Analgesic, anxiolytic and anaesthetic effects of melatonin: New potential uses in pediatrics

International Journal of Molecular Sciences

Volumn 16, Issue 1, 2015, Pages 1209-1220

  Marseglia, Lucia ^a   D’Angelo, Gabriella ^a   Manti, Sara ^a   Aversa, Salvatore ^a   Arrigo, Teresa ^a   Reiter, Russel J ^b   Gitto, Eloisa ^a  

^a UNIVERSITY OF MESSINA   (Italy)

^b University of Texas Health Science Center   (United States)

Author keywords

Anaesthesia; Anxiety; Children; Melatonin; Pain; Premedication

Indexed keywords

ANESTHETIC AGENT; FENTANYL; MELATONIN; MELATONIN RECEPTOR; MIDAZOLAM; 4 AMINOBUTYRIC ACID; ANALGESIC AGENT; ANXIOLYTIC AGENT;

ANALGESIC ACTIVITY; ANXIETY; ARTICLE; CIRCADIAN RHYTHM; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; ELECTROENCEPHALOGRAPHY; HUMAN; INFLAMMATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PAIN; PREMEDICATION; PROTEIN EXPRESSION; SEDATION; SLEEP QUALITY; SYSTEMATIC REVIEW (TOPIC); TRANQUILIZING ACTIVITY; ANXIETY DISORDERS; BRAIN DISEASES; CHILD; METABOLISM;

ANALGESICS; ANESTHETICS, GENERAL; ANTI-ANXIETY AGENTS; ANXIETY DISORDERS; BRAIN DISEASES; CHILD; ELECTROENCEPHALOGRAPHY; GAMMA-AMINOBUTYRIC ACID; HUMANS; MAGNETIC RESONANCE IMAGING; MELATONIN; PAIN;

EID: 84920528717     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms16011209     Document Type: Article

References (78)

1. Gitto, E.; Marseglia, L.; Manti, S.; D’Angelo, G.; Barberi, I.; Salpietro, C.; Reiter, R.J. Protective role of melatonin in neonatal diseases. Oxid. Med. Cell. Longev. 2013, doi:10.1155/2013/980374.
2. Ross, C.; Davies, P.; Whitehouse, W. Melatonin treatment for sleep disorders in children with neurodevelopmental disorders: An observational study. Dev. Med. Child Neurol. 2002, 44, 339-344.
3. Hardeland, R.; Poeggeler, B. Melatonin beyond its classical functions. Open Physiol. J. 2008, 1, 1-23.
4. Golombek, D.A.; Escolar, E.; Burin, L.J.; de Brito Sánchez, M.G.; Fernández Duque, D.; Cardinali, D.P. Chronopharmacology of melatonin: Inhibition by benzodiazepine antagonism. Chronobiol. Int. 1992, 9, 124-131.
5. Golombek, D.A.; Pévet, P.; Cardinali, D.P. Melatonin effects on behavior: Possible mediation by the central GABAergic system. Neurosci. Biobehav. Rev. 1996, 20, 403-412.
6. Muñoz-Hoyos, A.; Sánchez-Forte, M.; Molina-Carballo, A.; Escames, G.; Martin-Medina, E.; Reiter, R.J.; Molina-Font, J.A.; Acuña-Castroviejo, D. Melatonin’s role as an anticonvulsant and neuronal protector: Experimental and clinical evidence. J. Child Neurol. 1998, 13, 501-509.
7. Molina-Carballo, A.; Muñoz-Hoyos, A.; Sánchez-Forte, M.; Uberos-Fernández, J.; Moreno-Madrid, F.; Acuña-Castroviejo, D. Melatonin increases following convulsive seizures may be related to its anticonvulsant properties at physiological concentrations. Neuropediatrics 2007, 38, 122-125.
8. Solmaz, I.; Gürkanlar, D.; Gökçil, Z.; Göksoy, C.; Ozkan, M.; Erdoğan, E. Antiepileptic activity of melatonin in guinea pigs with pentylenetetrazol-induced seizures. Neurology 2009, 31, 989-995
9. Cardinali, D.P.; Pandi-Perumal, S.R.; Niles, L.P. Melatonin and its receptors: Biological function in circadian sleep-wake regulation. In Neurochemistry of Sleep and Wakefulness; Monti, J.M., Pandi-Perumal, S.R., Sinton, C.M., Eds.; Cambridge University Press: Cambridge, UK, 2008; pp. 283-314.
10. Shavali, S.; Ho, B.; Govitrapong, P.; Ajjimaporn, A.; Klongpanichapak, S.; Ebadi M. 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. 2005, 64, 471-479.
11. Ebadi, M.; Govitrapong, P.; Phansuwan-Pujito, P.; Nelson, F.; Reiter, R.J. Pineal opioid receptors and analgesic action of melatonin. J. Pineal Res. 1998, 24, 193-200.
12. Citera, G.; Arias, M.A.; Maldonado-Cocco, J.A.; Lázaro, M.A.; Rosemffet, M.G.; Brusco, L.I.; Scheines, E.J.; Cardinalli, D.P. The effect of melatonin in patients with fibromyalgia: A pilot study. Clin. Rheumatol. 2000, 19, 9-13.
13. Mozaffari, S.; Rahimi, R.; Abdollahi, M. Implications of melatonin therapy in irritable bowel syndrome: A systematic review. Curr. Pharm. Des. 2010, 16, 3646-3655.
14. Peres, M.F.; Zukerman, E.; Cunha Tanuri, F.; Moreira, F.R.; Cipolla-Neto, J. Melatonin 3 mg is effective for migraine prevention. Neurology 2004, 63, 757.
15. Naguib, M.; Gottumukkala, V.; Goldstein, P.A. Melatonin and anesthesia: A clinical perspective. J. Pineal Res. 2007, 42, 12-21.
16. Reiter, R.J. Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocr. Rev. 1991, 12, 151-180.
17. Gordon, N. The therapeutics of melatonin: A paediatric perspective. Brain Dev. 2000, 22, 213-217.
18. Herxheimer, A. Does melatonin help people sleep? Br. Med. J. 2006, 332, 373-374.
19. Merskey, H.; Albe-Fessard, D.G.; Bonica, J.J. International association for the study of pain: Pain terms: A list with definitions and notes on usage. Pain 1979, 6, 249-252.
20. Anand, K.J. Clinical importance of pain and stress in preterm neonates. Biol. Neonate 1998, 73, 1-9.
21. Fitzgerald, M.; Millard, C.; MacIntosh, N. Hyperalgesia in premature infants. Lancet 1988, 1, 292.
22. Carbajal, R.; Chauvet, X.; Couderc, S.; Olivier-Martin, M. Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates. Br. Med. J. 1999, 319, 1393-1397.
23. Grunau, R.V.E. Long-term consequences of pain in human neonates. In Pain in Neonates, 3rd ed.; Anand, J.K.S., Stevens, B.J., McGrath, P.J., Eds.; Elsevier: Amsterdam, The Netherlands, 2007; pp. 55-76.
24. Srinivasan, V.; Lauterbach, E.C.; Ho, K.Y.; Acuña-Castroviejo, D.; Zakaria, R.; Brzezinski, A. Melatonin in antinociception: Its therapeutic applications. Curr. Neuropharmacol. 2012, 10, 167-178.
25. Lakin, M.L.; Miller, C.H.; Stott, M.L.; Winters, W.D. Involvement of the pineal gland and melatonin in murine analgesia. Life Sci. 1981, 29, 2543-2551.
26. Odagaki, Y.; Nishi, N.; Koyama, T. Functional coupling of GABA(B) receptors with G proteins that are sensitive to N-ethylmaleimide treatment, suramin, and benzalkonium chloride in rat cerebral cortical membranes. J. Neural Transm. 2000, 107, 1101-1116.
27. Patel, S.; Naeem, S.; Kesingland, A.; Froestl, W.; Capogna, M.; Urban, L.; Fox, A. The effects of GABA(B) agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain 2001, 90, 217-226.
28. Wilhelmsen, M.; Amirian, I.; Reiter, R.J.; Rosenberg, J.; Gögenur, I. Analgesic effects of melatonin: A review of current evidence from experimental and clinical studies. J. Pineal Res. 2011, 51, 270-277.
29. Esposito, E.; Paterniti, I.; Mazzon, E.; Bramanti, P.; Cuzzocrea, S. Melatonin reduces hyperalgesia associated with inflammation. J. Pineal Res. 2010, 49, 321-331.
30. Morris, R.W.; Lutsch, E.F. Daily susceptibility rhythm to morphine analgesia. J. Pharm. Sci. 1969, 58, 374-376.
31. Bornschein, R.L.; Crockett, R.S.; Smith, R.P. Diurnal variations in the analgesic effectiveness of morphine in mice. Pharmacol. Biochem. Behav. 1977, 6, 621-626.
32. Crockett, R.S.; Bornschein, R.L.; Smith, R.P. Diurnal variation in response to thermal stimulation: Mouse-hotplate test. Physiol. Behav. 1977, 18, 193-196.
33. Pickard, G.E. Circadian rhythm of nociception in the golden hamster. Brain Res. 1987, 425, 395-400.
34. Christina, A.; Merlin, N.; Vijaya, C.; Jayaprakash, S.; Murugesh, N. Daily rhythm of nociception in rats. J. Circadian Rhythm. 2004, 25, 2.
35. Davis, G.C.; Buchsbaum, M.S.; Bunney, W.E., Jr. Naloxone decreases diurnal variation in pain sensitivity and somatosensory evoked potentials. Life Sci. 1978, 23, 1449-1459.
36. Henry, J. Circulating opioids: Possible physiological roles in central nervous function. Neurosci. Biobehav. Rev. 1982, 6, 229-245.
37. Lutsch, E.F.; Morris, R.W. Light reversal of a morphine-induced analgesia susceptibility rhythm in mice. Experientia 1971, 27, 420-421.
38. Rosenfeld, J.P.; Rice, P.E. Diurnal rhythms in nociceptive thresholds of rats. Physiol. Behav. 1979, 23, 419-420.
39. Bar-Or, A.; Brown, G.M. Pineal involvement in the diurnal rhythm of nociception in the rat. Life Sci. 1989, 44, 1067-1075.
40. John, T.M.; Brown, M.C.; Wideman, L.; Brown, G.M. Melatonin replacement nullifies the effect of light-induced functional pinealectomy on nociceptive rhythm in the rat. Physiol. Behav. 1994, 55, 735-739.
41. Gitto, E.; Aversa, S.; Salpietro, C.D.; Barberi, I.; Arrigo, T.; Trimarchi, G.; Reiter, R.J.; Pellegrino, S. Pain in neonatal intensive care: Role of melatonin as an analgesic antioxidant. J. Pineal Res. 2012, 52, 291-295.
42. Grachev, I.D.; Fredickson, B.E.; Apkarian, A.V. Dissociating anxiety from pain: Mapping the neuronal marker N-acetyl aspartate to perception distinguishes closely interrelated characteristics of chronic pain. Mol. Psychiatry 2001, 6, 256-260.
43. Ploghaus, A.; Narain, C.; Beckmann, C.F.; Clare, S.; Bantick, S.; Wise, R.; Matthews, P.M.; Rawlins, J.N.; Tracey, I. Exacerbation of pain by anxiety is associated with activity in a hippocampal network. J. Neurosci. 2001, 21, 9896-9903.
44. Basket, J.J.; Cockrem, J.F.; Todd, M.A. Melatonin levels in hospitalized elderly patients: A comparison with community based volunteers. Age Ageing 1991, 20, 430-434.
45. Tzischinsky, O.; Laive, P. Melatonin possesses time-dependent hypnotic effects. Sleep 1994, 17, 638-645.
46. Weaver, D.R.; Stehle, J.H.; Stopa, E.G.; Reppert, S.M. Melatonin receptors in human hypothalamus and pituitary: Implications for circadian and reproductive responses to melatonin. J. Clin. Endocrinol. Metab. 1993, 76, 295-301.
47. Golombek, D.A.; Martini, M.; Cardinali, D.P. Melatonin as an anxiolytic in rats: Time dependence and interaction with the central GABAergic system. Eur. J. Pharmacol. 1993, 237, 231-236.
48. Golus, P.; King, M.G. The effects of melatonin on open field behavior. Pharmacol. Biochem. Behav. 1981, 15, 883-885.
49. Papp, M.; Litwa, E.; Gruca, P.; Mocaër, E. Anxiolytic-like activity of agomelatine and melatonin in three animal models of anxiety. Behav. Pharmacol. 2006, 17, 9-18.
50. Wan, Q.; Man, H.Y.; Liu, F.; Braunton, J.; Niznik, H.B.; Pang, S.F.; Brown, G.M.; Wang, Y.T. Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors. Nat. Neurosci. 1999, 2, 401-403.
51. Naguib, M.; Samarkandi, A.H. The comparative dose-response effect of melatonin and midazolam for premedication of adult patients: A double-blinded placebo-controlled study. Anesth. Analg. 2000, 91, 473-479.
52. Samarkandi, A.; Naguib, M.; Riad, W.; Thalaj, A.; Alotibi, W.; Aldammas, F.; Albassam, A. Melatonin vs. midazolam premedication in children: A double-blind, placebo-controlled study. Eur. J. Anaesthesiol. 2005, 22, 189-196.
53. Kain, Z.N.; MacLaren, J.E.; Herrmann, L.; Mayes, L.; Rosenbaum, A.; Hata, J.; Lerman, J. Preoperative melatonin and its effects on induction and emergence in children undergoing anesthesia and surgery. Anesthesiology 2009, 111, 44-49.
54. Isik, B.; Baygin, O.; Bodur, H. Premedication with melatonin vs. midazolam in anxious children. Paediatr. Anaesth. 2008, 18, 635-641
55. McCann, M.; Kain, Z. Management of preoperative anxiety in children: An update. Anesth. Analg. 2001, 93, 98-105.
56. Acil, M.; Basgul, E.; Celiker, V.; Karagöz, A.H.; Demir, B.; Aypar, U. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Eur. J. Anaesthesiol. 2004, 21, 553-557.
57. Jarratt, J. Perioperative melatonin use. Anaesth. Intensive Care 2011, 39, 171-181.
58. Rudolph, U.; Antkowiak, B. Molecular and neuronal substrates for general anaesthetics. Nat. Rev. Neurosci. 2004, 5, 709-720.
59. Campagna, J.A.; Miller, K.W.; Forman, S.A. Mechanisms of actions of inhaled anesthetics. N. Engl. J. Med. 2003, 348, 2110-2124.
60. Coloma, F.M.; Niles, L.P. Melatonin enhancement of [3H]-γ-aminobutyric acid and [3H]muscimol binding in rat brain. Biochem. Pharmacol. 1988, 37, 1271-1274.
61. Wang, F.; Li, J.; Wu, C.; Yang, J.; Xu, F.; Zhao, Q. The GABAA receptor mediates the hypnotic activity of melatonin in rats. Pharmacol. Biochem. Behav. 2003, 74, 573-578.
62. Duranti, E.; Stankov, B.; Spadoni, G.; Duranti, A.; Lucini, V.; Capsoni, S.; Biella, G.; Fraschini, F. 2-Bromomelatonin: Synthesis and characterization of a potent melatonin agonist. Life Sci. 1992, 51, 479-485.
63. Naguib, M.; Baker, M.T.; Flood, P.; Trieu, V.; Tao, C. Melatonin and its analogs do not induce general anesthesia by potentiating the responsiveness of postsynaptic GABA receptors. Am. Soc. Anesthesiol. 2004, 101, A817.
64. Naguib, M.; Hammond, D.L.; Schmid, P.G., 3rd; Baker, M.T.; Cutkomp, J.; Queral, L.; Smith, T. Pharmacological effects of intravenous melatonin: Comparative studies with thiopental and propofol. Br. J. Anaesth. 2003, 90, 504-507.
65. Schmidt, C.M.; Knief, A.; Deuster, D.; Matulat, P.; am Zehnhoff-Dinnesen, A.G. Melatonin is a useful alternative to sedation in children undergoing brainstem audiometry with an age dependent success rate—A field report of 250 investigations. Neuropediatrics 2007, 38, 2-4.
66. Sury, M.R.J.; Hatch, D.J.; Deeley, T.; Dicks-Mireaux, C.; Chong, W.K. Development of a nurse-led sedation service for paediatric magnetic resonance imaging. Lancet 1999, 353, 1667-1671.
67. Wassmer, E.; Fogarty, M.; Page, A.; Johnson, K.; Quin, E.; Seri, S.; Whitehouse, W. Melatonin as a sedation substitute for diagnostic procedures: MRI and EEG. Dev. Med. Child Neurol. 2001, 43, 136.
68. Johnson, K.; Page, A.; Williams, H.; Wassemer, E.; Whitehouse, W. The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination. Clin. Radiol. 2002, 57, 502-506.
69. Sury, M.R.; Fairweather, K. The effect of melatonin on sedation of children undergoing magnetic resonance imaging. Br. J. Anaesth. 2006, 97, 220-225.
70. Wassmer, E.; Quinn, E.; Seri, S.; Whitehouse, W. The acceptability of sleep deprived electroencephalograms. Seizure 1999, 8, 434-435.
71. Wassmer, E.; Quinn, E.; Whitehouse, W.; Johnson, K.; Quin, E.; Seri, S.; Whitehouse, W. Melatonin as a sleep inductor for electroencephalogram recordings in children. Clin. Neurophysiol. 2001, 112, 683-685.
72. Ashrafi, M.R.; Mohammadi, M.; Tafarroji, J.; Shabanian, R.; Salamati, P.; Zamani, G.R. Melatonin vs. chloral hydrate for recording sleep EEG. Eur. J. Paediatr. Neurol. 2010, 4, 235-238.
73. Naguib, M.; Samarkandi, A.H.; Moniem, M.A.; Mansour, Eel-D.; Alshaer, A.A.; Al-Ayyaf, H.A.; Fadin, A.; Alharby, S.W. The effects of melatonin premedication on propofol and thiopental induction dose-response curves: A prospective, randomized, double-blind study. Anesth. Analg. 2006, 103, 1448-1452.
74. Carr, R.; Wasdell, M.B.; Hamilton, D.; Weiss, M.D.; Freeman, R.D.; Tai, J.; Rietveld, W.J.; Jan, J.E. Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders. J. Pineal Res. 2007, 43, 351-359.
75. Seabra, M.L.; Bignotto, M.; Pinto, L.R., Jr.; Tufik, S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J. Pineal Res. 2000, 29, 193-200.
76. Pévet, P. The internal time-giver role of melatonin: A key for our health. Rev. Neurol. (Paris) 2014, 170, 646-652.
77. Fallah, R.; Shoroki, F.F.; Ferdosian, F. Safety and Efficacy of melatonin in pediatric migraine prophylaxis. Curr. Drug Saf. 2014, in press.
78. Al-Omary, F.A. Melatonin: Comprehensive profile. Profiles Drug Subst. Excip. Relat. Methodol. 2013, 38, 159-226.