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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/27903642/behavioral-characterization-of-kappa-opioid-receptor-agonist-spiradoline-and-cannabinoid-receptor-agonist-cp55940-mixtures-in-rats
#2
Vanessa Minervini, Sujata S Dahal, Charles France
Pain is a significant clinical problem and there is a need for more effective treatments with reduced adverse effects that currently limit the use of mu opioid receptor agonists. Synthetic kappa opioid receptor agonists have no abuse liability and well-documented antinociceptive effects; however, adverse effects (diuresis, dysphoria) preclude their use in the clinic. Combining kappa opioids with non-opioid drugs (cannabinoid receptor agonists) allows for smaller doses of each drug to produce antinociception...
November 30, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27899885/interacting-cannabinoid-and-opioid-receptors-in-the-nucleus-accumbens-core-control-adolescent-social-play
#3
Antonia Manduca, Olivier Lassalle, Marja Sepers, Patrizia Campolongo, Vincenzo Cuomo, Giovanni Marsicano, Brigitte Kieffer, Louk J M J Vanderschuren, Viviana Trezza, Olivier J J Manzoni
Social play behavior is a highly rewarding, developmentally important form of social interaction in young mammals. However, its neurobiological underpinnings remain incompletely understood. Previous work has suggested that opioid and endocannabinoid neurotransmission interact in the modulation of social play. Therefore, we combined behavioral, pharmacological, electrophysiological, and genetic approaches to elucidate the role of the endocannabinoid 2-arachidonoylglycerol (2-AG) in social play, and how cannabinoid and opioid neurotransmission interact to control social behavior in adolescent rodents...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27894149/2-3-5-4-tetrahydroxystilbene-2-o-%C3%AE-d-glucoside-attenuates-ischemia-reperfusion-induced-brain-injury-in-rats-by-promoting-angiogenesis
#4
Ying Mu, Zhaohui Xu, Xuanxuan Zhou, Huinan Zhang, Qian Yang, Yunlong Zhang, Yanhua Xie, Juan Kang, Feng Li, Siwang Wang
Cerebral ischemia can cause brain infarcts, which are difficult to recover due to poor angiogenesis. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside is a natural polyphenol, has antioxidant and anti-inflammatory activity, and can protect from ischemic neuronal injury. However, little is known about the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside on brain microcirculation after stroke. This study aimed at investigating the influence of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside on brain lesions and angiogenesis after stroke...
November 28, 2016: Planta Medica
https://www.readbyqxmd.com/read/27890744/gene-expression-of-pro-opiomelanocortin-and-melanocortin-receptors-is-regulated-in-the-hypothalamus-and-mesocorticolimbic-system-following-nicotine-administration
#5
Damla E Tapinc, Rabia Ilgin, Egemen Kaya, Oguz Gozen, Muzeyyen Ugur, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Pro-opiomelanocortin (POMC)-derived peptides and their receptors have been shown to play important roles in natural and drug-induced reward and reinforcement. Reward process may involve the regulation of POMC gene expression and the gene expression of POMC-derived peptide receptors. The present study investigated the alterations observed in the transcript levels of POMC, melanocortin 3 (MC3R), melanocortin 4 (MC4R) and mu-opioid receptors (MOR) in the hypothalamus and mesocorticolimbic system during nicotine exposure...
November 24, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27889435/role-of-hmgb1-translocation-to-neuronal-nucleus-in-rat-model-with-septic-brain-injury
#6
Yafei Li, Xihong Li, Yi Qu, Jichong Huang, Tingting Zhu, Fengyan Zhao, Shiping Li, Dezhi Mu
High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining...
November 23, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27882998/dopamine-and-opioid-neurotransmission-in-behavioral-addictions-a-comparative-pet-study-in-pathological-gambling-and-binge-eating
#7
Joonas Majuri, Juho Joutsa, Jarkko Johansson, Valerie Voon, Kati Alakurtti, Riitta Parkkola, Tuuli Lahti, Hannu Alho, Jussi Hirvonen, Eveliina Arponen, Sarita Forsback, Valtteri Kaasinen
Although behavioral addictions share many clinical features with drug addictions, they show strikingly large variation in their behavioral phenotypes (such as in uncontrollable gambling or eating). Neurotransmitter function in behavioral addictions is poorly understood but has important implications in understanding its relationship with substance use disorders and underlying mechanisms of therapeutic efficacy. Here, we compare opioid and dopamine function between two behavioral addiction phenotypes: pathological gambling (PG) and binge eating disorder (BED)...
November 24, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27878277/synthetic-paclitaxel-octreotide-conjugate-reverses-the-resistance-of-paclitaxel-in-a2780-taxol-ovarian-cancer-cell-line
#8
Yang Shen, Xiao-Yu Zhang, Xi Chen, Li-Li Fan, Mu-Lan Ren, Yong-Ping Wu, Kenneth Chanda, Shi-Wen Jiang
The high mortality of ovarian cancer is partly due to the frequent resistance of ovarian cancer to current chemotherapy agents such as paclitaxel and platinum. Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some tumors through binding to somatostatin receptor (SSTR) and activation of Ras-, Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor growth inhibition with reduced toxicity...
November 18, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27876117/neonatal-abstinence-syndrome-and-the-gastrointestinal-tract
#9
Denise Maguire, Maureen Gröer
Development of a healthy gut microbiome is essential in newborns to establish immunity and protection from pathogens. Recent studies suggest that infants who develop dysbiosis may be at risk for lifelong adverse health consequences. Exposure to opioid drugs during pregnancy is a factor of potential importance for microbiome health that has not yet been investigated. Since these infants are born after an entire gestation exposed to mu opioid receptor agonists and have severe gastrointestinal and neurological symptoms, we hypothesize that these infants are at risk for dysbiosis...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27870313/hypothalamic-specific-proopiomelanocortin-deficiency-reduces-alcohol-drinking-in-male-and-female-mice
#10
Yan Zhou, Marcelo Rubinstein, Malcolm J Low, Mary Jeanne Kreek
Opioid receptor antagonist naltrexone reduces alcohol consumption and relapse in both humans and rodents. The present study investigated whether hypothalamic proopiomelanocortin (POMC) neurons (producing beta-endorphin and melanocortins) play a role in alcohol drinking behaviors. Both male and female mice with targeted deletion of two neuronal Pomc enhancers nPE1 and nPE2 (nPE-/-), resulting in hypothalamic-specific POMC deficiency, were studied in short-access (4-h/day) drinking-in-the-dark (DID, alcohol in one bottle), intermittent access (IA, 24-hour cycles of alcohol access every other day, alcohol vs...
November 21, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27867511/is-tapentadol-different-from-classical-opioids-a-review-of-the-evidence
#11
Richard M Langford, Roger Knaggs, Paul Farquhar-Smith, Anthony H Dickenson
Tapentadol is a single molecule able to deliver analgesia by two distinct mechanisms, a feature which differentiates it from many other analgesics. Pre-clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist activity and noradrenaline re-uptake inhibition. From these, one may predict that tapentadol would be applicable across a broad spectrum of pain from nociceptive to neuropathic. The evidence in animal models suggests that norepinephrine re-uptake inhibition (NRI) is a key mechanism and may even predominate over opioid actions in chronic (and especially neuropathic) pain states, reinforcing that tapentadol is different to classical opioids and may, therefore, be an a priori choice for the treatment of neuropathic and mixed pain...
November 2016: British Journal of Pain
https://www.readbyqxmd.com/read/27862489/amygdala-mu-opioid-receptors-mediate-the-motivating-influence-of-cue-triggered-reward-expectations
#12
Nina T Lichtenberg, Kate M Wassum
Environmental reward-predictive stimuli can retrieve from memory a specific reward expectation that allows them to motivate action and guide choice. This process requires the basolateral amygdala (BLA), but little is known about the signaling systems necessary within this structure. Here we examined the role of the neuromodulatory opioid receptor system in the BLA in such cue-directed action using the outcome-specific Pavlovian-to-instrumental transfer (PIT) test in rats. Inactivation of BLA mu-, but not delta-opioid receptors was found to dose-dependently attenuate the ability of a reward-predictive cue to selectively invigorate the performance of actions directed at the same unique predicted reward (i...
November 12, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27861362/effects-of-target-controlled-infusion-of-high-dose-naloxone-on-pain-and-hyperalgesia-in-a-human-thermal-injury-model-a-study-protocol-a-randomized-double-blind-placebo-controlled-crossover-trial-with-an-enriched-design
#13
Anders D Springborg, Elisabeth K Jensen, Bradley K Taylor, Mads U Werner
Mu-opioid-receptor antagonists have been extensively studied in experimental research as pharmacological tools uncovering mechanisms of pain modulation by the endogenous opioid system. In rodents, administration of high doses of mu-opioid-receptor antagonists after the resolution of an inflammatory injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone infusion...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27857679/bold-imaging-in-awake-wild-type-and-mu-opioid-receptor-knock-out-mice-reveals-on-target-activation-maps-in-response-to-oxycodone
#14
Kelsey Moore, Dan Madularu, Sade Iriah, Jason R Yee, Praveen Kulkarni, Emmanuel Darcq, Brigitte L Kieffer, Craig F Ferris
Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (μ) opioid receptor knock-outs (MuKO) in response to oxycodone (OXY). Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27857228/dopamine-regulates-renal-osmoregulation-during-hyposaline-stress-via-drd1-in-the-spotted-scat-scatophagus-argus
#15
Maoliang Su, Xingjiang Mu, Lang Gui, Peipei Zhang, Jianan Zhou, Jie Ma, Junbin Zhang
Dopamine is an important regulator of renal natriuresis and is critical for the adaptation of many animals to changing environmental salinity. However, the molecular mechanisms through which dopamine promotes this adaptation remain poorly understood. We studied the effects of dopamine on renal hypo-osmoregulation in the euryhaline fish Scatophagus argus (S. argus) during abrupt transfer from seawater (SW) to freshwater (FW). Following the transfer, serum dopamine concentration was decreased, and dopamine activated expression of the dopamine receptor 1 (designated SaDRD1) in the kidney, triggering the osmoregulatory signaling cascade...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852962/anatomy-and-immunochemical-characterization-of-the-non-arterial-peptidergic-diffuse-dural-innervation-of-the-rat-and-rhesus-monkey-implications-for-functional-regulation-and-treatment-in-migraine
#16
Frank L Rice, Jennifer Y Xie, Phillip J Albrecht, Emily Acker, Justin Bourgeois, Edita Navratilova, David W Dodick, Frank Porreca
OBJECTIVE: The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. METHODS: We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey...
November 16, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27849613/endogenous-central-amygdala-mu-opioid-receptor-signaling-promotes-sodium-appetite-in-mice
#17
Craig M Smith, Lesley L Walker, Tanawan Leeboonngam, Michael J McKinley, Derek A Denton, Andrew J Lawrence
Due to the importance of dietary sodium and its paucity within many inland environments, terrestrial animals have evolved an instinctive sodium appetite that is commensurate with sodium deficiency. Despite a well-established role for central opioid signaling in sodium appetite, the endogenous influence of specific opioid receptor subtypes within distinct brain regions remains to be elucidated. Using selective pharmacological antagonists of opioid receptor subtypes, we reveal that endogenous mu-opioid receptor (MOR) signaling strongly drives sodium appetite in sodium-depleted mice, whereas a role for kappa (KOR) and delta (DOR) opioid receptor signaling was not detected, at least in sodium-depleted mice...
November 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27842940/nalmefene-for-the-management-of-alcohol-dependence-review-on-its-pharmacology-mechanism-of-action-and-meta-analysis-on-its-clinical-efficacy
#18
Karl Mann, Lars Torup, Per Sørensen, Antoni Gual, Robert Swift, Brendan Walker, Wim van den Brink
Nalmefene, a mu- and delta-opioid receptor (MOR, DOR) antagonist and a partial kappa-opioid receptor (KOR) agonist, is approved in the European Union and other countries for the reduction of alcohol consumption in alcohol dependent patients with a high drinking risk level according to WHO ("target population"). This review presents an overview of nalmefene׳s pharmacology, its mechanisms of action and a meta-analysis on its efficacy in reducing alcohol consumption. The review was based on a systematic search of the literature...
November 11, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27836661/phosphorylation-of-poly-rc-binding-protein-1-pcbp1-contributes-to-stabilization-of-mu-opioid-receptor-mor-mrna-via-interaction-with-au-rich-element-rna-binding-protein-1-auf1-and-poly-a-binding-protein-pabp
#19
Cheol Kyu Hwang, Yadav Wagley, Ping-Yee Law, Li-Na Wei, Horace H Loh
Gene regulation at the post-transcriptional level is frequently based on cis- and trans-acting factors on target mRNAs. We found a C-rich element (CRE) in mu-opioid receptor (MOR) 3'-untranslated region (UTR) to which poly (rC) binding protein 1 (PCBP1) binds, resulting in MOR mRNA stabilization. RNA immunoprecipitation and RNA EMSA revealed the formation of PCBP1-RNA complexes at the element. Knockdown of PCBP1 decreased MOR mRNA half-life and protein expression. Stimulation by forskolin increased cytoplasmic localization of PCBP1 and PCBP1/MOR 3'-UTR interactions via increased serine phosphorylation that was blocked by protein kinase A (PKA) or (phosphatidyl inositol-3) PI3-kinase inhibitors...
November 9, 2016: Gene
https://www.readbyqxmd.com/read/27834829/mirnas-and-mirna-polymorphisms-modify-drug-response
#20
REVIEW
Mu-Peng Li, Yao-Dong Hu, Xiao-Lei Hu, Yan-Jiao Zhang, Yong-Long Yang, Chun Jiang, Jie Tang, Xiao-Ping Chen
Differences in expression of drug response-related genes contribute to inter-individual variation in drugs' biological effects. MicroRNAs (miRNAs) are small noncoding RNAs emerging as new players in epigenetic regulation of gene expression at post-transcriptional level. MiRNAs regulate the expression of genes involved in drug metabolism, drug transportation, drug targets and downstream signal molecules directly or indirectly. MiRNA polymorphisms, the genetic variations affecting miRNA expression and/or miRNA-mRNA interaction, provide a new insight into the understanding of inter-individual difference in drug response...
November 8, 2016: International Journal of Environmental Research and Public Health
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