Chronic Pain and Sleep

Sleep disturbances are common in individuals experiencing chronic pain.

Subjective measures of sleep in various chronic pain conditions mostly demonstrate a high number of complaints of disrupted and unrefreshing sleep.

Polysomnographic studies of patients with chronic pain have been less conclusive; many studies have shown that patients with chronic pain have a fragmented slow wave sleep with intrusion of alpha waves, while others report few perceptible changes in the sleep of patients with chronic pain.

Experimental studies in healthy humans have shown that the pain-sleep relationship is bidirectional: pain stimuli provoke changes in sleep architecture and partial or complete sleep deprivation lowers pain thresholds in healthy individuals.

The International Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (i.e, experience of pain in the absence of tissue damage).

Pain is a defensive response by the organism to prevent further damage from occurring. Sleep, on the other hand, is a basic biological function as essential for survival as food and water.

Animal studies have shown that total sleep deprivation in rats causes death in less than 1 month [1]. Sleep deprivation in humans was not born with industrialization; the first known writings on its effects date from ancient Egypt circa 1300 BC.

Both chronic pain and sleep disturbances are widespread in the general population [2].

As many as one-third of the population suffers from frequent or persistent pain, and an equal number have sleep disturbances. Individuals suffering from painful physical conditions often have concomitant sleep disturbances [3-11].

Pain and sleep problems are especially prevalent among the elderly [3,2].

The direction of cause and effect of this association is not yet fully understood and is still a matter of debate. There is experimental evidence that pain augments arousals during sleep, causing sleep disruption. However, it is unlikely that this association is only unidirectional, as illustrated by partial or complete sleep deprivation studies in humans.


Study of the relationship between pain and sleep deprivation in healthy individuals is not new, with the oldest article written on this topic in 1898 [12].

Some studies have investigated the effect of a single night of total sleep deprivation on pain tolerance thresholds, while others have examined the outcomes of sleep restriction, or the effects of selective sleep stage deprivation.

Moldofsky et al. assessed the effects of selective non-rapid eye movement sleep (NREM) deprivation over three consecutive nights in six healthy subjects [13]. Selective deprivation of sleep stage 4 was associated with an increased sensitivity to pressure pain and more musculoskeletal pain.

A similar experiment was conducted in seven healthy subjects deprived of REM sleep. REM deprived subjects did not show increased muscle tenderness or more musculoskeletal pain after sleep deprivation [14].

Similar conclusions were obtained in an uncontrolled study involving 12 healthy middle-aged women [15], who were deprived of slow-wave sleep (SWS) for three consecutive nights with minimal alterations of total sleep time, sleep efficiency, and other sleep stages. After the third night, the women showed a 24% decrease in musculoskeletal pain threshold and reported increased discomfort, tiredness, fatigue, and reduced vigor.

Another study investigated the effect of delta wave sleep (sleep stages 3 and 4) interruption in 13 healthy volunteers (six control and seven experimental subjects) for three consecutive nights [16]. Delta wave sleep interruption was not associated with a lowering of pain thresholds compared with the control group in any of the three conditions (baseline, deprivation, and recovery).

A double-blind crossover experiment on pain tolerance thresholds with nine healthy male subjects was conducted over two periods of six consecutive nights (night 1 adaptation, night 2 baseline, night 3 total sleep deprivation, night 4 and night 5 SWS or REM interruption, and night 6 recovery) [17]. Total sleep deprivation, but not REM sleep interruption, was associated with a decreased tolerance to pressure pain. SWS interruption was associated with greater pain tolerance on the recovery day, suggesting an analgesic effect related to SWS recovery.

Kundermann et al. investigated the effects of two nights of total sleep deprivation on thermal pain thresholds in 20 healthy volunteers [18]. Sleep-deprived individuals showed a significant decrease in heat pain and cold pain thresholds, but warmth and cold detection thresholds remained unaffected.

These experimental studies show that partial or complete sleep deprivation produced hyperalgesic changes [13-20]. Deprivation of SWS may also be associated with a decrease in pain tolerance. None of these studies found a significant association between REM deprivation and tolerance to pain.

Therefore, if pain affects the quality of sleep, it appears that the reverse is also true: sleep deprivation can lower pain thresholds, increasing the level of experienced pain.


The effects of pain on objective and subjective measures of sleep quality and quantity have been documented in both clinical and general populations.

The most commonly studied pain conditions are:

  • headaches
  • rheumatic pain and arthritis
  • back pain and fibromyalgia.

Polysomnography (PSG) studies have shown that patients with pain have:

  • longer sleep latency
  • shorter sleep duration
  • a fragmented SWS with intrusion of alpha waves [25-31]

Sleep disturbances may be as a consequence of pain, but there is also experimental evidence revealing that widespread pain can precipitate sleep deprivation [15,16].

Human studies show that disruption of sleep physiology influences daytime musculoskeletal pain and fatigue [13, 32-34], and alpha anomalies in the sleep of patients with chronic pain have been reported on numerous occasions.


Sleep disturbances are a common complaint in subjects with rheumatic pain.

Along with back pain, rheumatic pain was the greatest predictor of disrupted sleep and non-restorative sleep in a sample of 18 980 individuals representative of the general population of five European countries [2].

The Canadian Community Health Survey examined the association between arthritis and insomnia symptoms in 118 336 adults. As in the Ohayon study, they found that insomnia and non-restorative sleep were twice as common in individuals with arthritis as in those without [35].

In outpatient and pain clinic studies, 54-70% of patients with rheumatoid arthritis (RA) complained of sleep disturbances. A 24-month longitudinal study found that 60% of the 254 RA patients reported a mild or moderate interference of sleep from pain, with 14% reporting severe interference [36]. Leigh et al. found no difference in the report of sleep problems between 439 hospitalized rheumatic and non-rheumatic patients, with the exception of pain during sleep [37].

A number of PSG studies have been conducted in patients with RA. One study found that RA patients had increased alpha sleep on EEG and an increased number of periodic movements of the legs, compared with healthy subjects [27]. The study also reported that morning stiffness, pain, and joint tenderness related to awakenings from sleep (wake after sleep onset), SWS, and REM sleep.Another study involving 19 patients with RA reported that normal sleep architecture was preserved but a severe sleep fragmentation was seen compared with age- and gender-matched healthy control subjects [38]. A study of children and adolescents with polyarticular juvenile RA (JRA) reported higher indexes of periodic leg movements (number of movements/h), isolated leg movements, and greater sleep fragmentation than in matched healthy controls [39].

Zamir et al. found that in addition to greater sleep fragmentation, JRA children had higher scores on the multiple sleep latency test (MSLT), indicating a tendency for daytime sleepiness and increased length of afternoon naps [40]. A PSG study in 14 patients with osteoarthritis reported a greater percentage of stage 1 sleep and a significantly smaller percentage of stage 2 sleep compared with 16 matched healthy controls [41]. Motility during sleep was also assessed. Patients suffering from osteoarthritis moved more during sleep than controls; however, this difference was non-significant [42].

Of three studies using the MSLT to measure daytime sleepiness in RA patients, two studies found that the majority of RA patients had MSLT results indicating excessive daytime sleepiness [29,43], while the third study found no evidence of sleepiness [38].


Second only to headaches, back pain is the most common neurological complaint in the US. Back pain persisting for >3 months is considered chronic.

Chronic back pain affects 14-35% of the general population, depending on the country studied, [44-47] and nearly half of all subjects with chronic back pain complain of sleep disturbances [2]. A 28-year longitudinal study involving a cohort of 902 metal industry workers has shown that sleep disturbances (insomnia and/or nightmares) predicted a 2.1-fold increased risk of back-related hospitalizations in workers with only one sleep disturbance, and a 2.4-fold risk in workers with both sleep disturbances [48].

Only two PSG studies of chronic back pain have been undertaken:

  • One study reported that patients with chronic lower back pain had less restful sleep and more alpha EEG sleep compared with controls [49].
  • The second study compared four depressed subjects suffering chronic lower back pain with six non-depressed subjects with chronic lower back pain, and 11 controls [50]. The three groups had comparable sleep architecture; however, EEG power spectral analyses revealed that the two groups with chronic lower back pain had lower sigma power than the controls, which could contribute to poor sleep quality.

Studies have also used actigraphy measures to assess the relationship between chronic lower back pain and sleep. Lavie et al., reported that patients with chronic lower back pain did not have significantly different actigraph measures from patients with RA or from controls [28].

Cesta et al., found that workers who had lower back pain reported more disturbed and unrefreshing sleep, and had longer awakenings (as measured by the actigraph) than controls [51]. In another study, 18 patients with chronic lower back pain who wore an Actiwatch for 6 days and 5 nights recorded pain levels every 90 min during the daytime [52]. No association was found between pain levels and sleep the following night, or between sleep and pain levels the next day.


Headache is the most common neurological complaint. In studies conducted in the general population, headaches and/or migraines have been associated with nightmares [53,54], snoring [53,10,55], sleep excess [55,56], insomnia [56-58], and sleep deprivation [59].

The relationship between headaches and sleep is complex. Many patients who received a consultation for headaches suffer from sleep disturbances and have an identifiable sleep disorder [6,7, 60] and treatment of the sleep disorder often alleviates or reduces the headache. However, headaches are not specific to any sleep disorder [7,8]. Several clinical studies have shown that the treatment of obstructive sleep apnea syndrome considerably improves symptoms of morning headache [11,61-63]. However, the relationship between obstructive sleep apnea syndrome, headaches, and morning headaches is more complex and other factors may influence this association. A clinical study of 312 patients who consulted a sleep center for snoring revealed that headaches and morning headaches were not correlated with sleep apnea index and architectural sleep parameters, nor with excessive daytime sleepiness, but were strongly correlated with mood disorders [62]. Similarly, anxiety and depressive disorders were identified as the strongest predictors of morning headaches in a general-population based study [53].


Fibromyalgia is characterized by:

  • widespread pain lasting >3 months in joints, muscles, tendons, and other soft tissues
  • non-restorative sleep [64,65]
  • chronic fatigue
  • morning stiffness

The cause of this disorder is unknown and its prevalence in the general population is estimated at 1-3% [66-69].

Objective and subjective sleep disturbances are present in nearly 75% of patients with fibromyalgia [70].

Several PSG studies have investigated patients with fibromyalgia. An early study by Moldofsky et al. described NREM anomalies in these patients [13], characterized by alpha intrusion on delta waves, which were likely to be related to unrefreshing sleep, diffuse pain, and mood symptoms. Another study comparing 10 fibromyalgia patients with 14 healthy controls found alpha-delta patterns were present in almost all the patients who had fragmented sleep, reduced REM, and SWS [71].

Delta decay across sleep cycles was different in patients with fibromyalgia compared with healthy controls. Alpha activity was greater and declined more when compared to controls. Alpha-delta ratio increased through progressive sleep cycles, a finding not observed in controls. Alpha intrusion has also been observed in RA [29,30].

A study by Horne and Schackell enrolled 11 subjects with fibromyalgia and 15 symptom-free controls who all claimed to be good sleepers [72]. Mean percentage alpha-like activity in sleep stages 2, 3, 4 and NREM sleep were greatest for the fibromyalgia group, but not significantly different from those of the controls. The overlap in the distribution of NREM alpha-like activity in sleep between the two groups suggested that alpha activity was unrelated to musculoskeletal symptoms.


Medication effects can also influence the restorative quality of sleep.

Some studies in healthy subjects have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) cause some disruptions in sleep architecture. Namely, an increase in sleep latency, greater WASO, increased in stage 2 and SWS and reduced sleep efficiency were observed with aspirin and ibuprofen [73,74]. On the other hand, in patients with pain, the use of NSAIDs did not modify the sleep architecture but improve the subjective perception of sleep quality [75].

Opioids are known to induce sedative side effects. In healthy volunteers, opioids increased the duration of stage 2 sleep and decreased the duration of SWS [75]. Opioid therapy may also worsen or induce sleep-disordered breathing through an action at mu receptors [77,78].

Tricyclic antidepressants are also used in the management of pain. In healthy volunteers, Tricyclic antidepressants increased total sleep time, stage 2 sleep and reduced arousals. They also increased REM latency and decreased the total REM sleep duration [79-81]. Patients with fibromyalgia or with neuropathic pain who were treated with tricyclic antidepressants reported improvement in the subjective assessment of sleep quality [82,83].

Benzodiazepine and nonbenzodiazepine hypnotics are frequently prescribed in patients with chronic pain: up to 70% of them took regularly hypnotics [84-86]. Benzodiazepines are known to reduce sleep latency, to increase stage 1 and 2 sleep and to increase total sleep time but they also reduce SWS and REM sleep. On the other hand, nonbenzodiazepines are less likely to alter sleep stages but are as effective to improve sleep quality.

The rare polysomnographic studies that examine the effects of hypnotics on pain and sleep in patients with chronic pain found there was no change in sleep parameters during the hypnotic treatment as compared to before initiating the treatment. Changes were in the subjective assessment of sleep quality, which was improved under treatment [87,88].


It can be tempting to rely only on objective measures to evaluate the importance of sleep disorders in patients with chronic pain. However, lack of PSG evidence does not necessarily indicate there is no sleep disturbance. Changes in the EEG can be very subtle and detected only with more sophisticated measures such as EEG power spectral analyses.

The presence of primary sleep disorders, such obstructive sleep apnea syndrome and periodic limb movement disorder, and the presence of psychiatric disorders may add to the complexity of the relationship between chronic pain and sleep. PSG studies have mainly been conducted in small numbers of patients, and have rarely controlled for the presence of primary sleep disorders or psychiatric disorders.

After 30 years of research on this topic, the specific nature of the relationship between chronic pain and sleep remains largely uncertain.


  1. Everson CA, Bergmann BM, Rechtschaffen A. Sleep deprivation in the rat: III. Total sleep deprivation. Sleep. 1989;12:13-21.
  2. Ohayon MM. Relationship between chronic painful physical condition and insomnia. J Psychiatr Res. 2005;39:151-159.
  3. Asplund R. Daytime sleepiness and napping amongst the elderly in relation to somatic health and medical treatment. J Intern Med. 1996;239:261-267.
  4. Carli G, Montesano A, Rapezzi S, Paluffi G. Differential effects of persistent nociceptive stimulation on sleep stages. Behav Brain Res 1987; 26: 89-98.
  5. Suzuki S, Dennerstein L, Greenwood KM, Armstrong SM, Satohisa E. Sleeping patterns during pregnancy in Japanese women. J Psychosom Obstet Gynaecol. 1994;15:19-26.
  6. Paiva T, Batista A, Martins P, Martins A. The relationship between headache and sleep disturbances. Headache 1995; 35: 590-596.
  7. Paiva T, Farinha A, Martins A, Batista A, Guilleminault C. Chronic headaches and sleep disorders. Arch Intern Med 1997; 157: 1701-1705.
  8. Aldrich MS, Chauncey JB. Are morning headaches part of obstructive sleep apnea syndrome? Arch Intern Med 1990; 150: 1265-1267.
  9. Poceta JS, Dalessio DJ. Identification and treatment of sleep apnea in patients with chronic headache. Headache 1995; 35: 586-589.
  10. Ulfberg J, Carter N, Talback M, Edling C. Headache, snoring and sleep apnoea. J Neurol 1996;243:621-625.
  11. Loh NK, Dinner DS, Foldvary N, Skobieranda F, Yew WW. Do patients with obstructive sleep apnea wake up with headaches? Arch Intern Med 1999; 159: 1765-1768.
  12. Patrick GTW, Gilbert JA. On the effects of loss of sleep. Psychol Rev 1898;3:469-483.
  13. Moldofsky H, Scarisbrick P, England R, Smythe H. Musculoskeletal symptoms and non-REM sleep disturbance in patients with 'fibrositis syndrome' and healthy subjects. Psychosomatic Med 1975; 37: 341-351.
  14. Moldofsky H, Scarisbrick P. Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation. Psychosomatic Med 1976;38: 35-44.
  15. Lentz MJ, Landis CA, Rothermel J, Shaver JL. Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women. J Rheumatol 1999;26:1586-1592.
  16. Older SA, Battafarano DF, Danning CL, Ward JA, Grady EP, Derman S, Russell IJ. The effects of delta wave sleep interruption on pain thresholds and fibromyalgia-like symptoms in healthy subjects; correlations with insulin-like growth factor I. J Rheumatol 1998;25: 1180-1186.
  17. Onen SH, Alloui A, Gross A, Eschallier A, Dubray C. The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects. J Sleep Res. 2001;10:35-42.
  18. Kundermann B, Spernal J, Huber MT, Krieg JC, Lautenbacher S. Sleep deprivation affects thermal pain thresholds but not somatosensory thresholds in healthy volunteers. Psychosom Med. 2004;66:932-937.
  19. Arima T, Svensson P, Rasmussen C, Nielsen KD, Drewes AM, Arendt-Nielsen L. The relationship between selective sleep deprivation, nocturnal jaw-muscle activity and pain in healthy men. J Oral Rehabil. 2001;28:140-148.
  20. Roehrs T, Hyde M, Blaisdell B, Greenwald M, Roth T. Sleep loss and REM sleep loss are hyperalgesic. Sleep. 2006;29:145-151.
  21. Beydoun A, Morrow TJ, Shen JF, Casey KL. Variability of laser-evoked potentials: attention, arousal and lateralized differences. Electroencephalogr Clin Neurophysiol 1993; 88:173-181.
  22. Drewes AM, Nielsen KD, Arendt-Nielsen L, Birket-Smith L, Hansen LM. The effect of cutaneous and deep pain on the electroencephalogram during sleep--an experimental study. Sleep. 1997;20:632-640.
  23. Lavigne G, Zucconi M, Castronovo C, Manzini C, Marchettini P, Smirne S. Sleep arousal response to experimental thermal stimulation during sleep in human subjects free of pain and sleep problems. Pain. 2000;84:283-290.
  24. Lavigne GJ, Zucconi M, Castronovo V, Manzini C, Veglia F, Smirne S, Ferini-Strambi L. Heart rate changes during sleep in response to experimental thermal (nociceptive) stimulations in healthy subjects. Clin Neurophysiol. 2001;112:532-535.
  25. Gudbjornsson B, Broman JE, Hetta J, Hallgren R. Sleep disturbances in patients with primary Sjogren's syndrome. Br J Rheumatol 1993; 32: 1072-1076.
  26. Wittig RM, Zorick FJ, Blumer D, Heilbronn M, Roth T. Disturbed sleep in patients complaining of chronic pain. J Nerv Ment Dis 1982; 170: 429-431.
  27. Drewes AM, Svendsen L, Taagholt SJ, Bjerregard K, Nielsen KD, Hansen B. Sleep in rheumatoid arthritis: a comparison with healthy subjects and studies of sleep/wake interactions. Br J Rheumatol 1998; 37: 71-81.
  28. Lavie P, Epstein R, Tzischinsky O, Gilad D, Nahir M, Lorber M, Scharf Y. Actigraphic measurements of sleep in rheumatoid arthritis: comparison of patients with low back pain and healthy controls. J Rheumatol. 1992;19:362-365.
  29. Mahowald MW, Mahowald ML, Bundlie SR, Ytterberg SR. Sleep fragmentation in rheumatoid arthritis. Arthritis Rheum 1989; 32: 974-983.
  30. Moldofsky H, Lue FA, Smythe HA. Alpha EEG sleep and morning symptoms in rheumatoid arthritis. J Rheumatol 1983; 10: 373-379.
  31. Schneider-Helmert D, Whitehouse I, Kumar A et al. Insomnia and alpha sleep in chronic non-organic pain as compared to primary insomnia. Neuropsychobiol 2001; 43: 54-58.
  32. Affleck G, Urrows S, Tennen H, Higgins P, Abeles M. Sequential daily relations of sleep, pain intensity, and attention to pain among women with fibromyalgia. Pain 1996; 68:363-368.
  33. Jamieson AH, Alford CA, Bird HA, Hindmarch I, Wright V. The effect of sleep and nocturnal movement on stiffness, pain, and psychomotor performance in ankylosing spondylitis. Clin Exp Rheumatol 1995; 13: 73-78.
  34. Raymond I, Nielsen TA, Lavigne G, Manzini C, Choiniere M. Quality of sleep and its daily relationship to pain intensity in hospitalized adult burn patients. Pain 2001; 92: 381-388.
  35. Power JD, Perruccio AV, Badley EM. Pain as a mediator of sleep problems in arthritis and other chronic conditions. Arthritis Rheum. 2005;53:911-919.
  36. Nicassio PM, Wallston KA. Longitudinal relationships among pain, sleep problems, and depression in rheumatoid arthritis. J Abnorm Psychol. 1992;101:514-520.
  37. Leigh TJ, Bird HA, Hindmarch I, Wright V. A comparison of sleep in rheumatic and non-rheumatic patients. Clin Exp Rheumatol. 1987;5:363-365.
  38. Hirsch M, Carlander B, Verge M, Tafti M, Anaya JM, Billiard M, Sany J. Objective and subjective sleep disturbances in patients with rheumatoid arthritis. A reappraisal. Arthritis Rheum. 1994;37:41-49.
  39. Passarelli CM, Roizenblatt S, Len CA, Moreira GA, Lopes MC, Guilleminault C, Tufik S, Hilario MO. A Case Control Sleep Study in Children with Polyarticular Juvenile Rheumatoid Arthritis. J Rheumatol. 2006; [Epub ahead of print]
  40. Zamir G, Press J, Tal A, Tarasiuk A. Sleep fragmentation in children with juvenile rheumatoid arthritis. J Rheumatol 1998; 25: 1191-1197.
  41. Leigh TJ, Hindmarch I, Bird HA, Wright V. Comparison of sleep in osteoarthritic patients and age and sex matched healthy controls. Ann Rheum Dis. 1988;47:40-42.
  42. Leigh TJ, Bird HA, Hindmarch I, Wright V. Measurement of nocturnal motility: behaviour of osteoarthritic patients and controls. Rheumatol Intl 1988; 8: 67- 70.
  43. Walsh JK, Muehlbach MJ, Lauter SA, Hilliker NA, Schweitzer PK. Effects of triazolam on sleep, daytime sleepiness, and morning stiffness in patients with rheumatoid arthritis. J Rheumatol. 1996;23:245-252.
  44. Dillon C, Paulose-Ram R, Hirsch R, Gu Q. Skeletal muscle relaxant use in the United States: data from the Third National Health and Nutrition Examination Survey (NHANES III). Spine. 2004;29:892-896.
  45. Smith BH, Elliott AM, Hannaford PC, Chambers WA, Smith WC. Factors related to the onset and persistence of chronic back pain in the community: results from a general population follow-up study. Spine. 2004;29:1032-1040.
  46. Stranjalis G, Tsamandouraki K, Sakas DE, Alamanos Y. Low back pain in a representative sample of Greek population: analysis according to personal and socioeconomic characteristics. Spine. 2004;29:1355-1360.
  47. Raspe H, Matthis C, Croft P, O'Neill T; European Vertebral Osteoporosis Study Group. Variation in back pain between countries: the example of Britain and Germany. Spine. 2004 May 1;29:1017-1021.
  48. Kaila-Kangas L, Kivimaki M, Harma M, Riihimaki H, Luukkonen R, Kirjonen J, Leino-Arjas P. Sleep disturbances as predictors of hospitalization for back disorders-a 28-year follow-up of industrial employees. Spine. 2006;31:51-56.
  49. Hartman K, Pivik RT. Sleep variations in motor and EEG activities in chronic low back pain subjects: relationship to sleep quality. Sleep Res 1995; 24: 393.
  50. Harman K, Pivik RT, D'Eon JL, Wilson KG, Swenson JR, Matsunaga L. Sleep in depressed and nondepressed participants with chronic low back pain: electroencephalographic and behaviour findings. Sleep 2002;25:775-783.
  51. Cesta A, Moldofsky H, Lue FA Hogg-Johnson S, Frank J, Bombardier C. Sleep and musculoskeletal pain in workers following a soft tissue injury. Sleep 1998; 21: 289.
  52. Liszka-Hackzell JJ, Martin DP. Analysis of nighttime activity and daytime pain in patients with chronic back pain using a self-organizing map neural network. J Clin Monit Comput 2005;19:411-414.
  53. Ohayon MM. Prevalence and Risk Factors of Morning Headaches in the General Population Arch Intern Med. 2004; 164: 97-102.
  54. Thoman EB. Snoring, nightmares, and morning headaches in elderly women: a preliminary study. Biol Psychol. 1997;46:275-284.
  55. Jennum P, Hein HO, Suadicani P, Gyntelberg F. Headache and cognitive dysfunctions in snorers. A cross-sectional study of 3323 men aged 54 to 74 years: the Copenhagen Male Study. Arch Neurol. 1994;51:937-942.
  56. Inamorato E, Minatti-Hannuch SN, Zukerman E. The role of sleep in migraine attacks. Arq Neuropsiquiatr. 1993;51:429-432.
  57. Kim K, Uchiyama M, Liu X, Shibui K, Ohida T, Ogihara R, Okawa M. Somatic and psychological complaints and their correlates with insomnia in the Japanese general population. Psychosom Med. 2001;63:441-446.
  58. Cook NR, Evans DA, Funkenstein HH, Scherr PA, Ostfeld AM, Taylor JO, Hennekens CH. Correlates of headache in a population-based cohort of elderly. Arch Neurol. 1989;46:1338-1344.
  59. Takeshima T, Ishizaki K, Fukuhara Y, Ijiri T, Kusumi M, Wakutani Y, Mori M, Kawashima M, Kowa H, Adachi Y, Urakami K, Nakashima K. Population-based door-to-door survey of migraine in Japan: the Daisen study. Headache 2004;44:8-19.
  60. Drake ME Jr, Pakalnis A, Andrews JM, Bogner JE. Nocturnal sleep recording with cassette EEG in chronic headaches. Headache. 1990;30:600-603.
  61. Nobre ME, Filho PF, Dominici M. Cluster headache associated with sleep apnoea. Cephalalgia. 2003;23:276-279.
  62. Neau JP, Paquereau J, Bailbe M, Meurice JC, Ingrand P, Gil R. Relationship between sleep apnoea syndrome, snoring and headaches. Cephalalgia. 2002;22:333-339.
  63. Kiely JL, Murphy M, McNicholas WT. Subjective efficacy of nasal CPAP therapy in obstructive sleep apnoea syndrome: a prospective controlled study. Eur Respir J. 1999;13:1086-1090.
  64. Kolar E, Hartz A, Roumm A, Ryan L, Jones R, Kirchdoerfer E. Factors associated with severity of symptoms in patients with chronic unexplained muscular aching. Ann Rheum Dis. 1989;48:317-321.
  65. Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol Suppl 2005;75:6-21.
  66. Kassam A, Patten SB. Major depression, fibromyalgia and labour force participation: a population-based cross-sectional study. BMC Musculoskelet Disord. 2006;19;7:4.
  67. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arth Rheum 1995;38:19-28.
  68. Prescott E, Kjoller M, Jacobsen S, Bulow PM, Danneskiold-Samsoe B, Kamper-Jorgensen F. Fibromyalgia in the adult Danish population: I. A prevalence study. Scand J Rheumatol. 1993;22:233-237.
  69. Makela M, Heliovaara M. Prevalence of primary fibromyalgia in the Finnish population. BMJ. 1991;303:216-219.
  70. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33:160-172.
  71. Branco J, Atalaia A, Paiva T. Sleep cycles and alpha-delta sleep in fibromyalgia syndrome. J Rheumatol. 1994;21:1113-1117.
  72. Horne JA, Shackell BS. Alpha-like EEG activity in non-REM sleep and the fibromyalgia (fibrositis) syndrome. Electroencephalogr Clin Neurophysiol. 1991 Oct;79:271-276.
  73. Horne JA. Aspirin and nonfebrile waking oral temperature in healthy men and women: links with SWS changes? Sleep. 1989;1:516-521.
  74. Murphy PJ, Badia P, Myers BL, Boecker MR, Wright KP Jr. Nonsteroidal anti-inflammatory drugs affect normal sleep patterns in humans. Physiol Behav. 1994;55:1063-1066.
  75. Lavie P, Nahir M, Lorber M, Scharf Y.Nonsteroidal antiinflammatory drug therapy in rheumatoid arthritis patients. Lack of association between clinical improvement and effects on sleep. Arthritis Rheum. 1991;34:655-659.
  76. Walder B, Tramer MR, Blois R. The effects of two single doses of tramadol on sleep: a randomized, cross-over trial in healthy volunteers. Eur J Anaesthesiol. 2001;18:36-42.
  77. Farney RJ, Walker JM, Cloward TV, Rhondeau S. Sleep-disordered breathing associated with long-term opioid therapy. Chest. 2003;123:632-639.
  78. Teichtahl H, Prodromidis A, Miller B, Cherry G, Kronborg I. Sleep-disordered breathing in stable methadone programme patients: a pilot study. Addiction. 2001;96:395-403.
  79. Chalon S, Pereira A, Lainey E, Vandenhende F, Watkin JG, Staner L, Granier LA. Comparative effects of duloxetine and desipramine on sleep EEG in healthy subjects. Psychopharmacology (Berl). 2005;177:357-365.
  80. Wilson SJ, Bailey JE, Alford C, Nutt DJ. Sleep and daytime sleepiness the next day following single night-time dose of fluvoxamine, dothiepin and placebo in normal volunteers. J Psychopharmacol. 2000;14:378-386.
  81. Feuillade P, Pringuey D, Belugou JL, Robert P, Darcourt G. Trimipramine: acute and lasting effects on sleep in healthy and major depressive subjects. J Affect Disord. 1992;24:135-145.
  82. Arnold LM, Keck PE Jr, Welge JA. Antidepressant treatment of fibromyalgia. A meta-analysis and review. Psychosomatics. 2000;41:104-113.
  83. Menefee LA, Cohen MJ, Anderson WR, Doghramji K, Frank ED, Lee H. Sleep disturbance and nonmalignant chronic pain: a comprehensive review of the literature. Pain Med. 2000;1:156-172.
  84. Hardo PG, Kennedy TD. Night sedation and arthritic pain. J R Soc Med. 1991;84:73-75.
  85. King SA, Strain JJ. Benzodiazepine use by chronic pain patients. Clin J Pain. 1990;6:143-147.
  86. Drewes AM. Pain and sleep disturbances with special reference to fibromyalgia and rheumatoid arthritis. Rheumatology (Oxford). 1999;38:1035-1038.
  87. Walsh JK, Muehlbach MJ, Lauter SA, Hilliker NA, Schweitzer PK. Effects of triazolam on sleep, daytime sleepiness, and morning stiffness in patients with rheumatoid arthritis. J Rheumatol. 1996;23:245-252.
  88. Drewes AM, Bjerregard K, Taagholt SJ, Svendsen L, Nielsen KD. Zopiclone as night medication in rheumatoid arthritis. Scand J Rheumatol. 1998;27:180-187.