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https://www.readbyqxmd.com/read/28230181/dezocine-exhibits-antihypersensitivity-activities-in-neuropathy-through-spinal-%C3%AE-opioid-receptor-activation-and-norepinephrine-reuptake-inhibition
#1
Yong-Xiang Wang, Xiao-Fang Mao, Teng-Fei Li, Nian Gong, Ma-Zhong Zhang
Dezocine is the number one opioid painkiller prescribed and sold in China, occupying 44% of the nation's opioid analgesics market today and far ahead of the gold-standard morphine. We discovered the mechanisms underlying dezocine antihypersensitivity activity and assessed their implications to antihypersensitivity tolerance. Dezocine, given subcutaneously in spinal nerve-ligated neuropathic rats, time- and dose-dependently produced mechanical antiallodynia and thermal antihyperalgesia, significantly increased ipsilateral spinal norepinephrine and serotonin levels, and induced less antiallodynic tolerance than morphine...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220483/pharmacokinetics-and-pharmacodynamics-of-metamizol-in-co-administration-with-morphine-under-acute-and-chronic-treatments-in-arthritic-rats
#2
Patricia Esmeralda Carrillo-Calzadilla, Francisco Javier López-Muñoz, Luis Alfonso Moreno-Rocha, José Raúl Medina-López, Alma Rosa Cortés-Arroyo, Adriana Miriam Domínguez-Ramírez
OBJECTIVE: To investigate the relationship between metamizol pharmacokinetics and the antinociceptive effect produced after subcutaneous administration of metamizol (177.8 mg/kg) alone or in combination with morphine (3.2 mg/kg), under acute and chronic treatments. METHODS: Antinociception was assessed using the pain-induced functional impairment model in rat (PIFIR). Serial blood samples were collected from the same animals to study the pharmacokinetics of metamizol...
February 21, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28219988/sex-differences-in-microglia-activity-within-the-periaqueductal-gray-of-the-rat-a-potential-mechanism-driving-the-dimorphic-effects-of-morphine
#3
H H Doyle, L N Eidson, D M Sinkiewicz, A Z Murphy
Although morphine remains the primary drug prescribed for alleviation of severe or persistent pain, both preclinical and clinical studies have shown that females require 2-3 times more morphine than males to produce comparable levels of analgesia. In addition to binding to the neuronal μ opioid receptor (MOR), morphine binds to the innate immune receptor toll-like receptor 4 (TLR4) localized primarily on microglia. Morphine action at TLR4 initiates a neuroinflammatory response that directly opposes the analgesic effects of morphine...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28207529/comparison-of-the-pro-postoperative-analgesia-of-intraoperative-dexmedetomidine-with-and-without-loading-dose-following-general-anesthesia-a-prospective-randomized-controlled-clinical-trial
#4
Wei Fan, Haikou Yang, Yong Sun, Jun Zhang, Guangming Li, Ying Zheng, Yi Liu
Intraoperative dexemdetomidine (DEX) with or without loading dose is well-established to improve postoperative pain control in patient-controlled analgesia (PCA). This study was designed to compare the pro-analgesia effect between the 2 in patients received general anesthesia.Seventy patients shceduced abdominal surgery under general anesthesia were randomly assigned into 3 groups which were maintained using propofol/remifentanil/Ringer solution (PRR), propofol/remifentanil/dexmedetomidine with (PRDw) or without (PRDo) a loading dose of dexmedetomidine before induction...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28203684/crushed-sublingual-versus-oral-ticagrelor-administration-strategies-in-patients-with-unstable-angina-a-pharmacokinetic-pharmacodynamic-study
#5
Piotr Niezgoda, Joanna Sikora, Malwina Barańska, Adam Sikora, Katarzyna Buszko, Emilia Siemińska, Michał Piotr Marszałł, Jolanta M Siller-Matula, Bernd Jilma, Dimitrios Alexopoulos, Tomasz Fabiszak, Jacek Kubica
Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina...
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28135212/bifunctional-peptide-based-opioid-agonist-nociceptin-antagonist-ligand-for-dual-treatment-of-nociceptive-and-neuropathic-pain
#6
Camille Lagard, Lucie Chevillard, Karel Guillemyn, Patricia Risède, Jean-Louis Laplanche, Mariana Spetea, Steven Ballet, Bruno Mégarbane
Drugs able to treat both nociceptive and neuropathic pain effectively without major side effects are lacking. We developed a bifunctional peptide-based hybrid (KGNOP1) that structurally combines a mu-opioid receptor agonist (KGOP1) with antinociceptive activity and a weak nociceptin receptor antagonist (KGNOP3) with anti-neuropathic pain activity. We investigated KGNOP1-related behavioral effects after intravenous administration in rats by assessing thermal nociception, cold hyperalgesia in a model of neuropathic pain induced by chronic constriction injury of the sciatic nerve, and plethysmography parameters including inspiratory time (TI) and minute ventilation (VM) in comparison to the well-known opioid analgesics, tramadol and morphine...
March 2017: Pain
https://www.readbyqxmd.com/read/28130265/effect-of-tamoxifen-and-brain-penetrant-pkc-and-jnk-inhibitors-on-tolerance-to-opioid-induced-respiratory-depression-in-mice
#7
Sarah L Withey, Rob Hill, Abigail Lyndon, William L Dewey, Eamonn Kelly, Graeme Henderson
Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound tolerance to the respiratory depressant effects of the drug (Hill et al., 2016, Neuropsychopharmacol 41:762-773). The aim of the present study was to investigate whether tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Jun N-terminal kinase (JNK). We found that whilst mice treated for up to six days with morphine developed tolerance, as measured by the reduced responsiveness to an acute challenge dose of morphine, administration of the brain-penetrant PKC inhibitors tamoxifen and calphostin C, restored the ability of acute morphine to produce respiratory depression in morphine-treated mice...
January 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28125510/dendrosomal-nanocurcumin-prevents-morphine-self-administration-behavior-in-rats-despite-ca1-damage
#8
Jalaleden Norozi, Majid Hassanpour-Ezatti, Hojjat A Alaei
Dendrosomal nanocurcumin (DNC) is fabricated from esterification of oleic acid and polyethylene glycol residues with curcumin. DNC has shown antioxidant, neuroprotective, and neurogenesis-enhancing effects. In addition, it can attenuate morphine tolerance. Morphine self-administration is associated with neurodegenerative changes of CA1 neurons in the adult hippocampus. The present study evaluated the effect of DNC pretreatment on morphine self-administration and hippocampal damage. Rats were pretreated with DNC (5 and 10 mg/kg, intraperitoneally) 30 min before a morphine self-administration paradigm performed in 2-h/sessions for 12 days under a FR-1 schedule...
January 25, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28121211/heated-intravenous-fluids-alone-fail-to-prevent-hypothermia-in-cats-under-general-anaesthesia
#9
Geraldine Jourdan, Caroline Didier, Erwan Chotard, Sandra Jacques, Patrick Verwaerde
Objectives The objective was to evaluate the clinical efficiacy of a constant rate infusion of heated fluid as the sole means of preventing intraoperative hypothermia in cats. Methods This randomised, prospective, clinical study was conducted at a university teaching veterinary hospital. Female cats (American Society of Anesthesiologists [ASA] grade I) undergoing elective surgery by laparotomy under general anaesthesia (acepromazine 0.05 mg/kg SC; morphine 0.2 mg/kg IV; propofol IV titrated, isoflurane 2% in 100% oxygen) were randomised in two groups...
January 1, 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28088507/patient-reported-outcomes-and-opioid-use-in-outpatients-with-chronic-pain
#10
Lisa R Witkin, David Zylberger, Neel Mehta, Madeleine Hindenlang, Christopher Johnson, Jacob Kean, Susan D Horn, Charles E Inturrisi
: The Weill Cornell Medical College (WCMC) Pain Registry database contains patient characteristics, treatments, and outcomes for a prospective cohort of 1159 chronic pain patients who were seen at the WCMC Pain Medicine outpatient clinic from 7/08/2011 to 12/10/2014. Patients aged 45-64 comprised 43% followed by age >=65 at 37%. Fifty-eight percent were female. Average pain intensity (Brief Pain Inventory) was reported as mild by 22.3% of patients, moderate by 34.7%, and severe by 43...
January 11, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28060227/preoperative-opioid-use-is-associated-with-early-revision-after-total-knee-arthroplasty-a-study-of-male-patients-treated-in-the-veterans-affairs-system
#11
Alon Ben-Ari, Howard Chansky, Irene Rozet
BACKGROUND: Opioid use is endemic in the U.S. and is associated with morbidity and mortality. The impact of long-term opioid use on joint-replacement outcomes remains unknown. We tested the hypothesis that use of opioids is associated with adverse outcomes after total knee arthroplasty (TKA). METHODS: We performed a retrospective analysis of patients who had had TKA within the U.S. Veterans Affairs (VA) system over a 6-year period and had been followed for 1 year postoperatively...
January 4, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28040448/randomized-clinical-trial-of-postoperative-belladonna-and-opium-rectal-suppositories-in-vaginal-surgery
#12
K Butler, J Yi, M Wasson, J Klauschie, D Ryan, J Hentz, J Cornella, P Magtibay, R Kho
BACKGROUND: Following vaginal surgery oral and parenteral narcotics are commonly used for pain relief and their use may exacerbate the incidence of sedation, nausea, and vomiting; ultimately delaying convalescence. Previous studies have demonstrated that rectal analgesia following surgery results in lower pain scores and less intravenous morphine consumption. Belladonna and opium (B&O) rectal suppositories may be used to relieve pain and minimize side effects; however their efficacy has not been confirmed...
December 28, 2016: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28034513/suppression-of-the-acute-upregulation-of-phosphorylated-extracellular-regulated-kinase-in-ventral-tegmental-area-by-a-%C3%AE-opioid-receptor-agonist-is-related-to-resistance-to-rewarding-effects-in-a-mouse-model-of-bone-cancer
#13
Atsushi Nakamura, Hiroko Ono, Azusa Ando, Mikie Hinata, Kazuki Niidome, Shigeki Omachi, Gaku Sakaguchi, Shunji Shinohara
We investigated the mechanisms underlying the suppression of the rewarding effects of opioids using the femur bone cancer (FBC) mouse model. The rewarding and antinociceptive effects of subcutaneously administered morphine and oxycodone in the FBC model mice were assessed using the conditioned place preference test and the von-Frey test. In FBC mice, antinociceptive doses of morphine (30 mg/kg) and oxycodone (5 mg/kg) did not produce the rewarding effects but excessive doses of morphine (300 mg/kg) and oxycodone (100 mg/kg) did...
December 8, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28007642/suppressing-effect-of-saikosaponin-a-an-active-ingredient-of-bupleurum-falcatum-on-chocolate-self-administration-and-reinstatement-of-chocolate-seeking-in-rats
#14
Irene Lorrai, Paola Maccioni, Mauro A M Carai, Alessandro Capra, M Paola Castelli, Antonella Riva, Paolo Morazzoni, Gian Luigi Gessa, Giancarlo Colombo
Recent lines of experimental evidence have indicated that saikosaponin A (SSA) - a bioactive ingredient of the medicinal plant, Bupleurum falcatum L. - suppressed alcohol, morphine, and cocaine self-administration in rats. The present paper was designed to assess whether the protective properties of SSA on addiction-related behaviors generalize to a hyperpalatable food such as a chocolate-flavored beverage (CFB). To this end, rats were initially trained to lever-respond for CFB [5% (w/v) Nesquik(®) powder in water] under fixed ratio (FR) 10 (FR10) schedule of reinforcement...
December 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27940077/the-discriminative-stimulus-effects-of-i-v-nicotine-in-rhesus-monkeys-pharmacokinetics-and-apparent-pa2-analysis-with-dihydro-%C3%AE-erythroidine
#15
Megan J Moerke, Andy Z X Zhu, Rachel F Tyndale, Martin A Javors, Lance R McMahon
Quantitative analysis of antagonism is infrequently used to identify nAChRs mediating behavioral effects. Here, nicotine (0.032 mg/kg i.v.) was established as a discriminative stimulus in rhesus monkeys responding under a fixed ratio 5 schedule; pharmacokinetics and underlying nAChR mechanism(s) were examined. When measured up to 4 h in venous blood, the training dose resulted in the following mean pharmacokinetic parameters: nicotine Cmax = 71.7 ng/ml, t1/2 = 116 min, and clearance = 6.25 ml/min/kg; cotinine Cmax = 191 ng/ml; and 3OH-cotinine Cmax = 63 ng/ml...
December 8, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27939192/ultrasound-guided-serratus-anterior-plane-block-versus-thoracic-epidural-analgesia-for-thoracotomy-pain
#16
Asmaa Elsayed Khalil, Nasr Mahmoud Abdallah, Ghada M Bashandy, Tarek Abdel-Haleem Kaddah
OBJECTIVE: Thoracotomy is one of the most painful surgical procedures. The aim of this study was to assess the efficacy and safety of ultrasound-guided serratus anterior plane block (SAPB) compared with thoracic epidural analgesia (TEA) for controlling acute thoracotomy pain. DESIGN: A prospective, randomized, observer-blinded, controlled study. SETTING: The study was performed as a single-institution study in the National Cancer Institute, Cairo University, Egypt...
August 21, 2016: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/27929349/effects-of-paclitaxel-on-mechanical-sensitivity-and-morphine-reward-in-male-and-female-c57bl6-mice
#17
Harshini Neelakantan, Sara Jane Ward, Ellen Ann Walker
This study evaluated the hypothesis that a paclitaxel treatment regimen sufficient to produce mechanical allodynia would alter sensitivities of male and female mice to the conditioned rewarding and reinforcing effects of morphine. Saline or paclitaxel were administered on Days 1, 3, 5, and 7 in male and female C57Bl/6 mice to induce morphine-reversible mechanical allodynia as measured by the Von Frey filament test. Paclitaxel treatment did not change sensitivity to morphine conditioned place preference (CPP) relative to saline treatment in either male or female mice...
December 2016: Experimental and Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27919821/specific-micrornas-comparisons-in-hypoxia-and-morphine-preconditioning-against-hypoxia-reoxgenation-injury-with-and-without-heart-failure
#18
Hai-Juan Zhu, Zheng-Yi Han, Shu-Fang He, Shi-Yun Jin, Shi-Jin Xu, Xiang-Dong Fang, Ye Zhang
AIMS: Ischemia reperfusion (I/R) injury is an inevitable event arising during the cardiovascular diseases development and the process of potent surgical treatments. microRNAs (miRNAs) are critical regulators of multiple cell processes including I/R injury. The present study aims to quantify miRNA alterations and regulated genes upon hypoxia-reoxygenation (H/R) injury in a rat heart failure model comparing with normal cardiomyocytes. MAIN METHODS: Chronic heart failure was established by injecting doxorubicin (2mg/kg/week) for 6weeks, then H/R was performed on primary cultured cardiomyocytes isolated from normal and failed heart...
February 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27902847/food-deprivation-facilitates-reinstatement-of-morphine-induced-conditioned-place-preference-role-of-intra-accumbal-dopamine-d2-like-receptors-in-associating-reinstatement-of-morphine-cpp-with-stress
#19
Fatemeh Sadeghzadeh, Vahab Babapour, Abbas Haghparast
The high rate of relapse to drug use is one of the main problems in the treatment of addiction. Stress plays the essential role in drug abuse and relapse; nevertheless, little is known about the mechanisms underlying stress and relapse. Accordingly, the effects of intra-accumbal administration of Sulpiride, as a dopamine D2-like receptor antagonist, on an ineffective morphine dose + food deprivation(FD)- and morphine priming-induced reinstatement of conditioned place preference (CPP). About 104 adult male albino Wistar rats weighing 200-280 g were bilaterally implanted by cannula into the nucleus accumbens (NAc)...
April 2017: Synapse
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
#20
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...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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