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Current Views on Chronic Pain and Its Relationship to the State of Sleep

Chronic pain is a unique pathophysiological state characterized by the formation of stable neurotransmitter, morphological, and behavioral patterns. Sleep has a facilitating influence on many pain syndromes by blocking signal conduction via the nociceptive pathways, the release of specific neurotransmitters, and the lack of conscious perception during this period. Restriction to the duration of sleep and impairment to its structure are accompanied by increased pain, while improvements in sleep in some cases allow pain to be decreased.

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  1. 1.

    Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms, H. Merskey and N. Bogduk (eds.), Prepared by the International Association for the Study of Pain and the Task Force on Taxonomy, IASP Press, Seattle (1994), 2nd ed.

  2. 2.

    N. N. Yakhno and M. L. Kukushkin (eds.), Pain: Practical Guidelines for Doctors, Russian Academy of Medical Sciences Press, Moscow (2011).

    Google Scholar 

  3. 3.

    N. N. Yakhno and M. L. Kukushkin, “Chronic pain: medical-biological and social-economic aspects,” Vest. Ross. Akad. Med. Nauk., 9, 54–58 (2012).

    Article  Google Scholar 

  4. 4.

    H. Breivik, B. Collett, V. Ventafridda, R. Cohen, and D. Gallacher, “Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment,” Eur. J. Pain, 10, 287–333 (2006),

    Article  Google Scholar 

  5. 5.

    S. B. McMahon and M. Koltzenburg (eds.), Wall and Melzack’s Textbook of Pain, Elsevier Churchill Livingstone (2015), 5th ed.

  6. 6.

    D. Buskila, “Genetics of chronic pain states,” Best Pract. Res. Clin. Rheumatol., 21, 535–547 (2007),

    CAS  Article  Google Scholar 

  7. 7.

    M. L. Kukushkin and N. K. Khitrov, General Pain Pathology, Meditsina, Moscow (2004).

    Google Scholar 

  8. 8.

    R. R. Edwards, “Genetic predictors of acute and chronic pain,” Curr. Rheumatol. Rep., 8, 411–417 (2006),

    CAS  Article  Google Scholar 

  9. 9.

    L. Diatchenko, G. D. Slade, A. G. Nackley, K. Bhalang, A. Sigurdsson, I. Belfer, D. Goldman, K. Xu, S. A. Shabalina, D. Shagin, M. B. Max, S. S. Makarov, and W. Maixner, “Genetic basis for individual variations in pain perception and the development of a chronic pain condition,” Hum. Mol. Genet., 14, No. 1, 135–143 (2005),

    CAS  Article  Google Scholar 

  10. 10.

    M. L. Lacroix-Fralish and J. S. Mogil, “Progress in genetic studies of pain and analgesia,” Annu. Rev. Pharmacol. Toxicol., 49, 97–121 (2009),

    CAS  Article  Google Scholar 

  11. 11.

    F. Seifert and C. Maihofner, “Functional and structural imaging of pain-induced neuroplasticity,” Curr. Opin. Anaesthesiol., 24, 515–523 (2011),

    Article  Google Scholar 

  12. 12.

    A. K. Jetzer, A. Morel, M. Magnin, and D. Jeanmonod, “Crossmodal plasticity in the human thalamus: evidence from intraoperative macrostimulations,” Neuroscience, 164, 1867–1875 (2009),

    CAS  Article  Google Scholar 

  13. 13.

    M. G. Pshennikova, V. S. Smirnova, V. N. Grafova, M. V. Shimkovich, I. Yu. Malyshev, and M. L. Kukushkin, “Resistance to the development of neuropathic pain syndrome in August rats and a population of Wistar rats with different innate levels of resistance to stress,” Bol’, 2, 13–16 (2008).

    Google Scholar 

  14. 14.

    D. Buskila, P. Sarzi-Puttini, and J. N. Ablin, “The genetics of fibromyalgia syndrome,” Pharmacogenomics, 8, 67–74 (2007),

    CAS  Article  Google Scholar 

  15. 15.

    A. V. Osipov and M. L. Kukushkin, “Effects of stress on the development of deafferentation pain syndrome in rats after transection of the sciatic nerve,” Byull. Eksperim. Biol. Med., 115, No. 5, 471–473 (1993).

    CAS  Google Scholar 

  16. 16.

    E. Kohlschütter, “Messungen der Festigkeit des Schlafes,” Z. Ration. Med., 17, 209–253 (1863).

    Google Scholar 

  17. 17.

    M. Steriade, D. A. McCormick, and T. J. Sejnowski, “Thalamocortical oscillations in the sleeping and aroused brain,” Science, 262, No. 5134, 679–685 (1993).

    CAS  Article  Google Scholar 

  18. 18.

    J. H. Peever and B. J. Sessle, “Sensory and motor processing during sleep and wakefulness,” in: Principles and Practice of Sleep Medicine, M. H. Kryger, T. Roth, and W. C. Dement (eds.), Elsevier, Philadelphia (2016).

  19. 19.

    G. Sandrini, I. Milanov, B. Rossi, L. Murri, E. Alfonsi, A. Moglia, and G. Nappi, “Effects of sleep on spinal nociceptive reflexes in humans,” Sleep, 24, No. 1, 13–17 (2001).

    CAS  Article  Google Scholar 

  20. 20.

    S. S. Ødegård, P. M. Omland, K. B. Nilsen, M. Stjern, G. B. Gravdahl, and T. Sand, “The effect of sleep restriction on laser evoked potentials, thermal sensory and pain thresholds and suprathreshold pain in healthy subjects,” Clin. Neurophysiol., 126, No. 10, 1979–1978 (2015),

    Article  Google Scholar 

  21. 21.

    T. Roehrs, M. Hyde, B. Blaisdell, M. Greenwald, and T. Roth, “Sleep loss and REM sleep loss are hyperalgesic,” Sleep, 29, No. 2, 145–151 (2006).

    Article  Google Scholar 

  22. 22.

    T. A. Roehrs, E. Harris, S. Randall, and T. Roth, “Pain sensitivity and recovery from mild chronic sleep loss,” Sleep, 35, No. 12, 1667–1672 (2012),

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    P. H. Finan, B. R. Goodin, and M. T. Smith, “The association of sleep and pain: An update and a path forward,” Pain, 14, No. 12, 1539–1552 (2013),

    Article  Google Scholar 

  24. 24.

    M. T. Smith and J. A. Haythornthwaite, “How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature,” Sleep Med. Rev., 8, 119–132 (2004),

    Article  Google Scholar 

  25. 25.

    D. J. Taylor, L. J. Mallory, K. L. Lichstein, H. H. Durrence, B. W. Riedel, and A. J. Bush, “Comorbidity of chronic insomnia with medical problems,” Sleep, 30, 213–218 (2007).

    Article  Google Scholar 

  26. 26.

    M. T. Smith, M. Perlis, M. S. Smith, D. E. Giles, and T. P. Carmody, “Sleep quality and presleep arousal in chronic pain,” J. Behav. Med., 23, 1–13 (2000).

    CAS  Article  Google Scholar 

  27. 27.

    L. Kelman, “The triggers or precipitants of the acute migraine attack,” Cephalalgia, 27, 394–402 (2007),

    CAS  Article  Google Scholar 

  28. 28.

    P. K. Sahota and J. D. Dexter, “Sleep and headache syndromes: A clinical review,” Headache, 30, 80–84 (1990).

    CAS  Article  Google Scholar 

  29. 29.

    P. R. Holland, “Headache and sleep: Shared pathophysiological mechanisms,” Cephalalgia, 34, No. 10, 725–744 (2014),

    Article  Google Scholar 

  30. 30.

    E. B. Arushanyan and E. V. Beier, “The epiphyseal hormone melatonin – a universal natural adaptogen,” Usp. Fiziol. Nauk., 43, No. 2, 82–100 (2012).

    Google Scholar 

  31. 31.

    E. B. Arushanyan, “Comparative assessment of epiphyseal melatonin and benzodiazepine anxiolytics,” Eksp. Klin. Farmakol., 75, No. 3, 35–40 (2012).

    CAS  Google Scholar 

  32. 32.

    C. Laurido, T. Pelissie, R. Soto-Moyano, L. Valladares, F. Flores, and A. Hernandez, “Effect of melatonin on rat spinal cord nociceptive transmission,” Neuroreport, 13, No. 1, 89–91 (2002).

    CAS  Article  Google Scholar 

  33. 33.

    S. M. El-Shenawy, O. M. Abdel-Salam, A. R. Baiuomy, S. El-Batran, and M. S. Arbid, “Studies on the inflammatory and anti-nociceptive effect of melatonin in the rat,” Pharmacol. Res., 46, 3:235–243 (2002).

    CAS  Article  Google Scholar 

  34. 34.

    M. Ambriz-Tututi and V. Granados-Soto, “Oral and spinal melatonin reduces tactile allodynia in rats via activation of MT2 and opioid receptors,” Pain, 132, 3:273–280 (2007),

    CAS  Article  Google Scholar 

  35. 35.

    V. Srinivasan, E. C. Lauterbach, K. Y. Ho, D. Acuna-Castroviejo, R. Zakaria, and A. Brzezinski, “Melatonin in antinociception: Its therapeutic applications,” Curr. Neuropharmacol., 10, 167–178 (2012),

    CAS  Article  Google Scholar 

  36. 36.

    M. Wilhelmsen, I. Amirian, R. J. Reiter, J. Rosenberg, and I. Gogenur, “Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies,” J. Pineal Res., 51, No. 3, 270–277 (2011),

    CAS  Article  Google Scholar 

  37. 37.

    S. A. Hussain, H. Al-Khalifa, N. A. Jasim, and F. I. Gorial, “Adjuvant use of melatonin for treatment of fibromyalgia,” J. Pineal Res., 50, 267–271 (2011),

    Article  Google Scholar 

  38. 38.

    V. M. Koval’zon, “The role of the orexinergic system of the brain in regulating waking and sleep,” Effektiv. Farmakoter. Nevrol. Psikhiatr., Spec. Iss., Sleep and Its Disorders-4, 19, 6–14 (2016).

    Google Scholar 

  39. 39.

    T. Yamamoto, N. Nozaki-Taguchi, and T. Chiba, “Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test,” Brit. J. Pharmacol., 137, 170–176 (2002),

    CAS  Article  Google Scholar 

  40. 40.

    I. V. Estabrooke, M. T. McCarthy, E. Ko, T. C. Chou, R. M. Chemelli, M. Yanagisawa, C. B. Saper, and T. E. Scammell, “Fos expression in orexin neurons varies with behavioral state,” J. Neurosci., 21, No. 5, 1656–1662 (2001).

    CAS  Article  Google Scholar 

  41. 41.

    S. V. Mahler, D. E. Moorman, R. J. Smith, M. H. James, and G. Aston- Jones, “Motivational activation: a unifying hypothesis of orexin/hypocretin function,” Nat. Neurosci., 17, 1298–1303 (2014),

    CAS  Article  Google Scholar 

  42. 42.

    A. Inutsuka, A. Yamashita, S. Chowdhur, J. Nakai, M. Ohkura, T. Taguchi, and A. Yamanaka, “The integrative role of orexin/hypocretin neurons in nociceptive perception and analgesic regulation,” Sci. Rep., 6, 29480 (2016),

  43. 43.

    M. G. Poluektov (ed.), Somnology and Sleep Medicine: National Guidelines in Memory of A. M. Vein and Ya. I. Levin, Medforum, Moscow (2016).

  44. 44.

    S. R. Currie, K. G. Wilson, and D. Curran, “Clinical significance and predictors of treatment response to cognitive-behavior therapy for insomnia secondary to chronic pain,” J. Behav. Med., 25, 135–153 (2002).

    Article  Google Scholar 

  45. 45.

    J. D. Edinger, W. K. Wohlgemuth, A. D. Krystal, and J. R. Rice, “Behavioral insomnia therapy for fibromyalgia patients: a randomized clinical trial,” Arch. Intern. Med., 165, No. 21, 2527–2535 (2005),

    Article  Google Scholar 

  46. 46.

    M. Vitiello, B. Rybarczyk, and E. Stephanski, “Sleep as analgesic: improving sleep and pain in older adults [abstract No. 0302],” Sleep, 30, Suppl. A, 103–194 (2007).

    Google Scholar 

  47. 47.

    N. K. Tang, “Cognitive-behavioral therapy for sleep abnormalities of chronic pain patients,” Curr. Rheumatol. Rep., 11, No. 6, 451–460 (2009).

    Article  Google Scholar 

  48. 48.

    M. Grönblad, J. Nykanen, Y. Konttinen, E. Jarvinen, and T. Helve, “Effect of zopiclone on sleep quality, morning stiffness, widespread tenderness and pain and general discomfort in primary fibromyalgia patients. A double-blind randomized trial,” Clin. Rheumatol., 12, 186–191 (1993).

    Article  Google Scholar 

  49. 49.

    H. Moldofsky, F. A. Lue, C. Mously, B. Roth-Schechter, and W. J. Reynolds, “The effect of zolpidem in patients with fibromyalgia: a dose ranging, double blind, placebo controlled, modified crossover study,” J. Rheumatol., 23, 529–533 (1996).

    CAS  PubMed  Google Scholar 

  50. 50.

    T. A. Roehrs, “Does effective management of sleep disorders improve pain symptoms?” Drugs, 69, No. 2, 5–11 (2009),

    CAS  Article  Google Scholar 

  51. 51.

    J. K. Walsh, M. J. Muehlbach, S. A. Lauter, N. A. Hilliker, and P. K. Schweitzer, “Effects of triazolam on sleep, daytime sleepiness, and morning stiffness in patients with rheumatoid arthritis,” J. Rheumatol., 23, No. 2, 245–252 (1996).

    CAS  PubMed  Google Scholar 

  52. 52.

    P. Morillas-Arques, C. M. Rodriguez-Lopez, R. Molina-Barea, F. Rico-Villademoros, and E. P. Calandre, “Trazodone for the treatment of fibromyalgia: an open-label, 12-week study,” BMC Musculoskelet. Disord., 11, 204 (2010),

  53. 53.

    B. Saletu, W. Prause, P. Anderer, M. Mandl, M. Aigner, O. Mikova, and G. M. Saletu-Zyhlarz, “Insomnia in somatoform pain disorder: sleep laboratory studies on differences to controls and acute effects of trazodone, evaluated by the Somnolyzer 24×7 and the Siesta database,” Neuropsychobiology, 51, No. 3, 148–63 (2005),

    Article  Google Scholar 

  54. 54.

    M. G. Poluektov, Ya. I. Levin, V. A. Mikhailov, S. L. Babak, and K. N. Strygin, “Use of Trittico (trazodone) for the treatment of sleep impairments in depression: results of a multicenter trial,” Effektiv. Farmakoter. Nevrol. Psikhiatr., Spec. Iss., Sleep and Its Disorders, 12, 82–90 (2013).

    Google Scholar 

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Correspondence to M. L. Kukushkin.

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Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 117, No. 4, Iss. II, Sleep Disorder, pp. 19–27, April, 2017.

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Kukushkin, M.L., Poluektov, M.G. Current Views on Chronic Pain and Its Relationship to the State of Sleep. Neurosci Behav Physi 49, 13–19 (2019).

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  • sleep
  • chronic pain
  • insomnia