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opioid genetics

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https://www.readbyqxmd.com/read/28343361/genetic-dissociation-of-morphine-analgesia-from-hyperalgesia-in-mice
#1
Gina F Marrone, Valerie Le Rouzic, Andras Varadi, Jin Xu, Anjali M Rajadhyaksha, Susruta Majumdar, Ying-Xian Pan, Gavril W Pasternak
RATIONALE: Morphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM). OBJECTIVES: This study explored the relative contributions of 7TM and 6TM variants in a range of morphine actions...
March 25, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28339912/pharmacogenomics-and-patient-treatment-parameters-to-opioid-treatment-in-chronic-pain-a-focus-on-morphine-oxycodone-tramadol-and-fentanyl
#2
Renae A Lloyd, Elizabeth Hotham, Catherine Hall, Marie Williams, Vijayaprakash Suppiah
Objective. : Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl...
February 24, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28333316/convergent-balancing-selection-on-the-mu-opioid-receptor-in-primates
#3
Carolyn G Sweeney, Juliette M Rando, Helen N Panas, Gregory M Miller, Donna M Platt, Eric J Vallender
The mu opioid receptor is involved in many natural processes including stress response, pleasure, and pain. Mutations in the gene also have been associated with opiate and alcohol addictions as well as with responsivity to medication targeting these disorders. Two common and mutually exclusive polymorphisms have been identified in humans, A118G (N40D), found commonly in non-African populations, and C17T (V6A), found almost exclusively in African populations. While A118G has been studied extensively for associations and in functional assays, C17T is much less well understood...
March 15, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28323671/codeine-and-opioid-metabolism-implications-and-alternatives-for-pediatric-pain-management
#4
Vidya Chidambaran, Senthilkumar Sadhasivam, Mohamed Mahmoud
PURPOSE OF REVIEW: Use of perioperative opioids for surgical pain management of children presents clinical challenges because of concerns of serious adverse effects including life-threatening respiratory depression. This is especially true for children with history of obstructive sleep apnea. This review will explore current knowledge of clinically relevant factors and genetic polymorphisms that affect opioid metabolism and postoperative outcomes in children. RECENT FINDINGS: Within the past several years, an increasing number of case reports have illustrated clinically important respiratory depression, anoxic brain injuries and even death among children receiving appropriate weight-based dosages of codeine and other opioids for analgesia at home setting particularly following tonsillectomy...
March 18, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28298794/anesthetic-implications-in-a-child-with-crouzon-syndrome
#5
Ajeet Kumar, Nitika Goel, Chandni Sinha, Abhishek Singh
Crouzon syndrome (CS) is an autosomal dominant genetic disorder characterized by craniofacial dysostosis. Premature fusion of skull base leads to midfacial hypoplasia, shallow orbit, mandibular prognathism, overcrowding of upper teeth, high-arched palate, and upper airway obstruction. It is important for anesthesiologists managing such patients to recognize and avoid potential airway complications. Here, we present a case of a 10-year-old child with CS posted for ptosis correction surgery. Use of peripheral nerve blocks to cut down opioid requirement, inhalational induction, and maintenance are key aspects in successful management of such cases...
January 2017: Anesthesia, Essays and Researches
https://www.readbyqxmd.com/read/28284950/naloxone-exacerbates-memory-impairments-and-depressive-like-behavior-after-mild-traumatic-brain-injury-mtbi-in-mice-with-upregulated-opioid-system-activity
#6
Anna Lesniak, Pawel Leszczynski, Magdalena Bujalska-Zadrozny, Chaim G Pick, Mariusz Sacharczuk
The neuroprotective role of the endogenous opioid system in the pathophysiological sequelae of brain injury remains largely ambiguous. Noteworthy, almost no data is available on how its genetically determined activity influences the outcome of mild traumatic brain injury. Thus, the aim of our study was to examine the effect of opioid receptor blockage on cognitive impairments produced by mild traumatic brain injury in mice selectively bred for high (HA) and low (LA) swim-stress induced analgesia that show innate divergence in opioid system activity...
March 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28282362/gene-to-gene-interactions-regulate-endogenous-pain-modulation-in-fibromyalgia-patients-and-healthy-controls-antagonistic-effects-between-opioid-and-serotonin-related-genes
#7
Tour Jeanette, Löfgren Monika, Mannerkorpi Kaisa, Gerdle Björn, Larsson Anette, Palstam Annie, Bileviciute-Ljungar Indre, Bjersing Jan, Ingvar Martin, Ernberg Malin, Schalling Martin, Kosek Eva
Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of three functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls (HC). Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531) and the serotonin-1a receptor (5-HT1a) gene (rs6296)...
March 7, 2017: Pain
https://www.readbyqxmd.com/read/28273335/a-cis-eqtl-in-oprm1-is-associated-with-subjective-response-to-alcohol-and-alcohol-use
#8
Jacqueline M Otto, Ian R Gizer, Joseph D Deak, Kimberly A Fleming, Bruce D Bartholow
BACKGROUND: A functional polymorphism within the mu-opioid receptor (OPRM1) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM1, rs3778150, is robustly associated with heroin dependence, and fully explained a smaller observed association with rs1799971. Given evidence that the rs3778150-C allele is associated with decreased OPRM1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM1 that increases risk for a variety of alcohol use phenotypes...
March 8, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28263461/current-concepts-in-methadone-metabolism-and-transport
#9
Evan D Kharasch
Methadone is a cornerstone therapy for opioid addiction and a public health strategy for HIV/AIDS and hepatitis C reduction. Methadone is also used for acute and chronic pain. As use for chronic pain has grown, so too have adverse events. Constitutive and acquired (drug interactions) inter- and intraindividual variability in methadone pharmacokinetics and pharmacodynamics confounds reliable clinical use. Identification of enzymes and transporters responsible for methadone disposition has been a long-sought ideal...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28241234/laparoscopic-total-pancreatectomy-with-islet-autotransplantation-and-intraoperative-islet-separation-as-a-treatment-for-patients-with-chronic-pancreatitis
#10
Caleb J Fan, Kenzo Hirose, Christi M Walsh, Michael Quartuccio, Niraj M Desai, Vikesh K Singh, Rita R Kalyani, Daniel S Warren, Zhaoli Sun, Marie N Hanna, Martin A Makary
Importance: Pain management of patients with chronic pancreatitis (CP) can be challenging. Laparoscopy has been associated with markedly reduced postoperative pain but has not been widely applied to total pancreatectomy with islet autotransplantation (TPIAT). Objective: To examine the feasibility of using laparoscopic TPIAT (L-TPIAT) in the treatment of CP. Design, Setting, and Participants: Thirty-two patients with CP presented for TPIAT at a tertiary hospital from January 1, 2013, through December 31, 2015...
February 22, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28236139/iron-dopamine-genetics-and-hormones-in-the-pathophysiology-of-restless-legs-syndrome
#11
REVIEW
Farhan H Khan, Caitlyn D Ahlberg, Christopher A Chow, Divya R Shah, Brian B Koo
Restless legs syndrome (RLS) is a common, chronic neurologic condition, which causes a persistent urge to move the legs in the evening that interferes with sleep. Human and animal studies have been used to study the pathophysiologic state of RLS and much has been learned about the iron and dopamine systems in relation to RLS. Human neuropathologic and imaging studies have consistently shown decreased iron in different brain regions including substantia nigra and thalamus. These same areas also demonstrate a state of relative dopamine excess...
February 24, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28199203/neurogenetics-of-acute-and-chronic-opiate-opioid-abstinence-treating-symptoms-and-the-cause
#12
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
#13
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
#14
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
#15
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
#16
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...
March 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
#17
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
#18
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
#19
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
#20
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)
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