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opioid genetics

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https://www.readbyqxmd.com/read/28911965/physiological-roles-of-cns-muscarinic-receptors-gained-from-knockout-mice
#1
REVIEW
Morgane Thomsen, Gunnar Sørensen, Ditte Dencker
Because the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level...
September 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28904010/vitamin-d-supplementation-to-palliative-cancer-patients-protocol-of-a-double-blind-randomised-controlled-trial-palliative-d
#2
Maria Helde-Frankling, Jenny Bergqvist, Caritha Klasson, Marie Nordström, Jonas Höijer, Peter Bergman, Linda Björkhem-Bergman
BACKGROUND: According to a small pilot study on palliative cancer patients at our ward, vitamin D supplementation had beneficial effects on pain (measured as opioid consumption), infections and quality of life (QoL) without having any significant side effects. OBJECTIVE: The primary objective of the 'Palliative-D' study is to test the hypothesis that vitamin D supplementation for 12 weeks reduces opioid consumption. The secondary objectives are to study if reduction of antibiotic consumption and fatigue as well as improvement in QoL assessments can be observed...
September 13, 2017: BMJ Supportive & Palliative Care
https://www.readbyqxmd.com/read/28892154/pharmacogenetics-of-opioid-analgesics-in-dogs
#3
REVIEW
K Kongara
Genetic variation causes interindividual variability in drug absorption, distribution, metabolism and excretion. These pharmacokinetic processes will influence the observed efficacy and toxicity of a drug. Polymorphisms in the genes encoding the metabolizing enzymes, transport proteins and receptors have been linked to the inconsistency in responses to opioid treatment in humans and laboratory animals. Pharmacogenetics is relatively less developed field in veterinary medicine compared to significant advances in knowledge on genetic basis of variation in drug responses and clinical applications in human medicine...
September 11, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28877966/t-cell-mediation-of-pregnancy-analgesia-affecting-chronic-pain-in-mice
#4
Sarah F Rosen, Boram Ham, Shannon Drouin, Nadia Boachie, Anne-Julie Chabot-Dore, Jean-Sebastien Austin, Luda Diatchenko, Jeffrey S Mogil
It has been consistently reported that many female chronic pain sufferers have an attenuation of symptoms during pregnancy. Rats display increased pain tolerance during pregnancy, due to an increase in opioid receptors in the spinal cord. These past studies did not consider the role of non-neuronal cells, now appreciated to play an important role in chronic pain processing. Using an inflammatory (complete Freund's adjuvant) or neuropathic (spared nerve injury) model of persistent pain, we observe that young adult female mice in early pregnancy switch from a micgrolia-independent to a microglia-dependent pain hypersensitivity mechanism...
September 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28857330/increased-habenular-connectivity-in-opioid-users-is-associated-with-an-%C3%AE-5-subunit-nicotinic-receptor-genetic-variant
#5
Kaylah Curtis, Humsini Viswanath, Kenia M Velasquez, David L Molfese, Mark J Harding, Eduardo Aramayo, Philip R Baldwin, Elisa Ambrosi, Alok Madan, Michelle Patriquin, B Christopher Frueh, J Christopher Fowler, Thomas R Kosten, David A Nielsen, Ramiro Salas
BACKGROUND AND OBJECTIVES: Opioid use disorder (OUD) is a chronic disorder with relapse based on both desire for reinforcement (craving) and avoidance of withdrawal. The aversive aspect of dependence and relapse has been associated with a small brain structure called the habenula, which expresses large numbers of both opioid and nicotinic receptors. Additionally, opioid withdrawal symptoms can be induced in opioid-treated rodents by blocking not only opioid, but also nicotinic receptors...
August 31, 2017: American Journal on Addictions
https://www.readbyqxmd.com/read/28818631/topical-medical-cannabis-tmc-a-new-treatment-for-wound-pain-three-cases-of-pyoderma-gangrenosum
#6
Vincent Maida, Jason Corban
Pain associated with integumentary wounds is highly prevalent yet it remains an area of significant unmet need within healthcare. Currently, systemically administered opioids are the mainstay of treatment. However, recent publications are casting opioids in a negative light given their high side effect profile, inhibition of wound healing, and association with accidental overdose, incidents that are frequently fatal. Thus, novel analgesic strategies for wound-related pain need to be investigated. The ideal methods of pain relief for wound patients are modalities that are topical, lack systemic side effects, non-invasive, self-administered, and display rapid onset of analgesia...
August 14, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28811180/development-of-an-opioid-self-administration-assay-to-study-drug-seeking-in-zebrafish
#7
Gabriel D Bossé, Randall T Peterson
The zebrafish (Danio rerio) has become an excellent tool to study mental health disorders, due to its physiological and genetic similarity to humans, ease of genetic manipulation, and feasibility of small molecule screening. Zebrafish have been shown to exhibit characteristics of addiction to drugs of abuse in non-contingent assays, including conditioned place preference, but contingent assays have been limited to a single assay for alcohol consumption. Using inexpensive electronic, mechanical, and optical components, we developed an automated opioid self-administration assay for zebrafish, enabling us to measure drug seeking and gain insight into the underlying biological pathways...
August 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28807672/pharmacological-characterization-of-novel-synthetic-opioids-nso-found-in-the-recreational-drug-marketplace
#8
REVIEW
Michael H Baumann, Susruta Majumdar, Valerie Le Rouzic, Amanda Hunkele, Rajendra Uprety, Xi Ping Huang, Jin Xu, Bryan L Roth, Ying-Xian Pan, Gavril W Pasternak
Novel synthetic opioids (NSO) are increasingly encountered in illicit heroin and counterfeit pain pills. Many NSO are resurrected from older biomedical literature or patent applications, so limited information is available about their biological effects. Here we examined the pharmacology of three structurally-distinct NSO found in the recreational drug market: N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylbutyramide (butyrylfentanyl), 3,4-dichloro-N-[(1R,2R)-2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) and 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine (MT-45)...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28801372/multi-variant-genetic-panel-for-genetic-risk-of-opioid-addiction
#9
Keri Donaldson, Laurence Demers, Kirk Taylor, Joe Lopez, Sherman Chang
Over 116 million people worldwide have chronic pain and prescription dependence. In the US, opioids account for the majority of overdose deaths, and in 2014, almost 2 million Americans abused or were dependent on prescription opioids. Genetic factors may play a key role in opioid prescription addiction. Herein, we describe genetic variations between opioid addicted and non-addicted populations and derive a predictive model determining risk of opioid addiction. This case cohort study compares the frequency of 16 single nucleotide polymorphisms involved in the brain reward pathways in patients with and without opioid addiction...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28780411/increased-ethanol-drinking-in-humanized-mice-expressing-the-mu-opioid-receptor-a118g-polymorphism-are-mediated-through-sex-specific-mechanisms
#10
Angela N Henderson-Redmond, Tammy E Lowe, Xi B Tian, Daniel J Morgan
The A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (Oprm1) has been implicated in mediating the rewarding effects of alcohol. Clinical and preclinical studies suggest that the G allele may confer a genetic vulnerability to alcohol dependence, though it remains unknown whether these effects are sex-specific. We used male and female mice homozygous for the "humanized" 118AA or 118GG alleles to determine whether the A118G SNP potentiates ethanol consumption in a sex-specific manner in both the two-bottle choice and drinking-in-the-dark (DID) paradigms...
August 2, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28770976/non-steroidal-anti-inflammatory-drugs-nsaids-for-chronic-non-cancer-pain-in-children-and-adolescents
#11
REVIEW
Christopher Eccleston, Tess E Cooper, Emma Fisher, Brian Anderson, Nick Mr Wilkinson
BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important...
August 2, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28768313/treatment-of-hailey-hailey-disease-with-low-dose-naltrexone
#12
Lauren N Albers, Jack L Arbiser, Ron J Feldman
Importance: Hailey-Hailey disease is a severe genetic blistering disease of intertriginous skin locations that can lead to poor quality of life and increased morbidities. Multiple therapies are available with inconsistent outcomes and potentially severe adverse effects. Objective: To determine whether low-dose naltrexone is an effective treatment for Hailey-Hailey disease. Design, Setting, and Participants: This study was a case series performed at a dermatology outpatient clinic of 3 patients with severe Hailey-Hailey disease recalcitrant to at least 4 therapies...
August 2, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28745932/genetic-deletion-of-microglial-panx1-attenuates-morphine-withdrawal-but-not-analgesic-tolerance-or-hyperalgesia-in-mice
#13
Nicole E Burma, Heather Leduc-Pessah, Tuan Trang
Opioids are among the most powerful analgesics for managing pain, yet their repeated use can lead to the development of severe adverse effects. In a recent study, we identified the microglial pannexin-1 channel (Panx1) as a critical substrate for opioid withdrawal. Here, we investigated whether microglial Panx1 contributes to opioid-induced hyperalgesia (OIH) and opioid analgesic tolerance using mice with a tamoxifen-inducible deletion of microglial Panx1. We determined that escalating doses of morphine resulted in thermal pain hypersensitivity in both Panx1-expressing and microglial Panx1-deficient mice...
July 26, 2017: Channels
https://www.readbyqxmd.com/read/28745577/advanced-cancer-pain-the-search-for-genetic-factors-correlated-with-interindividual-variability-in-opioid-requirement
#14
Maja Matic, Joost Lm Jongen, Laure Elens, Saskia N de Wildt, Dick Tibboel, Peter Ae Sillevis Smitt, Ron Hn van Schaik
AIM: To assess association between genetic variants and opioid requirement in cancer patients. MATERIALS & METHODS: A prospective observational trial of 243 advanced cancer patients with inadequate analgesia treated by the palliative care team was analyzed for ABCB1, ARRB2, COMT, GCH1, IL1RN, KCNJ6, OPRM1, RHBDF2, SCN9A and Stat6 polymorphisms. RESULTS: For patients carrying OPRM1 118AG/GG and COMT 472GG (Val158Val) or these genotypes alone, a significant higher median percentage dose increase was observed (95...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28738753/genetic-predictors-of-celiac-disease-lactose-intolerance-and-vitamin-d-function-and-presence-of-peptide-morphins-in-urine-of-children-with-neurodevelopmental-disorders
#15
Katarina Bojović, Biljana Stanković, Nikola Kotur, Dijana Krstić-Milošević, Vladimir Gašić, Sonja Pavlović, Branka Zukić, Đurđica Ignjatović
Gastrointestinal disturbances, nutritional deficiencies, and food intolerances are frequently observed in children with neurodevelopmental disorders (NDD). To reveal possible association of celiac disease risk variants (HLA-DQ), lactose intolerance associated variant (LCT-13910C>T) as well as variant associated with vitamin D function (VDR FokI) with NDD, polymerase chain reaction-based methodology was used. Additionally, intestinal peptide permeability was estimated in NDD patients and healthy children by measuring the level of peptides in urine using high-performance liquid chromatography...
July 24, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28734904/identifying-novel-members-of-the-wntless-interactome-through-genetic-and-candidate-gene-approaches
#16
Jessica Petko, Trevor Tranchina, Goral Patel, Robert Levenson, Stephanie Justice-Bitner
Wnt signaling is an important pathway that regulates several aspects of embryogenesis, stem cell maintenance, and neural connectivity. We have recently determined that opioids decrease Wnt secretion, presumably by inhibiting the recycling of the Wnt trafficking protein Wntless (Wls). This effect appears to be mediated by protein-protein interaction between Wls and the mu-opioid receptor (MOR), the primary cellular target of opioid drugs. The goal of this study was to identify novel protein interactors of Wls that are expressed in the brain and may also play a role in reward or addiction...
July 20, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28704923/production-of-cow-s-milk-free-from-beta-casein-a1-and-its-application-in-the-manufacturing-of-specialized-foods-for-early-infant-nutrition
#17
Miguel Á Duarte-Vázquez, Carlos García-Ugalde, Laura M Villegas-Gutiérrez, Blanca E García-Almendárez, Jorge L Rosado
Beta-casein (BC) is frequently expressed as BC A2 and BC A1 in cow's milk. Gastrointestinal digestion of BC A1 results in the release of the opioid peptide beta-casomorphin 7 (BCM7) which is less likely to occur from BC A2. This work was aimed to produce milk containing BC A2 with no BC A1 (BC A2 milk) using genetically selected CSN2 A2A2 Jersey cows. Additionally, we aimed to develop an infant formula (IF) suitable for healthy full-term infants during the first six months of life based on BC A2 milk. The concentration of BCM7 released from BC A2 IF, from commercially available IFs as well as from human milk and raw cow's milk was evaluated after simulated gastrointestinal digestion (SGID)...
July 12, 2017: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28704071/social-monogamy-in-nonhuman-primates-phylogeny-phenotype-and-physiology
#18
Jeffrey A French, Jon Cavanaugh, Aaryn C Mustoe, Sarah B Carp, Stephanie L Womack
Monogamy as a social system has been both a scientific puzzle and a sociocultural issue for decades. In this review, we examine social monogamy from a comparative perspective with a focus on primates, our closest genetic relatives. We break down monogamy into component elements, including pair-bonding and partner preference, mate guarding or jealousy, social attachment, and biparental care. Our survey of primates shows that not all features are present in species classified as socially monogamous, in the same way that human monogamous relationships may not include all elements-a perspective we refer to as "monogamy à la carte...
July 13, 2017: Journal of Sex Research
https://www.readbyqxmd.com/read/28692418/contribution-of-genetic-polymorphisms-and-haplotypes-in-drd2-bdnf-and-opioid-receptors-to-heroin-dependence-and-endophenotypes-among-the-han-chinese
#19
Xuan Gao, Youxin Wang, Minglin Lang, Li Yuan, Albert Stuart Reece, Wei Wang
Heroin and drug dependence are major contributors to global health burden worldwide, but their underlying mechanisms remain elusive and may vary from population to population. Reward- and memory-related candidate genes dopamine D2 receptor (DRD2) and brain-derived neurotrophic factor (BDNF), as well as the opioid receptor genes (OPRM1, OPRD1, and OPRK1), have been implicated in drug dependence, but relatively little is known on their contributions to heroin dependence in populations worldwide. Hence, we evaluated the contributions of the above five candidate genes in heroin dependence and several important related endophenotypes (the onset age of heroin use and subjective response to first heroin use), at single single-nucleotide polymorphism as well as haplotype levels, in a Han Chinese population sample...
July 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28656735/an-analysis-of-genetic-association-in-opioid-dependence-susceptibility
#20
D Nagaya, Z Zahari, M Saleem, B H Yahaya, S C Tan, N M Yusoff
WHAT IS KNOWN: Drug addiction is a novelty-seeking personality trait that is associated with the candidate genes OPRD1 (opioid delta receptors), OPRK1 (opioid kappa receptors) and PDYN (prodynorphin). However, associations between single nucleotide polymorphisms (SNPs) rs1042114 (80G>T) of the OPRD1 gene, rs702764 (843 A>G) of the OPRK1 gene, and rs910080 (3' UTR _743T>C), rs1997794 (5' UTR -381A>G) and rs1022563 (3' UTR) of the PDYN gene and novelty seeking remain controversial as reported results have not been reproducible...
June 27, 2017: Journal of Clinical Pharmacy and Therapeutics
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