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https://www.readbyqxmd.com/read/29029015/an-experimental-study-comparing-the-respiratory-effects-of-tapentadol-and-oxycodone-in-healthy-volunteers
#1
R van der Schrier, K Jonkman, M van Velzen, E Olofsen, A M Drewes, A Dahan, M Niesters
Background: There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg. Methods: Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design...
October 4, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29028742/intraoperative-esmolol-as-an-adjunct-for-perioperative-opioid-and-postoperative-pain-reduction-a-systematic-review-meta-analysis-and-meta-regression
#2
Amanda M Gelineau, Michael R King, Karim S Ladha, Sara M Burns, Timothy Houle, T Anthony Anderson
BACKGROUND: Esmolol is an ultrashort β-1 receptor antagonist. Recent studies suggest a role for esmolol in pain response modulation. The authors performed a meta-analysis to determine if the intraoperative use of esmolol reduces opioid consumption or pain scores. METHODS: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, pubget, and Google Scholar were searched. Studies were included if they were randomized, placebo- or opioid-controlled trials written in English, and performed on patients 18 years of age or older...
October 11, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29026331/poorly-controlled-postoperative-pain-prevalence-consequences-and-prevention
#3
REVIEW
Tong J Gan
This review provides an overview of the clinical issue of poorly controlled postoperative pain and therapeutic approaches that may help to address this common unresolved health-care challenge. Postoperative pain is not adequately managed in greater than 80% of patients in the US, although rates vary depending on such factors as type of surgery performed, analgesic/anesthetic intervention used, and time elapsed after surgery. Poorly controlled acute postoperative pain is associated with increased morbidity, functional and quality-of-life impairment, delayed recovery time, prolonged duration of opioid use, and higher health-care costs...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29025923/plasticity-of-signaling-by-spinal-estrogen-receptor-alpha-kappa-opioid-receptor-and-mglurs-over-the-rat-reproductive-cycle-regulates-spinal-endomorphin-2-antinociception-relevance-of-endogenous-biased-agonism
#4
Nai-Jiang Liu, Vijaya Murugaiyan, Emiliya M Storman, Stephen A Schnell, Arjun Kumar, Martin W Wessendorf, Alan R Gintzler
We previously showed that intrathecal application of endomorphin 2 [EM2; the highly specific endogenous mu-opioid receptor (MOR) ligand] induces antinociception that varies with stage of the rat estrous cycle -- minimal during diestrus and prominent during proestrus. Earlier studies, however, did not identify proestrus-activated signaling strategies that enable spinal EM2 antinociception. We now report that in female rats, increased spinal dynorphin release and kappa-opioid receptor (KOR) signaling, as well as the emergence of glutamate-activated mGluR1 signaling, are critical to the transition from an EM2 non-responsive (during diestrus) to an analgesically responsive state (during proestrus)...
October 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29022702/development-of-bright-and-biocompatible-nanoruby-and-its-application-to-background-free-time-gated-imaging-of-g-protein-coupled-receptors
#5
Varun K A Sreenivasan, Wan Aizuddin W Razali, Kai Zhang, Rashmi R Pillai, Avishkar Saini, Denitza Denkova, Marina Santiago, Hannah Brown, Jeremy Thompson, Mark Connor, Ewa M Goldys, Andrei V Zvyagin
At the forefront of development of fluorescent probes for biological imaging applications are enhancements aimed at increasing their brightness, contrast, and photostability, especially towards demanding applications of single molecule detection. In comparison with existing probes, nanorubies exhibit unlimited photostability and a long emission lifetime (3.7 ms), which enable continuous imaging at single-particle sensitivity in highly scattering and fluorescent biological specimens. However, their wide application as fluorescence probes has so far been hindered by the absence of facile methods for scaled-up high volume production and molecularly-specific targeting...
October 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29020799/is-there-a-role-for-5-ht3-receptor-antagonists-in-the-treatment-of-opioid-induced-pruritus
#6
Saima Rashid, Disha D Trivedi, Mudher Al-Shathir, Marie Moulton, Steven J Baumrucker
Pruritus is an unpleasant irritation symptom that can be related to various systemic and dermatological conditions. Although underreported, pruritus is a common adverse event noted after use of opioid pain medications. This article reviews the current understanding of the mechanism of opioid-induced pruritus (OIP) and various pharmacological therapies. 5-Hydroxytryptamine 3 (5-HT3) receptor antagonists are potentially effective for treating OIP and may be a valuable treatment option if further controlled studies are encouraging...
January 1, 2017: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/29020387/reversal-of-stress-induced-social-interaction-deficits-by-buprenorphine
#7
Caroline A Browne, Edgardo Falcon, Shivon A Robinson, Olivier Berton, Irwin Lucki
Background: Patients with post-traumatic stress disorder (PTSD) frequently report persistent problems with social interactions, emerging after a traumatic experience. Chronic social defeat stress (CSDS) is a widely used rodent model of stress that produces robust and sustained social avoidance behavior. The avoidance of other rodents can be reversed by 28 days of treatment with selective serotonin reuptake inhibitors (SSRIs), the only pharmaceutical class approved by the U. S. Food and Drug Administration for treating PTSD...
August 31, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29016850/mice-lacking-cyclin-dependent-kinase-like-5-manifest-autistic-and-adhd-like-behaviors
#8
Cian-Ling Jhang, Tzyy-Nan Huang, Yi-Ping Hsueh, Wenlin Liao
Neurodevelopmental disorders frequently share common clinical features and appear high rate of comorbidity, such as those present in patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While characterizing behavioral phenotypes in the mouse model of cyclin-dependent kinase-like 5 (CDKL5) disorder, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding CDKL5, we found that these mice manifested behavioral phenotypes mimicking multiple key features of ASD, such as impaired social interaction and communication, as well as increased stereotypic digging behaviors...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29016552/the-efficacy-of-peripheral-opioid-antagonists-in-opioid-induced-constipation-and-postoperative-ileus-a-systematic-review-of-the-literature
#9
Eric S Schwenk, Alexander E Grant, Marc C Torjman, Stephen E McNulty, Jaime L Baratta, Eugene R Viscusi
Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective μ-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting μ-opioid receptor antagonists target the μ-opioid receptor without reversing analgesia...
October 6, 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28993838/delta-opioid-receptor-expression-and-function-in-primary-afferent-somatosensory-neurons
#10
Amaury François, Grégory Scherrer
The functional diversity of primary afferent neurons of the dorsal root ganglia (DRG) generates a variety of qualitatively and quantitatively distinct somatosensory experiences, from shooting pain to pleasant touch. In recent years, the identification of dozens of genetic markers specifically expressed by subpopulations of DRG neurons has dramatically improved our understanding of this diversity and provided the tools to manipulate their activity and uncover their molecular identity and function. Opioid receptors have long been known to be expressed by discrete populations of DRG neurons, in which they regulate cell excitability and neurotransmitter release...
October 10, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28993835/delta-opioid-receptors-and-modulation-of-mood-and-emotion
#11
Isaac J Dripps, Emily M Jutkiewicz
Depression is a pervasive and debilitating mental disorder that is inadequately treated by current pharmacotherapies in a majority of patients. Although opioids have long been known to regulate mood states, the use of opioids to treat depression is rarely discussed. This chapter explores the preclinical and clinical evidence supporting the antidepressant-like effects of opioid ligands, and in particular, delta opioid receptor (DOR) agonists. DOR agonists have been shown to produce antidepressant-like effects in a number of animal models...
October 10, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28992386/interaction-between-the-%C3%AE-opioid-receptor-gene-and-the-number-of-heavy-drinking-peers-on-alcohol-use
#12
Michelle J Zaso, Stephen A Maisto, Stephen J Glatt, John M Belote, Aesoon Park
BACKGROUND: The presence of heavy drinking peers may trigger genetic vulnerabilities to alcohol use. Limited correlational findings, albeit mixed as a function of age, suggest that carriers of a μ-opioid receptor (OPRM1) G allele may be more vulnerable than noncarriers to alcohol-promoting perceived peer environments. However, research has not yet examined such genetic susceptibility to actual (rather than perceived) peer environments through an experimental, ad libitum alcohol administration design...
October 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28991183/orexin-receptor-multimerization-versus-functional-interactions-neuropharmacological-implications-for-opioid-and-cannabinoid-signalling-and-pharmacogenetics
#13
Miles D Thompson, Takeshi Sakurai, Innocenzo Rainero, Mary C Maj, Jyrki P Kukkonen
Orexins/hypocretins are neuropeptides formed by proteolytic cleavage of a precursor peptide, which are produced by neurons found in the lateral hypothalamus. The G protein-coupled receptors (GPCRs) for these ligands, the OX₁ and OX₂ orexin receptors, are more widely expressed throughout the central nervous system. The orexin/hypocretin system has been implicated in many pathways, and its dysregulation is under investigation in a number of diseases. Disorders in which orexinergic mechanisms are being investigated include narcolepsy, idiopathic sleep disorders, cluster headache and migraine...
October 8, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28991118/truncated-%C3%AE-opioid-receptors-with-6-transmembrane-domains-are-essential-for-opioid-analgesia
#14
Zhigang Lu, Jin Xu, Mingming Xu, Grace C Rossi, Susruta Majumdar, Gavril W Pasternak, Ying-Xian Pan
BACKGROUND: Most clinical opioids act through μ-opioid receptors. They effectively relieve pain but are limited by side effects, such as constipation, respiratory depression, dependence, and addiction. Many efforts have been made toward developing potent analgesics that lack side effects. Three-iodobenzoyl-6β-naltrexamide (IBNtxA) is a novel class of opioid active against thermal, inflammatory, and neuropathic pain, without respiratory depression, physical dependence, and reward behavior...
October 4, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28991111/an-intraplantar-hypertonic-saline-assay-in-mice-for-rapid-screening-of-analgesics
#15
Yahya I Asiri, Timothy Fung, Stephan K W Schwarz, Khalid A Asseri, Ian D Welch, Catherine A Schuppli, Alasdair M Barr, Richard A Wall, Ernest Puil, Bernard A MacLeod
BACKGROUND: Development of new analgesics is limited by shortcomings of existing preclinical screening assays such as wide variations in response, suitability for a narrow range of analgesics, and propensity to induce tissue damage. Our aim was to determine the feasibility of a new in vivo animal assay as an analgesic screen based on nociceptive responses (licking and biting) after intraplantar (i.pl.) injection of hypertonic saline (HS) in mice. METHODS: With approval from the Institutional Animal Care Committee, we conducted a randomized, investigator-blinded in vivo study in adult CD-1 mice...
October 5, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28989282/spotlight-on-eluxadoline-for-the-treatment-of-patients-with-irritable-bowel-syndrome-with-diarrhea
#16
REVIEW
Konstantinos C Fragkos
BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) has limited options for treatment currently, including mainly anti-motility medications, antispasmodics, and antidepressants. This review discusses the properties of a new drug, eluxadoline, a gut-targeting mu- and kappa-opioid receptor agonist and a delta-opioid receptor antagonist, and its efficacy and safety in patients with IBS-D. MATERIALS AND METHODS: A systematic review of the literature was undertaken to identify studies that had investigated eluxadoline as a treatment in IBS-D...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28988976/role-of-endogenous-melatoninergic-system-in-development-of-hyperalgesia-and-tolerance-induced-by-chronic-morphine-administration-in-rats
#17
Yuchao Fan, Xiao Liang, Rurong Wang, Li Song
Morphine is a widely used analgesic for various types of pain. However, its efficacy is impeded by development of hyperalgesia and tolerance. Melatonin has antinociceptive effect and is involved in morphine-induced hyperalgesia and tolerance but the mechanism of its involvement remains to be defined. In this study, we established a rat model of morphine-induced hyperalgesia and tolerance. We determined the serum level of melatonin and expression of μ-opioid receptor (MOR), melatonin receptor (MT1, MT2) and protein kinase C γ(PKCγ) in the spinal dorsal horn of the rats with morphine-induced hyperalgesia and tolerance...
October 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28987634/heterodimerization-of-apelin-and-opioid-receptors-and-cardiac-inotropic-and-lusitropic-effects-of-apelin-in-2k1c-hypertension-role-of-perk1-2-and-pkc
#18
Farzaneh Rostamzadeh, Hamid Najafipour, Mahboobeh Yeganeh-Hajahmadi, Saeed Esmaeili-Mahani, Siyavash Joukar, Maryam Iranpour
AIMS: Kappa Opioid receptors (KORs) change the impact of apelin on the phosphorylated ERK1/2 (pERK1/2). However, the role of interaction between KOR and apelin receptors (APJ) on the cardiac contractility effects of apelin and in regulation of pERK1/2 and PKC in the heart of renovascular hypertensive (2K1C) rats is unknown. MAIN METHODS: Hemodynamic factors, the heterodimerization of KOR and APJ, the expression of KOR mRNA and protein and pERK1/2 in the left ventricle of 2K1C rats were measured following APJ, KOR, PKC and Gi path inhibition by F13A, nor-BNI, chelerythrine and PTX respectively...
October 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28987324/toll-like-receptors-and-their-role-in-persistent-pain
#19
REVIEW
Michael J Lacagnina, Linda R Watkins, Peter M Grace
One of the fundamental mechanisms whereby the innate immune system coordinates inflammatory signal transduction is through Toll-like receptors (TLRs), which function to protect and defend the host organism by initiating inflammatory signaling cascades in response to tissue damage or injury. TLRs are positioned at the neuroimmune interface, and accumulating evidence suggests that the inflammatory consequences of TLR activation on glia (including microglia and astrocytes), sensory neurons, and other cell types can influence nociceptive processing and lead to states of exaggerated and unresolved pain...
October 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28986540/reactive-metabolites-of-acetaminophen-activate-and-sensitize-the-capsaicin-receptor-trpv1
#20
Mirjam J Eberhardt, Florian Schillers, Esther M Eberhardt, Linus Risser, Jeanne de la Roche, Christine Herzog, Frank Echtermeyer, Andreas Leffler
The irritant receptor TRPA1 was suggested to mediate analgesic, antipyretic but also pro-inflammatory effects of the non-opioid analgesic acetaminophen, presumably due to channel activation by the reactive metabolites parabenzoquinone (pBQ) and N-acetyl-parabenzoquinonimine (NAPQI). Here we explored the effects of these metabolites on the capsaicin receptor TRPV1, another redox-sensitive ion channel expressed in sensory neurons. Both pBQ and NAPQI, but not acetaminophen irreversibly activated and sensitized recombinant human and rodent TRPV1 channels expressed in HEK 293 cells...
October 6, 2017: Scientific Reports
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