Skip to main content
SpringerLink
Log in

Melatonin in Clinical Status of Patients with Fibromyalgia Syndrome

  • Chapter
  • First Online:
Melatonin, Neuroprotective Agents and Antidepressant Therapy

Abstract

The fibromyalgia syndrome (FM) is a chronic rheumatic condition characterized by the presence of chronic and widespread pain and other symptoms, such as fatigue, sleep disturbances, anxiety, and depression. The pathophysiology of FM is not yet fully understood; however, neuroendocrine disorders, including those related to the production of melatonin by the pineal gland appear to exert strong influence on the genesis and evolution of this condition. The difficulty in understanding the pathophysiology of FM affects the development of effective therapeutic approaches. Currently, the most widely used drug classes for the treatment of FM are tricyclic antidepressants, analgesics, anti-inflammatory drugs, and modulators of sleep. However, the isolated use of these drugs does not cause the remission of all symptoms; besides, the association between these drugs for patients with FM finds no support in the literature. In this context, the therapeutic use of melatonin and or their agonists such as agomelatine and ramelteon have been tested as an alternative to the treatment of FM and are showing good results in relieving core symptoms of FM, and they have good safety and present few adverse effects. It is believed that the success of these drugs is due, at least in part, the chronotropic, analgesic, and anxiolytic antioxidants and melatonin.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

4P-PDOT:

4-phenyl-2-propionamidotetralin

5-HT2C:

Serotonin receptors

6-SMT:

6-Sufatoxymelatonin

BMI:

Body mass index

cAMP:

Cyclic adenosine monophosphate

cGMP:

Cyclic guanosine monophosphate

CNS:

Central nervous system

COX:

Cyclooxygenase

ELISA:

Enzyme-linked immunosorbent assay

FIQ:

Fibromyalgia Impact Questionnaire

FM:

Fibromyalgia

GABA:

Gamma-aminobutyric acid

MT:

Melatonergic receptors

NMDA:

N-methyl-D-aspartate

NO:

Nitric oxide

PSQI:

Pittsburgh Sleep Quality Index

QR2:

Quinone reductase type 2

ROR:

Retinoid-related orphan receptor

SF36:

Medical Outcomes Study Questionnaire 36-Item Short-Form Health Survey

SS:

Symptom Severity Scale

SWLS:

Satisfaction with Life Scale

WPI:

Widespread Pain Index

References

  1. Wolfe F, et al. The American College of Rheumatology 1990 Criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum. 1990;33(2):160–72.

    Article  CAS  PubMed  Google Scholar 

  2. Branco JC, et al. Prevalence of fibromyalgia: a survey in five European countries. Semin Arthritis Rheum. 2010;39(6):448–53.

    Article  PubMed  Google Scholar 

  3. Bazzichi L, et al. Fibromyalgia: a critical digest of the recent literature. Clin Exp Rheumatol. 2011;29(6 Suppl 69):S1–11.

    CAS  PubMed  Google Scholar 

  4. Sarzi-Puttini P, et al. Dysfunctional syndromes and fibromyalgia: a 2012 critical digest. Clin Exp Rheumatol. 2012;30(6 Suppl 74):143–51.

    PubMed  Google Scholar 

  5. Spaeth M. Epidemiology, costs, and the economic burden of fibromyalgia. Arthritis Res Ther. 2009;11(3):117.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Vanecek J. Cellular mechanisms of melatonin action. Physiol Rev. 1998;78(3):687–721.

    CAS  PubMed  Google Scholar 

  7. Bailey MJ, et al. Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling. J Biol Chem. 2009;284(12):7606–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Masruha M, et al. Low urinary 6-sulphatoxymelatonin concentrations in acute migraine. J Headache Pain. 2008;9(4):221–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Masruha MR, et al. Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities. Headache. 2010;50(3):413–9.

    Article  PubMed  Google Scholar 

  10. Hirata F, et al. In vitro and in vivo formation of two new metabolites of melatonin. J Biol Chem. 1974;249(4):1311–3.

    CAS  PubMed  Google Scholar 

  11. Pernambuco AP, et al. The involvement of melatonin in the clinical status of patients with fibromyalgia syndrome. Clin Exp Rheumatol. 2014;33(1 Suppl 88):S14–9.

    PubMed  Google Scholar 

  12. Wikner J, et al. Fibromyalgia – a syndrome associated with decreased nocturnal melatonin secretion. Clin Endocrinol (Oxf). 1998;49(2):179–83.

    Article  CAS  Google Scholar 

  13. Uberos J, et al. Normalization of the sleep-wake pattern and melatonin and 6-sulphatoxy-melatonin levels after a therapeutic trial with melatonin in children with severe epilepsy. J Pineal Res. 2011;50(2):192–6.

    CAS  PubMed  Google Scholar 

  14. Srinivasan V, et al. Melatonin in antinociception: its therapeutic applications. Curr Neuropharmacol. 2012;10(2):167–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ochoa-Sanchez R, et al. Anxiolytic effects of the melatonin MT(2) receptor partial agonist UCM765: comparison with melatonin and diazepam. Prog Neuropsychopharmacol Biol Psychiatry. 2012;39(2):318–25.

    Article  CAS  PubMed  Google Scholar 

  16. Wolfe F, Hauser W. Fibromyalgia diagnosis and diagnostic criteria. Ann Med. 2011;43(7):495–502.

    Article  PubMed  Google Scholar 

  17. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311(15):1547–55.

    Article  CAS  PubMed  Google Scholar 

  18. Bellato E, et al. Fibromyalgia syndrome: etiology, pathogenesis, diagnosis, and treatment. Pain Res Treat. 2012;2012:426130.

    PubMed  PubMed Central  Google Scholar 

  19. Hassett AL, Williams DA. Non-pharmacological treatment of chronic widespread musculoskeletal pain. Best Pract Res Clin Rheumatol. 2011;25(2):299–309.

    Article  PubMed  Google Scholar 

  20. de Zanette SA, et al. Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy, controlled trial. BMC Pharmacol Toxicol. 2014;15(1):40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wilhelmsen M, et al. Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies. J Pineal Res. 2011;51(3):270–7.

    Article  CAS  PubMed  Google Scholar 

  22. Hussain SA, et al. Adjuvant use of melatonin for treatment of fibromyalgia. J Pineal Res. 2011;50(3):267–71.

    Article  CAS  PubMed  Google Scholar 

  23. Altun A, Ugur-Altun B. Melatonin: therapeutic and clinical utilization. Int J Clin Pract. 2007;61(5):835–45.

    Article  CAS  PubMed  Google Scholar 

  24. Tan DX, et al. Melatonin as a naturally occurring co-substrate of quinone reductase-2, the putative MT3 melatonin membrane receptor: hypothesis and significance. J Pineal Res. 2007;43(4):317–20.

    Article  CAS  PubMed  Google Scholar 

  25. Srinivasan V, et al. Melatonin and its agonists in pain modulation and its clinical application. Arch Ital Biol. 2012;150(4):274–89.

    PubMed  Google Scholar 

  26. Noseda R, et al. Melatonin-induced inhibition of spinal cord synaptic potentiation in rats is MT2 receptor-dependent. Neurosci Lett. 2004;360(1–2):41–4.

    Article  CAS  PubMed  Google Scholar 

  27. Laurido C, et al. Effect of melatonin on rat spinal cord nociceptive transmission. Neuroreport. 2002;13(1):89–91.

    Article  CAS  PubMed  Google Scholar 

  28. Ambriz-Tututi M, et al. Melatonin: a hormone that modulates pain. Life Sci. 2009;84(15–16):489–98.

    Article  CAS  PubMed  Google Scholar 

  29. Herrero JF, Laird JMA, Lopez-Garcia JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol. 2000;61(2):169–203.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang Y, et al. Involvement of a NO-cyclic GMP-PKG signaling pathway in nitrous oxide-induced antinociception in mice. Eur J Pharmacol. 2011;654(3):249–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cury Y, et al. Pain and analgesia: the dual effect of nitric oxide in the nociceptive system. Nitric Oxide. 2011;25(3):243–54.

    Article  CAS  PubMed  Google Scholar 

  32. Chiang RP, Huang CT, Tsai YJ. Melatonin reduces median nerve injury-induced mechanical hypersensitivity via inhibition of microglial p38 mitogen-activated protein kinase activation in rat cuneate nucleus. J Pineal Res. 2013;54(2):232–44.

    Article  CAS  PubMed  Google Scholar 

  33. Laste G, et al. Melatonin administration reduces inflammatory pain in rats. J Pain Res. 2012;5:359–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Pardini M, et al. Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study. Eur Neuropsychopharmacol. 2014;24(6):939–44.

    Article  CAS  PubMed  Google Scholar 

  35. Senel K, et al. Melatonin levels in premenopausal women with fibromyalgia syndrome. Rheumatol Int. 2013;33(6):1609–10.

    Article  CAS  PubMed  Google Scholar 

  36. Akerstedt T, Gillberg M, Wetterberg L. The circadian covariation of fatigue and urinary melatonin. Biol Psychiatry. 1982;17(5):547–54.

    CAS  PubMed  Google Scholar 

  37. Acuna-Castroviejo D, Escames G, Reiter RJ. Melatonin therapy in fibromyalgia. J Pineal Res. 2006;40(1):98–9.

    Article  CAS  PubMed  Google Scholar 

  38. Srinivasan V, et al. Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci. 2009;119(6):821–46.

    Article  CAS  PubMed  Google Scholar 

  39. Archer SN, et al. Mistimed sleep disrupts circadian regulation of the human transcriptome. Proc Natl Acad Sci U S A. 2014;111(6):E682–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Akerstedt T, Gillberg M. Experimentally displaced sleep: effects on sleepiness. Electroencephalogr Clin Neurophysiol. 1982;54(2):220–6.

    Article  CAS  PubMed  Google Scholar 

  41. Hardeland R. Tasimelteon, a melatonin agonist for the treatment of insomnia and circadian rhythm sleep disorders. Curr Opin Investig Drugs. 2009;10(7):691–701.

    CAS  PubMed  Google Scholar 

  42. Pandi-Perumal SR, et al. Drug insight: the use of melatonergic agonists for the treatment of insomnia-focus on ramelteon. Nat Clin Pract Neurol. 2007;3(4):221–8.

    Article  CAS  PubMed  Google Scholar 

  43. Hardeland R, et al. Melatonin – a pleiotropic, orchestrating regulator molecule. Prog Neurobiol. 2011;93(3):350–84.

    Article  CAS  PubMed  Google Scholar 

  44. Srinivasan V, et al. Melatonin agonists in primary insomnia and depression-associated insomnia: are they superior to sedative-hypnotics? Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(4):913–23.

    Article  CAS  PubMed  Google Scholar 

  45. Pandi-Perumal SR, et al. Ramelteon: a review of its therapeutic potential in sleep disorders. Adv Ther. 2009;26(6):613–26.

    Article  CAS  PubMed  Google Scholar 

  46. Gooneratne NS, et al. Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults. J Pineal Res. 2012;52(4):437–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Epstein SA, et al. Psychiatric disorders in patients with fibromyalgia. A multicenter investigation. Psychosomatics. 1999;40(1):57–63.

    Article  CAS  PubMed  Google Scholar 

  48. dos Santos EB, et al. An evaluation of anxiety and depression symptoms in fibromyalgia. Rev Esc Enferm USP. 2012;46(3):590–6.

    Article  PubMed  Google Scholar 

  49. Ismail SA, Mowafi HA. Melatonin provides anxiolysis, enhances analgesia, decreases intraocular pressure, and promotes better operating conditions during cataract surgery under topical anesthesia. Anesth Analg. 2009;108(4):1146–51.

    Article  CAS  PubMed  Google Scholar 

  50. Nava F, Carta G. Melatonin reduces anxiety induced by lipopolysaccharide in the rat. Neurosci Lett. 2001;307(1):57–60.

    Article  CAS  PubMed  Google Scholar 

  51. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000.

    Google Scholar 

  52. Rosenstein RE, Cardinali DP. Central gabaergic mechanisms as targets for melatonin activity in brain. Neurochem Int. 1990;17(3):373–9.

    Article  CAS  PubMed  Google Scholar 

  53. Golombek DA, Pevet P, Cardinali DP. Melatonin effects on behavior: possible mediation by the central GABAergic system. Neurosci Biobehav Rev. 1996;20(3):403–12.

    Article  CAS  PubMed  Google Scholar 

  54. Guardiola LB, Lenegre A, Porsoldt RD. Combined effect of diazepam and melatonin in two tests for anxiolytic activity in the mouse. Pharmacol Biochem Behav. 1992;41:405–8.

    Article  Google Scholar 

  55. Khezri MB, Oladi MR, Atlasbaf A. Effect of melatonin and gabapentin on anxiety and pain associated with retrobulbar eye block for cataract surgery: a randomized double-blind study. Indian J Pharmacol. 2013;45(6):581–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Nave R, et al. Hypnotic and hypothermic effects of melatonin on daytime sleep in humans: lack of antagonism by flumazenil. Neurosci Lett. 1996;214(2–3):123–6.

    Article  CAS  PubMed  Google Scholar 

  57. Papp M, et al. Anxiolytic-like activity of agomelatine and melatonin in three animal models of anxiety. Behav Pharmacol. 2006;17(1):9–18.

    CAS  PubMed  Google Scholar 

  58. Larson J, et al. Impaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice. Neurosci Lett. 2006;393(1):23–6.

    Article  CAS  PubMed  Google Scholar 

  59. Wan Q, et al. Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors. Nat Neurosci. 1999;2(5):401–3.

    Article  CAS  PubMed  Google Scholar 

  60. Comai S, Gobbi G. Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology. J Psychiatry Neurosci. 2014;39(1):6–21.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ochoa-Sanchez R, et al. Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT2 melatonin receptor ligand. J Neurosci. 2011;31(50):18439–52.

    Article  CAS  PubMed  Google Scholar 

  62. Rosenstein RE, Cardinali DP. Melatonin increases in vivo GABA accumulation in rat hypothalamus, cerebellum, cerebral cortex and pineal gland. Brain Res. 1986;398(2):403–6.

    Article  CAS  PubMed  Google Scholar 

  63. Garfinkel D, et al. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999;159(20):2456–60.

    Article  CAS  PubMed  Google Scholar 

  64. Bunney WE, Bunney BG. Molecular clock genes in man and lower animals: possible implications for circadian abnormalities in depression. Neuropsychopharmacology. 2000;22(4):335–45.

    Article  CAS  PubMed  Google Scholar 

  65. Shekleton JA, et al. Sleep disturbance and melatonin levels following traumatic brain injury. Neurology. 2010;74(21):1732–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Quera Salva MA, et al. Circadian rhythms, melatonin and depression. Curr Pharm Des. 2011;17(15):1459–70.

    Article  CAS  PubMed  Google Scholar 

  67. Bellipanni G, et al. Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study. Exp Gerontol. 2001;36(2):297–310.

    Article  CAS  PubMed  Google Scholar 

  68. Ruhé HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry. 2007;12(4):331–59.

    Article  CAS  PubMed  Google Scholar 

  69. Kennedy SH, Emsley R. Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol. 2006;16(2):93–100.

    Article  CAS  PubMed  Google Scholar 

  70. Norman TR, Burrows GD. Emerging treatments for major depression. Expert Rev Neurother. 2007;7(2):203–13.

    Article  CAS  PubMed  Google Scholar 

  71. Press J, et al. Normal melatonin levels in patients with fibromyalgia syndrome. J Rheumatol. 1998;25(3):551–5.

    CAS  PubMed  Google Scholar 

  72. Webb SM. Fibromyalgia and melatonin: are they related? Clin Endocrinol (Oxf). 1998;49(2):161–2.

    Article  CAS  Google Scholar 

  73. Korszun A, et al. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol. 1999;26(12):2675–80.

    CAS  PubMed  Google Scholar 

  74. Klerman EB, et al. Circadian rhythms of women with fibromyalgia. J Clin Endocrinol Metab. 2001;86(3):1034–9.

    CAS  PubMed  Google Scholar 

  75. Loevinger BL, et al. Delineating psychological and biomedical profiles in a heterogeneous fibromyalgia population using cluster analysis. Clin Rheumatol. 2012;31(4):677–85.

    Article  PubMed  Google Scholar 

  76. Dijk DJ, et al. Amplitude reduction and phase shifts of melatonin, cortisol and other circadian rhythms after a gradual advance of sleep and light exposure in humans. PLoS One. 2012;7(2):e30037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Nathan PJ, Burrows GD, Norman TR. The effect of dim light on suppression of nocturnal melatonin in healthy women and men. J Neural Transm. 1997;104(6–7):643–8.

    Article  CAS  PubMed  Google Scholar 

  78. Gooley JJ, et al. Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. J Clin Endocrinol Metab. 2011;96(3):E463–72.

    Article  CAS  PubMed  Google Scholar 

  79. Citera G, et al. The effect of melatonin in patients with fibromyalgia: a pilot study. Clin Rheumatol. 2000;19(1):9–13.

    Article  CAS  PubMed  Google Scholar 

  80. Reiter RJ, Acuna-Castroviejo D, Tan DX. Melatonin therapy in fibromyalgia. Curr Pain Headache Rep. 2007;11(5):339–42.

    Article  PubMed  Google Scholar 

  81. Bruno A, et al. Agomelatine in the treatment of fibromyalgia: a 12-week, open-label, uncontrolled preliminary study. J Clin Psychopharmacol. 2013;33(4):507–11.

    Article  CAS  PubMed  Google Scholar 

  82. Calandre EP, et al. Agomelatine for the treatment of patients with fibromyalgia and depressive symptomatology: an uncontrolled, 12-week, pilot study. Pharmacopsychiatry. 2014;47(2):67–72.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Morphology, Cell Biology Institute, Federal University of Minas Gerais, Av. Antônio Carlos, 6627, Campus Pampulha, 31270-910, Belo Horizonte, MG, Brazil

    Andrei Pereira Pernambuco MSc, PhD & Débora d’ Ávila Reis MSc, PhD

  2. Department of Health Sciences, University Centre of Formiga (UNIFOR-MG) – Centre for Research and Extension (CEPEP), Av. Dr. Arnaldo de Senna 328, Água Vermelha, 35570-000, Formiga, MG, Brazil

    Andrei Pereira Pernambuco MSc, PhD

  3. Department of Health Sciences, University of Itaúna, Mg 431Road, Km 45, s/n. White Campus, 35680-142, Itaúna, MG, Brazil

    Andrei Pereira Pernambuco MSc, PhD

  4. Arthritis and Musculoskeletal Research Group – AMRG, Faculty of Health Sciences, The University of Sydney, Room S227, S Block, Cumberland Campus, 2141, Sydney, NSW, Australia

    Marina de Barros Pinheiro MSc

Authors
  1. Andrei Pereira Pernambuco MSc, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marina de Barros Pinheiro MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Débora d’ Ávila Reis MSc, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrei Pereira Pernambuco MSc, PhD .

Editor information

Editors and Affiliations

  1. Vice-Rectorate for Research and Sci, Camilo José Cela University Vice-Rectorate for Research and Sci, Madrid, Spain

    Francisco López-Muñoz

  2. International Medical Sciences Research Study Center, Sri Sathya Sai Medical Educational & Research Foundation, Coimbatore, India

    Venkataramanujam Srinivasan

  3. Department of Neurosciences and Ima, University of Chieti Department of Neurosciences and Ima, Italy, Italy

    Domenico de Berardis

  4. Department of Biomedical Sciences (Pharmacology Area), University of Alcalá, Madrid, Spain

    Cecilio Álamo

  5. Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan

    Takahiro A. Kato

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer India

About this chapter

Cite this chapter

Pernambuco, A.P., de Barros Pinheiro, M., d’ Ávila Reis, D. (2016). Melatonin in Clinical Status of Patients with Fibromyalgia Syndrome. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_12

Download citation

  • DOI: https://doi.org/10.1007/978-81-322-2803-5_12

  • Published:

  • Publisher Name: Springer, New Delhi

  • Print ISBN: 978-81-322-2801-1

  • Online ISBN: 978-81-322-2803-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation