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https://www.readbyqxmd.com/read/29352503/in-vivo-effects-of-%C3%AE-opioid-receptor-agonist-%C3%AE-opioid-receptor-antagonist-peptidomimetics-following-acute-and-repeated-administration
#1
Jessica P Anand, Kelsey E Kochan, Anthony F Nastase, Deanna Montgomery, Nicholas W Griggs, John R Traynor, Henry I Mosberg, Emily M Jutkiewicz
BACKGROUND AND PURPOSE: Mu opioid receptor (μ-receptor) agonists are used for pain management, but produce adverse effects including tolerance, dependence, and euphoria. The co-administration of a μ-receptor agonist with a delta opioid receptor (δ-receptor) antagonist has been shown to produce antinociception with reduced development of some side effects. We characterized the effects of three μ-receptor agonist/δ-receptor antagonist peptidomimetics in vivo after acute and repeated administration to determine if this profile provides a viable alternative to traditional opioid analgesics...
January 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29331953/efficacy-tolerability-and-acceptability-of-oxycodone-for-cancer-related-pain-in-adults-an-updated-cochrane-systematic-review
#2
REVIEW
Mia Schmidt-Hansen, Michael I Bennett, Stephanie Arnold, Nathan Bromham, Jennifer S Hilgart
OBJECTIVES: To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI, Conference Proceedings Citation Index-Science, BIOSIS, PsycINFO and four trials registries to November 2016. RESULTS: We included 23 randomised controlled trials with 2144 patients analysed for efficacy and 2363 for safety. Meta-analyses showed no significant differences between controlled-release (CR) and immediate-release oxycodone in pain intensity or adverse events but did show significantly better pain relief after treatment with CR morphine compared with CR oxycodone...
January 13, 2018: BMJ Supportive & Palliative Care
https://www.readbyqxmd.com/read/29316911/the-standardized-withania-somnifera-dunal-root-extract-alters-basal-and-morphine-induced-opioid-receptor-gene-expression-changes-in-neuroblastoma-cells
#3
Francesca Felicia Caputi, Elio Acquas, Sanjay Kasture, Stefania Ruiu, Sanzio Candeletti, Patrizia Romualdi
BACKGROUND: Behavioral studies demonstrated that the administration of Withania somnifera Dunal roots extract (WSE), prolongs morphine-elicited analgesia and reduces the development of tolerance to the morphine's analgesic effect; however, little is known about the underpinning molecular mechanism(s). In order to shed light on this issue in the present paper we explored whether WSE promotes alterations of μ (MOP) and nociceptin (NOP) opioid receptors gene expression in neuroblastoma SH-SY5Y cells...
January 10, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29310376/perioperative-analgesia-after-intrathecal-fentanyl-and-morphine-or-morphine-alone-for-cesarean-section-a-randomized-controlled-study
#4
RANDOMIZED CONTROLLED TRIAL
Wojciech Weigl, Andrzej Bieryło, Monika Wielgus, Świetlana Krzemień-Wiczyńska, Marcin Kołacz, Michał J Dąbrowski
OBJECTIVES: Intrathecal morphine is used in the postoperative management of pain after caesarean section (CS), but might not be optimal for intraoperative analgesia. We hypothesized that intrathecal fentanyl could supplement intraoperative analgesia when added to a local anesthetic and morphine without affecting management of postoperative pain. METHODS: This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29291353/fluorescently-labelled-morphine-derivatives-for-bioimaging-studies
#5
Raymond Lam, Arisbel B Gondin, Meritxell Canals, Barrie Kellam, Stephen J Briddon, Bim Graham, Peter J Scammells
Opioids, like morphine, are the mainstay analgesics for the treatment and control of pain. Despite this, they often exhibit severe side effects that limit dose; patients often become tolerant and dependent on these drugs, which remains a major health concern. The analgesic actions of opioids are primarily mediated via the μ-opioid receptor, a member of the G protein-coupled receptor superfamily. Thus far, development of small molecule fluorescent ligands for this receptor has resulted in antagonists, somewhat limiting the use of these probes...
January 1, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29237389/venlafaxine-attenuates-the-development-of-morphine-tolerance-and-dependence-role-of-l-arginine-nitric-oxide-cgmp-pathway
#6
Mohammad Taghi Mansouri, Bahareh Naghizadeh, Behnam Ghorbanzadeh, Soheila Alboghobeish, Gholamreza Houshmand, Neda Amirgholami
BACKGROUND: Severe pain reduce quality of life in patients with various diseases, often because chronic morphine therapy results in reduced analgesic effectiveness, or tolerance, leading to escalating doses and distressing adverse effects. Nitric oxide (NO) play a role in morphine tolerance and dependence. OBJECTIVE: Venlafaxine, an antidepressant, is known to modulate nitric oxide (NO) pathway in nervous tissues. In the present study the effect of systemic venlafaxine (VLF) on the development of morphine tolerance and dependence, acute morphine-induced antinociception, and the probable involvement of the L-arginine/NO/cGMP pathway in these effects were investigated in mice...
December 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29231613/-effects-of-electroacupuncture-on-expression-of-%C3%AE-opioid-receptor-in-nucleus-ceruleus-in-rats-with-bone-cancer-pain-morphine-tolerance
#7
Taofang Fu, Lingling Wang, Junying Du, Feng Chen, Junfan Fang, Yi Liang, Jianqiao Fang
OBJECTIVE: To observe the effects of electroacupuncture (EA) on pain behavior in rats with bone cancer pain and morphine tolerance, and to explore partial action mechanism. METHODS: Forty-two SD healthy female rats were randomly divided into a sham operation group (7 rats), a bone cancer pain group (8 rats), a morphine tolerance group (9 rats), an EA group (9 rats) and a sham EA group (9 rats). The rats in the sham operation group were treated with injection of phosphate buffer saline at medullary cavity of left-side tibia, and the rats in the remaining groups were injected with MRMT-1 breast cancer cells...
May 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29229211/the-use-of-rapid-onset-fentanyl-in-children-and-young-people-for-breakthrough-cancer-pain
#8
Lucy Coombes, Kimberley Burke, Anna-Karenia Anderson
BACKGROUND AND AIMS: No published studies have looked at the dosing and use of rapid onset fentanyl preparations in children. The primary aim of this study was to assess whether there is a correlation between effective dose of rapid onset fentanyl and background oral morphine equivalent analgesia in children less than 18 years old. Secondary objectives included establishing whether there is a correlation between effective dose of rapid onset fentanyl and age and weight. Reported side effects were also reviewed...
October 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29223124/activation-of-mitochondrial-katp-channels-mediates-neuroprotection-induced-by-chronic-morphine-preconditioning-in-hippocampal-ca-1-neurons-following-cerebral-ischemia
#9
Maedeh Arabian, Nahid Aboutaleb, Mansoureh Soleimani, Marjan Ajami, Rouhollah Habibey, Hamidreza Pazoki-Toroudi
PURPOSE: Pharmacologic preconditioning, through activating several mechanisms and mediators, can increase the tolerance of different tissues against ischemia/reperfusion (I/R) injury. Recent studies have shown that morphine preconditioning has protective effects in different organs, especially in the heart. Nevertheless, its mechanisms are not well elucidated in the brain. The present study aimed to clarify whether the activation of mitochondrial KATP (mKATP) channels in chronic morphine (CM) preconditioning could decrease hippocampus damage following I/R injury...
December 6, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/29209205/potentiation-of-morphine-induced-antinociception-by-propranolol-the-involvement-of-dopamine-and-gaba-systems
#10
Elham A Afify, Najlaa M Andijani
Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate), (visceral, acetic acid), and (inflammatory, formalin test) in mice and quantified by measuring the percent maximum possible effect, the percent inhibition of acetic acid-evoked writhing response, and the area under the curve values of number of flinches for treated mice, respectively...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29192123/the-slowly-signaling-g-protein-biased-cb2-cannabinoid-receptor-agonist-ly2828360-suppresses-neuropathic-pain-with-sustained-efficacy-and-attenuates-morphine-tolerance-and-dependence
#11
Xiaoyan Lin, Amey S Dhopeshwarkar, Megan Huibregtse, Ken Mackie, Andrea G Hohmann
The CB2 cannabinoid agonist LY2828360 lacked both toxicity and efficacy in a clinical trial for osteoarthritis. Whether LY2828360 suppresses neuropathic pain has not been reported and its signaling profile is unknown. In vitro, LY2828360 was a slowly acting but efficacious G protein-biased CB2 agonist, inhibiting cAMP accumulation and activating ERK1/2 signaling while failing to recruit arrestin, activate inositol phosphate signaling or internalize CB2 receptors. In wildtype (WT) mice, LY2828360 (3 mg/kg/day i...
November 30, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29191784/nanoparticulate-peptide-delivery-exclusively-to-the-brain-produces-tolerance-free-analgesia
#12
Lisa Godfrey, Antonio Iannitelli, Natalie L Garrett, Julian Moger, Ian Imbert, Tamara King, Frank Porreca, Ramesh Soundararajan, Aikaterini Lalatsa, Andreas G Schätzlein, Ijeoma F Uchegbu
The delivery of peptide drugs to the brain is challenging, principally due to the blood brain barrier and the low metabolic stability of peptides. Exclusive delivery to the brain with no peripheral exposure has hitherto not been demonstrated with brain quantification data. Here we show that polymer nanoparticles encapsulating leucine5-enkephalin hydrochloride (LENK) are able to transport LENK exclusively to the brain via the intranasal route, with no peripheral exposure and nanoparticle localisation is observed within the brain parenchyma...
November 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29191644/preclinical-assessment-of-utility-of-m6s-for-multimodal-acute-and-chronic-pain-treatment-in-diabetic-neuropathy
#13
Jai Shankar K Yadlapalli, Navdeep Dogra, Anqi W Walbaum, Paul L Prather, Peter A Crooks, Maxim Dobretsov
AIMS: Previous reports from our laboratory have established that morphine-6-O-sulfate (M6S) is a mixed μ/δ opioid receptor (OR) agonist and a potential improved alternative to morphine for treatment of chronic multimodal pain in non-diabetic rats. This study extends the antinociceptive effects of M6S and morphine in STZ-induced diabetic rats. MATERIALS AND METHODS: Effects of morphine and M6S were studied across a range of pain modalities, using hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold (PPT) tests...
November 27, 2017: Life Sciences
https://www.readbyqxmd.com/read/29189367/oxycodone-ingestion-patterns-in-acute-fracture-pain-with-digital-pills
#14
Peter R Chai, Stephanie Carreiro, Brendan J Innes, Brittany Chapman, Kristin L Schreiber, Robert R Edwards, Adam W Carrico, Edward W Boyer
BACKGROUND: Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction...
December 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29189168/targeting-cytokines-for-morphine-tolerance-a-narrative-review
#15
Dai-Qiang Liu, Ya-Qun Zhou, Feng Gao
BACKGROUND: Despite its various side effects, morphine has been widely used in clinics for decades due to its powerful analgesic effect. Morphine tolerance is one of the major side effects which hinders its long-term usage for pain therapy. Currently, the thorough cellular and molecular mechanisms underlying morphine tolerance remain largely uncertain. METHODS: We searched the PubMed database with Medical subject headings (MeSH) including 'morphine tolerance', 'cytokines', 'interleukin 1', 'interleukin 1 beta', 'interleukin 6', 'tumor necrosis factor alpha', 'interleukin 10', 'chemokines'...
November 28, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/29187328/survey-of-the-prescription-of-step-2-analgesics-in-persons-aged-75-years-and-older-in-general-practitioners
#16
Adrien Brocard, Sofia Da Silva, Maurice Giroud, Alain Putot, Patrick Manckoundia
Although step-2 analgesics (S2A) are recommended when step-1 analgesics (S1A) are ineffective or in cases of moderate to severe pain, their efficacy varies. This study evaluated the place attributed by general practitioners (GPs) to S2A in the treatment of nociceptive pain in elderly persons (EP). Descriptive, transversal and declarative study conducted among GPs in Burgundy. In total, 115 GPs took part in the survey. Among these, 60.8% had at least one consultation/day for pain. After paracetamol, which was systematically preferred, 56...
December 1, 2017: Gériatrie et Psychologie Neuropsychiatrie du Vieillissement
https://www.readbyqxmd.com/read/29178967/blocking-atp-sensitive-potassium-channel-alleviates-morphine-tolerance-by-inhibiting-hsp70-tlr4-nlrp3-mediated-neuroinflammation
#17
Jie Qu, Xue-You Tao, Peng Teng, Yan Zhang, Ci-Liang Guo, Liang Hu, Yan-Ning Qian, Chun-Yi Jiang, Wen-Tao Liu
BACKGROUND: Long-term use of morphine induces analgesic tolerance, which limits its clinical efficacy. Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. In our study, we investigated whether other existing alternative pathways caused morphine-induced activation of TLR4 in microglia. We focused on heat shock protein 70 (HSP70), a damage-associated molecular pattern (DAMP), which was released from various cells upon stimulations under the control of KATP channel and bound with TLR4-inducing inflammation...
November 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29175519/a-new-tridecapeptide-with-an-octaarginine-vector-has-analgesic-therapeutic-potential-and-prevents-morphine-induced-tolerance
#18
Vladimir A Kashkin, Elena V Shekunova, Michail I Titov, Ivan I Eliseev, Maxim A Gureev, Yuri B Porozov, Marina N Makarova, Valery G Makarov
A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr-d-Arg-Phe-Gly-NH2 was modified with the inclusion of a (d-Arg)8 vector to prevent the action of endopeptidase and to increase the duration of the analgesic action of the tetrapeptide when administered orally. The aim of this study was to estimate the analgesic efficacy of the tetrapeptide with (d-Arg)8 (tridecapeptide, TDP) in experimental models of acute and chronic pain...
January 2018: Peptides
https://www.readbyqxmd.com/read/29174820/effect-of-rat-parental-morphine-exposure-on-passive-avoidance-memory-and-morphine-conditioned-place-preference-in-male-offspring
#19
Ardeshir Akbarabadi, Saba Niknamfar, Nasim Vousooghi, Mitra-Sadat Sadat-Shirazi, Heidar Toolee, Mohammad-Reza Zarrindast
Drug addiction is a chronic disorder resulted from complex interaction of genetic, environmental, and developmental factors. Epigenetic mechanisms play an important role in the development and maintenance of addiction and also memory formation in the brain. We have examined passive avoidance memory and morphine conditioned place preference (CPP) in the offspring of male and/or female rats with a history of adulthood morphine consumption. Adult male and female animals received chronic oral morphine for 21days and then were maintained drug free for 10days...
November 22, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/29171155/interactions-of-2s-6s-2r-6r-hydroxynorketamine-a-secondary-metabolite-of-r-s-ketamine-with-morphine
#20
Tuomas O Lilius, Hanna Viisanen, Viljami Jokinen, Mikko Niemi, Eija A Kalso, Pekka V Rauhala
Ketamine and its primary metabolite norketamine attenuate morphine tolerance by antagonising N-methyl-D-aspartate (NMDA) receptors. Ketamine is extensively metabolised to several other metabolites. The major secondary metabolite (2S,6S;2R,6R)-hydroxynorketamine (6-hydroxynorketamine) is not an NMDA antagonist. However, it may modulate nociception through negative allosteric modulation of α7 nicotinic acetylcholine receptors. We studied whether 6-hydroxynorketamine could affect nociception or the effects of morphine in acute or chronic administration settings...
November 24, 2017: Basic & Clinical Pharmacology & Toxicology
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