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morphine tolerance

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https://www.readbyqxmd.com/read/27922111/mir-365-targets-%C3%AE-arrestin-2-to-reverse-morphine-tolerance-in-rats
#1
Jian Wang, Wei Xu, Tao Zhong, Zongbin Song, Yu Zou, Zhuofeng Ding, Qulian Guo, Xinzhong Dong, Wangyuan Zou
Morphine tolerance is a challenging clinical problem that limits its clinical application in pain treatment. Non-coding microRNAs (miRNAs) modulate gene expression in a post transcriptional manner, and their dysregulation causes various diseases. However, the significance of miRNAs in morphine tolerance is still poorly understood. In the present study, we hypothesized that microRNA-365 (miR-365) is a key functional small RNA that reverses morphine tolerance through regulation of β-arrestin 2 in rats. Here, microarray analysis and quantitative real-time PCR showed that miR-365 was robustly decreased in the spinal cord after chronic morphine administration...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27915431/time-dependent-postmortem-redistribution-of-morphine-and-its-metabolites-in-blood-and-alternative-matrices-application-of-ct-guided-biopsy-sampling
#2
Sandra N Staeheli, Dominic Gascho, Lars C Ebert, Thomas Kraemer, Andrea E Steuer
Interpretation of postmortem morphine concentrations in forensic toxicology provides several pitfalls such as missing information on tolerance, analyte stability, or postmortem redistribution (PMR). Recently, it had been shown that computed tomography (CT)-guided collection of biopsies using a robotic arm (virtobot) provides a valuable strategy for systematic studies on time-dependent PMR. Using this technique, time-dependent PMR of morphine and its metabolites was investigated in 12 cases. At admission to the institute (t1), femoral and heart blood (right ventricle) as well as biopsies from the right lung, the right kidney, liver, spleen, and muscle tissue were collected...
December 3, 2016: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/27900763/parecoxib-propacetamol-and-their-combination-for-analgesia-after-total-hip-arthroplasty-a-randomized-non-inferiority-trial
#3
F Camu, A Borgeat, R J Heylen, E J Viel, M E Boye, R Y Cheung
BACKGROUND: This study assessed non-inferiority of parecoxib vs. combination parecoxib+propacetamol and compared the opioid-sparing effects of parecoxib, propacetamol, and parecoxib+propacetamol vs. placebo after total hip arthroplasty. METHODS: In this randomized, placebo-controlled, parallel-group, non-inferiority study, patients received one of four IV treatments after surgery: parecoxib 40 mg bid (n = 72); propacetamol 2 g qid (n = 71); parecoxib 40 mg bid plus propacetamol 2 g qid (n = 72); or placebo (n = 38) with supplemental IV patient-controlled analgesia (morphine)...
November 30, 2016: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/27899254/thalidomide-attenuates-the-development-and-expression-of-antinociceptive-tolerance-to-%C3%AE-opioid-agonist-morphine-through-l-arginine-inos-and-nitric-oxide-pathway
#4
Muhammad Imran Khan, Sattar Ostadhadi, Faiza Mumtaz, Majid Momeny, Farima Moghaddaskho, Mahsa Hassanipour, Shahram Ejtemaei-Mehr, Ahmad Reza Dehpour
Morphine is a μ-opioid analgesic drug which is used in the treatment and management of chronic pain. However, due to development of antinociceptive tolerance its clinical use is limited. Thalidomide is an old glutamic acid derivative which recently reemerged because of its potential to counteract a number of disorders including neurodegenerative disorders. The potential underlying mechanisms and effects of thalidomide on morphine-induced antinociceptive tolerance is still elusive. Hence, the present study was designed to explore the effect of thalidomide on the development and expression of morphine antinociceptive tolerance targeting l-arginine-nitric oxide (NO) pathway in mice and T98G human glioblastoma cell line...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27892451/upregulation-of-c-x-c-motif-ligand-13-cxcl13-attenuates-morphine-analgesia-in-rats-with-cancer-induced-bone-pain
#5
Shi-Feng Wang, Cheng-Gong Dong, Xue Yang, Jian-Jun Yin
BACKGROUND The aim of this study was to investigate the role of chemokine (C-X-C motif) ligand 13 (CXCL13) in morphine tolerance in rats with cancer-induced bone pain (CIBP). MATERIAL AND METHODS We established a rat CIBP model and a rat CIBP-morphine tolerance (BM) model. BM rats were intrathecally administered rmCXCL13, neutralizing anti-CXCL13, and normal saline, while the control group rats underwent a sham operation and were injected with normal saline. The morphine analgesia was assessed by measuring mechanical withdrawal threshold (MWT) and mechanical withdrawal duration (MWD) at various time points...
November 28, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27891611/pharmacokinetics-cannot-explain-the-increased-effective-dose-requirement-for-morphine-and-midazolam-in-rats-during-their-extended-administration-alone-or-in-combination
#6
Stefan J Schaller, Saad M Alam, Jianren Mao, Yanli Zhao, Manfred Blobner, David J Greenblatt, J A Jeevendra Martyn
OBJECTIVES: Chronic administration of morphine and midazolam, alone or in combination, can induce tolerance to their effects. Data showed that co-administration of morphine and midazolam increased effective dose requirement of morphine, exceeding that observed with morphine alone. METHODS: To elucidate the pharmacokinetic component to the tolerance, we administered midazolam (2 mg/kg) and morphine (10 mg/kg) alone or their combination daily to rats for 12 days followed by a pharmacokinetic study on day 13...
November 28, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27890603/a-novel-inhibitor-of-endocannabinoid-catabolic-enzymes-sheds-light-on-behind-the-scene-interplay-between-chronic-pain-analgesic-tolerance-and-heroin-dependence
#7
Josée Guindon
From the Aristotelian ancient Greece, pain has been associated with appetites or emotions and is opposite to pleasure. Reward and addiction is also linked to pleasure and compulsive drug seeking reinstates pleasure. Alleviation of chronic pain can induce a euphoric phase similar to what is found in addiction. Both chronic pain and addiction are recognized as a disease of the central nervous system. They share many characteristics and brain regions/mechanisms. Evidence points to the usefulness of cannabinoids as a new class of agents to add to the pharmaceutical toolbox in the management of chronic pain...
November 25, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27875800/evaluation-of-tspo-pet-imaging-a-marker-of-glial-activation-to-study-the-neuroimmune-footprints-of-morphine-exposure-and-withdrawal
#8
Sylvain Auvity, Sébastien Goutal, Benoît Thézé, Catarina Chaves, Benoît Hosten, Bertrand Kuhnast, Wadad Saba, Raphaël Boisgard, Irène Buvat, Salvatore Cisternino, Nicolas Tournier
INTRODUCTION: A growing area of research suggests that neuroimmunity may impact the pharmacology of opioids. Microglia is a key component of the brain immunity. Preclinical and clinical studies have demonstrated that microglial modulators may improve morphine-induced analgesia and prevent the development of tolerance and dependence. Positron emission tomography (PET) using translocator protein 18kDa (TSPO) radioligand is a clinically validated strategy for the non-invasive detection of microglial activation...
November 8, 2016: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/27872689/role-of-nitric-oxide-on-dopamine-release-and-morphine-dependency
#9
REVIEW
Amir Arash Motahari, Hedayat Sahraei, Gholam Hossein Meftahi
The catastrophic effects of opioids use on public health and the economy are documented clearly in numerous studies. Repeated morphine administration can lead to either a decrease (tolerance) or an increase (sensitization) in its behavioral and rewarding effects. Morphine-induced sensitization is a major problem and plays an important role in abuse of the opioid drugs. Studies reported that morphine may exert its effects by the release of nitric oxide (NO). NO is a potent neuromodulator, which is produced by nitric oxide synthase (NOS)...
October 2016: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/27870477/ascending-single-dose-double-blind-placebo-controlled-safety-study-of-noribogaine-in-opioid-dependent-patients
#10
Paul Glue, Gavin Cape, Donna Tunnicliff, Michelle Lockhart, Fred Lam, Noelyn Hung, C Tak Hung, Sarah Harland, Jane Devane, R S Crockett, John Howes, Borje Darpo, Meijian Zhou, Holger Weis, Lawrence Friedhoff
Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level)...
November 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27865771/cholinergic-activation-affects-the-acute-and-chronic-antinociceptive-effects-of-morphine
#11
Kinga Gawel, Ewa Gibula-Bruzda, Marcin Dziedzic, Malgorzata Jenda-Wojtanowska, Marta Marszalek-Grabska, Jerzy Silberring, Jolanta H Kotlinska
Current studies indicate that the cholinergic and opioid systems interact to modulate pain. In the present work, we investigated the influence of the cholinesterase inhibitors, donepezil (0.5; 1 or 3mg/kg, i.p.) and rivastigmine (0.03; 0.5 or 1mg/kg, i.p.), on the acute antinociceptive effects of morphine (5mg/kg, i.p.) in the hot plate test in mice. Herein, both inhibitors were found to enhance and prolong the analgesic effects of morphine without affecting latencies themselves. In an extension of this work, we determined which cholinergic receptors subtype mediates the enhancement of analgesic effects of morphine, following inhibition of cholinesterases...
November 16, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/27860208/randomized-double-blind-trial-of-oral-methylnaltrexone-for-the-treatment-of-opioid-induced-constipation-in-patients-with-chronic-noncancer-pain
#12
Richard Rauck, Neal E Slatkin, Nancy Stambler, Joseph R Harper, Robert J Israel
BACKGROUND: Subcutaneous methylnaltrexone, a peripherally acting μ-opioid receptor antagonist, improves opioid-induced constipation (OIC) in patients with chronic noncancer pain. An oral methylnaltrexone formulation has been developed. METHODS: In this phase 3, double-blind trial, adults with chronic noncancer pain receiving opioid doses of ≥50 mg/d oral morphine equivalents with OIC were randomly assigned to oral methylnaltrexone (150 mg, 300 mg, or 450 mg) or placebo once daily (QD) for 4 weeks followed by as-needed dosing for 8 weeks...
November 17, 2016: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/27855689/metformin-reduces-morphine-tolerance-by-inhibiting-microglial-mediated-neuroinflammation
#13
Yinbing Pan, Xiaodi Sun, Lai Jiang, Liang Hu, Hong Kong, Yuan Han, Cheng Qian, Chao Song, Yanning Qian, Wentao Liu
BACKGROUND: Tolerance seriously impedes the application of morphine in clinical medicine. Thus, it is necessary to investigate the exact mechanisms and efficient treatment. Microglial activation and neuroinflammation in the spinal cord are thought to play pivotal roles on the genesis and maintaining of morphine tolerance. Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception. Metformin, a biguanide class of antidiabetic drugs and activator of AMPK, has a potential anti-inflammatory effect...
November 17, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27847477/reverse-of-acute-and-chronic-morphine-tolerance-by-lithocholic-acid-via-down-regulating-ugt2b7
#14
Zizhao Yang, Li Li, Haihong Hu, Mingcheng Xu, Jingkai Gu, Zaijie Jim Wang, Lushan Yu, Su Zeng
Lithocholic acid (LCA) deposited in human livers always induces drastic pains which need analgesic drug, like morphine to release. Our research showed that LCA can effectively inhibit uridine 5'-diphospho-glucuronosyltransferase 2B7 (UGT2B7) in morphine tolerance-like human normal liver cells, HL-7702, then increase μ-opioid receptor (MOR) and calcium-calmodulin dependent protein kinase IIα (CaMKIIα) expression. In vivo assay, UGT2B7 was significantly repressed in the livers of acute or chronic morphine tolerance mice pretreated with LCA (10, 50, and 100 mg/kg, p...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27803778/association-of-morphine-induced-analgesic-tolerance-with-changes-in-gene-expression-of-glun1-and-mor1-in-rat-spinal-cord-and-midbrain
#15
Shamseddin Ahmadi, Fatemeh Miraki, Jalal Rostamzadeh
OBJECTIVES: We aimed to examine association of gene expression of MOR1 and GluN1 at mRNA level in the lumbosacral cord and midbrain with morphine tolerance in male Wistar rats. MATERIALS AND METHODS: Analgesic effects of morphine administrated intraperitoneally at doses of 0.1, 1, 5 and 10 mg/kg were examined using a hot plate test in rats with and without a history of 15 days morphine (10 mg/kg) treatment. Morphine-induced analgesic tolerance was also assessed on days 1, 5, 10 and 15 of chronic morphine injections...
September 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27796936/ajoene-restored-behavioral-patterns-and-liver-glutathione-level-in-morphine-treated-c57bl6-mice
#16
Jaesuk Yun, Sergiy Oliynyk, Yeonju Lee, Jieun Kim, Kyunghwa Yun, Raok Jeon, Jae-Ha Ryu, Seikwan Oh
Oxidative stress exacerbates drug dependence induced by administration of opiate analgesics such as morphine-induced tolerance and physical dependence associated with the reduction in hepatic glutathione (GSH) level. Ajoene obtained from garlic (Allium sativum L.) has been reported for anti-tumorigenic, anti-oxidative and neuroprotective properties, however, little is known about its effect on morphine-induced dependence. Therefore, this study aimed at the effect of ajoene on physical and/or psychological dependence and liver GSH content in morphine-treated mice...
October 28, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27774136/combined-interactions-with-i1-i2-imidazoline-binding-sites-and-%C3%AE-2-adrenoceptors-to-manage-opioid-addiction
#17
Maria Elena Giusepponi, Carlo Cifani, Maria Vittoria Micioni Di Bonaventura, Laura Mattioli, Alan Hudson, Eleonora Diamanti, Fabio Del Bello, Mario Giannella, Valerio Mammoli, Corinne Dalila Paoletti, Alessandro Piergentili, Maria Pigini, Wilma Quaglia
Tolerance and dependence associated with chronic opioid exposure result from molecular, cellular, and neural network adaptations. Such adaptations concern opioid and nonopioid systems, including α2-adrenoceptors (α2-ARs) and I1- and I2-imidazoline binding sites (IBS). Agmatine, one of the hypothesized endogenous ligands of IBS, targeting several systems including α2-ARs and IBS, proved to be able to regulate opioid-induced analgesia and to attenuate the development of tolerance and dependence. Interested in the complex pharmacological profile of agmatine and considering the nature of its targets, we evaluated two series of imidazolines, rationally designed to simultaneously interact with I1-/I2-IBS or I1-/I2-IBS/α2-ARs...
October 13, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27771111/ziconotide-intrathecal-delivery-as-treatment-for-secondary-therapeutic-failure-of-motor-cortex-stimulation-after-6%C3%A2-years
#18
J Voirin, I Darie, D Fischer, A Simon, I Rohmer-Heitz, F Proust
INTRODUCTION: Motor cortex stimulation is a well-known treatment modality for refractory neuropathic pain. Nevertheless, some cases of therapeutic failure have been described but alternative therapies for these cases are rarely reported. CASE REPORT: The patient presented with neuropathic pain in his right arm due to a cervical syrinx which was surgically treated by a shunt in 2003 with no clinical improvement. As alternative therapy, after an evaluation by repetitive magnetic transcranial stimulation with significant benefit, motor cortex stimulation was successfully implanted in 2004...
October 19, 2016: Neuro-Chirurgie
https://www.readbyqxmd.com/read/27756950/role-of-fosaprepitant-a-neurokinin-type-1-receptor-antagonist-in-morphine-induced-antinociception-in-rats
#19
Pranav Prasoon, Shivani Gupta, Rahul Kumar, Mayank Gautam, Saroj Kaler, Subrata Basu Ray
OBJECTIVES: Opioids such as morphine form the cornerstone in the treatment of moderate to severe pain. However, opioids also produce serious side effects such as tolerance. Fosaprepitant is a substance P (SP) receptor antagonist, which is used for treating chemotherapy-induced nausea and vomiting. SP is an important neuropeptide mediating transmission of pain at the spinal level. Thus, it was hypothesized that combining morphine with fosaprepitant would increase the antinociceptive effect of morphine...
July 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/27749531/application-of-radiofrequency-thermocoagulation-combined-with-adriamycin-injection-in-dorsal-root-ganglia-for-controlling-refractory-pain-induced-by-rib-metastasis-of-lung-cancer-a-strobe-compliant-article
#20
Guang-Lun Xie, Da-Peng Guo, Zhi-Gang Li, Chang Liu, Wei Zhang
This study aimed to observe the therapeutic effects and adverse reactions of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia on lung cancer rib metastasis-related refractory pain which has no response to conventional therapy.This study contained 27 patients with lung cancer rib metastasis-related moderate or severe pain which had no response to conventional therapy. Under computed tomography (CT)-guidance, radiofrequency puncture need reached the corresponding intervertebral foramens to ensure needle point near dorsal root ganglia (DRG) by sensory and motor stimulation tests, and then radiofrequency thermocoagulation was performed on each corresponding DRG followed by injection of 0...
October 2016: Medicine (Baltimore)
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