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https://www.readbyqxmd.com/read/28199203/neurogenetics-of-acute-and-chronic-opiate-opioid-abstinence-treating-symptoms-and-the-cause
#1
Kenneth Blum, Mark S Gold, William Jacobs, William Vaughn McCall, Marcelo Febo, David Baron, Kristina Dushaj, Zsolt Demetrovics, Rajendra D Badgaiyan
This review begins with a comprehensive history of opioid dependence and treatment in the United States. The focus is an evidence-based treatment model for opioid/opiate dependent individuals. The role of reward genetic polymorphisms and the epigenetic modifications that lead to vulnerability to use and misuse of opiates/opioid to treat pain are reviewed. The neurochemical mechanisms of acute opiate withdrawal and opiate/opioid reward mechanisms are explored with a goal of identifying specific treatment targets...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28188737/genetic-variation-in-the-behavioral-effects-of-buprenorphine-in-female-mice-derived-from-a-murine-model-of-the-oprm1-a118g-polymorphism
#2
Caroline A Browne, Rebecca L Erickson, Julie A Blendy, Irwin Lucki
Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain...
February 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28185645/mu-opioid-receptors-in-gamma-aminobutyric-acidergic-forebrain-neurons-moderate-motivation-for-heroin-and-palatable-food
#3
Pauline Charbogne, Olivier Gardon, Elena Martín-García, Helen L Keyworth, Aya Matsui, Anna E Mechling, Thomas Bienert, Taufiq Nasseef, Anne Robé, Luc Moquin, Emmanuel Darcq, Sami Ben Hamida, Patricia Robledo, Audrey Matifas, Katia Befort, Claire Gavériaux-Ruff, Laura-Adela Harsan, Dominik von Elverfeldt, Jurgen Hennig, Alain Gratton, Ian Kitchen, Alexis Bailey, Veronica A Alvarez, Rafael Maldonado, Brigitte L Kieffer
BACKGROUND: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. METHODS: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons...
December 26, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28179809/sex-in-the-brain-hormones-and-sex-differences
#4
Jordan Marrocco, Bruce S McEwen
Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions...
December 2016: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28174137/reward-loss-and-addiction-opportunities-for-cross-pollination
#5
REVIEW
Leonardo A Ortega, José L Solano, Carmen Torres, Mauricio R Papini
Paradigms used to study the response to and consequences of exposure to reward loss have been underutilized in approaches to the psychobiology of substance use disorders. We propose here that bringing these two areas into contact will help expanding our understanding of both reward loss and addictive behavior, hence opening up opportunities for cross-pollination. This review focuses on two lines of research that point to parallels. First, several neurochemical systems involved in addiction are also involved in the modulation of the behavioral effects of reward loss, including opioid, GABA, and dopamine receptors...
February 4, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28162426/-200-opioids-and-genetics-rs2740574-in-cyp3a4-may-impact-the-risk-of-opioid-abuse-misuse-and-or-addiction
#6
J Blanchard, N Anand, B Meshkin, S Kantorovich, E Fung
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28153853/epigenetic-activation-of-mu-opioid-receptor-mor-gene-via-increased-expression-and-function-of-mitogen-and-stress-activated-protein-kinase-1-msk1
#7
Yadav Wagley, Ping-Yee Law, Li-Na Wei, Horace H Loh
Since the discovery of mu opioid receptor (MOR) gene two decades ago, various regulatory factors have been shown to interact with the MOR promoter and modulate transcript levels. However, the majority of early transcriptional studies on MOR gene have not addressed how intracellular signaling pathways mediate extracellular modulators. In this study, we demonstrate that MOR epigenetic regulation requires multiple co-ordinated signals converged at the MOR promoter, involving mitogen-activated protein kinase (MAPK) activation and mitogen-and stress-activated protein kinase (MSK1) - similar ranges of intracellular signaling pathways that are activated by opioid agonists...
February 2, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28135387/the-opioid-epidemic-what-does-it-mean-for-nurses
#8
Laura G Leahy
The United States is facing a major crisis with the current opioid epidemic. Tens of thousands of individuals are dying each year due to abuse and misuse of heroin and prescription opiate drugs. Nurses play an integral role in these aspects of health care and offer solutions by providing education; preventive measures; treatments, including medication-assisted treatments (MATs); and ongoing recovery options for individuals with opioid use disorders. Nurses provide education, issue prescriptions and dispense medications, and provide overall physical and mental health care to patients struggling with this "disease of the brain," and with the signing of the Comprehensive Addiction and Recovery Act, advanced practice RNs will soon be able to include MATs related to buprenorphine as part of their treatment plan...
January 1, 2017: Journal of Psychosocial Nursing and Mental Health Services
https://www.readbyqxmd.com/read/28121959/patients-with-cyp3a4-1g-genetic-polymorphism-consumed-significantly-lower-amount-of-sufentanil-in-general-anesthesia-during-lung-resection
#9
Huidong Zhang, Minghao Chen, Xiaodong Wang, Songyang Yu
CYP3A4, an isoform of cytochrome P450 enzymes, is responsible for the metabolism of 45% to 60% of currently prescribed drugs. It has been shown that CYP3A4*1G, a single nucleotide polymorphism (SNP), affects the enzymatic activity of CYP3A4. Sufentanil, a synthetic opioid commonly used for the induction and maintenance of general anesthesia, analgesia, and sedation, is mainly metabolized by CYP3A4. So far, the impact of CYP3A4*1G on sufentanil metabolism has not been investigated. In the present study, we first determined the frequency of CYP3A4*1G polymorphism in patients of Chinese Han nationality who underwent lung resection, and then compared the amount of sufentanil used in general anesthesia during the surgical procedure between wild type and mutant patients...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28115739/genome-wide-association-study-of-therapeutic-opioid-dosing-identifies-a-novel-locus-upstream-of-oprm1
#10
A H Smith, K P Jensen, J Li, Y Nunez, L A Farrer, H Hakonarson, S D Cook-Sather, H R Kranzler, J Gelernter
Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the μ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study of usual daily methadone dose. In African-American (AA) OD subjects (n=383), we identified a genome-wide significant association between therapeutic methadone dose (mean=68...
March 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28106092/pharmacological-characterisation-of-the-highly-nav1-7-selective-spider-venom-peptide-pn3a
#11
Jennifer R Deuis, Zoltan Dekan, Joshua S Wingerd, Jennifer J Smith, Nehan R Munasinghe, Rebecca F Bhola, Wendy L Imlach, Volker Herzig, David A Armstrong, K Johan Rosengren, Frank Bosmans, Stephen G Waxman, Sulayman D Dib-Hajj, Pierre Escoubas, Michael S Minett, Macdonald J Christie, Glenn F King, Paul F Alewood, Richard J Lewis, John N Wood, Irina Vetter
Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits NaV1.7 (IC50 0.9 nM) with at least 40-1000-fold selectivity over all other NaV subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by NaV1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092323/brain-substrates-of-reward-processing-and-the-%C3%AE-opioid-receptor-a-pathway-into-pain
#12
Frauke Nees, Susanne Becker, Sabina Millenet, Tobias Banaschewski, Luise Poustka, Arun Bokde, Uli Bromberg, Christian Büchel, Patricia J Conrod, Sylvane Desrivières, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Dimitri Papadopoulos Orfanos, Tomáš Paus, Michael N Smolka, Henrik Walter, Rob Whelan, Gunter Schumann, Herta Flor
The processing of reward and reinforcement learning seems to be important determinants of pain chronicity. However, reward processing is already altered early in life and if this is related to the development of pain symptoms later on is not known. The aim of this study was first to examine whether behavioural and brain-related indicators of reward processing at the age of 14 to 15 years are significant predictors of pain complaints 2 years later, at 16 to 17 years. Second, we investigated the contribution of genetic variations in the opioidergic system, which is linked to the processing of both, reward and pain, to this prediction...
February 2017: Pain
https://www.readbyqxmd.com/read/28074005/synergistic-regulation-of-serotonin-and-opioid-signaling-contributes-to-pain-insensitivity-in-nav1-7-knockout-mice
#13
Jörg Isensee, Leonhardt Krahé, Katharina Moeller, Vanessa Pereira, Jane E Sexton, Xiaohui Sun, Edward Emery, John N Wood, Tim Hucho
Genetic loss of the voltage-gated sodium channel Nav1.7 (Nav1.7(-/-)) results in lifelong insensitivity to pain in mice and humans. One underlying cause is an increase in the production of endogenous opioids in sensory neurons. We analyzed whether Nav1.7 deficiency altered nociceptive heterotrimeric guanine nucleotide-binding protein-coupled receptor (GPCR) signaling, such as initiated by GPCRs that respond to serotonin (pronociceptive) or opioids (antinociceptive), in sensory neurons. We found that the nociceptive neurons of Nav1...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28071341/identification-of-novel-hits-as-highly-prospective-dual-agonists-for-mu-and-kappa-opioid-receptors-an-integrated-in-silico-approach
#14
Indrani Bera, Mrinal Vishwas Marathe, Pavan V Payghan, Nanda Ghoshal
Opioid agonists are used clinically for the treatment of acute and chronic pain, however, their clinical use is limited due to the presence of undesired side effects. Dual agonists, simultaneously targeting mu and kappa opioid receptors, show fewer side effects than that of selective agonists. In the present work, 2D- and 3D- Quantitative Structure Activity Relationship studies were performed on a series of aminomorphinan derivatives as dual agonists, using a wide range of descriptors. The aim of the study was to identify the structural requirements for the activity of these compounds towards mu and kappa opioid receptors and using the models, with best external predictability, for predicting the activities of new hits obtained from shape based virtual screening of drug like compounds from ZINC database...
January 16, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28057931/the-oprm1-a118g-polymorphism-modulates-the-descending-pain-modulatory-system-for-individual-pain-experience-in-young-women-with-primary-dysmenorrhea
#15
Shyh-Yuh Wei, Li-Fen Chen, Ming-Wei Lin, Wei-Chi Li, Intan Low, Ching-Ju Yang, Hsiang-Tai Chao, Jen-Chuen Hsieh
The mu-opioid receptor (OPRM1) A118G polymorphism underpins different pain sensitivity and opioid-analgesic outcome with unclear effect on the descending pain modulatory system (DPMS). Primary dysmenorrhea (PDM), the most prevalent gynecological problem with clear painful and pain free conditions, serves as a good clinical model of spontaneous pain. The objective of this imaging genetics study was therefore to explore if differences in functional connectivity (FC) of the DPMS between the OPRM1 A118G polymorphisms could provide a possible explanation for the differences in pain experience...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28045073/insensitivity-to-pain-induced-by-a-potent-selective-closed-state-nav1-7-inhibitor
#16
M Flinspach, Q Xu, A D Piekarz, R Fellows, R Hagan, A Gibbs, Y Liu, R A Neff, J Freedman, W A Eckert, M Zhou, R Bonesteel, M W Pennington, K A Eddinger, T L Yaksh, M Hunter, R V Swanson, A D Wickenden
Pain places a devastating burden on patients and society and current pain therapeutics exhibit limitations in efficacy, unwanted side effects and the potential for drug abuse and diversion. Although genetic evidence has clearly demonstrated that the voltage-gated sodium channel, Nav1.7, is critical to pain sensation in mammals, pharmacological inhibitors of Nav1.7 have not yet fully recapitulated the dramatic analgesia observed in Nav1.7-null subjects. Using the tarantula venom-peptide ProTX-II as a scaffold, we engineered a library of over 1500 venom-derived peptides and identified JNJ63955918 as a potent, highly selective, closed-state Nav1...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28035534/oprd1-genetic-variation-and-human-disease
#17
Richard C Crist, Toni-Kim Clarke
The OPRD1 gene encodes the delta-opioid receptor, which has multiple functions including regulating reward pathways. The gene contains more than 2,000 verified genetic variants but only 2 currently have evidence for specific functions: rs1042114 disrupts maturation of the receptor and rs569356 affects OPRD1 expression. These polymorphisms and others in the gene have been found to be associated with human diseases. The most reproducible data are associations between opioid addiction and three variants in intron 1 (rs2236861, rs2236857, and rs3766951), which have been described in a number of independent populations...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28035528/delta-opioid-receptors-learning-and-motivation
#18
L P Pellissier, C N Pujol, J A J Becker, J Le Merrer
Delta opioid receptor (DOR) displays a unique, highly conserved, structure and an original pattern of distribution in the central nervous system, pointing to a distinct and specific functional role among opioid peptide receptors. Over the last 15 years, in vivo pharmacology and genetic models have allowed significant advances in the understanding of this role. In this review, we will focus on the involvement of DOR in modulating different types of hippocampal- and striatal-dependent learning processes as well as motor function, motivation, and reward...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28012859/endogenous-opiates-and-behavior-2015
#19
REVIEW
Richard J Bodnar
This paper is the thirty-eighth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2015 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia, stress and social status, tolerance and dependence, learning and memory, eating and drinking, drug abuse and alcohol, sexual activity and hormones, pregnancy, development and endocrinology, mental illness and mood, seizures and neurologic disorders, electrical-related activity and neurophysiology, general activity and locomotion, gastrointestinal, renal and hepatic functions, cardiovascular responses, respiration and thermoregulation, and immunological responses...
February 2017: Peptides
https://www.readbyqxmd.com/read/27996183/relationship-between-abcb1-polymorphisms-and-cold-pain-sensitivity-among-healthy-opioid-naive-malay-males
#20
Zalina Zahari, Chee Siong Lee, Muslih Abdulkarim Ibrahim, Nurfadhlina Musa, Mohd Azhar Mohd Yasin, Yeong Yeh Lee, Soo Choon Tan, Nasir Mohamad, Rusli Ismail
BACKGROUND: Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males. METHODS: Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT)...
December 20, 2016: Pain Practice: the Official Journal of World Institute of Pain
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