​Sleep problems are frequently seen in several chronic pain populations (Pachman et al. 2012;Raizenblatt et al. 2011; Buchwald et al. 1994; Parmelee et al. 2015; Sezgin et al. 2015; Purushothaman et al. 2013; Tang et al. 2007). While the function of sleep is not yet fully discovered, it is known that a lack of sleep can have a negative impact on the general health. Common consequences of sleep deprivation are concentration and memory issues, obesity, cardiovascular diseases, high blood pressure, depression, pro-inflammatory state and metabolic disorders (Chua et al. 2017; Gumenyuk et al. 2014; van Heugten-van der Kloet et al. 2014; Alberca-Reina et al. 2015; Miller et al. 2007; Alvarez et al. 2004; Balkin et al. 2008). Ample evidence indicates a bidirectional relationship between pain and sleep (McBeth et al. 2015;Finan et al. 2013). However, sleep problems are poorly assessed and targeted in current treatment of chronic pain patients (Cheatle et al. 2016; Tang et al. 2007). It is suggested that interventions targeting sleep in patients with chronic pain may produce improvements in pain symptoms (Cheatle et al. 2016; Tang et al. 2007; Finan et al. 2014). To improve sleep, a good understanding of sleep regulation mechanisms and influencing factors is needed (Cheatle et al. 2016;Nijs et al. 2018). 

Sleep is mainly controlled by two processes: 1) Sleep homeostasis or sleep pressure (Process S)and the inner/body clock or the circadian clock (Process C)(Borbély et al. 2016;Goel et al. 2013; Dierickx et al. 2016; Fisher et al. 2013). 

The homeostatic process (process S)is driven by sleep debt. While awake, the sleep debt increases until the sleep pressure is high enough to fall asleep. Once asleep, the sleep debt declines until awakening is triggered due to both low sleep pressure (process S) and increasing alertness (process C; see following paragraph). Napping throughout the day leads to lower sleep pressure at the end of the day and possible sleep difficulties. On the other hand, restricting sleep and avoiding taking naps will increase sleep debt, resulting in higher sleep pressure (Borbély et al. 2016;Goel et al. 2013; Dierickx et al. 2016; Fisher et al. 2013).

The circadian clock (Process C)is an internal timekeeping system with a near-24h period. It is an underlying mechanism regulating different processes of the body at a molecular level (Borbély et al. 2016;Dierickx et al. 2016; Fisher et al. 2013; Dierickx et al. 2018; Wever et al. 1975; Wright et al. 2001). Almost every tissue of our body has its own peripheral clock, sometimes even at single-cell level. These clocks help to maintain local circadian tissue physiology (Dierickx et al. 2016; Fisher et al. 2013; Dierickx et al. 2018). The central core clock, also called “Master clock”, is located in the suprachiasmatic nucleus (SCN), a part of the anterior hypothalamus in the brain, and synchronises all peripheral clocks (Borbély et al. 2016; Dierickx et al. 2016; Fisher et al. 2013; Dierickx et al. 2018). 

This whole process (Process C) makes us feel less alert at night and more alert at day (Goel et al. 2013;Fisher et al. 2013). This also explains why some people (e.g. shift workers) have difficulties to fall asleep in the morning after they stayed awake for a whole night.

Our daily life consists of a 24-h cycle of day and night. Although, when there would be no external cues (e.g. temperature, light, food metabolites, …), the cycle of most individuals would generally be one hour longer  (Wever et al. 1975; Wright et al. 2001). The circadian clock relies on those external cues, also known as “Zeitgebers”, for synchronisation to our surroundings. 

Light is the main synchronizer, forcing us to adapt to a 24-h period. It is possible to advance or delay our circadian rhythm by adapting the light exposure and other synchronizers (Dierickx et al. 2016; Wever et al. 1975; Wright et al. 2001; Wright et al. 2013). When you expose yourself to light in the morning (e.g. morning walk after sunrise), you are more likely to advance your rhythm. This could be useful to reduce or prevent jetlag (Eastman et al. 2005). However, when you expose yourself to light late in the evening, you’re most likely delaying your rhythm (Wever et al. 1975;Wright et al. 2001; Wright et al. 2013). This is what happens during the weekend with many people, particularly late chronotypes. They stay up later than usual and delay their clock, resulting in a “social jetlag” the following Monday (Wittman et al. 2006). Besides, the adaption to cues from the environment is limited to certain level. When the rhythm of the environmental cues changes to fast, the circadian clock does not have the time to adapt and a misalignment will occur (Eastman et al. 2005).

It is important for clinicians and patients to realize that the things we do during the day impacts our sleep at night and vice versa. Most patients will complain about their sleep when they do not feel rested and awake during the day. These patients mostly show inadequate sleep habits and behaviour to compensate their bad sleep (e.g. napping in the afternoon). By giving insight in the mechanisms of sleep regulation, the first steps are made to address and adapt inadequate sleep behaviour (Cheatle et al. 2016;Nijs et al. 2018). 

Thomas Bilterys

Thomas Bilterys is a doctoral researcher at the Vrije Universiteit Brussel (Brussels, Belgium) and Ghent university (Ghent, Belgium). His research and clinical interest goes out to chronic pain and associated sleep problems.

2018 Pain in Motion

References and further reading: 

1. Pachman DR, Barton DL, Swetz KM, Loprinzi CL. Troublesome symptoms in cancer survivors: fatigue, insomnia, neuropathy, and pain. J Clin Oncol. 2012 Oct 20;30(30):3687-96.
2. Roizenblatt S, Neto NS, Tufik S. Sleep disorders and fibromyalgia. Curr Pain Headache Rep. 2011 Oct;15(5):347-57.
3. Buchwald D, Pascualy R, Bombardier C, Kith P. Sleep disorders in patients with chronic fatigue. Clin Infect Dis. 1994 Jan;18 Suppl 1:S68-72.
4. Parmelee PA, Tighe CA, Dautovich ND. Sleep disturbance in osteoarthritis: linkages with pain, disability, and depressive symptoms. Arthritis Care Res (Hoboken). 2015 Mar;67(3):358-65.
5. Sezgin M, Hasanefendioğlu EZ, Sungur MA, Incel NA, Çimen ÖB, Kanık A, Şahin 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(3):433-41.
6. 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 Apr;21(1):68-70.
7. Tang NK, Wright KJ, Salkovskis PM. Prevalence and correlates of clinical insomnia co-occurring with chronic back pain. J Sleep Res. 2007 Mar;16(1):85-95.
8. Chua EC, Fang E, Gooley JJ. Effects of total sleep deprivation on divided attention performance. PLoS One. 2017 Nov 22;12(11):e0187098.
9. Gumenyuk V, Howard R, Roth T, Korzyukov O, Drake CL. Sleep loss, circadian mismatch, and abnormalities in reorienting of attention in night workers with shift work disorder. Sleep. 2014 Mar 1;37(3):545-56.
10. van Heugten-van der Kloet D, Giesbrecht T, Merckelbach H. Sleep loss increases dissociation and affects memory for emotional stimuli. J Behav Ther Exp Psychiatry. 2015 Jun;47:9-17.
11. Alberca-Reina E, Cantero JL, Atienza M. Impact of sleep loss before learning on cortical dynamics during memory retrieval. Neuroimage. 2015 Dec;123:51-62.
12. Miller MA, Cappuccio FP. Inflammation, sleep, obesity and cardiovascular disease. Curr Vasc Pharmacol. 2007 Apr;5(2):93-102.
13. Alvarez GG, Ayas NT. The impact of daily sleep duration on health: a review of the literature. Prog Cardiovasc Nurs. 2004 Spring;19(2):56-9.
    https://www.ncbi.nlm.nih.gov/pubmed/15133379
    
    
14. Balkin TJ, Rupp T, Picchioni D, Wesensten NJ. Sleep loss and sleepiness: current issues. Chest. 2008 Sep;134(3):653-660.
15. McBeth J, Wilkie R, Bedson J, Chew-Graham C, Lacey RJ. Sleep disturbance and chronic widespread pain. Curr Rheumatol Rep. 2015 Jan;17(1):469.
16. Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain. 2013 Dec;14(12):1539-52.
17. Cheatle MD, Foster S, Pinkett A, Lesneski M, Qu D, Dhingra L. Assessing and Managing Sleep Disturbance in Patients with Chronic Pain. Anesthesiol Clin. 2016 Jun;34(2):379-93.
18. Tang NK, Wright KJ, Salkovskis PM. Prevalence and correlates of clinical insomnia co-occurring with chronic back pain. J Sleep Res. 2007 Mar;16(1):85-95.
19. Finan PH, Buenaver LF, Coryell VT, Smith MT. Cognitive-Behavioral Therapy for Comorbid Insomnia and Chronic Pain. Sleep Med Clin. 2014 Jun 1;9(2):261-274.
20. Nijs J, Mairesse O, Neu D, Leysen L, Danneels L, Cagnie B, Meeus M, Moens M, Ickmans K, Goubert D. Sleep Disturbances in Chronic Pain: Neurobiology, Assessment, and Treatment in Physical Therapist Practice. Phys Ther. 2018 May 1;98(5):325-335.
21. Borbély AA, Daan S, Wirz-Justice A, Deboer T. The two-process model of sleep regulation: a reappraisal. J Sleep Res. 2016 Apr;25(2):131-43.
22. Goel N, Basner M, Rao H, Dinges DF. Circadian rhythms, sleep deprivation, and human performance. Prog Mol Biol Transl Sci. 2013;119:155-90.
23. Dierickx P, Pré BD, Feyen DAM, Geijsen N, Veen TV Doevendans PA, Laake LWV. Circadian rhythms in stem cell biology and function. Stem cells and Cardiac Regeneration. Stem Cell Biology and Regenerative Medicine. 2016: 57-78
24. Fisher SP, Foster RG, Peirson SN. The circadian control of sleep. Handb Exp Pharmacol. 2013;(217):157-83.
25. Dierickx P, Van Laake LW, Geijsen N. Circadian clocks: from stem cells to tissue homeostasis and regeneration. EMBO Rep. 2018 Jan;19(1):18-28.
26. Wever R. The circadian multi-oscillatory system of man. Int J Chronobiol. 1975;3(1):19-55.
27. Wright KP Jr, Hughes RJ, Kronauer RE, Dijk DJ, Czeisler CA. Intrinsic near-24-h pacemaker period determines limits of circadian entrainment to a weak synchronizer in humans. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14027-32.
28. Wright KP Jr1, McHill AW, Birks BR, Griffin BR, Rusterholz T, Chinoy ED. Entrainment of the human circadian clock to the natural light-dark cycle. Curr Biol. 2013 Aug 19;23(16):1554-8.
29. Eastman CI, Gazda CJ, Burgess HJ, Crowley SJ, Fogg LF. Advancing circadian rhythms before eastward flight: a strategy to prevent or reduce jet lag. Sleep. 2005 Jan;28(1):33-44.
30. Wittmann M, Dinich J, Merrow M, Roenneberg T. Social jetlag: misalignment of biological and social time. Chronobiol Int. 2006;23(1-2):497-509.

https://www.ncbi.nlm.nih.gov/pubmed/23008320

https://www.ncbi.nlm.nih.gov/pubmed/21594765

https://www.ncbi.nlm.nih.gov/pubmed/8148456

https://www.ncbi.nlm.nih.gov/pubmed/25283955

https://www.ncbi.nlm.nih.gov/pubmed/25322735

https://www.ncbi.nlm.nih.gov/pubmed/23629992

https://www.ncbi.nlm.nih.gov/pubmed/17309767

https://www.ncbi.nlm.nih.gov/pubmed/29166387

https://www.ncbi.nlm.nih.gov/pubmed/24587577

https://www.ncbi.nlm.nih.gov/pubmed/25462597

https://www.ncbi.nlm.nih.gov/pubmed/26302671

https://www.ncbi.nlm.nih.gov/pubmed/17430213

https://www.ncbi.nlm.nih.gov/pubmed/18779203

https://www.ncbi.nlm.nih.gov/pubmed/25604572

https://www.ncbi.nlm.nih.gov/pubmed/24290442

https://www.ncbi.nlm.nih.gov/pubmed/27208716

https://www.ncbi.nlm.nih.gov/pubmed/17309767

https://www.ncbi.nlm.nih.gov/pubmed/25477769

https://www.ncbi.nlm.nih.gov/pubmed/29425327

https://www.ncbi.nlm.nih.gov/pubmed/26762182

https://www.ncbi.nlm.nih.gov/pubmed/23899598

https://link.springer.com/chapter/10.1007/978-3-319-25427-2_5#citeas

https://www.ncbi.nlm.nih.gov/pubmed/23604479

https://www.ncbi.nlm.nih.gov/pubmed/29258993

https://www.ncbi.nlm.nih.gov/pubmed/1193771

https://www.ncbi.nlm.nih.gov/pubmed/11717461

https://www.ncbi.nlm.nih.gov/pubmed/23910656

https://www.ncbi.nlm.nih.gov/pubmed/15700719

https://www.ncbi.nlm.nih.gov/pubmed/16687322

Free PDF available from: 

Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain. 2013 Dec;14(12):1539-52.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046588/pdf/nihms521705.pdf

Finan PH, Buenaver LF, Coryell VT, Smith MT. Cognitive-Behavioral Therapy for Comorbid Insomnia and Chronic Pain. Sleep Med Clin. 2014 Jun 1;9(2):261-274.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248667/pdf/nihms591095.pdf

Cheatle MD, Foster S, Pinkett A, Lesneski M, Qu D, Dhingra L. Assessing and Managing Sleep Disturbance in Patients with Chronic Pain. Anesthesiol Clin. 2016 Jun;34(2):379-93.

https://www.anesthesiology.theclinics.com/article/S1932-2275(16)00008-2/pdf

Goel N, Basner M, Rao H, Dinges DF. Circadian rhythms, sleep deprivation, and human performance. Prog Mol Biol Transl Sci. 2013;119:155-90.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963479/pdf/nihms562935.pdf

Borbély AA, Daan S, Wirz-Justice A, Deboer T. The two-process model of sleep regulation: a reappraisal. J Sleep Res. 2016 Apr;25(2):131-43.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jsr.12371