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      Role of Principal Ionotropic and Metabotropic Receptors in Visceral Pain

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          Abstract

          Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. It also leads to a significant economic burden due to workdays lost and reduced productivity. Further, long-term use of non-specific medications is also associated with side effects affecting the quality of life. Despite years of extensive research and the availability of several therapeutic options, management of patients with chronic visceral pain is often inadequate, resulting in frustration for both patients and physicians. This is, most likely, because the mechanisms associated with chronic visceral pain are different from those of acute pain. Accumulating evidence from years of research implicates several receptors and ion channels in the induction and maintenance of central and peripheral sensitization during chronic pain states. Understanding the specific role of these receptors will facilitate to capitalize on their unique properties to augment the therapeutic efficacy while at the same time minimizing unwanted side effects. The aim of this review is to provide a concise review of the recent literature that reports on the role of principal ionotropic receptors and metabotropic receptors in the modulation visceral pain. We also include an overview of the possibility of these receptors as potential new targets for the treatment of chronic visceral pain conditions.

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          Most cited references102

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          Metabotropic glutamate receptors: physiology, pharmacology, and disease.

          The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that participate in the modulation of synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signaling partners. A great deal of progress has been made in determining the mechanisms by which mGluRs are activated, proteins with which they interact, and orthosteric and allosteric ligands that can modulate receptor activity. The widespread expression of mGluRs makes these receptors particularly attractive drug targets, and recent studies continue to validate the therapeutic utility of mGluR ligands in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia.
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              Pharmacology and functions of metabotropic glutamate receptors.

              P Conn, J P Pin (1997)
              In the mid to late 1980s, studies were published that provided the first evidence for the existence of glutamate receptors that are not ligand-gated cation channels but are coupled to effector systems through GTP-binding proteins. Since those initial reports, tremendous progress has been made in characterizing these metabotropic glutamate receptors (mGluRs), including cloning and characterization of cDNA that encodes a family of eight mGluR subtypes, several of which have multiple splice variants. Also, tremendous progress has been made in developing new highly selective mGluR agonists and antagonists and toward determining the physiologic roles of the mGluRs in mammalian brain. These findings have exciting implications for drug development and suggest that the mGluRs provide a novel target for development of therepeutic agents that could have a significant impact on neuropharmacology.
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                Author and article information

                Journal
                J Neurogastroenterol Motil
                J Neurogastroenterol Motil
                Journal of Neurogastroenterology and Motility
                Korean Society of Neurogastroenterology and Motility
                2093-0879
                2093-0887
                April 2015
                : 21
                : 2
                : 147-158
                Affiliations
                Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
                Author notes
                [* ]Correspondence: Jyoti N Sengupta, PhD, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA Tel: +1-414-456-4011, Fax: +1-414-456-6361, E-mail: sengupta@ 123456mcw.edu
                Article
                jnm-21-147
                10.5056/jnm15026
                4398235
                25843070
                06d996dc-febf-4bb3-815a-f1bd070e71e8
                © 2015 The Korean Society of Neurogastroenterology and Motility

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 February 2015
                : 24 February 2015
                : 26 March 2015
                Categories
                Special Review

                Neurology
                ligand-gated ion channels,receptors, metabotropic glutamate,visceral pain
                Neurology
                ligand-gated ion channels, receptors, metabotropic glutamate, visceral pain

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