google Scholar PubMed

36. Shiri, R, Karppinen, J, Leino-Arjas, P, Solovieva, S, Viikari-Juntura, E. The association between smoking and low back pain: a meta-analysis. Am J Med 2010;123:87–35. https://doi.org/10.1016/j.amjmed.2009.05.028.Search in Google Scholar PubMed

37. Pinheiro, MB, Ferreira, ML, Refshauge, K, Ordonana, JR, Machado, GC, Prado, LR, et al.. 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. https://doi.org/10.1002/acr.22619.Search in Google Scholar PubMed

38. Haskell, WL, Lee, IM, Pate, RR, Powell, KE, Blair, SN, Franklin, BA, et al.. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc 2007;39:1423–34. https://doi.org/10.1249/mss.0b013e3180616b27.Search in Google Scholar PubMed

39. 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 Publ Health 2014;24:924–9. https://doi.org/10.1093/eurpub/ckt198.Search in Google Scholar PubMed

40. Strand, BH, Dalgard, OS, Tambs, K, Rognerud, M. Measuring the mental health status of the Norwegian population: a comparison of the instruments SCL-25, SCL-10, SCL-5 and MHI-5 (SF-36). Nord J Psychiatr 2003;57:113–8. https://doi.org/10.1080/08039480310000932.Search in Google Scholar PubMed

41. Derogatis, LR, Lipman, RS, Rickels, K, Uhlenhuth, EH, Covi, L. The Hopkins Symptom Checklist (HSCL): a self-report symptom inventory. Behav Sci 1974;19:1–15. https://doi.org/10.1002/bs.3830190102.Search in Google Scholar PubMed

42. Heuch, I, Heuch, I, Hagen, K, Zwart, JA. Does high blood pressure reduce the risk of chronic low back pain? The Nord-Trondelag Health Study. Eur J Pain 2014;18:590–8. https://doi.org/10.1002/j.1532-2149.2013.00398.x.Search in Google Scholar PubMed

43. Budhiraja, R, Parthasarathy, S, Budhiraja, P, Habib, MP, Wendel, C, Quan, SF. Insomnia in patients with COPD. Sleep 2012;35:369–75. https://doi.org/10.5665/sleep.1698.Search in Google Scholar PubMed PubMed Central

44. Dario, A, Ferreira, M, Refshauge, K, Harmer, A, Sanchez-Romera, J, Perez-Riquelme, F, et al.. Mapping the association between back pain and type 2 diabetes: a cross-sectional and longitudinal study of adult Spanish twins. PLoS One 2017;12:e0174757. https://doi.org/10.1371/journal.pone.0174757.Search in Google Scholar PubMed PubMed Central

45. Sofi, F, Cesari, F, Casini, A, Macchi, C, Abbate, R, Gensini, GF. Insomnia and risk of cardiovascular disease: a meta-analysis. Eur J Prev Cardiol 2014;21:57–64. https://doi.org/10.1177/2047487312460020.Search in Google Scholar PubMed

46. Baykara, RA, Bozgeyik, Z, Akgul, O, Ozgocmen, S. Low back pain in patients with rheumatoid arthritis: clinical characteristics and impact of low back pain on functional ability and health related quality of life. J Back Musculoskelet Rehabil 2013;26:367–74. https://doi.org/10.3233/bmr-130393.Search in Google Scholar PubMed

47. Luyster, FS, Chasens, ER, Wasko, MC, Dunbar-Jacob, J. Sleep quality and functional disability in patients with rheumatoid arthritis. J Clin Sleep Med 2011;7:49–55. https://doi.org/10.5664/jcsm.28041.Search in Google Scholar

48. Luyster, FS, Strollo, PJJr., Holguin, F, Castro, M, Dunican, EM, Fahy, J, et al.. Association between insomnia and asthma burden in the severe asthma research program (SARP) III. Chest 2016;150:1242–50. https://doi.org/10.1016/j.chest.2016.09.020.Search in Google Scholar PubMed PubMed Central

49. Luo, J, Sands, M, Wactawski-Wende, J, Song, Y, Margolis, KL. Sleep disturbance and incidence of thyroid cancer in postmenopausal women the Women’s Health Initiative. Am J Epidemiol 2013;177:42–9. https://doi.org/10.1093/aje/kws193.Search in Google Scholar PubMed PubMed Central

50. Lu, JL, Freire, AX, Molnar, MZ, Kalantar-Zadeh, K, Kovesdy, CP. Association of chronic insomnia with mortality and adverse renal outcomes. Mayo Clin Proc 2018;93:1563–70. https://doi.org/10.1016/j.mayocp.2018.05.032.Search in Google Scholar PubMed

51. Zou, G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol 2004;159:702–6. https://doi.org/10.1093/aje/kwh090.Search in Google Scholar PubMed

52. Andersson, T, Alfredsson, L, Kallberg, H, Zdravkovic, S, Ahlbom, A. Calculating measures of biological interaction. Eur J Epidemiol 2005;20:575–9. https://doi.org/10.1007/s10654-005-7835-x.Search in Google Scholar PubMed

53. Skarpsno, ES, Mork, PJ, Marcuzzi, A, Lund Nilsen, TI, Meisingset, I. Subtypes of insomnia and the risk of chronic spinal pain: the HUNT study. Sleep Med 2021;85:15–20. https://doi.org/10.1016/j.sleep.2021.06.029.Search in Google Scholar PubMed

54. Zhang, J, Lam, SP, Li, SX, Li, AM, Wing, YK. The longitudinal course and impact of non-restorative sleep: a five-year community-based follow-up study. Sleep Med 2012;13:570–6. https://doi.org/10.1016/j.sleep.2011.12.012.Search in Google Scholar PubMed

55. 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. https://doi.org/10.1016/j.spinee.2018.06.349.Search in Google Scholar PubMed

56. Stannus, OP, Jones, G, Blizzard, L, Cicuttini, FM, Ding, C. Associations between serum levels of inflammatory markers and change in knee pain over 5 years in older adults: a prospective cohort study. Ann Rheum Dis 2013;72:535–40. https://doi.org/10.1136/annrheumdis-2011-201047.Search in Google Scholar PubMed

57. Spector, TD, Hart, DJ, Nandra, D, Doyle, DV, Mackillop, N, Gallimore, JR, et al.. Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 1997;40:723–7. https://doi.org/10.1002/art.1780400419.Search in Google Scholar PubMed

58. Lee, H, Herbert, RD, McAuley, JH. Mediation analysis. JAMA 2019;321:697–8. https://doi.org/10.1001/jama.2018.21973.Search in Google Scholar PubMed

59. Skarpsno, ES, Nilsen, TIL, Sand, T, Hagen, K, Mork, PJ. Do physical activity and body mass index modify the association between chronic musculoskeletal pain and insomnia? Longitudinal data from the HUNT study, Norway. J Sleep Res 2017;27:32–9. https://doi.org/10.1111/jsr.12580.Search in Google Scholar PubMed

60. Skarpsno, ES, Mork, PJ, Nilsen, TIL, Nordstoga, AL. Influence of sleep problems and co-occurring musculoskeletal pain on long-term prognosis of chronic low back pain: the HUNT Study. J Epidemiol Community Health 2020;74:283–9. https://doi.org/10.1136/jech-2019-212734.Search in Google Scholar PubMed

61. Quan, SF, Katz, R, Olson, J, Bonekat, W, Enright, PL, Young, T, et al.. Factors associated with incidence and persistence of symptoms of disturbed sleep in an elderly cohort: the Cardiovascular Health Study. Am J Med Sci 2005;329:163–72. https://doi.org/10.1097/00000441-200504000-00001.Search in Google Scholar PubMed

62. Dowd, JB, Goldman, N, Weinstein, M. Sleep duration, sleep quality, and biomarkers of inflammation in a Taiwanese population. Ann Epidemiol 2011;21:799–806. https://doi.org/10.1016/j.annepidem.2011.07.004.Search in Google Scholar PubMed PubMed Central

63. Irwin, MR. Sleep and inflammation: partners in sickness and in health. Nat Rev Immunol 2019;19:702–15. https://doi.org/10.1038/s41577-019-0190-z.Search in Google Scholar PubMed

64. Statistics Norway. Population. Available from: https://www.ssb.no/en/befolkning/statistikker/folkemengde/aar-per-1-januar.Search in Google Scholar

65. Statistics Norway. Educational attainment of the population. Available from: https://www.ssb.no/en/utdanning/statistikker/utniv/aar.Search in Google Scholar

66. 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. https://doi.org/10.1016/j.sleep.2014.01.018.Search in Google Scholar PubMed

67. Riemann, D, Spiegelhalder, K, Feige, B, Voderholzer, U, Berger, M, Perlis, M, et al.. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev 2010;14:19–31. https://doi.org/10.1016/j.smrv.2009.04.002.Search in Google Scholar PubMed

68. 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 Psychiatr 2016;80:40–52. https://doi.org/10.1016/j.biopsych.2015.05.014.Search in Google Scholar PubMed PubMed Central

69. Quartana, PJ, Finan, PH, Page, GG, Smith, MT. Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers. Brain Behav Immun 2015;47:228–37. https://doi.org/10.1016/j.bbi.2014.12.010.Search in Google Scholar PubMed PubMed Central

Received: 2021-10-29
Accepted: 2022-03-08
Published Online: 2022-04-14

© 2022 Walter de Gruyter GmbH, Berlin/Boston