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morphine tolerance

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https://www.readbyqxmd.com/read/28092666/loss-of-%C3%AE-opioid-receptor-signaling-in-nociceptors-but-not-microglia-abrogates-morphine-tolerance-without-disrupting-analgesia
#1
Gregory Corder, Vivianne L Tawfik, Dong Wang, Elizabeth I Sypek, Sarah A Low, Jasmine R Dickinson, Chaudy Sotoudeh, J David Clark, Ben A Barres, Christopher J Bohlen, Grégory Scherrer
Opioid pain medications have detrimental side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). Tolerance and OIH counteract opioid analgesia and drive dose escalation. The cell types and receptors on which opioids act to initiate these maladaptive processes remain disputed, which has prevented the development of therapies to maximize and sustain opioid analgesic efficacy. We found that μ opioid receptors (MORs) expressed by primary afferent nociceptors initiate tolerance and OIH development...
January 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28077540/leukemia-inhibitory-factor-lif-potentiates-antinociception-activity-and-inhibits-tolerance-induction-of-opioids
#2
H J Tu, K H Kang, S Y Ho, H C Liou, H H Liou, C P Lin, W M Fu
BACKGROUND: The efficacy of opioids typically decreases after long-term use owing to the development of tolerance. Glial activation and the upregulation of proinflammatory cytokines are related to the induction of tolerance. We investigated the effect of leukemia inhibitory factor (LIF) on morphine analgesia and tolerance. METHODS: LIF concentrations in rat spinal cords were measured by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) after morphine administration...
October 2016: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28074831/rgs9-2-modulates-responses-to-oxycodone-in-pain-free-and-chronic-pain-states
#3
Sevasti Gaspari, Valeria Cogliani, Lefteris Manouras, Ethan M Anderson, Vasiliki Mitsi, Kleopatra Avrampou, Fiona B Carr, Venetia Zachariou
Regulator of G protein signalling 9-2 (RGS9-2) is a striatal enriched signal transduction modulator, known to play a critical role in the development of addiction-related behaviours following exposure to psychostimulants or opioids. RGS9-2 controls the function of several GPCRs, including dopamine and mu opioid (MOR) receptors. We previously showed that RGS9-2 complexes negatively control morphine analgesia, and promote the development of morphine tolerance. In contrast, RGS9-2 positively modulates the actions of other opioid analgesics, such as fentanyl and methadone...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28068780/long-acting-injectable-naltrexone-induction-a-randomized-trial-of-outpatient-opioid-detoxification-with-naltrexone-versus-buprenorphine
#4
Maria Sullivan, Adam Bisaga, Martina Pavlicova, C Jean Choi, Kaitlyn Mishlen, Kenneth M Carpenter, Frances R Levin, Elias Dakwar, John J Mariani, Edward V Nunes
OBJECTIVE: At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone. METHOD: Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone...
January 10, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28067693/intraoperative-ketamine-reduces-immediate-postoperative-opioid-consumption-after-spinal-fusion-surgery-in-chronic-pain-patients-with-opioid-dependency-a-randomized-blinded-trial
#5
Rikke Vibeke Nielsen, Jonna Storm Fomsgaard, Hanna Siegel, Robertas Martusevicius, Lone Nikolajsen, Jørgen Berg Dahl, Ole Mathiesen
Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared to placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0-24 h postoperatively...
January 6, 2017: Pain
https://www.readbyqxmd.com/read/28063968/lack-of-genetic-association-between-oct1-abcb1-and-ugt2b7-variants-and-morphine-pharmacokinetics
#6
L M Nielsen, E Sverrisdóttir, T B Stage, S Feddersen, K Brøsen, L L Christrup, A M Drewes, A E Olesen
AIM: A high inter-individual variation in the pharmacokinetics and pharmacodynamics of morphine has been observed. Genetic polymorphisms in genes encoding the organic cation transporter isoform 1 (OCT1), the efflux transporter p-glycoprotein (ABCB1), and the UDP-glucuronosyltransferase-2B7 (UGT2B7) may influence morphine pharmacokinetics and thus, also pharmacodynamics. The aim of this study was to evaluate the association between OCT1, ABCB1, and UGT2B7 variants, and morphine pharmacokinetics and -dynamics in healthy volunteers...
January 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28062186/protective-effects-of-atorvastatin-against-morphine-induced-tolerance-and-dependence-in-mice
#7
Nasim Sadat Pajohanfar, Ehsan Mohebbi, Abolfazl Rad, Akbar Pejhan, Samad Nazemi, Bahareh Amin
[Background] In this study, we evaluated the effects of atorvastatin, a lipid-lowering medication on morphine-induced tolerance and dependence in mice. [Methods] Tolerance was induced by subcutaneous administration of morphine (20 mg/kg) to animals, twice a day for 9 days. Atorvastatin was given at the doses of 5, 10 and 20 mg/kg, 30 min before each morphine administration, once daily for 9 days. Hot plate test was employed to assess antinociceptive effect of morphine on days 1, 3, 5, 7 and 9. Dependence was evaluated by naloxone-precipitated withdrawal syndrome...
January 3, 2017: Brain Research
https://www.readbyqxmd.com/read/28059869/a-longitudinal-supra-inguinal-fascia-iliaca-compartment-block-reduces-morphine-consumption-after-total-hip-arthroplasty
#8
Matthias Desmet, Kris Vermeylen, Imré Van Herreweghe, Laurence Carlier, Filiep Soetens, Stijn Lambrecht, Kathleen Croes, Hans Pottel, Marc Van de Velde
BACKGROUND AND OBJECTIVES: The role of a fascia iliaca compartment block (FICB) for postoperative analgesia after total hip arthroplasty (THA) remains questionable. High-dose local anesthetics and a proximal injection site may be essential for successful analgesia. High-dose local anesthetics may pose a risk for local anesthetic systemic toxicity. We hypothesized that a high-dose longitudinal supra-inguinal FICB is safe and decreases postoperative morphine consumption after anterior approach THA...
January 3, 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28059034/midazolam-plus-haloperidol-as-adjuvant-analgesics-to-morphine-in-opium-dependent-patients-a-randomized-clinical-trial
#9
Mohammad Afzalimoghaddam, Maryam Edalatifard, Amir Nejati, Mehdi Momeni, Nader Isavi, Ehsan Karimialavijeh
BACKGROUND: Tolerance to opioids among opium-dependent patients creates obstacles for proper pain management of these patients in the emergency department (ED). The aim of the present study was to investigate the efficacy of intramuscular (IM) haloperidol plus midazolam on morphine analgesia among opium-dependent patients. METHODS: Opium-dependent adults who were admitted to the ED for new-onset severe pain in the limbs or abdomen (within 24 hours of admission and a pain score of over six, using a numerical rating scale [NRS]) were recruited...
January 6, 2017: Current Drug Abuse Reviews
https://www.readbyqxmd.com/read/28034782/spinal-trpc6-channels-contributes-to-morphine-induced-antinociceptive-tolerance-and-hyperalgesia-in-rats
#10
Hua Jin, Ying-Tong Sun, Guang-Qiong Guo, Da-Lin Chen, Yu-Jin Li, Gao-Peng Xiao, Xin-Nan Li
The chronic administration of opioids results in the development of morphine analgesic tolerance and withdrawl-induced hyperalgesia, which limits their clinical utility in pain treatment. However, the cellular mechanisms underlying opioid-induced tolerance and hyperalgesia are not fully understood. The transient receptor potential canonical channel TRPC6 is important for brain development and function, as it regulates cytosolic, endoplasmic reticulum, and mitochondrial Ca(2+) levels in neural cells. Here, we report that TRPC6 expression in the spinal cord was up-regulated after chronic morphine treatment...
December 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28025375/intrathecal-therapy-for-cancer-related-pain
#11
REVIEW
Brian M Bruel, Allen W Burton
OBJECTIVE: The increasing incidence of cancer survivorship has shifted treatment of cancer-related pain from short-term analgesia to long-term chronic pain management. As a result, alternatives to oral analgesics, such as intrathecal therapy, may be beneficial for patients with cancer-related pain. The authors review the use of intrathecal therapy in the management of cancer-related pain. METHODS: The Medline database was searched for English-language articles that included "ziconotide" or "morphine" AND ("cancer" OR "malignant") AND "intrathecal" in title or abstract...
December 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28006946/a-novel-experimental-model-of-acute-respiratory-distress-syndrome-in-pig
#12
M Otáhal, M Mlček, I Vítková, O Kittnar
Acute respiratory distress syndrome (ARDS) is severe medical condition occurring in critically ill patients and with mortality of 33-52 % is one of the leading causes of death in critically ill patients. To better understand pathophysiology of ARDS and to verify novel therapeutical approaches a reliable animal model is needed. Therefore we have developed modified lavage model of ARDS in the pig. After premedication (ketamine and midazolam) 35 healthy pigs were anesthetized (propofol, midazolam, morphin, pipecuronium) and orotracheally intubated and ventilated...
December 22, 2016: Physiological Research
https://www.readbyqxmd.com/read/28004735/blockade-of-neuronal-dopamine-d2-receptor-attenuates-morphine-tolerance-in-mice-spinal-cord
#13
Wen-Ling Dai, Feng Xiong, Bing Yan, Zheng-Yu Cao, Wen-Tao Liu, Ji-Hua Liu, Bo-Yang Yu
Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27989510/concurrent-bullatine-a-enhances-morphine-antinociception-and-inhibits-morphine-antinociceptive-tolerance-by-indirect-activation-of-spinal-%C3%AE%C2%BA-opioid-receptors
#14
Qian Huang, Ming-Li Sun, Yuan Chen, Xin-Yan Li, Yong-Xiang Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Bullatine A, a C20-diterpenoid alkaloid and one of the major effective ingredients in Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao), can block pain hypersensitivity in a variety of rodent models through expression of spinal microglial dynorphin A. AIM OF THE STUDY: To assess the interaction between bullatine A and morphine on antinociception in acute nociception and pain hypersensitivity states, with the exogenous synthetic dynorphin A as a comparison MATERIALS AND METHODS: Spinal nerve ligation-induced neuropathic rats and naïve mice were used for assessing the acute and chronic interactions of bullatine A/dynorphin A with morphine...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27964861/pain-opioids-and-sleep-implications-for-restless-legs-syndrome-treatment
#15
Claudia Trenkwalder, Walter Zieglgänsberger, Sam H Ahmedzai, Birgit Högl
Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described...
November 5, 2016: Sleep Medicine
https://www.readbyqxmd.com/read/27927796/g9a-inhibits-creb-triggered-expression-of-mu-opioid-receptor-in-primary-sensory-neurons-following-peripheral-nerve-injury
#16
Lingli Liang, Jian-Yuan Zhao, Xiyao Gu, Shaogen Wu, Kai Mo, Ming Xiong, Brianna Marie Lutz, Alex Bekker, Yuan-Xiang Tao
Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27926984/involvement-of-chemokine-cxcl11-in-the-development-of-morphine-tolerance-in-rats-with-cancer-induced-bone-pain
#17
Genhua Guo, Yawen Peng, Bingrui Xiong, Daiqiang Liu, Huilian Bu, Xuebi Tian, Hui Yang, Zhen Wu, Fei Cao, Feng Gao
Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXCL11 in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer-induced bone pain (CIBP). Then morphine was intrathecally administered twice daily for 7 consecutive days to induce drug tolerance...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27922111/mir-365-targets-%C3%AE-arrestin-2-to-reverse-morphine-tolerance-in-rats
#18
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
#19
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
#20
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)...
January 2017: Acta Anaesthesiologica Scandinavica
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