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opioid genetics

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https://www.readbyqxmd.com/read/28632076/association-of-oprd1-gene-variants-with-opioid-dependence-in-addicted-male-individuals-undergoing-methadone-treatment-in-the-north-of-iran
#1
Alireza Sharafshah, Hedyeh Fazel, Ali Albonaim, Vahid Omarmeli, Sajjad Rezaei, Ebrahim Mirzajani, Farzam Ajamian, Parvaneh Keshavarz
Genetic association of rs678849 along with neuroimaging and biomarker phenotypes, parallel with the known involvements of the OPRD1 in drug abuse, provided additional support for targeting these receptors as potential therapeutic targets in both neurodegenerative diseases and neuropsychiactric disorders such as Alzheimer's disease. Samples were selected among 202 opium-addicted participants undergoing methadone treatment and 202 healthy controls. Genomic DNA of all subjects was extracted from whole blood samples through a Salting Out procedure...
March 1, 2017: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/28622282/towards-a-neurobiological-understanding-of-alexithymia
#2
REVIEW
Nicolás Meza-Concha, Marcelo Arancibia, Felicia Salas, Rosa Behar, Germán Salas, Hernán Silva, Rocío Escobar
Although the specialized literature on the etiology of alexithymia is controversial, neurobiological research has shown relevant advances. The aim of this review is to analyze the available evidence regarding the neurophysiological bases of alexithymia. A comprehensive review of available articles from Medline/PubMed, EBSCO and SciELO was conducted. Previously, alexithymia was linked to a reduced interhemispheric brain connection. From a childhood traumatic perspective, the right prefrontal cortex and the default mode network would experience alterations, first hypermetabolic (dopaminergic and glutamatergic dysregulation) and then hypometabolic-dissociative (serotonergic and opioid dysregulation), resulting in a distorted interoceptive and emotional awareness...
May 29, 2017: Medwave
https://www.readbyqxmd.com/read/28621702/short-duration-physical-activity-prevents-the-development-of-activity-induced-hyperalgesia-through-opioid-and-serotoninergic-mechanisms
#3
Lucas V Lima, Josimari M DeSantana, Lynn A Rasmussen, Kathleen A Sluka, Lucas Vasconcelos Lima
Regular physical activity prevents development of chronic muscle pain through modulation of central mechanisms that involve rostral ventromedial medulla (RVM). We tested if pharmacological blockade or genetic deletion of mu-opioid receptors in physically active mice modulates excitatory and inhibitory systems in the RVM in an activity-induced hyperalgesia model. We examined response frequency to mechanical stimulation of the paw, muscle withdrawal thresholds, and expression of phosphorylation of the NR1 subunit of the NMDA receptor (p-NR1) and serotonin transporter (SERT) in the RVM...
June 8, 2017: Pain
https://www.readbyqxmd.com/read/28619017/borderline-personality-disorder-and-childhood-trauma-exploring-the-affected-biological-systems-and-mechanisms
#4
Nadia Cattane, Roberta Rossi, Mariangela Lanfredi, Annamaria Cattaneo
BACKGROUND: According to several studies, the onset of the Borderline Personality Disorder (BPD) depends on the combination between genetic and environmental factors (GxE), in particular between biological vulnerabilities and the exposure to traumatic experiences during childhood. We have searched for studies reporting possible alterations in several biological processes and brain morphological features in relation to childhood trauma experiences and to BPD. We have also looked for epigenetic mechanisms as they could be mediators of the effects of childhood trauma in BPD vulnerability...
June 15, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating
#5
Lisa R Goldberg, Stacey L Kirkpatrick, Neema Yazdani, Kimberly P Luttik, Olga A Lacki, R Keith Babbs, David F Jenkins, W Evan Johnson, Camron D Bryant
Genetic and pharmacological studies indicate that casein kinase-1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0...
June 8, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28558008/expression-of-anaesthetic-and-analgesic-drug-target-genes-in-excised-breast-tumour-tissue-association-with-clinical-disease-recurrence-or-metastasis
#6
C Connolly, S F Madden, D J Buggy, H C Gallagher
BACKGROUND: Retrospective analyses suggest anaesthetic-analgesics technique during cancer surgery may affect recurrence/metastasis. This could involve direct effects of anaesthetic-analgesic drugs on cancer cells. While μ-opioid receptor over-expression in lung tumours is associated with greater metastasis, other anaesthetic-analgesic receptor targets in cancer recurrence/metastasis remain unexplored. Therefore, we evaluated the association between genetic expression of anaesthetic-analgesic receptor targets and recurrence/metastasis, using a repository of breast cancer gene expression and matching clinical data...
2017: PloS One
https://www.readbyqxmd.com/read/28555114/attitudes-about-future-genetic-testing-for-posttraumatic-stress-disorder-and-addiction-among-community-based-veterans
#7
Michelle R Lent, Stuart N Hoffman, H Lester Kirchner, Thomas G Urosevich, Joseph J Boscarino, Joseph A Boscarino
This study explored attitudes toward hypothetical genetic testing for posttraumatic stress disorder (PTSD) and addiction among veterans. We surveyed a random sample of community-based veterans (n = 700) by telephone. One year later, we asked the veterans to provide a DNA sample for analysis and 41.9% of them returned the DNA samples. Overall, most veterans were not interested in genetic testing neither for PTSD (61.7%) nor for addiction (68.7%). However, bivariate analyses suggested there was an association between having the condition of interest and the likelihood of genetic testing on a 5-point scale (p < 0...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28552458/opioid-addiction-who-are-your-real-friends
#8
REVIEW
Shoshana Eitan, Michael A Emery, M L Shawn Bates, Christopher Horrax
Opioid addiction is a chronic and relapsing mental health disorder. However, only some individuals exposed to opioids, either recreationally or during the course of pain management, will develop addiction. The reasons why some individuals develop addiction and some are spared are not fully understood. Studies indicate that it is likely a combination of genetic predispositions and environmental conditions. Given the role of environmental factors in human addiction, this review examines the role of social environments and social interactions in the development of opioid addictive-like behaviors in rodent studies...
May 25, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28548579/genetic-variation-of-the-mu-opioid-receptor-oprm1-and-dopamine-d2-receptor-drd2-is-related-to-smoking-differences-in-patients-with-schizophrenia-but-not-bipolar-disorder
#9
Mika Hirasawa-Fujita, Michael J Bly, Vicki L Ellingrod, Gregory W Dalack, Edward F Domino
It is not known why mentally ill persons smoke excessively. Inasmuch as endogenous opioid and dopaminergic systems are involved in smoking reinforcement, it is important to study mu opioid receptor (OPRM1) A118G (rs1799971), dopamine D2 receptor (DRD2) Taq1A (rs1800497) genotypes, and sex differences among patients with schizophrenia or bipolar disorder. Smokers and nonsmokers with schizophrenia (n=177) and bipolar disorder (n=113) were recruited and genotyped. They were classified into three groups: current smoker, former smoker, and never smoker by tobacco smoking status self-report...
2017: Clinical Schizophrenia & related Psychoses
https://www.readbyqxmd.com/read/28526149/pharmacogenomics-in-anesthesia
#10
REVIEW
Ramsey Saba, Alan D Kaye, Richard D Urman
A significant number of commonly administered medications in anesthesia show wide clinical interpatient variability. Some of these include neuromuscular blockers, opioids, local anesthetics, and inhalation anesthetics. Individual genetic makeup may account for and predict cardiovascular outcomes after cardiac surgery. These interactions can manifest at any point in the perioperative period and may also only affect a specific system. A better understanding of pharmacogenomics will allow for more individually tailored anesthetics and may ultimately lead to better outcomes, decreased hospital stays, and improved patient satisfaction...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28523735/variability-in-prescription-opioid-intake-and-reinforcement-amongst-129-substrains
#11
Susan M Jimenez, Aiden F Healy, Michal A Coelho, Chelsea N Brown, Tod E Kippin, Karen K Szumlinski
Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity, and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence...
May 19, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28485408/genetic-and-pharmacological-antagonism-of-nk1-receptor-prevents-opiate-abuse-potential
#12
A J Sandweiss, M I McIntosh, A Moutal, R Davidson-Knapp, J Hu, A K Giri, T Yamamoto, V J Hruby, R Khanna, T M Largent-Milnes, T W Vanderah
Development of an efficacious, non-addicting analgesic has been challenging. Discovery of novel mechanisms underlying addiction may present a solution. Here we target the neurokinin system, which is involved in both pain and addiction. Morphine exerts its rewarding actions, at least in part, by inhibiting GABAergic input onto substance P (SP) neurons in the ventral tegmental area (VTA), subsequently increasing SP release onto dopaminergic neurons. Genome editing of the neurokinin 1 receptor (NK1R) in the VTA renders morphine non-rewarding...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28472364/association-between-polymorphisms-in-the-purinergic-p2y12-receptor-gene-and-severity-of-both-cancer-pain-and-postoperative-pain
#13
Masahiko Sumitani, Daisuke Nishizawa, Makoto Nagashima, Kazutaka Ikeda, Hiroaki Abe, Ryoji Kato, Hiroshi Ueda, Yoshitsugu Yamada
Background.:  Despite the widespread use of opioids for the treatment of cancer pain, results from several surveys consistently show that pain is still prevalent in some patients with malignant diseases. The purinergic P2Y12 receptor is a primary site leading to microglial activation and hyperalgesic pain behaviors and is considered a key regulator in the prevention of the aggravation of clinical pain conditions. Genetic variability in the P2RY12 gene may contribute to individual differences in pain and opioid sensitivity...
May 4, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28470102/oct1-genetic-variants-are-associated-with-postoperative-morphine-related-adverse-effects-in-children
#14
Rajiv Balyan, Xue Zhang, Vidya Chidambaran, Lisa J Martin, Tomoyuki Mizuno, Tsuyoshi Fukuda, Alexander A Vinks, Senthilkumar Sadhasivam
AIM: Large interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events. Respiratory depression (RD) and postoperative nausea and vomiting (PONV) are significant adverse drug response of intravenous morphine in the perioperative setting limiting its efficacy in achieving adequate surgical pain relief. OCT1 is a transporter in the liver that transports morphine from the bloodstream into hepatocytes. Earlier we reported association of genetic polymorphisms in OCT1 with morphine PK, and lower morphine clearance in Caucasian children as compared with African-American (AA) children...
May 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28453659/udp-glucuronosyltransferase-ugt-2b-subfamily-interspecies-differences-in-carnivores
#15
Takamitsu Kondo, Yoshinori Ikenaka, Shouta M M Nakayama, Yusuke K Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomyama, Shinsuke Tanabe, Mayumi Ishizuka
UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of chemicals. Previous studies showed that Felidae and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous (e.g., estrogens, androgens, and bile acids) and exogenous compounds (opioids, NSAIDs, and environmental pollutants)...
April 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28434951/role-of-crf1-receptor-in-post-incisional-plasma-extravasation-and-nociceptive-responses-in-mice
#16
Asunción Romero, Juan-Antonio García-Carmona, María-Luisa Laorden, Margarita M Puig
The corticotropin-releasing factor (CRF) is involved in a number of physiological functions including pain perception. The purpose of this study was to evaluate the role of CRF1 receptor in the long-lasting post-surgical changes in somatic nociceptive thresholds and in local inflammatory responses, using genetically engineered mice lacking functional CRF1 receptor. Animals underwent a plantar incision under anaesthesia with remifentanil (80μg/kg s.c.) and sevoflurane. Mechanical thresholds (von Frey) and plasma extravasation (Evan's blue) were evaluated at different time points...
April 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28425121/role-of-the-dynorphin-kappa-opioid-receptor-system-in-the-motivational-effects-of-ethanol
#17
Rachel I Anderson, Howard C Becker
Evidence has demonstrated that dynorphin (DYN) and the kappa opioid receptor (KOR) system contribute to various psychiatric disorders, including anxiety, depression, and addiction. More recently, this endogenous opioid system has received increased attention as a potential therapeutic target for treating alcohol use disorders. In this review, we provide an overview and synthesis of preclinical studies examining the influence of alcohol (ethanol) exposure on DYN/KOR expression and function, as well as studies examining the effects of DYN/KOR manipulation on ethanol's rewarding and aversive properties...
April 20, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28415063/neuron-restrictive-silencer-factor-mediated-downregulation-of-%C3%AE-opioid-receptor-contributes-to-the-reduced-morphine-analgesia-in-bone-cancer-pain
#18
Chao Zhu, Jun Tang, Tan Ding, Lei Chen, Wei Wang, Xiao-Peng Mei, Xiao-Tao He, Wen Wang, Li-Dong Zhang, Yu-Lin Dong, Zhuo-Jing Luo
Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively...
May 2017: Pain
https://www.readbyqxmd.com/read/28409480/genetic-testing-for-opioid-pain-management-a-primer
#19
Deepti Agarwal, Mercy A Udoji, Andrea Trescot
Patients see their primary care physicians (PCPs) for a variety of medical conditions, chronic pain being one of the most common. An increased use of prescription medications (especially opioids) has led to an increase in adverse drug reactions and has heightened our awareness of the variability in response to medications. Opioids and other pain adjuvants are widely used, and drug-drug interactions involving these analgesics can be problematic and potentially lethal. Pharmacogenetics has improved our understanding of drug efficacy and response, opened doors to individual tailoring of medical management, and created a series of ethical and economic considerations...
June 2017: Pain and Therapy
https://www.readbyqxmd.com/read/28379874/effects-of-single-nucleotide-polymorphisms-on-surgical-and-post-surgical-opioid-requirements-a-systematic-review-and-meta-analysis
#20
Siu-Wai Choi, David M H Lam, Stanley S C Wong, Haydn H C Shiu, Amy X M Wang, Chi-Wai Cheung
OBJECTIVES: There is great heterogeneity in the way individuals respond to medications. Inherited differences, such as Single Nucleotide Polymorphisms (SNP), can influence the efficacy and toxicity of drugs. This meta-analysis aims to collate data from studies investigating the effect of SNPs on post-operative and/or intra-operative opioid requirements. METHODS: This meta-analysis was conducted following PRISMA guidelines. Eligibility criteria for studies in this meta-analysis were reporting amount of post-operative and/or intra-operative opioid used as the primary outcome and genotyping patients for SNPs in one of the following genes; OPRM1, CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7 or ABCB1...
April 4, 2017: Clinical Journal of Pain
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