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https://www.readbyqxmd.com/read/27903758/oprm1-and-comt-gene-gene-interaction-is-associated-with-postoperative-pain-and-opioid-consumption-after-orthopedic-trauma
#1
Heba Khalil, Susan M Sereika, Feng Dai, Sheila Alexander, Yvette Conley, Gary Gruen, Li Meng, Peter Siska, Ivan Tarkin, Richard Henker
BACKGROUND: mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) contribute to the neurotransmission pathway of pain. COMT affects mu receptor expression and density in the brain. The aim of this study was to explore the OPRM1 and COMT interaction effects on postoperative pain and opioid consumption. METHODS: This cross-sectional exploratory study used genotype and clinical data from 153 postoperative patients. Using multiple regression analyses, four single-nucleotide polymorphisms of COMT (rs6269, rs4633, rs4818, and rs4680), their haplotypes, and diplotypes were considered for their interactions with A118G of OPRM1 regarding postoperative pain and opioid consumption...
November 30, 2016: Biological Research for Nursing
https://www.readbyqxmd.com/read/27826798/contribution-of-pharmacogenetic-testing-to-modeled-medication-change-recommendations-in-a-long-term-care-population-with-polypharmacy
#2
Elaine A Sugarman, Ali Cullors, Joel Centeno, David Taylor
BACKGROUND: Among long-term care facility residents, polypharmacy is common, and often appropriate, given the need to treat multiple, complex, chronic conditions. Polypharmacy has, however, been associated with increased healthcare costs, adverse drug events, and drug interactions. The current study evaluates the potential medication cost savings of adding personalized pharmacogenetic information to traditional medication management strategies. METHODS: One hundred and twelve long-term care residents completed pharmacogenetic testing for targeted variants in the following genes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4/CYP3A5, HTR2A, HTR2C, SLC6A4, SLC6A2 COMT, OPRM1, SLCO1B1, VKORC1 and MTHFR...
November 8, 2016: Drugs & Aging
https://www.readbyqxmd.com/read/27818236/a-role-for-the-mu-opioid-receptor-in-the-antidepressant-effects-of-buprenorphine
#3
Shivon A Robinson, Rebecca L Erickson, Caroline A Browne, Irwin Lucki
Buprenorphine (BPN), a mixed opioid drug with high affinity for mu (MOR) and kappa (KOR) opioid receptors, has been shown to produce behavioral responses in rodents that are similar to those of antidepressant and anxiolytic drugs. Although recent studies have identified KORs as a primary mediator of BPN's effects in rodent models of depressive-like behavior, the role of MORs in BPN's behavioral effects has not been as well explored. The current studies investigated the role of MORs in mediating conditioned approach behavior in the novelty-induced hypophagia (NIH) test, a behavioral measure previously shown to be sensitive to chronic treatment with antidepressant drugs...
November 3, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27759945/dna-methylation-and-alcohol-use-disorders-progress-and-challenges
#4
Huiping Zhang, Joel Gelernter
BACKGROUND AND OBJECTIVES: Risk for alcohol use disorders (AUDs) is influenced by gene-environment interactions. Environmental factors can affect gene expression through epigenetic mechanisms such as DNA methylation. This review outlines the findings regarding the association of DNA methylation and AUDs. METHODS: We searched PubMed (by April 2016) and identified 29 studies that examined the association of DNA methylation and AUDs. We also evaluated the methods used in these studies...
October 19, 2016: American Journal on Addictions
https://www.readbyqxmd.com/read/27743985/mu-opioid-receptor-inhibition-decreases-voluntary-wheel-running-in-a-dopamine-dependent-manner-in-rats-bred-for-high-voluntary-running
#5
Gregory N Ruegsegger, Jacob D Brown, M Cathleen Kovarik, Dennis K Miller, Frank W Booth
The mesolimbic dopamine and opioid systems are postulated to influence the central control of physical activity motivation. We utilized selectively bred rats for high (HVR) or low (LVR) voluntary running behavior to examine (1) inherent differences in mu-opioid receptor (Oprm1) expression and function in the nucleus accumbens (NAc), (2) if dopamine-related mRNAs, wheel-running, and food intake are differently influenced by intraperitoneal (i.p.) naltrexone injection in HVR and LVR rats, and (3) if dopamine is required for naltrexone-induced changes in running and feeding behavior in HVR rats...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27742580/mechanical-allodynia-corresponds-to-oprm1-downregulation-within-the-descending-pain-network-of-male-and-female-rats-exposed-to-neonatal-immune-challenge
#6
Siyang Yan, Amanda C Kentner
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation...
October 11, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27725223/next-generation-sequencing-of-human-opioid-receptor-genes-based-on-a-custom-ampliseq%C3%A2-library-and-ion-torrent-personal-genome-machine
#7
Dario Kringel, Jörn Lötsch
BACKGROUND: The opioid system is involved in the control of pain, reward, addictive behaviors and vegetative effects. Opioids exert their pharmacological actions through the agonistic binding at opioid receptors and variation in the coding genes has been found to modulate opioid receptor expression or signaling. However, a limited selection of functional opioid receptor variants is perceived as insufficient in providing a genetic diagnosis of clinical phenotypes and therefore, unrestricted access to opioid receptor genetics is required...
October 8, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27685027/pharmacoepigenetics-of-the-role-of-dna-methylation-in-%C3%AE-opioid-receptor-expression-in-different-human-brain-regions
#8
Claudia Knothe, Bruno G Oertel, Alfred Ultsch, Mattias Kettner, Peter Harald Schmidt, Cora Wunder, Stefan W Toennes, Gerd Geisslinger, Jörn Lötsch
AIM: Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of μ-opioid receptor expression across the brain. METHODS: In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, μ-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein...
September 29, 2016: Epigenomics
https://www.readbyqxmd.com/read/27671662/deletion-of-the-mu-opioid-receptor-gene-in-mice-reshapes-the-reward-aversion-connectome
#9
Anna E Mechling, Tanzil Arefin, Hsu-Lei Lee, Thomas Bienert, Marco Reisert, Sami Ben Hamida, Emmanuel Darcq, Aliza Ehrlich, Claire Gaveriaux-Ruff, Maxime J Parent, Pedro Rosa-Neto, Jürgen Hennig, Dominik von Elverfeldt, Brigitte Lina Kieffer, Laura-Adela Harsan
Connectome genetics seeks to uncover how genetic factors shape brain functional connectivity; however, the causal impact of a single gene's activity on whole-brain networks remains unknown. We tested whether the sole targeted deletion of the mu opioid receptor gene (Oprm1) alters the brain connectome in living mice. Hypothesis-free analysis of combined resting-state fMRI diffusion tractography showed pronounced modifications of functional connectivity with only minor changes in structural pathways. Fine-grained resting-state fMRI mapping, graph theory, and intergroup comparison revealed Oprm1-specific hubs and captured a unique Oprm1 gene-to-network signature...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27649267/ethnicity-dependent-influence-of-innate-immune-genetic-markers-on-morphine-pca-requirements-and-adverse-effects-in-postoperative-pain
#10
Andrew A Somogyi, Alex T Sia, Ene-Choo Tan, Janet K Coller, Mark R Hutchinson, Daniel T Barratt
Although several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2, TLR4, MYD88, MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA, TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition to OPRM1, COMT, and ABCB1 genetic variability identified previously...
July 14, 2016: Pain
https://www.readbyqxmd.com/read/27648914/tetrapeptide-endomorphin-analogs-require-both-full-length-and-truncated-splice-variants-of-the-mu-opioid-receptor-gene-oprm1-for-analgesia
#11
Gina F Marrone, Zhigang Lu, Grace Rossi, Ankita Narayan, Amanda Hunkele, Sarah Marx, Jin Xu, John Pintar, Susruta Majumdar, Ying-Xian Pan, Gavril W Pasternak
The mu opioid receptor gene undergoes extensive alternative splicing. Mu opioids can be divided into three classes based on the role of different groups of splice variants. Morphine and methadone require only full length seven transmembrane (7TM) variants for analgesia, whereas IBNtxA (3'-iodobenzyol-6β-naltrexamide) needs only truncated 6TM variants. A set of endomorphin analogs fall into a third group that requires both 6TM and 7TM splice variants. Unlike morphine, endomorphin 1 and 2, DAPP (Dmt,d-Ala-Phe-Phe-NH2), and IDAPP (3'-iodo-Dmt-d-Ala-Phe-Phe-NH2) analgesia was lost in an exon 11 knockout mouse lacking 6TM variants...
October 10, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27636225/an-expert-review-of-pharmacogenomics-of-sickle-cell-disease-therapeutics-not-yet-ready-for-global-precision-medicine
#12
Khuthala Mnika, Gift D Pule, Collet Dandara, Ambroise Wonkam
Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a state-of-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids...
October 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27594419/neural-response-to-alcohol-taste-cues-in-youth-effects-of-the-oprm1-gene
#13
Ozlem Korucuoglu, Thomas E Gladwin, Frank Baas, Roel J T Mocking, Henricus G Ruhé, Paul F C Groot, Reinout W Wiers
Genetic variations in the mu-opioid receptor (OPRM1) gene have been related to high sensitivity to rewarding effects of alcohol. The current study focuses on the neural circuitry underlying this phenomenon using an alcohol versus water taste-cue reactivity paradigm in a young sample at relatively early stages of alcohol use, thus limiting the confound of variations in duration of alcohol use. Drinkers (17-21 years old) were selected on genotype carrying the AA-(n = 20) or the AG-(n = 16) variant of the A118G single nucleotide polymorphism (SNP) of the OPRM1 gene (rs1799971), and underwent functional magnetic resonance imaging (fMRI)...
September 5, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27541715/genetic-variants-associated-with-thermal-pain-sensitivity-in-a-paediatric-population
#14
Maja Matic, Gerbrich E van den Bosch, Saskia N de Wildt, Dick Tibboel, Ron H N van Schaik
Pain sensitivity is an inherited factor that varies strongly between individuals. We investigated whether genetic polymorphisms in the candidate genes COMT, OPRM1, OPRD1, TAOK3, TRPA1, TRPV1, and SCN9A are contributing to experimental pain variability between children. Our study included 136 children and adolescents (8-18 years). Cold and heat pain thresholds were determined with a Thermal Sensory Analyzer. Women and young children were significantly more sensitive to pain (P < 0.05). After correction for age, gender, reaction time, and correction for multiple testing, OPRM1 118A>G G-allele carriers (AG and GG) rated the hot stimulus as significantly less painful than did OPRM1 118A>G AA genotyped individuals (2[1-5] vs 7 [3-9], respectively; P = 0...
November 2016: Pain
https://www.readbyqxmd.com/read/27515451/cyp2b6-and-oprm1-receptor-polymorphisms-at-methadone-clinics-and-novel-oprm1-haplotypes-a-cross-sectional-study
#15
Ahmad Abdulrahman Almeman, R Ismail, Markus Perola
INTRODUCTION: Methadone is accepted as an alternative therapy in opioid use disorders worldwide. Methadone responsiveness , however, is affected by a range of CYP450 enzymes and OPRM1 polymorphisms. OBJECTIVE: This study sought to detect CYP2B6 and OPRM1 variants and their genotypes, as major contributors to inter-variability in methadone responsiveness and methadone dose requirements. METHODS: We carried out a prospective experimental one-phase pharmacogenetic study in four addiction clinics in Malaysia...
August 10, 2016: Drug Metabolism Letters
https://www.readbyqxmd.com/read/27510425/low-%C3%AE-opioid-receptor-status-in-alcohol-dependence-identified-by-combined-positron-emission-tomography-and-post-mortem-brain-analysis
#16
Derik Hermann, Natalie Hirth, Matthias Reimold, Anil Batra, Michael N Smolka, Sabine Hoffmann, Falk Kiefer, Hamid R Noori, Wolfgang H Sommer, Gerald Reischl, Christian la Fougère, Karl Mann, Rainer Spanagel, Anita C Hansson
Blockade of the μ-opioid receptor (MOR) by naltrexone reduces relapse risk in a subpopulation of alcohol-dependent patients. Previous positron-emission-tomography (PET) studies using the MOR ligand [(11)C]carfentanil have found increased MOR availability in abstinent alcoholics, which may reflect either increased MOR expression or lower endogenous ligand concentration. To differentiate between both effects, we investigated two cohorts of alcoholic subjects using either post-mortem or clinical PET analysis...
September 21, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27484010/oprm1-genotype-interacts-with-serotonin-system-dysfunction-to-predict-alcohol-heightened-aggression-in-primates
#17
Carlos A Driscoll, Stephen G Lindell, Melanie L Schwandt, Stephen J Suomi, J Dee Higley, Markus Heilig, Christina S Barr
Although the notion that alcohol promotes violence is widespread, not all individuals are aggressive while intoxicated. Genetic variation could be a contributing factor to individual differences in alcohol-heightened aggression. The present study examines the effects of OPRM1C77G genotype on responses to threat in rhesus macaques under normal conditions and following alcohol administration. Prior studies have shown that a low CSF level of 5-HIAA is a trait marker for individuals prone to escalated aggression...
August 3, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27459726/a-gene-by-sex-interaction-for-nicotine-reward-evidence-from-humanized-mice-and-epidemiology
#18
R E Bernardi, K Zohsel, N Hirth, J Treutlein, M Heilig, M Laucht, R Spanagel, W H Sommer
It has been proposed that vulnerability to nicotine addiction is moderated by variation at the μ-opioid receptor locus (OPRM1), but results from human studies vary and prospective studies based on genotype are lacking. We have developed a humanized mouse model of the most common functional OPRM1 polymorphism rs1799971_A>G (A118G). Here we use this model system together with a cohort of German youth to examine the role of the OPRM1 A118G variation on nicotine reward. Nicotine reinforcement was examined in the humanized mouse model using i...
2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27447243/association-study-of-drd2-a2-a1-drd3-ser9gly-d%C3%AE-h-1021c-t-oprm1-a118g-and-grik1-rs2832407c-a-polymorphisms-with-alcohol-dependence
#19
Georgia Ragia, Ivan Veresies, Louiza Veresie, Kyriakos Veresies, Vangelis G Manolopoulos
BACKGROUND: The reinforcing effects of alcohol are mediated through complex interactions between multiple neurochemical systems. Genes of dopaminergic (DRD2, DRD3 and DβH), opioid (OPRM1) and glutaminergic (GRIK1) systems mediate the dependent behavior via different mechanisms; however, they all target the serotonergic and dopaminergic pathways in the ventral tegmental area. METHODS: In the present study, DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A polymorphisms and their interactions were analyzed in 72 alcohol-dependent patients and 74 controls of Greek-Cypriot origin, using the PCR-RFLP method...
September 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27400929/%C3%AE-adrenergic-receptor-gene-expression-in-hiv-associated-neurocognitive-impairment-and-encephalitis-implications-for-mor-1k-subcellular-localization
#20
Seth M Dever, Myosotys Rodriguez, Nazira El-Hage
We previously reported that mRNA expression of the unique alternatively spliced OPRM1 isoform μ-opioid receptor-1K (MOR-1K), which exhibits excitatory cellular signaling, is elevated in HIV-infected individuals with combined neurocognitive impairment (NCI) and HIV encephalitis (HIVE). It has recently been shown that the β2-adrenergic receptor (β2-AR) chaperones MOR-1K, normally localized intracellularly, to the cell surface. Here, we found mRNA expression of the adrenoceptor beta 2 (ADRB2) gene is also elevated in NCI-HIVE individuals, as well as that β2-AR protein expression is elevated in HIV-1-infected primary human astrocytes treated with morphine, and discuss the implications for MOR-1K subcellular localization in this condition...
December 2016: Journal of Neurovirology
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