Is there a role for melatonin in fibromyalgia?

Kim Lawson; Kim Lawson

doi:10.3934/molsci.2019.4.73

AIMS Molecular Science

2019, Volume 6, Issue 4: 73-86. doi: 10.3934/molsci.2019.4.73

Previous Article Next Article

Review

Is there a role for melatonin in fibromyalgia?

Kim Lawson ^,

Department of Biosciences and Chemistry, Biomolecular Sciences Research Centre, Sheffield Hallam University, Faculty of Health and Wellbeing, Sheffield S1 1WB, United Kingdom

Received: 30 August 2019 Accepted: 25 November 2019 Published: 26 November 2019

Fibromyalgia, characterised by persistent pain, fatigue, sleep disturbance and cognitive dysfunction, is a central sensitivity syndrome that also involves abnormality in peripheral generators and in the hypothalamic pituitary adrenal axis. Heterogeneity of clinical expression of fibromyalgia with a multifactorial aetiology has made the development of effective therapeutic strategies challenging. Physiological properties of the neurohormone melatonin appear related to the symptom profile exhibited by patients with fibromyalgia and thus disturbance of it’s production would be compatible with the pathophysiology. Altered levels of melatonin have been observed in patients with fibromyalgia which are associated with lower secretion during dark hours and higher secretion during daytime. However, inconsistencies of available clinical evidence limit conclusion of a relationship between levels of melatonin and symptom profiles in patients with fibromyalgia. Administration of melatonin to patients with fibromyalgia has demonstrated suppression of many symptoms and an improved quality of life consistent with benefit as a therapy for the management of this condition. Further studies with larger samples, however, are required to explore the potential role of melatonin in the pathophysiology of fibromyalgia and determine the optimal dosing regimen of melatonin for the management of fibromyalgia.
- melatonin,
- fibromyalgia,
- sleep,
- persistent pain,
- fatigue,
- anxiety
Citation: Kim Lawson. Is there a role for melatonin in fibromyalgia?[J]. AIMS Molecular Science, 2019, 6(4): 73-86. doi: 10.3934/molsci.2019.4.73

Related Papers:

Abstract

Fibromyalgia, characterised by persistent pain, fatigue, sleep disturbance and cognitive dysfunction, is a central sensitivity syndrome that also involves abnormality in peripheral generators and in the hypothalamic pituitary adrenal axis. Heterogeneity of clinical expression of fibromyalgia with a multifactorial aetiology has made the development of effective therapeutic strategies challenging. Physiological properties of the neurohormone melatonin appear related to the symptom profile exhibited by patients with fibromyalgia and thus disturbance of it’s production would be compatible with the pathophysiology. Altered levels of melatonin have been observed in patients with fibromyalgia which are associated with lower secretion during dark hours and higher secretion during daytime. However, inconsistencies of available clinical evidence limit conclusion of a relationship between levels of melatonin and symptom profiles in patients with fibromyalgia. Administration of melatonin to patients with fibromyalgia has demonstrated suppression of many symptoms and an improved quality of life consistent with benefit as a therapy for the management of this condition. Further studies with larger samples, however, are required to explore the potential role of melatonin in the pathophysiology of fibromyalgia and determine the optimal dosing regimen of melatonin for the management of fibromyalgia.

Abbreviation ACR: American College of Rheumatology; BDNF: Brain-derived neurotrophic factor; cAMP: Cyclic adenosine monophosphate; CNS: Central nervous system; CS: Central sensitization; CSF: Cerebrospinal fluid; DNIC: Diffuse noxious inhibitory control; FIQ: Fibromyalgia Impact Questionnaire; GABA: Gamma-aminobutyric acid; HPA: Hypothalamic pituitary adrenal axis; HRQOL: Health-related quality of life; MT: Melatonergic; NO: Nitric oxide; NMDA: N-methyl-D-aspartate; RCT: Randomized controlled trial; 6-SMT: 6-sulfatoxymelatonin;

Conflict of interest

The author declares no conflict of interest for the contributions in this manuscript.

References

[1]	Lawson K (2017) Emerging pharmacological strategies for the treatment of fibromyalgia. World J Pharmacol 6: 1–10. doi: 10.5497/wjp.v6.i1.1
[2]	Borchers AT, Gershwin ME (2016) Fibromyalgia: a critical and comprehensive review. Clinic Rev Allerg Immunol 49: 100–151.
[3]	Clauw DJ (2014) Fibromyalgia: a clinical review. JAMA 311: 1547–1555. doi: 10.1001/jama.2014.3266
[4]	Üçeyler N, Zeller D, Kahn AK, et al. (2013) Small fibre pathology in patients with fibromyalgia syndrome. Brain 136: 1857–1867. doi: 10.1093/brain/awt053
[5]	Wolfe F, Smythe HA, Yunus MB, et al. (1990) The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 33: 160–172.
[6]	Macfarlane GJ, Kronisch C, Dean LE, et al. (2017) EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis 76: 318–328. doi: 10.1136/annrheumdis-2016-209724
[7]	Wolfe F, Clauw DJ, Fitzcharles MA, et al. (2010) The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 62: 600–610. doi: 10.1002/acr.20140
[8]	Queiroz LP (2013) Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep 17: 356. doi: 10.1007/s11916-013-0356-5
[9]	Sluka KA, Clauw DJ (2016) Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience 338: 114–129. doi: 10.1016/j.neuroscience.2016.06.006
[10]	Fayed N, Garcia-Campayo J, Magallón R, et al. (2010) Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate. Arthritis Res Ther 12: R134. doi: 10.1186/ar3072
[11]	Pyke TL, Osmotherly PG, Baines S (2017) Measuring glutamate levels in the brains of fibromyalgia patients and a potential role for glutamate in the pathophysiology of fibromyalgia symptoms: a Systematic Review. Clin J Pain 33: 944–954. doi: 10.1097/AJP.0000000000000474
[12]	Wood PB, Schweinhardt P, Jaeger E, et al. (2007) Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci 25: 3576–3582. doi: 10.1111/j.1460-9568.2007.05623.x
[13]	Vanecek J (1998) Cellular mechanisms of melatonin action. Physiol Rev 78: 687–721. doi: 10.1152/physrev.1998.78.3.687
[14]	Hardeland R, Cardinali DP, Srinivasan V, et al. (2011) Melatonin – A pleiotropic, orchestrating regulator molecule. Prog Neurobiol 93: 350–384. doi: 10.1016/j.pneurobio.2010.12.004
[15]	Ambriz-Tututi M, Rocha-González HI, Cruz SL, et al. (2009) Melatonin: a hormone that modulates pain. Life Sci 84: 489–498. doi: 10.1016/j.lfs.2009.01.024
[16]	Masruha M, de Souza Vieira DS, Minett TS, et al. (2008) Low urinary 6-sulfatoxymelatonin concentrations in acute migraine. J Headache Pain 9: 221–224. doi: 10.1007/s10194-008-0047-5
[17]	Masruha MR, Lin J, de Souza Vieira DS, et al. (2010) Urinary 6-sulfatoxymelatonin levels are depressed in chronic migraine and several comorbidities. Headache 50: 413–419. doi: 10.1111/j.1526-4610.2009.01547.x
[18]	Srinivasan V, Pandi-Perumal SR, Trahkt I, et al. (2009) Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci 119: 821–846. doi: 10.1080/00207450802328607
[19]	Srinivasan V, Lauterbach EC, Ho KY, et al. (2012) Melatonin in antinociception: its therapeutic applications. Curr Neuropharmacol 10: 167–178. doi: 10.2174/157015912800604489
[20]	Noseda R, Hernández A, Valladares L, et al. (2004) Melatonin-induced inhibition of spinal cord synaptic potentiation in rats is MT2 receptor-dependent. Neurosci Lett 360: 41–44. doi: 10.1016/j.neulet.2004.01.080
[21]	Laurido C, Pelissie T, Soto-Moyano R, et al. (2002) Effect of melatonin on rat spinal cord nociceptive transmission. Neuroreport 13: 89–91. doi: 10.1097/00001756-200201210-00021
[22]	Chen WW, Zhang X, Huang WJ. (2016) Pain control by melatonin: Physiological and pharmacological effects. Exp Ther Med 12: 1963–1968. doi: 10.3892/etm.2016.3565
[23]	Wilhelmsen M, Amirian I, Reiter RJ, et al. (2011) Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies. J Pineal Res 51: 270–277. doi: 10.1111/j.1600-079X.2011.00895.x
[24]	Herrero JF, Laird JM, López-García JA (2000) Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol 61: 169–203. doi: 10.1016/S0301-0082(99)00051-9
[25]	Akerstedt T, Gillberg M, Wetterberg L (1982) The circadian covariation of fatigue and urinary melatonin. Biol Psychiatry 17: 547–554.
[26]	Pardini M, Cordano C, Benassi F, et al. (2014) Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study. Eur Neuropsychopharmacol 24: 939–944. doi: 10.1016/j.euroneuro.2014.02.010
[27]	San L, Arranz B (2008) Agomelatine: a novel mechanism of antidepressant action involving the melatonergic and the serotonergic system. Eur Psychiatry 23: 396–402. doi: 10.1016/j.eurpsy.2008.04.002
[28]	Ismail SA, Mowafi HA (2009) Melatonin provides anxiolysis, enhances analgesia, decreases intraocular pressure, and promotes better operating conditions during cataract surgery under topical anesthesia. Anesth Analg 108: 1146–1151. doi: 10.1213/ane.0b013e3181907ebe
[29]	Nava F, Carta G (2001) Melatonin reduces anxiety induced by lipopolysaccharide in the rat. Neurosci Lett 307: 57–60. doi: 10.1016/S0304-3940(01)01930-9
[30]	Wan Q, Man HY, Liu F, et al. (1999) Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors. Nat Neurosci 2: 401–403. doi: 10.1038/8062
[31]	Comai S, Gobbi G (2014) Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: a novel target in psychopharmacology. J Psychiatry Neurosci 39: 6–21. doi: 10.1503/jpn.130009
[32]	Bunney WE, Bunney BG (2000) Molecular clock genes in man and lower animals: possible implications for circadian abnormalities in depression. Neuropsychopharmacol 22: 335–345. doi: 10.1016/S0893-133X(99)00145-1
[33]	Quera Salva MA, Hartley S, Barbot F, et al. (2011) Circadian rhythms, melatonin and depression. Curr Pharm Des 17: 1459–1470. doi: 10.2174/138161211796197188
[34]	Srinivasan V, Brzezinski A, Pandi-Perumal SR, et al. (2011) Melatonin agonists in primary insomnia and depression-associated insomnia: are they superior to sedative-hypnotics? Prog Neuropsychopharmacol Biol Psychiatry 35: 913–923. doi: 10.1016/j.pnpbp.2011.03.013
[35]	Rizzi M, Sarzi-Puttini P, Atzeni F, et al. (2004) Cyclic alternating pattern: a new marker of sleep alteration in patients with fibromyalgia? J Rheumatol 31: 1193–1199.
[36]	Wikner J, Hirsch U, Wetterberg L, et al. (1998) Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion. Clin Endocrinol (Oxf) 49: 179–183. doi: 10.1046/j.1365-2265.1998.00503.x
[37]	Press J, Phillip M, Neumann L, et al. (1998) Normal melatonin levels in patients with fibromyalgia syndrome. J Rheumatol 25: 551–555.
[38]	Korszun A, Sackett-Lundeen L, Papadopoulos E, et al. (1999) Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol 26: 2675–2680.
[39]	Klerman EB, Goldenberg DL, Brown EN, et al. (2001) Circadian rhythms of women with fibromyalgia. J Clin Endocrinol Metab 86: 1034–1039.
[40]	Senel K, Baygutalp F, Baykal T, et al. (2013) Melatonin levels in premenopausal women with fibromyalgia syndrome. Rheumatol Int 33: 1609–1610. doi: 10.1007/s00296-011-2315-y
[41]	Pernambuco AP, Schetino LP, Viana RS, et al. (2015) The involvement of melatonin in the clinical status of patients with fibromyalgia syndrome. Clin Exp Rheumatol 33(Suppl 88): S14–19.
[42]	Caumo W, Hidalgo MP, Souza A, et al. (2019) Melatonin is a biomarker of circadian dysregulation and is correlated with major depression and fibromyalgia symptom severity. J Pain Res 12: 545–556. doi: 10.2147/JPR.S176857
[43]	Webb SM (1998) Fibromyalgia and melatonin: are they related? Clin Endocrinol (Oxf) 49: 161–162. doi: 10.1046/j.1365-2265.1998.00548.x
[44]	Musshoff U, Riewenherm D, Berger E, et al. (2002) Melatonin receptors in rat hippocampus: molecular and functional investigations. Hippocampus 12: 165–173. doi: 10.1002/hipo.1105
[45]	Citera G, Arias MA, Maldonado-Cocco JA, et al. (2000) The effect of melatonin in patients with fibromyalgia: a pilot study. Clin Rheumatol 19: 9–13. doi: 10.1007/s100670050003
[46]	Acuna-Castroviejo D, Escames G, Reiter RJ (2006) Melatonin therapy in fibromyalgia. J Pineal Res 40: 98–99. doi: 10.1111/j.1600-079X.2005.00278.x
[47]	Hussain SA, Al-Khalifa II, Jasim NA, et al. (2011) Adjuvant use of melatonin for treatment of fibromyalgia. J Pineal Res 50: 267–271. doi: 10.1111/j.1600-079X.2010.00836.x
[48]	de Zanette SA, Vercelino R, Laste G, et al. (2014) 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 15: 40. doi: 10.1186/2050-6511-15-40
[49]	Castaño MY, Garrido M, Delgado-Adamez J, et al. (2018) Oral melatonin administration improves the objective and subjective sleep quality, increases 6-sulfatoxymelatonin levels and total antioxidant capacity in patients with fibromyalgia. J Appl Biomed 16: 186–191. doi: 10.1016/j.jab.2018.01.005
[50]	Castaño MY, Garrido M, Rodríguez AB, et al. (2019) Melatonin Improves Mood Status and Quality of Life and Decreases Cortisol Levels in Fibromyalgia. Biol Res Nurs 21: 22–29. doi: 10.1177/1099800418811634
[51]	Sánchez-Domínguez B, Bullón P, Román-Malo L, et al. (2015) Oxidative stress, mitochondrial dysfunction and, inflammation common events in skin of patients with Fibromyalgia. Mitochondrion 21: 69–75. doi: 10.1016/j.mito.2015.01.010
[52]	Fatima G, Das SK, Mahdi AA (2017) Some oxidative and antioxidative parameters and their relationship with clinical symptoms in women with fibromyalgia syndrome. Int J Rheum Dis 20: 39–45. doi: 10.1111/1756-185X.12550
[53]	Torres-Farfan C, Richter HG, Rojas-García P, et al. (2003) mt1 Melatonin receptor in the primate adrenal gland: inhibition of adrenocorticotropin-stimulated cortisol production by melatonin. J Clin Endocrinol Metab 88: 450–458. doi: 10.1210/jc.2002-021048
[54]	Mahdi AA, Fatima G, Das SK, et al. (2011) Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome. Indian J Biochem Biophys 48: 82–87.
[55]	McLean SA, Williams DA, Harris RE, et al. (2005) Momentary relationship between cortisol secretion and symptoms in patients with fibromyalgia. Arthritis Rheum 52: 3660–3669. doi: 10.1002/art.21372
[56]	Bruno A, Micò U, Lorusso S, et al. (2013) Agomelatine in the treatment of fibromyalgia: a 12-week, open-label, uncontrolled preliminary study. J Clin Psychopharmacol 33: 507–511. doi: 10.1097/JCP.0b013e31829057ae
[57]	Calandre EP, Slim M, Garcia-Leiva JM, et al. (2014) Agomelatine for the treatment of patients with fibromyalgia and depressive symptomatology: an uncontrolled, 12-week, pilot study. Pharmacopsychiatry 47: 67–72. doi: 10.1055/s-0033-1363659
[58]	Finan PH, Goodin BR, Smith MT (2013) The association of sleep and pain: an update and a path forward. J Pain 14: 1539–1552. doi: 10.1016/j.jpain.2013.08.007

Reader Comments

Your name:*

Email:*
© 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)