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      Melatonin in Chronic Pain Syndromes

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          Abstract

          Melatonin is a neurohormone secreted by epiphysis and extrapineal structures. It performs several functions including chronobiotic, antioxidant, oncostatic, immune modulating, normothermal, and anxiolytic functions. Melatonin affects the cardiovascular system and gastrointestinal tract, participates in reproduction and metabolism, and body mass regulation. Moreover, recent studies have demonstrated melatonin efficacy in relation to pain syndromes. The present paper reviews the studies on melatonin use in fibromyalgia, headaches, irritable bowel syndrome, chronic back pain, and rheumatoid arthritis. The paper discusses the possible mechanisms of melatonin analgesic properties. On one hand, circadian rhythms normalization results in sleep improvement, which is inevitably disordered in chronic pain syndromes, and activation of melatonin adaptive capabilities. On the other hand, there is evidence of melatonin-independent analgesic effect involving melatonin receptors and several neurotransmitter systems.

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          Most cited references41

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          MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective.

          Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein-coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents.
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            Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies.

            Melatonin is an endogenous indoleamine, produced mainly by the pineal gland. Melatonin has been proven to have chronobiotic, antioxidant, antihypertensive, anxiolytic and sedative properties. There are also experimental and clinical data supporting an analgesic role of melatonin. In experimental studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid μ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby may reduce anxiety, which leads to lower levels of pain. In this paper, we review the current evidence regarding the analgesic properties of melatonin in animals and humans with chronic pain. © 2011 John Wiley & Sons A/S.
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              How rod, cone, and melanopsin photoreceptors come together to enlighten the mammalian circadian clock.

              In mammals, a small number of retinal ganglion cells express melanopsin, an opsin photopigment, allowing them to be directly photoreceptive. A major function of these so-called intrinsically photosensitive retinal ganglion cells (ipRGCs) is to synchronize (entrain) endogenous circadian clocks to the external light:dark cycle. Thanks to their intrinsic light response, ipRGCs can support photoentrainment even when the other retinal photoreceptors (rods and cones) are absent or inactive. However, in the intact retina the ipRGC light response is a composite of extrinsic (rod/cone) and intrinsic (melanopsin) influences. As a result all three photoreceptor classes contribute to the retinal pathways providing light information to the clock. Here, we consider what each photoreceptor type contributes to the clock light response. We review electrophysiological and behavioral data pertinent to this question, primarily from laboratory rodents, drawing them together to provide a conceptual model in which each photoreceptor class plays a distinct role in encoding the light environment. We finally use this model to highlight some of the important outstanding questions in this field. Copyright © 2012 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                andreidanilov@mail.ru
                Journal
                Pain Ther
                Pain Ther
                Pain and Therapy
                Springer Healthcare (Cheshire )
                2193-8237
                2193-651X
                16 March 2016
                16 March 2016
                June 2016
                : 5
                : 1
                : 1-17
                Affiliations
                Department of Neurology, Postdegree Training Institute, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
                Article
                49
                10.1007/s40122-016-0049-y
                4912970
                26984272
                1d098b17-bf6f-4b32-ae39-c2bbe35de958
                © The Author(s) 2016
                History
                : 27 November 2015
                Categories
                Review
                Custom metadata
                © Springer Healthcare 2016

                chronic pain,fibromyalgia,headache,irritable bowel syndrome,low back pain,melatonin,migraine,rheumatoid arthritis

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