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https://www.readbyqxmd.com/read/29149605/bias-factor-and-therapeutic-window-correlate-to-predict-safer-opioid-analgesics
#1
Cullen L Schmid, Nicole M Kennedy, Nicolette C Ross, Kimberly M Lovell, Zhizhou Yue, Jenny Morgenweck, Michael D Cameron, Thomas D Bannister, Laura M Bohn
Biased agonism has been proposed as a means to separate desirable and adverse drug responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe structural features of a series of mu-opioid-receptor (MOR)-selective agonists that preferentially activate receptors to couple to G proteins or to recruit βarrestin proteins. By comparing relative bias for MOR-mediated signaling in each pathway, we demonstrate a strong correlation between the respiratory suppression/antinociception therapeutic window in a series of compounds spanning a wide range of signaling bias...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29143891/in-search-of-the-ideal-promotility-agent-optimal-use-of-currently-available-promotility-agents-for-nutrition-therapy-of-the-critically-ill-patient
#2
REVIEW
Sarah J Diamond, Endashaw Omer, Laszlo Kiraly
PURPOSE OF REVIEW: Enteral nutrition therapy is essential in the management of critically ill patients. Prokinetic agents have been used successfully to aid in the delivery of nutrition and improve feeding tolerance in patients in the intensive care unit (ICU). The aim of this report is to review the existing promotility agents available for use in the critically ill as well as outline the role of potential investigative drugs in order to provide a guide to the management of this difficult and important clinical dilemma...
November 16, 2017: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/29138154/pharmacologic-management-of-chronic-neuropathic-pain-review-of-the-canadian-pain-society-consensus-statement
#3
REVIEW
Alex Mu, Erica Weinberg, Dwight E Moulin, Hance Clarke
OBJECTIVE: To provide family physicians with a practical clinical summary of the Canadian Pain Society (CPS) revised consensus statement on the pharmacologic management of neuropathic pain. QUALITY OF EVIDENCE: A multidisciplinary interest group within the CPS conducted a systematic review of the literature on the current treatments of neuropathic pain in drafting the revised consensus statement. MAIN MESSAGE: Gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are the first-line agents for treating neuropathic pain...
November 2017: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/29137427/association-of-opioid-receptor-mu-1-oprm1-a118g-polymorphism-rs1799971-with-nicotine-dependence
#4
Xiangyi Kong, Hao Deng, Theodore Alston, Yanguo Kong, Jingping Wang
Background and Object: Whether opioid-receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) is associated with nicotine dependence is controversial. We analyzed the combined results from published studies of this possibility. Methods: Literature reviews were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Web of Science, Chinese National Science Infrastructure (CNKI), PubMed, Embase and Google Scholar database searches using MeSH terms were conducted to find all relevant researches up to October 2016...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131554/the-pathophysiology-incidence-impact-and-treatment-of-opioid-induced-nausea-and-vomiting
#5
Theresa Mallick-Searle, Mechele Fillman
PURPOSE: Opioid medications are integral in managing acute moderate-to-severe pain. Opioid analgesics bind to μ (mu), κ (kappa), or δ (delta) opioid receptors in the brain, spinal cord, and digestive tract. However, opioids cause adverse effects that may interfere with their therapeutic use. Some adverse effects wane over time, but patients using opioids for acute pain struggle with opioid-induced nausea and vomiting (OINV) the entire time they take the opioid. This article discusses the underlying mechanisms, clinical implications, and treatment strategies of OINV...
November 2017: Journal of the American Association of Nurse Practitioners
https://www.readbyqxmd.com/read/29129606/transgenerational-blunting-of-morphine-induced-corticosterone-secretion-is-associated-with-dysregulated-gene-expression-in-male-offspring
#6
Fair M Vassoler, Anika M Toorie, Elizabeth M Byrnes
A number of parental experiences, even when occurring prior to conception, have been shown to induce transgenerational effects beyond the first generation. In the case of exposure to drugs of abuse, studies in rodents suggest that offspring demonstrate significant differences in how they respond to the drug to which their parent was exposed. We have previously observed significant alterations in morphine analgesia, conditioned place preference and self-administration in the offspring of females exposed to morphine during adolescent development...
November 9, 2017: Brain Research
https://www.readbyqxmd.com/read/29124992/efficacy-of-ketamine-for-postoperative-pain-following-robotic-thyroidectomy-a-prospective-randomised-study
#7
Jiwon Lee, Hee-Pyoung Park, Mu-Hui Jeong, Je-Do Son, Hyun-Chang Kim
Objective Although robotic thyroidectomy (RoT) is a minimally invasive surgery, percutaneous tunneling causes moderate to severe pain immediately postoperatively. We evaluated the efficacy of ketamine for postoperative pain management in patients following RoT. Methods Sixty-four patients scheduled for RoT were randomly divided into two groups. In the ketamine group (n = 32), ketamine was infused from induction of anaesthesia until the end of the procedure (0.15-mg/kg bolus with continuous infusion at 2 µg/kg/min)...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/29119706/insights-on-efficacious-doses-of-pamoras-for-patients-on-chronic-opioid-therapy-or-opioid-na%C3%A3-ve-patients
#8
K van Malderen, H Halawi, M Camilleri
BACKGROUND: Opioid-induced constipation (OIC) is a major side effect of opioid use. Centrally acting antagonists result in opioid withdrawal or worsening of pain and lead to use of peripherally acting mu-opioid receptor antagonists (PAMORAs). The required doses of the PAMORAs, methylnaltrexone and naloxegol, in the treatment of OIC are well established in chronic opioid users. OIC may occur after short duration of opioid treatment; the required doses of naloxone, naltrexone, and PAMORAs in opioid-naïve subjects (with no opioid use for at least 3 months) are unclear...
November 9, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29116553/effect-of-sinomenine-on-the-morphine-dependence-and-related-neural-mechanisms-in-mice
#9
Miao Fang, Junkui Li, Daoqi Zhu, Chaohua Luo, Chan Li, Chen Zhu, Menglin Fan, Ken Kin-Lam Yung, Zhixian Mo
Evidence suggests that the dopamine receptor rate-limiting enzyme, tyrosine hydroxylase (TH), and the glutamate receptor, N-methyl-D-aspartate receptor 2B (NR2B), contribute to morphine dependence. Previous studies show that chronic exposure to morphine changes the expression of opioid receptors. In this study, we focus on the effects of sinomenine on morphine-dependent mice and its related neural mechanisms. Conditioned place preference (CPP) mouse model was established using morphine (9 mg/kg, s.c.), and their expression levels of TH and NR2B were observed by immunohistochemistry...
November 8, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29105118/v1b-receptor-antagonist-ssr149415-and-naltrexone-synergistically-decrease-excessive-alcohol-drinking-in-male-and-female-mice
#10
Yan Zhou, Marcelo Rubinstein, Malcolm Low, Mary Jeanne Kreek
BACKGROUND: A recent clinical trial found that pharmacological blockade of V1b receptors reduces alcohol relapse in alcohol-dependent patients. SSR149415 is a selective V1b receptor antagonist that has potential for development as an alcohol dependency treatment. In this study, we investigated whether SSR149415 alone or in combination with the mu-opioid receptor [MOP-r] antagonist naltrexone (NTN) would alter excessive alcohol drinking in mice. METHODS: Both sexes of C57BL/6J (B6) mice were subjected to a chronic intermittent access (IA) drinking paradigm (two-bottle choice, 24-h access every other day) for 3 weeks...
November 3, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29097440/desensitization-and-tolerance-of-mu-opioid-receptors-on-pontine-kolliker-fuse-neurons
#11
Erica S Levitt, John T Williams
Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G protein-coupled inwardly rectifying potassium (GIRK) current was measured using whole-cell voltage-clamp recordings from KF and locus coeruleus (LC) neurons contained in acute rat brain slices...
November 2, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29094432/mu-opioid-receptors-in-gabaergic-neurons-of-the-forebrain-promote-alcohol-reward-and-drinking
#12
Sami Ben Hamida, Laura-Joy Boulos, Michael McNicholas, Pauline Charbogne, Brigitte Lina Kieffer
Mu opioid receptors (MORs) are widely distributed throughout brain reward circuits and their role in drug and social reward is well established. Substantial evidence has implicated MOR and the endogenous opioid system in alcohol reward, but circuit mechanisms of MOR-mediated alcohol reward and intake behavior remain elusive, and have not been investigated by genetic approaches. We recently created conditional knockout (KO) mice targeting the Oprm1 gene in GABAergic forebrain neurons. These mice (Dlx-MOR KO) show a major MOR deletion in the striatum, whereas receptors in midbrain (including the Ventral Tegmental Area or VTA) and hindbrain are intact...
November 2, 2017: Addiction Biology
https://www.readbyqxmd.com/read/29075135/dnmt3a-methylation-in-neuropathic-pain
#13
Cuijie Shao, Yong Gao, Dan Jin, Xin Xu, Shuying Tan, Hui Yu, Qingxiang Zhao, Li Zhao, Wansheng Wang, Deqiang Wang
BACKGROUND: Mu opioid receptor (MOR) plays a crucial role in mediating analgesic effects of opioids and is closely associated with the pathologies of neuropathic pain. Previous studies have reported that peripheral nerve injury downregulates MOR expression, but the epigenetic mechanisms remain unknown. OBJECTIVE: Therefore, we investigated DNA methyltransferase3a (DNMT3a) expression or methylation changes within MOR promoter in the spinal cord in a neuropathic pain induced by a chronic constriction injury (CCI) mouse model and further determined whether these injury-associated changes are reversible by pharmacological interventions...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29073492/tianeptine-is-associated-with-lower-risk-of-suicidal-ideation-worsening-during-the-first-weeks-of-treatment-onset-compared-with-other-antidepressants-a-naturalistic-study
#14
B Nobile, I Jaussent, Ph Gorwood, J Lopez Castroman, E Olié, S Guillaume, Ph Courtet
Worsening of suicidal ideation during the first weeks of antidepressant treatment is a poorly understood phenomenon that prompted regulatory bodies to issue specific warnings. To better understand the causes of this phenomenon, this study compared the risk of suicidal ideation worsening in patients taking different types of antidepressant medications. To this aim, 4017 depressed adult outpatients were followed by general practitioners and psychiatrists throughout France for 6 weeks after prescription of an antidepressant treatment...
October 16, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29073109/opioid-and-orexin-hedonic-hotspots-in-rat-orbitofrontal-cortex-and-insula
#15
Daniel C Castro, Kent C Berridge
Hedonic hotspots are brain sites where particular neurochemical stimulations causally amplify the hedonic impact of sensory rewards, such as "liking" for sweetness. Here, we report the mapping of two hedonic hotspots in cortex, where mu opioid or orexin stimulations enhance the hedonic impact of sucrose taste. One hedonic hotspot was found in anterior orbitofrontal cortex (OFC), and another was found in posterior insula. A suppressive hedonic coldspot was also found in the form of an intervening strip stretching from the posterior OFC through the anterior and middle insula, bracketed by the two cortical hotspots...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29070014/lack-of-associations-of-the-opioid-receptor-mu-1-oprm1-a118g-polymorphism-rs1799971-with-alcohol-dependence-review-and-meta-analysis-of-retrospective-controlled-studies
#16
REVIEW
Xiangyi Kong, Hao Deng, Shun Gong, Theodore Alston, Yanguo Kong, Jingping Wang
BACKGROUND: Studies have sought associations of the opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with alcohol-dependence, but findings are inconsistent. We summarize the information as to associations of rs1799971 (A > G) and the alcohol-dependence. METHODS: Systematically, we reviewed related literatures using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Embase, PubMed, Web of Knowledge, and Chinese National Knowledge Infrastructure (CNKI) databases were searched using select medical subject heading (MeSH) terms to identify all researches focusing on the present topic up to September 2016...
October 26, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/29055075/association-between-genetic-polymorphisms-and-pain-sensitivity-in-patients-with-hip-osteoarthritis
#17
Anne E Olesen, Lecia M Nielsen, Søren Feddersen, Joachim Erlenwein, Frank Petzke, Michael Przemeck, Lona L Christrup, Asbjørn M Drewes
BACKGROUND: Factors such as age, gender and genetic polymorphisms may explain individual difference in pain phenotype. Genetic associations to pain sensitivity have previously been investigated in osteoarthritis patients with focus on the P2X7, TRPV1 and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system...
October 20, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/29054370/accessibility-of-axonal-g-protein-coupled-mu-opioid-receptors-requires-conceptual-changes-of-axonal-membrane-targeting-for-pain-modulation
#18
Shaaban A Mousa, Mohammed Shaqura, Mohammed Al-Madol, Sascha Tafelski, Baled I Khalefa, Mehdi Shakibaei, Michael Schäfer
The mechanisms of axonal trafficking and membrane targeting are well established for sodium channels, which are the principle targets for perineurally applied local anaesthetics. However, they have not been thoroughly investigated for G protein coupled receptors such as mu-opioid receptors (MOR). Focusing on these axonal mechanisms, we found that axonal MOR functionality is quite distinct in two different pain states, i.e. hindpaw inflammation and nerve injury. We observed axonal membrane MOR binding and functional G protein coupling exclusively at sites of CCI nerve injury...
October 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29044528/endomorphins-potentiate-asic-currents-and-enhance-the-lactic-acid-mediated-increase-in-arterial-blood-pressure-effects-amplified-in-hindlimb-ischemia
#19
Mohamed Farrag, Julie K Drobish, Henry L Puhl, Joyce S Kim, Paul B Herold, Marc P Kaufman, Victor Ruiz-Velasco
Chronic muscle ischemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex...
October 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29040826/maintenance-on-naltrexone-amphetamine-decreases-cocaine-vs-food-choice-in-male-rhesus-monkeys
#20
Megan J Moerke, Matthew L Banks, Kejun Cheng, Kenner C Rice, S Stevens Negus
BACKGROUND: Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice...
December 1, 2017: Drug and Alcohol Dependence
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