Skip to main content
SpringerLink
Log in
Book cover

Advances in Pain Research: Mechanisms and Modulation of Chronic Pain pp 229–251Cite as

Melatonin: A New-Generation Therapy for Reducing Chronic Pain and Improving Sleep Disorder-Related Pain

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1099))

Abstract

Melatonin is an endogenous neurohormone that is produced in most living organisms, including unicellular and multicellular organisms, plants, vertebrates, and nonvertebrate animals. In diurnal animals, endogenous melatonin functions as a neurohormone and contributes to circadian rhythms. In nocturnal animals, endogenous melatonin no longer functions as a contributor to circadian rhythms. Circadian rhythms control the timing, quantity, and quality of hormones and neurotransmitters that the body produces and eventually secretes. An imbalance of these events creates disturbances in circadian rhythm. During disturbances of circadian rhythm, the body produces hormones, chemicals, and neurotransmitters in aberrant amounts or at the wrong time of day. The human circadian system is synchronized with physiological functions and metabolism. Many studies have reported that exogenous melatonin has analgesic and neuroprotective effects in chronic pain. Considering that chronotherapy may be beneficial for the treatment of chronic pain, the present review describes the properties, possible mechanisms, and function of melatonin in chronic pain.

This is a preview of subscription content, 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   99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   179.99
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

Learn about institutional subscriptions

References

  1. Acuña Castroviejo D, Escames G, Carazo A, León J, Khaldy H, Reiter RJ (2002) Melatonin, mitochondrial homeostasis and mitochondrial-related diseases. Curr Top Med Chem 2:133–151

    Article  PubMed  Google Scholar 

  2. Afkhamizadeh M, Sahebari M, Seyyed-hoseini S-R (2014) Morning melatonin serum values do not correlate with disease activity in rheumatoid arthritis: a cross-sectional study. Rheumatol Int 34:1145–1151

    Article  CAS  PubMed  Google Scholar 

  3. Ahn AH, Goadsby PJ (2013) Migraine and sleep: new connections. Cerebrum: the Dana forum on brain science. Dana Foundation

    Google Scholar 

  4. Alóe F, Azevedo APD, Hasan R (2005) Sleep-wake cycle mechanisms. Rev Bras Psiquiatr 27:33–39

    Article  PubMed  Google Scholar 

  5. Alstadhaug K, Bekkelund S, Salvesen R (2007a) Circannual periodicity of migraine? Eur J Neurol 14:983–988

    Article  CAS  PubMed  Google Scholar 

  6. Alstadhaug K, Salvesen R, Bekkelund S (2007b) Insomnia and circadian variation of attacks in episodic migraine. Headache 47:1184–1188

    Article  PubMed  Google Scholar 

  7. Altun A, Ugur-Altun B (2007) Melatonin: therapeutic and clinical utilization. Int J Clin Pract 61:835–845

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Areti A, Yerra VG, Naidu V, Kumar A (2014) Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol 2:289–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Arreola-Espino R, Urquiza-Marín H, Ambriz-Tututi M, Araiza-Saldaña CI, Caram-Salas NL, Rocha-González HI, Mixcoatl-Zecuatl T, Granados-Soto V (2007) Melatonin reduces formalin-induced nociception and tactile allodynia in diabetic rats. Eur J Pharmacol 577:203–210

    Article  CAS  PubMed  Google Scholar 

  11. Balzer I, Höcker B, Kapp H, Bartolomaeus B (2000) Occurrence and comparative physiology of melatonin in evolutionary diverse organisms. In: Driessche TV, Guisset JL, Petiau-de Vries GM (eds) The redox state and circadian rhythms. Springer, Dordrecht

    Google Scholar 

  12. Barrett T, Kent S, Voudouris N (2000) Does melatonin modulate beta-endorphin, corticosterone, and pain threshold? Life Sci 66:467–476

    Article  CAS  PubMed  Google Scholar 

  13. Bolten W, Gross M, Brabant T, Weck V, Labenz J (2013) Individual pain treatment with NSAIDs. MMW Fortschr Med 155(59–60):62

    Google Scholar 

  14. Bondi CD, Mckeon RM, Bennett JM, Ignatius PF, Brydon L, Jockers R, Melan MA, Witt-Enderby PA (2008) MT1 melatonin receptor internalization underlies melatonin-induced morphologic changes in Chinese hamster ovary cells and these processes are dependent on Gi proteins, MEK 1/2 and microtubule modulation. J Pineal Res 44:288–298

    Article  CAS  PubMed  Google Scholar 

  15. Bonmati-Carrion MA, Arguelles-Prieto R, Martinez-Madrid MJ, Reiter R, Hardeland R, Rol MA, Madrid JA (2014) Protecting the melatonin rhythm through circadian healthy light exposure. Int J Mol Sci 15:23448–23500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Budhiraja S, Singh J (2005) Adjuvant effect of melatonin on anesthesia induced by thiopental sodium, ketamine, and ether in rats. Methods Find Exp Clin Pharmacol 27:697–700

    Article  CAS  PubMed  Google Scholar 

  17. Buscemi N, Vandermeer B, Hooton N, Pandya r, Tjosvold l, Hartling l, Vohra s, Klassen t P, Baker G (2006) Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 332:385–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Callebert J, Jaunay J, Jallon J (1991) Control of Drosophila biorhythms. Adv Pineal Res 5:81–84

    CAS  Google Scholar 

  19. Callsen-Cencic P, Hoheisel U, Kaske A, Mense S, Tenschert S (1999) The controversy about spinal neuronal nitric oxide synthase: under which conditions is it up-or downregulated? Cell Tissue Res 295:183–194

    Article  CAS  PubMed  Google Scholar 

  20. Caumo W, Levandovski R, Hidalgo MPL (2009) Preoperative anxiolytic effect of melatonin and clonidine on postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy: a double-blind, randomized, placebo-controlled study. J Pain 10:100–108

    Article  CAS  PubMed  Google Scholar 

  21. Caumo W, Torres F, Moreira NLJR, Auzani JA, Monteiro CA, Londero G, Ribeiro DF, Hidalgo MPL (2007) The clinical impact of preoperative melatonin on postoperative outcomes in patients undergoing abdominal hysterectomy. Anesth Analg 105:1263–1271

    Article  CAS  PubMed  Google Scholar 

  22. Cavaletti G, Carozzi V, Chiorazzi A, Oggioni N, Rodriguez-Menendez V, Avezza F, Marmiroli P (2013) Chemotherapy-induced peripheral neuropathy in immunodeficient mice: new useful ready-to-use animal models. Ital J Anat Embryol 118:51

    Google Scholar 

  23. Chang F-Y (2014) Irritable bowel syndrome: the evolution of multi-dimensional looking and multidisciplinary treatments. World J Gastroenterol 20:2499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen C-Q, Fichna J, Bashashati M, LI Y-Y, Storr M (2011) Distribution, function and physiological role of melatonin in the lower gut. World J Gastroenterol 17:3888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chiang RPY, Huang CT, Tsai YJ (2013) 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 54:232–244

    Article  CAS  PubMed  Google Scholar 

  26. Costigan M, Woolf CJ (2000) Pain: molecular mechanisms. J Pain 1:35–44

    Article  CAS  PubMed  Google Scholar 

  27. Cutolo M, Maestroni G (2005) The melatonin-cytokine connection in rheumatoid arthritis. Ann Rheum Dis 64:1109–1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cutolo M, Maestroni G, Otsa K, Aakre O, Villaggio B, Capellino S, Montagna P, Fazzuoli L, Veldi T, Peets T (2005) Circadian melatonin and cortisol levels in rheumatoid arthritis patients in winter time: a north and south Europe comparison. Ann Rheum Dis 64:212–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Danilov A, Kurganova J (2016) Melatonin in chronic pain syndromes. Pain and therapy 5:1–17

    Article  PubMed  PubMed Central  Google Scholar 

  30. De Zanette SA, Vercelino R, Laste G, Rozisky JR, Schwertner A, Machado CB, Xavier F, De Souza ICC, Deitos A, Torres IL (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Demisch L, Demisch K, Nickelsen T (1988) Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects. J Pineal Res 5:317–322

    Article  CAS  PubMed  Google Scholar 

  32. Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G (2007) Hypothalamic activation in spontaneous migraine attacks. Headache 47:1418–1426

    PubMed  Google Scholar 

  33. Desler C, Lillenes MS, Tønjum T, Rasmussen LJ (2017) The role of mitochondrial dysfunction in the progression of Alzheimer’s disease. Curr Med Chem 24:1–10

    Google Scholar 

  34. Doghramji K (2007) Melatonin and its receptors: a new class of sleep-promoting agents. J Clin sleep Med 3:S17

    PubMed  PubMed Central  Google Scholar 

  35. El-Shenawy SM, Abdel-Salam OM, Baiuomy AR, El-Batran S, Arbid MS (2002) Studies on the anti-inflammatory and anti-nociceptive effects of melatonin in the rat. Pharmacol Res 46:235–243

    Article  CAS  PubMed  Google Scholar 

  36. Engstrøm M, Hagen K, Bjørk MH, Stovner LJ, Gravdahl GB, Stjern M, Sand T (2013) Sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study. J Headache Pain 14:12

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ennis ZN, Dideriksen D, Vægter HB, Handberg G, Pottegård A (2016) Acetaminophen for chronic pain: a systematic review on efficacy. Basic Clin Pharmacol Toxicol 118:184–189

    Article  CAS  PubMed  Google Scholar 

  38. Esposito E, Paterniti I, Mazzon E, Bramanti P, Cuzzocrea S (2010) Melatonin reduces hyperalgesia associated with inflammation. J Pineal Res 49:321–331

    Article  CAS  PubMed  Google Scholar 

  39. Fingland R, Cronin A, Keifer J, Shaheen J, Davies M, Bixler E (1999) Postoperative REM sleep inhibition: association with pain or cortisol? Reg Anesth Pain Med 24:4

    Google Scholar 

  40. Galley HF, Mccormick B, Wilson KL, Lowes DA, Colvin L, Torsney C (2017) Melatonin limits paclitaxel-induced mitochondrial dysfunction in vitro and protects against paclitaxel-induced neuropathic pain in the rat. J Pineal Res 63:e12444

    Article  CAS  PubMed Central  Google Scholar 

  41. Gogenur I (2010) Postoperative circadian disturbances. Dan Med Bull 57:B4205

    PubMed  Google Scholar 

  42. Gögenur I, Wildschiøtz G, Rosenberg J (2007) Circadian distribution of sleep phases after major abdominal surgery. Br J Anaesth 100:45–49

    Article  PubMed  Google Scholar 

  43. Gonçalves AL, Ferreira AM, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MFP (2016) Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 87:1127–1132

    Article  PubMed  Google Scholar 

  44. Govitrapong P, Pariyanonth M, Ebadi M (1992) The presence and actions of opioid receptors in bovine pineal gland. J Pineal Res 13:124–132

    Article  CAS  PubMed  Google Scholar 

  45. Grigg-Damberger MM, Ianakieva D (2017) Poor quality control of over-the-counter melatonin: what they say is often not what you get. J Clin Sleep Med 13:163

    Article  PubMed  PubMed Central  Google Scholar 

  46. Guglielmo R, Martinotti G, Di Giannantonio M, Janiri L (2013) A possible new option for migraine management: agomelatine. Clin Neuropharmacol 36:65–67

    Article  CAS  PubMed  Google Scholar 

  47. Hansson P (2004) Post-stroke pain case study: clinical characteristics, therapeutic options and long-term follow-up. Eur J Neurol 11:22–30

    Article  PubMed  Google Scholar 

  48. Hardeland R (1996) Ubiquitous melatonin-presence and effects in unicells, plants and animals. Trends Comp Biochem Physiol 2:25–45

    CAS  Google Scholar 

  49. Hardeland R (1999) Melatonin and 5-methoxytryptamine in non-metazoans. Reprod Nutr Dev 39:399–408

    Article  CAS  PubMed  Google Scholar 

  50. Hardeland R, Poeggeler B (2003) Non-vertebrate melatonin. J Pineal Res 34:233–241

    Article  CAS  PubMed  Google Scholar 

  51. Hernández-Pacheco A, Araiza-Saldaña CI, Granados-Soto V, Mixcoatl-Zecuatl T (2008) Possible participation of the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway in the peripheral antinociception of melatonin. Eur J Pharmacol 596:70–76

    Article  CAS  PubMed  Google Scholar 

  52. Hussain SAR, Al-Khalifa II, Jasim NA, Gorial FI (2011) Adjuvant use of melatonin for treatment of fibromyalgia. J Pineal Res 50:267–271

    Article  CAS  PubMed  Google Scholar 

  53. 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

    Article  CAS  PubMed  Google Scholar 

  54. Jick H (1994) Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 343:769–772

    Article  PubMed  Google Scholar 

  55. Kalsbeek A, Palm I, La Fleur S, Scheer F, Perreau-Lenz S, Ruiter M, Kreier F, Cailotto C, Buijs R (2006) SCN outputs and the hypothalamic balance of life. J Biol Rhythm 21:458–469

    Article  CAS  Google Scholar 

  56. Kärkelä J, Vakkuri O, Kaukinen S, Huang WQ, Pasanen M (2002) The influence of anaesthesia and surgery on the circadian rhythm of melatonin. Acta Anaesthesiol Scand 46:30–36

    Article  PubMed  Google Scholar 

  57. Kavaliers M (1989) β-Funaltrexamine disrupts the day-night rhythm of nociception in mice. Brain Res Bull 22:783–785

    Article  CAS  PubMed  Google Scholar 

  58. Kawabata A, Manabe S, Manabe Y, Takagi H (1994) Effect of topical administration of l-arginine on formalin-induced nociception in the mouse: a dual role of peripherally formed NO in pain modulation. Br J Pharmacol 112:547–550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kelman L, Rains JC (2005) Headache and sleep: examination of sleep patterns and complaints in a large clinical sample of migraineurs. Headache 45:904–910

    Article  PubMed  Google Scholar 

  60. Khaldy H, León J, Escames G, Bikjdaouene L, García JJ, Acuña-Castroviejo D (2002) Circadian rhythms of dopamine and dihydroxyphenyl acetic acid in the mouse striatum: effects of pinealectomy and of melatonin treatment. Neuroendocrinology 75:201–208

    Article  CAS  PubMed  Google Scholar 

  61. Kilic Ü, Kilic E, Reiter RJ, Bassetti CL, Hermann DM (2005) Signal transduction pathways involved in melatonin-induced neuroprotection after focal cerebral ischemia in mice. J Pineal Res 38:67–71

    Article  CAS  PubMed  Google Scholar 

  62. Klerman EB, Goldenberg DL, Brown EN, Maliszewski AM, Adler GK (2001) Circadian rhythms of women with fibromyalgia. J Clin Endocrinol Metab 86:1034–1039

    CAS  PubMed  Google Scholar 

  63. Klit H, Finnerup NB, Jensen TS (2009) Central post-stroke pain: clinical characteristics, pathophysiology, and management. Lancet Neurol 8:857–868

    Article  PubMed  Google Scholar 

  64. Klit H, Hansen AP, Marcussen NS, Finnerup NB, Jensen TS (2014) Early evoked pain or dysesthesia is a predictor of central poststroke pain. Pain 155:2699–2706

    Article  PubMed  Google Scholar 

  65. Laurido C, Pelissier T, Soto-Moyano R, Valladares L, Flores F, Hernández A (2002) Effect of melatonin on rat spinal cord nociceptive transmission. Neuroreport 13:89–91

    Article  CAS  PubMed  Google Scholar 

  66. Leon J, Acuña-Castroviejo D, Escames G, Tan DX, Reiter RJ (2005) Melatonin mitigates mitochondrial malfunction. J Pineal Res 38:1–9

    Article  CAS  PubMed  Google Scholar 

  67. Li S-R, Wang T, Wang R, Dai X, Chen Q (2005) Melatonin enhances antinociceptive effects of δ-, but not μ-opioid agonist in mice. Brain Res 1043:132–138

    Article  CAS  PubMed  Google Scholar 

  68. Lieberman HR, Waldhauser F, Garfield G, Lynch HJ, Wurtman RJ (1984) Effects of melatonin on human mood and performance. Brain Res 323:201–207

    Article  CAS  PubMed  Google Scholar 

  69. Lissoni P, Giani L, Zerbini S, Trabattoni P, Rovelli F (1998) Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms. Nat Immun 16:27–33

    Article  CAS  PubMed  Google Scholar 

  70. Liu Y, He H, Huang F (2014) Melatonin in pain modulation: analgesic or proalgesic? Pain Stud Treatment 2:50

    Article  Google Scholar 

  71. Liveing E (1873) On megrim, sick-headache, and some allied disorders: a contribution to the pathology of nerve-storms. Churchill, London

    Google Scholar 

  72. López-Canul M, Comai S, Domínguez-López S, Granados-Soto V, Gobbi G (2015) Antinociceptive properties of selective MT2 melatonin receptor partial agonists. Eur J Pharmacol 764:424–432

    Article  CAS  PubMed  Google Scholar 

  73. Lu W, Gwee K, Moochhalla S, Ho K (2005) Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double-blind placebo-controlled study. Aliment Pharmacol Ther 22:927–934

    Article  CAS  PubMed  Google Scholar 

  74. Luchetti F, Betti M, Canonico B, Arcangeletti M, Ferri P, Galli F, Papa S (2009) ERK MAPK activation mediates the antiapoptotic signaling of melatonin in UVB-stressed U937 cells. Free Radic Biol Med 46:339–351

    Article  CAS  PubMed  Google Scholar 

  75. Luchetti F, Canonico B, Curci R, Battistelli M, Mannello F, Papa S, Tarzia G, Falcieri E (2006) Melatonin prevents apoptosis induced by UV-B treatment in U937 cell line. J Pineal Res 40:158–167

    Article  CAS  PubMed  Google Scholar 

  76. Mahdi AA, Fatima G, Das SK, Verma NS (2011) Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome. Indian J Biochem Biophys 48:82–87

    CAS  PubMed  Google Scholar 

  77. Maitra S, Baidya DK, Khanna P (2013) Melatonin in perioperative medicine: current perspective. Saudi J Anaesth 7:315

    Article  PubMed  PubMed Central  Google Scholar 

  78. Makay B (2009) Is there a role of melatonin in the development of growing pains? Med Hypotheses 72:225

    Article  CAS  PubMed  Google Scholar 

  79. Martin M, Macias M, Escames G, Reiter R, Agapito M, Ortiz G, Acuña-Castroviejo D (2000) Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res 28:242–248

    Article  CAS  PubMed  Google Scholar 

  80. Matsumoto M (1999) The hypnotic effects of melatonin treatment on diurnal sleep in humans. Psychiatry Clin Neurosci 53:243–245

    Article  CAS  PubMed  Google Scholar 

  81. Mayo JC, Sainz RM, Tan D-X, Hardeland R, Leon J, Rodriguez C, Reiter RJ (2005) Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. J Neuroimmunol 165:139–149

    Article  CAS  PubMed  Google Scholar 

  82. Mcintyre IM, Norman TR, Burrows GD, Armstrong SM (1993) Alterations to plasma melatonin and cortisol after evening alprazolam administration in humans. Chronobiol Int 10:205–213

    Article  CAS  PubMed  Google Scholar 

  83. Mondaca M, Hernández A, Valladares L, Sierralta W, Noseda R, Soto-Moyano R (2004) Involvement of melatonin metabolites in the long-term inhibitory effect of the hormone on rat spinal nociceptive transmission. Pharmacol Biochem Behav 77:275–279

    Article  CAS  PubMed  Google Scholar 

  84. Moore RY, Speh JC (1993) GABA is the principal neurotransmitter of the circadian system. Neurosci Lett 150:112–116

    Article  CAS  PubMed  Google Scholar 

  85. Morgan PJ, Williams LM (1996) The pars tuberalis of the pituitary: a gateway for neuroendocrine output. Rev Reprod 1:153–161

    Article  CAS  PubMed  Google Scholar 

  86. Mowafi HA, Ismail SA (2008) Melatonin improves tourniquet tolerance and enhances postoperative analgesia in patients receiving intravenous regional anesthesia. Anesth Analg 107:1422–1426

    Article  CAS  PubMed  Google Scholar 

  87. Muñóz-Hoyos A, Fernández-García J, Molina-Carballo A, Macias M, Escames G, Ruiz-Cosano C, Acuña-Castroviejo D (2000) Effect of clonidine on plasma ACTH, cortisol and melatonin in children. J Pineal Res 29:48–53

    Article  PubMed  Google Scholar 

  88. Murphy PJ, Myers BL, Badia P (1996) Nonsteroidal anti-inflammatory drugs alter body temperature and suppress melatonin in humans. Physiol Behav 59:133–139

    Article  CAS  PubMed  Google Scholar 

  89. Naguib M, Gottumukkala V, Goldstein PA (2007) Melatonin and anesthesia: a clinical perspective. J Pineal Res 42:12–21

    Article  CAS  PubMed  Google Scholar 

  90. Nahleh Z, Pruemer J, Lafollette J, Sweany S (2010) Melatonin, a promising role in taxane-related neuropathy. Clin Med Insights Oncol 4., CMO:S4132

    Article  Google Scholar 

  91. Naseem M, Parvez S (2014) Role of melatonin in traumatic brain injury and spinal cord injury. Sci World J 2014:586270

    Article  Google Scholar 

  92. Noseda R, Hernández A, Valladares L, Mondaca M, Laurido C, Soto-Moyano R (2004) Melatonin-induced inhibition of spinal cord synaptic potentiation in rats is MT 2 receptor-dependent. Neurosci Lett 360:41–44

    Article  CAS  PubMed  Google Scholar 

  93. Olcese JM, Cao C, Mori T, Mamcarz MB, Maxwell A, Runfeldt MJ, Wang L, Zhang C, Lin X, Zhang G (2009) Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. J Pineal Res 47:82–96

    Article  CAS  PubMed  Google Scholar 

  94. Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, Cardinali DP (2008) Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol 85:335–353

    Article  CAS  PubMed  Google Scholar 

  95. Park HJ (2014) Chemotherapy induced peripheral neuropathic pain. Korean J Anesthesiol 67:4–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Pasternak GW (2007) When it comes to opiates, just say NO. J Clin Invest 117:3185–3187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Patel T, Kurdi MS (2015) A comparative study between oral melatonin and oral midazolam on preoperative anxiety, cognitive, and psychomotor functions. J Anaesthesiol Clin Pharmacol 31:37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Paul KN, Losee-Olson S, Pinckney L, Turek FW (2009) The ability of stress to alter sleep in mice is sensitive to reproductive hormones. Brain Res 1305:74–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Peres M, Gonçalves A (2013) Double-blind, placebo controlled, randomized clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. Neurology 80:S40.005

    Google Scholar 

  100. Perissin L, Boccalon S, Scaggiante B, Petrelli L, Ortolani F, Porro CA (2004) Diurnal changes of tonic nociceptive responses in mice: evidence for a proalgesic role of melatonin. Pain 110:250–258

    Article  CAS  PubMed  Google Scholar 

  101. Phansuwan-Pujito P, Ebadi M, Govitrapong P (2006) Immunocytochemical characterization of delta-opioid and mu-opioid receptor protein in the bovine pineal gland. Cells Tissues Organs 182:48–56

    Article  CAS  PubMed  Google Scholar 

  102. Pickard GE (1987) Circadian rhythm of nociception in the golden hamster. Brain Res 425:395–400

    Article  CAS  PubMed  Google Scholar 

  103. Poeggeler B, Balzer I, Hardeland R, Lerchl A (1991) Pineal hormone melatonin oscillates also in the dinoflagellate Gonyaulax polyedra. Naturwissenschaften 78:268–269

    Article  CAS  Google Scholar 

  104. Ray M, Mediratta P, Mahajan P, Sharma K (2004) Evaluation of the role of melatonin in formalin-induced pain response in mice. Indian J Med Sci 58:122

    CAS  PubMed  Google Scholar 

  105. Reiter RJ, Tan DX, Sainz RM, Mayo JC, Lopez-BURILLO S (2002) Melatonin: reducing the toxicity and increasing the efficacy of drugs. J Pharm Pharmacol 54:1299–1321

    Article  CAS  PubMed  Google Scholar 

  106. Rosenstein RE, Cardinali DP (1986) Melatonin increases in vivo GABA accumulation in rat hypothalamus, cerebellum, cerebral cortex and pineal gland. Brain Res 398:403–406

    Article  CAS  PubMed  Google Scholar 

  107. Rudra DS, Pal U, Maiti NC, Reiter RJ, Swarnakar S (2013) Melatonin inhibits matrix metalloproteinase-9 activity by binding to its active site. J Pineal Res 54:398–405

    Article  CAS  PubMed  Google Scholar 

  108. Sahota P (2003) Morning headaches in patients with sleep disorders. Sleep Med 4(5):377.

    Article  CAS  PubMed  Google Scholar 

  109. Schernhammer E, Schulmeister K (2004) Melatonin and cancer risk: does light at night compromise physiologic cancer protection by lowering serum melatonin levels? Br J Cancer 90:941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Shavali S, Ho B, Govitrapong P, Sawlom S, Ajjimaporn A, Klongpanichapak S, Ebadi M (2005) Melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by increasing the release of β-endorphin an endogenous opioid. Brain Res Bull 64:471–479

    Article  CAS  PubMed  Google Scholar 

  111. Shin DJ, Jeong CW, Lee SH, Yoon MH (2011) Receptors involved in the antinociception of intrathecal melatonin in formalin test of rats. Neurosci Lett 494:207–210

    Article  CAS  PubMed  Google Scholar 

  112. Siah KTH, Wong RKM, Ho KY (2014) Melatonin for the treatment of irritable bowel syndrome. World J Gastroenterol 20:2492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY (2005) Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut 54:1402–1407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Srinivasan V, Lauterbach EC, HO KY, Acuña-Castroviejo D, Zakaria R, Brzezinski A (2012) Melatonin in antinociception: its therapeutic applications. Curr Neuropharmacol 10:167–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Srinivasan V, Pandi-Perumal SR, Spence DW, Moscovitch A, Trakht I, Brown GM, Cardinali DP (2010) Potential use of melatonergic drugs in analgesia: mechanisms of action. Brain Res Bull 81:362–371

    Article  CAS  PubMed  Google Scholar 

  116. Srinivasan V, Spence DW, Pandi-Perumal SR, Brown GM, Cardinali DP (2011) Melatonin in mitochondrial dysfunction and related disorders. Int J Alzheimers Dis 2011:326320

    PubMed  PubMed Central  Google Scholar 

  117. Srinivasan V, Zakaria R, Singh HJ, Acuna-Castroviejo D (2013) Melatonin and its agonists in pain modulation and its clinical application. Arch Ital Biol 150:274–292

    Google Scholar 

  118. Starobova H, Vetter I (2017) Pathophysiology of chemotherapy-induced peripheral neuropathy. Front Mol Neurosci 10:174

    Article  PubMed  PubMed Central  Google Scholar 

  119. Stoschitzky K, Sakotnik A, Lercher P, Zweiker R, Maier R, Liebmann P, Lindner W (1999) Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol 55:111–115

    Article  CAS  PubMed  Google Scholar 

  120. Sultan SS (2010) Assessment of role of perioperative melatonin in prevention and treatment of postoperative delirium after hip arthroplasty under spinal anesthesia in the elderly. Saudi J Anaesth 4:169

    Article  PubMed  PubMed Central  Google Scholar 

  121. Tabeeva G, Sergeev A, Gromova S (2011) Possibilities of preventive treatment of migraine with the MT1-and MT2 agonist and 5-HT2с receptor antagonist agomelatin (valdoxan). Zh Nevrol Psikhiatr Im S S Korsakova 111:32–36

    CAS  PubMed  Google Scholar 

  122. Ulugol A, Dokmeci D, Guray G, Sapolyo N, Ozyigit F, Tamer M (2006) Antihyperalgesic, but not antiallodynic, effect of melatonin in nerve-injured neuropathic mice: possible involvements of the L-arginine–NO pathway and opioid system. Life Sci 78:1592–1597

    Article  CAS  PubMed  Google Scholar 

  123. Van Den Heuvel CJ, Ferguson SA, Macchi MM, Dawson D (2005) Melatonin as a hypnotic: con. Sleep Med Rev 9:71–80

    Article  PubMed  Google Scholar 

  124. Vijayalaxmi, Thomas CRJR, Reiter RJ, Herman TS (2002) Melatonin: from basic research to cancer treatment clinics. J Clin Oncol 20:2575–2601

    Article  CAS  PubMed  Google Scholar 

  125. Wang S, Tian Y, Song L, Lim G, Tan Y, You Z, Chen L, Mao J (2012) Exacerbated mechanical hyperalgesia in rats with genetically predisposed depressive behavior: role of melatonin and NMDA receptors. Pain 153:2448–2457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Weaver DR, Dallmann R (n.d.) Melatonin receptors: past, present and future

    Google Scholar 

  127. Weaver DR, Rivkees SA, Reppert SM (1989) Localization and characterization of melatonin receptors in rodent brain by in vitro autoradiography. J Neurosci 9:2581–2590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Wiech K, Tracey I (2009) The influence of negative emotions on pain: behavioral effects and neural mechanisms. NeuroImage 47:987–994

    Article  PubMed  Google Scholar 

  129. Wikner J, Hirsch U, Wetterberg L, Röjdmark S (1998) Fibromyalgia—a syndrome associated with decreased nocturnal melatonin secretion. Clin Endocrinol 49:179–183

    Article  CAS  Google Scholar 

  130. Wilhelmsen M, Amirian I, Reiter RJ, Rosenberg J, Gögenur I (2011) Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies. J Pineal Res 51:270–277

    Article  CAS  PubMed  Google Scholar 

  131. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L (1995) The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 38:19–28

    Article  CAS  PubMed  Google Scholar 

  132. Xiong X-C, Zhu Y, Ge R, Liu L-F, Yuan W (2015) Effect of melatonin on the extracellular-regulated kinase signal pathway activation and human osteoblastic cell line hFOB 1.19 proliferation. Int J Mol Sci 16:10337–10353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Xu R, Wu X, Di A, Xu J, Pang C, Pang S, Meng Z, Lu G-W, Wang Q, Wu Y (2000) Receptor and non-receptor mediated actions of melatonin. Neurosignals 9:53–75

    Article  Google Scholar 

  134. Yousaf F, Seet E, Venkatraghavan L, Abrishami A, Chung F (2010) Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative Period: A qualitative systematic review of randomized trials. Anesthesiology 113:968–976

    Article  CAS  PubMed  Google Scholar 

  135. Yu C, Wu G, Xu S, Chen C (2000) Melatonin influences the release of endogenous opioid peptides in rat periaqueductal gray. Sheng Li Xue Bao 52:207–210

    CAS  PubMed  Google Scholar 

  136. Zahn PK, Lansmann T, Berger E, Speckmann EJ, Musshoff U (2003) Gene expression and functional characterization of melatonin receptors in the spinal cord of the rat: implications for pain modulation. J Pineal Res 35:24–31

    Article  CAS  PubMed  Google Scholar 

  137. Zhu C, Xu Y, Duan Y, LI W, Zhang L, Huang Y, Zhao W, Wang Y, Li J, Feng T (2017) Exogenous melatonin in the treatment of pain: a systematic review and meta-analysis. Oncotarget 8:100582

    PubMed  PubMed Central  Google Scholar 

  138. Zurowski D, Nowak L, Machowska A, Wordliczek J, Thor P (2012) Exogenous melatonin abolishes mechanical allodynia but not thermal hyperalgesia in neuropathic pain. The role of the opioid system and benzodiazepine-gabaergic mechanism. J Physiol Pharmacol 63:641–647

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Tavleen Kaur & Bai-Chuang Shyu

  2. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Bai-Chuang Shyu

Authors
  1. Tavleen Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bai-Chuang Shyu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bai-Chuang Shyu .

Editor information

Editors and Affiliations

  1. Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Bai-Chuang Shyu

  2. Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Aichi, Japan

    Makoto Tominaga

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kaur, T., Shyu, BC. (2018). Melatonin: A New-Generation Therapy for Reducing Chronic Pain and Improving Sleep Disorder-Related Pain. In: Shyu, BC., Tominaga, M. (eds) Advances in Pain Research: Mechanisms and Modulation of Chronic Pain. Advances in Experimental Medicine and Biology, vol 1099. Springer, Singapore. https://doi.org/10.1007/978-981-13-1756-9_19

Download citation

Publish with us

Policies and ethics

Search

Navigation