Rol de los receptores nicotínicos de acetilcolina en mecanismos de dolor
Rol de los receptores nicotínicos de acetilcolina en mecanismos de dolor
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Introducción: los receptores nicotínicos de acetilcolina (nAChR) en el estudio y entendimiento del dolor se han evaluado ampliamente en las últimas dos décadas. Se consideran piezas importantes para el desarrollo de analgésicos.
Objetivo: identificar conceptos y avances acerca de los nAChR y su papel en la modulación del dolor.
Metodología: se realizó búsqueda en PubMed, MEDLINE, ScienceDirect, Scielo, OvidSP, EBSCOhost y en la Biblioteca Cochrane (incluyendo la base de datos Cochrane de revisiones sistemáticas y Cochrane controlled trials register). También en las plataformas de las Revistas JAMA, Lancet, New England Journal of Medicine y Anesthesiology. Las
búsquedas se limitaron a los idiomas inglés y español, así como documentos publicados entre 1970 y 2015.
Resultados: los nAChR son canales iónicos transmisores que constan de diferentes subtipos, cada uno de los cuales tiene una farmacología y fisiología específica, con diferente distribución anatómica en el cerebro. No se limitan solo a sitios postsinápticos, también se localizan a nivel pre, peri y extrasinápticos donde pueden modular la función neuronal por una variedad de acciones. Los nAChR neuronales difieren de los nAChR periféricos, ya que no tienen las subunidades γ, δ, ε o, en su confección y constan de varios complementos de α2–α9 y subunidades β2–β4. Actualmente, seis α (α2-α7) y tres β (β2-β4) subunidades se han identificado y clonado a partir de cerebro humano. Los nAChRs son interesantes para develar los mecanismos inherentes al dolor y desarrollar nuevos analgésicos. Los ligandos a nAChR α4β2 siguen siendo la estrategia más atractiva para explicar el dolor neuropático e inflamatorio. Subunidades nicotínicas α5 reducen los estados de dolor e inflamación sobre todo neuropática. La activación central y periférica del nAChR α7, reduce la nocicepción y el dolor inflamatorio agudo.
Conclusión: se observan avances en el conocimiento de los nAChR en los mecanismos del dolor. Amplios estudios se realizan a nivel preclínico para desarrollar nuevas estrategias terapéuticas y antiinflamatorias. Rev.cienc.biomed. 2015;6(1):118-129
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Umana I, Daniele C, McGehee D. Neuronal nicotinic receptors as analgesic targets: It’s a winding road. Biochemical Pharmacology. 2013;86:1208-14.
Brandt D. The cigarette century: the rise, fall and deadly persistence of the product that defined America. J of Popular Culture. 2008;(41)5:893-4.
Corti C. A history of smoking. London: George C. Harrap. 2007.
Hurts R, Rollema H, Bertrand D. Nicotinic acetylcholine receptors: From basic science to therapeutics. Pharmacology & Therapeutics 2013;137(2):22-54.
Davis L, Pollock LJ, Stone T. Visceral pain. Surgery Gynecology and Obstetrics 1932;55(2):418-27.
Criado M. El receptor nicotínico de acetilcolina. Instituto de Neurociencias, Sant Joan d’Alacant, Alicante, España. 2011.
Flores M, Segura J. Estructura y función de los receptores acetilcolina de tipo muscarínico y nicotínico. Rev Mex Neuroci 2005;6(4):315-26.
Díaz M, Gualix J, Gómez R, Castro R, Pintor J, Miras Portugal MT. Receptores nicotínicos neurales: interacción con receptores purinérgicos. Anal Real Acad Farm. 2000; 66(1):1-21.
Devillers-Thiéry A, Galzi JL, Eiselé JL, Bertrand S, Changeux JP. Functional architecture of the nicotinic acetylcholine receptor: a prototype of ligand-gated ion channels. J. Membr. Biol. 1993;136:97-112.
Karlin, A. and Akabas, M. H. Toward a structural basis for the function of nicolinic acetylcholine receptors and their cousins. Neuron. 1995;15:1231-44.
Paterson D, Nordberg A. Neuronal nicotinic receptors in the human brain. Progress in Neurobiology. 2000;61:75-111. Gotti C, Fornasari D, Clementi F. Human neuronal nicotinic receptors. Prog Neurobiol. 1997;53:199-37.
Sargent PB. The diversity of neuronal nicotinic acetylcholine receptors. Annu. Rev. Neurosci. 1993;16:403-43.
Elgoyhen A B, Johnson DS, Boulter J, Vetter DE, Heinemann S. α9: An acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell. 1994;79:705-15.
Galzi JL, Changeux JP. Neuronal nicotinic receptors: molecular organization and regulations. Neuropharmacology.1995;34:563-82.
Luetje CW, PatrJck J. Both OE- and /J-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors. J Neurosci. 1991;11: 837-45.
Levin ED, Simon BB. Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology. 1998;138:217-30.
Cartaud J, Benedetti E.L, Cohen J.B, Meunier J.C, Changeux J.P. Presence of a lattice structure in membrane fragments rich in nicotinic receptor protein from the electric
organ of Torpedo marmorata. FEBS Lett. 1973;33:109-13.
Sargent P.B. The diversity of neuronal nicotinic acetylcholine receptors. Annu Rev Neurosci. 1993;16:403-43.
Hogg RC, Bertrand D. Partial agonists as therapeutic agents at neuronal nicotinic acetylcholine receptors. Biochem Pharmacol. 2007;73:459-68.
Iwamoto ET. Characterization of the antinociception induced by nicotine in the pedunculopontine tegmental nucleus and the nucleus raphe magnus. J Pharmacol Exp Ther. 1991;257:120-33.
Conroy WG, Vernallis AB, Berg DK. The alpha 5 gene product assembles with multiple acetylcholine receptor subunits to form distinctive receptor subtypes in brain. Neuron. 1992;9:679-91.
Couturier S, Bertrand D, Matter J.M, Hernandez M.C, Bertrand S, Millar N, Valera S, Barkas T, Ballivet M. A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX. Neuron. 1990;5:847-56.
Ballantyne JC, Shin NS. Efficacy of opioids for chronic pain: a review of the evidence. Clinical J of Pain. 2008;24:469-78.
Hamann SR, Martin WR. Opioid and nicotinic analgesic and hyperalgesic loci in the rat brain stem. J of Pharmacology and Experimental Therapeutics. 1992; 261:707-15.
Sahley TL, Berntson GG. Antinociceptive effects of central and systemic administrations of nicotine in the rat. Psychopharmacology. 1979;65:279-83.
Fertig JB, Pomerleau OF, Sanders B. Nicotine-produced antinociception in minimally deprived smokers and ex-smokers. Addictive Behaviors. 1986;11: 239-48.
Henningfield JE, Miyasato K, Jasinski DR. Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine. J of Pharmacology and Experimental
Therapeutics. 1985;234:1-12.
Kottke TE, Brekke ML, Solberg LI, Hughes JR. A randomized trial to increase smoking intervention by physicians. Doctors helping smokers, Round I. JAMA 1989;261:2101-6.
Cepeda-Benito A, Reynoso J, McDaniel EH. Associative tolerance to nicotine analgesia in the rat: tail-flick and hot-plate tests. Experimental and Clinical Psychopharmacology.
; 6(2):248-54.
Hogg R.C, Raggenbass M, Bertrand D. Nicotinic acetylcholine receptors: from structure to brain function. Rev. Physiol. Biochem. Pharmacol. 2003;147:1-46.
Marubio L.M, del Mar Arroyo-Jimenez M, Cordero-Erausquin M, Léna C, Le Novère N, de Kerchove d’Exaerde A, Huchet M, Damaj M.I, Changeux J.P. Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature. 1999;398(5):805-10.
Damaj MI, Fonck C, Marks MJ, Deshpande P, Labarca C, Lester HA, Collins AC, Martin BR. Genetic approaches identify differential roles for α4β2 nicotinic receptors in acute models of antinoniception in mice. J. Pharmacol Exp Ther. 2007;321:1161-9.
Shi Y, Weingarten TN, Mantilla CB, Hooten WM, Warner DO. Smoking and pain: pathophysiology and clinical implications. Anesthesiology 2010;113:977-92.
Sher E, Chen Y, Sharples TJ, Broad LM, Benedetti G, Zwart R, McPhie GI, Pearson KH, Baldwinson T, De Filippi G. Physiological roles of neuronal nicotinic receptor subtypes:
new insights on the nicotinic modulation of neurotransmitter release, synaptic transmission and plasticity. Curr Top Med. Chem. 2004;4:283-97.
Nigori R, Jayarajan P, Abraham R, Shanmuganathan D, Rasheed M, Royapalley P, Goura V. Antinociceptive activity of α4β2* neuronal nicotinic receptor agonist A-366833 in experimental models of neuropathic and inflammatory pain. European J of Pharmacology. 2011;668:155-62
Kesingland AC, Gentry CT, Panesar MS, Bowes MA, Vernier JM, Cube R, Walker K, Urban L. Analgesic profile of the nicotinic acetylcholine receptor agonists, (+)- epibatidine and ABT-594 in models of persistent inflammatory and neuropathic pain. Pain. 2000;86:113-
Lynch JJ, Wade CL, Mikusa JP, Decker MW, Honore P. ABT-594 (a nicotinic acetylcholine agonist): antiallodynia in a rat chemotherapy-induced pain model. European J Pharmacol. 2005;509:43-8.
Galindo L, Hernández S, Galarraga E, Tapia D, Bargas J, Garduño J, Frías C, Drucker R, Mihailescu S. Serotoninergic dorsal raphe neurons possess functional postsynaptic nicotinic acetylcholine receptors. Synapse. 2008;62: 601-15.
Nakamura M, Jang S. Presynaptic nicotinic acetylcholine receptors enhance GABAergic synaptic transmission in rat periaqueductal gray neurons. European J of Pharmacology.
:640:178-84.
Bitner R.S, Nikkel A.L, Curzon P, Donnelly-Roberts D.L, Puttfarcken P.S, Namovic M, Jacobs I.C, Meyer M.D, Decker M.W. Reduced nicotinic receptor-mediated antinociception
following in vivo antisense knock-down in rat. Brain Res. 2000;871:66-74.
Cucchiaro G, Chaijale N, Commons K.G. The dorsal raphe nucleus as a site of action of the antinociceptive and behavioral effects of the α4 nicotinic receptor agonist epibatidine. J Pharmacol Exp Ther. 2005;313:389-94.
Rashid MH, Furue H, Yoshimura M, Ueda H. Tonic inhibitory role of alpha 4 beta 2 subtype of nicotinic acetylcholine receptors on nociceptive transmission in the spinal cord in mice. Pain. 2006;125:125-35.
Li X, Eisenach JC. Nicotinic acetylcholine receptor regulation of spinal norepinephrine release. Anesthesiology. 2002;96:1450-56.
Genzen R, McGehee D.S. Nicotinic modulation of GABAergic synaptic transmission in the spinal cord dorsal horn. Brain Res. 2005;1031:229-37.
Matsunaga K, Klein TW, Friedman H, Yamamoto Y. Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection bynicotine. J Immunol. 2001;167:6518- 24.
Hosur V, Leppanen S, Abutaha A, Loring R.H. Gene regulation of α4β2 nicotinic receptors: microarray analysis of nicotine-induced receptor up-regulation and anti-inflammatory effects. J Neurochem. 2009;111:848-58.
Heinemann S, Boulter J, Deneris E, Conolly J, Duvoisin R, Papke R. The brain nicotinic acetylcholine receptor gene family. Prog Brain Res. 1990;86:195-203.
Vincler M.A, Eisenach J.C. Immunocytochemical localization of the alpha3, alpha4, alpha5, alpha7, beta2, beta3 and beta4 nicotinic acetylcholine receptor subunits in the locus coeruleus of the rat. Brain Res. 2003;974:25-36.
De Biasi M. Nicotinic receptor mutant mice in the study of autonomic function. Curr. Drug Targets CNS Neurol. Disord. 2002;1:331-36.
Ramirez-Latorre J, Yu C.R, Qu X, Perin F, Karlin A, Role L. Functional contributions of alpha5 subunit to neuronal acetylcholine receptor channels. Nature. 1996;380:347-51.
Tapia L, Kuryatov A, Lindstrom J. Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors. Mol.
Pharmacol. 2007;71:769-76.
Bagdas D, AlSharari S, Freitas K, Tracy M, Imad Damaj M. The role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain. Biochemical Pharmacology. 2015. doi: 10.1016/j.bcp.2015.04.013.
Salas R, Orr-Urtreger A, Broide R.S, Beaudet A, Paylor R, De Biasi M. The nicotinic acetylcholine receptor subunit alpha 5 mediates short-term effects of nicotine in vivo. Mol.
Pharmacol. 2003;63:1059-66.
Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, et al. Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. Journal of Pharmacology and Experimental Therapeutics. 2010;334:137-46.
Salas R, Sturm R, Boulter J, De Biasi M. Nicotinic receptors in the habenulointerpeduncular system are necessary for nicotine withdrawal in mice. J. Neurosci. 2009;29:3014-18.
Wang N, Orr-Urtreger A, Chapman J, Rabinowitz R, Nachman R, Korczyn A.D. Autonomic function in mice lacking alpha5 neuronal nicotinic acetylcholine receptor subunit. J. Physiol. 2002;542:347-54.
Vincler M, Eisenach J.C. Plasticity of spinal nicotinic acetylcholine receptors following spinal nerve ligation. Neurosci. Res. 2004;48:139-45.
Lukas R.J, Changeux J.P, Le Nove` re N, Albuquerque E.X, Balfour D.J, Berg D.K, et al. International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits. Pharmacol Rev. 1999;51:397-401.
Shen JX, Yakel JL. Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system. Acta Pharmacol Sin. 2009;30(6):673-80.
Feuerbach D, Lingenhoehl K, Olpe H.R, Vassout A, Gentsch C, Chaperon F, Nozulak J, Enz A, Bilbe G, McAllister K, Hoyer D. The selective nicotinic acetylcholine receptor alpha7 agonist JN403 is active in animal models of cognition, sensory gating, epilepsy and pain. Neuropharmacology. 2009;56:254-63.
Kiguchi , Kobayashi Y, Maeda T, Tominaga S, Nakamura J, Fukazawa Y, Ozaki M, Kishioka S. Activation of nicotinic acetylcholine receptors on bone marrow-derived cells relieves neuropathic pain accompanied by peripheral neuroinflammation. Neurochem Int. 2012;61:1212-19.
Westman M, Saha S, Morshed M, Lampa J. Lack of acetylcholine nicotine alpha 7 receptor suppresses development of collagen-induced arthritis and adaptive immunity. Clin Exp Immunol. 2010;162:62-7.
Fujiwara N, Kobayashi K. Macrophages in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:281-86.
Ulloa L. The vagus nerve and the nicotinic anti-inflammatory pathway. Nat Rev Drug Discov. 2005;4:673-84.
De Rosa MJ, Dionisio L, Agriello E, Bouzat C, Esandi MC. Alpha 7 nicotinic acetylcholine receptor modulates lymphocyte activation. Life Sci. 2009;85:444-49.
Thomsen MS, Hansen HH, Timmerman DB, Mikkelsen JD. Cognitive improvement by activation of a7 nicotinic acetylcholine receptors: from animal models to human pathophysiology. Curr Pharm Des. 2010;16:323-43.
Rowley TJ, McKinstry A, Greenidge E, Smith W, Flood P. Antinociceptive and anti-inflammatory effects of choline in a mouse model of postoperative pain. Br J Anaesth.
;105(2):201-7.
Munro G, Hansen R, Erichsen H, Timmermann D, Christensen J, Hansen H. The alpha7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat. Br J Pharmacol. 2012;167:421-35.
Medhurst S.J, Hatcher J.P, Hille C.J, Bingham S, Clayton N.M, Billinton A, Chessell I.P. Activation of the alpha7-nicotinic acetylcholine receptor reverses complete freund adjuvant-induced mechanical hyperalgesia in the rat via a central site of action. J Pain. 2008;9:580-87.
Xiao HS, Huang QH, Zhang FX, Bao L, Lu YJ, Guo C, Yang L, Huang WJ, Fu G, Xu S.H, et al. Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sc. 2002:12;8360-65.
Gurun MS, Parker R, Eisenach JC, Vincler M. The effect of peripherally administered CDPcholine in an acute inflammatory pain model: the role of alpha7 nicotinic acetylcholine receptor. Anesth Analg. 2009:108;1680-87.
Freitas K, Ghosh S, Ivy Carroll F, Lichtman A, Damaj M. Effects of alpha 7 positive allosteric modulators in murine inflammatory and chronic neuropathic pain models. Neuropharmacology. 2013;65:156-64.
Bertrand D, Gopalakrishnan M. Allosteric modulation of nicotinic acetylcholine receptors. Biochemical Pharmacology. 2007;74:1155-63.
Faghih R, Gfesser G.A, Gopalakrishnan M. Advances in the discovery of novel positive allosteric modulators of the alpha7 nicotinic acetylcholine receptor. Recent Pat CNS Drug Discov. 2007;2:99-106.
Faghih R, Gopalakrishnan M, Briggs C.A. Allosteric modulators of the alpha7 nicotinic acetylcholine receptor. J Med Chem. 2008;51:701-12.
Timmermann DB, Grønlien JH, Kohlhaas KL, Nielsen EØ, Dam E, Jørgensen TD. et al. An allosteric modulator of the a 7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther. 2007;323:294-307.
Grønlien JH, Håkerud M, Ween H, Thorin-hagene K, Briggs C.A, Gopalakrishnan M, Malysz J. Distinct profiles of a7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes. Mol Pharmacol. 2007;72:715-24.
Freitas K, Negus SS, Carroll FI, Damaj MI. In vivo pharmacological interactions between a type II positive allosteric modulator of a7 nicotinic ACh receptors and nicotinic agonists in a murine tonic pain model. British J of Pharmacology. 2013;169:567-79.
Gao YJ and Ji RR. Chemokines, neuronal-glial interactions, and central processing of neuropathic
pain. Pharmacol Ther. 2010;26:56-68.
Zhang W, Liu Y, Hou B, Gu X, Ma Z. Activation of spinal alpha-7 nicotinic acetylcholine receptor attenuates remifentanil-induced postoperative hiperalgesia. Int J Clin Exp Med. 2015;8(2):1871-
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