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therapeutic uses of morphine

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https://www.readbyqxmd.com/read/28533287/trv0109101-a-g-protein-biased-agonist-of-the-%C3%A2%C2%B5-opioid-receptor-does-not-promote-opioid-induced-mechanical-allodynia-following-chronic-administration
#1
Michael Koblish, Richard Carr, Edward R Siuda, David H Rominger, William Gowen-MacDonald, Conrad L Cowan, Aimee L Crombie, Jonathan D Violin, Michael W Lark
Prescription opioids are a mainstay in the treatment of acute moderate to severe pain. However, chronic use leads to a host of adverse consequences including tolerance and opioid-induced hyperalgesia (OIH), leading to more complex treatment regimens and diminished patient compliance. Patients experiencing OIH paradoxically experience exaggerated nociceptive responses instead of pain reduction after chronic opioid usage. The development of OIH and tolerance tend to occur simultaneously and, thus, present a challenge when studying the molecular mechanisms driving each phenomenon...
May 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28529193/laparoscopy-has-a-therapeutic-role-in-the-management-of-abdominal-trauma-a-matched-pair-analysis
#2
Saurav Chakravartty, Ameet Patel, Diwakar R Sarma, Muhammad Noor, Spyros Panagiotopoulos, Ameet G Patel
INTRODUCTION: Laparoscopy is increasingly utilised as a diagnostic tool in management of abdominal trauma; however its role in therapeutic intervention remains unexplored. The aim of this study is to compare laparoscopy with laparotomy in the treatment of abdominal trauma in haemodynamically stable patients. METHODS: A review of patients undergoing surgery for abdominal trauma between January 2004-2014 identified 25 patients who underwent laparoscopy for therapeutic intervention (TL)...
May 18, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28519244/neonatal-abstinence-syndrome-update-on-diagnostic-and-therapeutic-strategies
#3
Genny Raffaeli, Giacomo Cavallaro, K Karel Allegaert, Enno Diederik Wildschut, Monica Fumagalli, Massimo Agosti, Dick Tibboel, Fabio Mosca
Substance use among pregnant women is a major public health issue. Both prescription opioid use and illicit opioid abuse have increased dramatically in recent years. Prolonged in utero drug exposure may result in neonatal abstinence syndrome (NAS), an acute multisystemic clinical entity that occurs in the first days of life. This syndrome is caused by abrupt discontinuation of fetal exposure to licit or illicit drugs chronically consumed by the mother during pregnancy and transmitted to the fetus through the placenta...
May 18, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28502631/a-brain-targeted-ampakine-compound-protects-against-opioid-induced-respiratory-depression
#4
Wei Dai, Dian Xiao, Xiang Gao, Xin-Bo Zhou, Tong-Yu Fang, Zheng Yong, Rui-Bin Su
The use of opioid drugs for pain relief can induce life-threatening respiratory depression. Although naloxone effectively counteracts opioid-induced respiratory depression, it diminishes the efficacy of analgesia. Our studies indicate that ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse respiratory depression without affecting analgesia at relatively low doses. Mice and rats were subcutaneously or intravenously injected with the opioid agonist TH-030418 to induce moderate or severe respiratory depression...
May 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28486096/key-pharmacogenomic-considerations-for-sickle-cell-disease-patients
#5
Alexandra Kolliopoulou, Apostolos Stratopoulos, Stavroula Siamoglou, Argyro Sgourou, Adamantia Papachatzopoulou, Theodora Katsila, George P Patrinos
Sickle cell disease (SCD), although a monogenic disease, exhibits a complex clinical phenotype that hampers optimum patient stratification and disease management, especially on hydroxyurea treatment. Moreover, theranostics, the combination of diagnostics to individualize and optimize therapeutic interventions, has not been firmly on the forefront of SCD research and clinical management to date. We suggest that if tailor-made theranostics in SCD is envisaged, pharmacogenomics is anticipated to be the way forward...
May 9, 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28465076/dexmedetomidine-as-an-adjuvant-for-perioperative-pain-management-in-adolescents-undergoing-bariatric-surgery-an-observational-cohort-study
#6
Janelle D Vaughns, Celeste Martin, Jonathon Nelson, Evan Nadler, Zenaide M Quezado
BACKGROUND: The anesthetic management of adolescents undergoing bariatric surgery presents a number of challenges, including increased risk of postoperative opioid-related respiratory depression. These patients could benefit from adjunctive analgesics with opioid-sparring effects to optimize perioperative pain control. Dexmedetomidine, a selective α2-adrenoreceptor agonist, has sedative and analgesic properties with no respiratory depressant effects. OBJECTIVE: To determine the effect of intraoperative dexmedetomidine on opioid requirement and perioperative pain management in obese adolescents undergoing bariatric surgery...
April 19, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28450396/heat-shock-protein-90-hsp90-promotes-opioid-induced-anti-nociception-by-an-erk-mitogen-activated-protein-kinase-mapk-mechanism-in-mouse-brain
#7
Wei Lei, Nathan Mullen, Sarah McCarthy, Courtney Brann, Philomena Richard, James Cormier, Katie Edwards, Edward J Bilsky, John M Streicher
Recent advances in developing opioid treatments for pain with reduced side effects have focused on the signaling cascades of the mu opioid receptor (MOR). However, few such signaling targets have been identified for exploitation. To address this need, we explored the role of Heat shock protein 90 (Hsp90) in opioid-induced MOR signaling and pain, which has only been studied in 4 previous papers. First, in 4 cell models of MOR signaling, we found that Hsp90 inhibition for 24 hours with the inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) had different effects on protein expression and opioid signaling in each line, suggesting that cell models may not be reliable for predicting pharmacology with this protein...
April 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442370/modulation-of-drug-choice-by-extended-drug-access-and-withdrawal-in-rhesus-monkeys-implications-for-negative-reinforcement-as-a-driver-of-addiction-and-target-for-medications-development
#8
REVIEW
S Stevens Negus, Matthew L Banks
Chronic drug exposure is hypothesized to recruit negative reinforcement processes that increase the magnitude and alter the mechanisms of drug reinforcement. Candidate substrates of negative reinforcement include increased signaling via stress-related neurotransmitters such as corticotropin releasing factor (CRF, acting at CRF receptors) or dynorphin (acting at kappa opioid receptors) and/or decreased signaling via reward-related neurotransmitters such as dopamine. Determinants of drug reinforcement can be examined with choice procedures, in which subjects choose between a drug of interest (e...
April 22, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28411112/morphine-use-in-the-emergency-department-and-outcomes-of-patients-with-acute-heart-failure-a-propensity-score-matching-analysis-based-on-the-eahfe-registry
#9
Òscar Miró, Víctor Gil, Francisco J Martín-Sánchez, Pablo Herrero, Javier Jacob, Alexandre Mebazaa, Veli-Pekka Harjola, José Ríos, Judd E Hollander, W Frank Peacock, Pere Llorens
OBJECTIVE: To determine the relationship between short-term mortality and intravenous morphine use in emergency department (ED) patients diagnosed with acute heart failure (AHF). METHODS: Consecutive AHF patients presenting to 34 Spanish EDs from 2011 to 2014 were eligible for inclusion. The subjects were divided into those with or without intravenous morphine treatment (M and WOM groups, respectively) during ED stay. The primary outcome was 30-day all-cause mortality, and secondary outcomes were mortality at different intermediate time points, in-hospital mortality, and length of hospital stay (LOS)...
April 11, 2017: Chest
https://www.readbyqxmd.com/read/28393895/sex-differences-in-regional-brain-glucose-metabolism-following-opioid-withdrawal-and-replacement
#10
Giovanni C Santoro, Joseph Carrion, Krishna Patel, Crystal Vilchez, Jennifer Veith, Jonathan D Brodie, Stephen L Dewey
Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex-specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared to males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using (18)FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement...
April 10, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28375887/randomized-controlled-trial-of-interscalene-block-compared-with-injectable-liposomal-bupivacaine-in-shoulder-arthroplasty
#11
RANDOMIZED CONTROLLED TRIAL
Surena Namdari, Thema Nicholson, Joseph Abboud, Mark Lazarus, Dean Steinberg, Gerald Williams
BACKGROUND: Shortcomings of interscalene brachial plexus blockade include technical failure and rebound pain. Bupivacaine liposome injectable suspension, a sustained release preparation, is used for surgical-site administration. The purpose of this study was to evaluate these 2 postoperative pain management strategies in patients undergoing shoulder arthroplasty. METHODS: In a non-blinded, randomized controlled trial of participants undergoing primary shoulder arthroplasty, patients were randomized to interscalene brachial plexus blockade or intraoperative soft-tissue infiltration of bupivacaine liposome injectable suspension...
April 5, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28368571/recent-advances-in-the-realm-of-allosteric-modulators-for-opioid-receptors-for-future-therapeutics
#12
Michael Remesic, Victor J Hruby, Frank Porreca, Yeon Sun Lee
Opioids, and more specifically μ-opioid receptor (MOR) agonists such as morphine, have long been clinically used as therapeutics for severe pain states but often come with serious side effects such as addiction and tolerance. Many studies have focused on bringing about analgesia from the MOR with attenuated side effects, but its underlying mechanism is not fully understood. Recently, focus has been geared toward the design and elucidation of the orthosteric site with ligands of various biological profiles and mixed subtype opioid activities and selectivities, but targeting the allosteric site is an area of increasing interest...
April 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28368370/mnsod-mediated-by-hsv-vectors-in-the-periaqueductal-gray-suppresses-morphine-withdrawal-in-rats
#13
T Iida, H Yi, S Liu, D Ikegami, W Zheng, Q Liu, K Takahashi, Y Kashiwagi, W F Goins, J C Glorioso, S Hao
Morphine appears to be the most active metabolite of heroin; therefore, the effects of morphine are important in understanding the ramifications of heroin abuse. Opioid physical dependence (withdrawal response) may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. However, the exact mechanisms of morphine withdrawal (MW) are not clear yet, and its treatment remains elusive. Periaqueductal gray (PAG) is one of the important sites in the pathogenesis of MW...
May 2017: Gene Therapy
https://www.readbyqxmd.com/read/28298041/randomized-double-blinded-placebo-controlled-trial-comparing-two-multimodal-opioid-minimizing-pain-management-regimens-following-transsphenoidal-surgery
#14
Deborah M Shepherd, Heidi Jahnke, William L White, Andrew S Little
OBJECTIVE Pain control is an important clinical consideration and quality-of-care metric. No studies have examined postoperative pain control following transsphenoidal surgery for pituitary lesions. The study goals were to 1) report postoperative pain scores following transsphenoidal surgery, 2) determine if multimodal opioid-minimizing pain regimens yielded satisfactory postoperative pain control, and 3) determine if intravenous (IV) ibuprofen improved postoperative pain scores and reduced opioid use compared with placebo...
March 3, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28275350/blockade-of-p2x4-receptors-inhibits-neuropathic-pain-related-behavior-by-preventing-mmp-9-activation-and-consequently-pronociceptive-interleukin-release-in-a-rat-model
#15
Agnieszka M Jurga, Anna Piotrowska, Wioletta Makuch, Barbara Przewlocka, Joanna Mika
Neuropathic pain is still an extremely important problem in today's medicine because opioids, which are commonly used to reduce pain, have limited efficacy in this type of pathology. Therefore, complementary therapy is needed. Our experiments were performed in rats to evaluate the contribution of the purinergic system, especially P2X4 receptor (P2X4R), in the modulation of glia activation and, consequently, the levels of nociceptive interleukins after chronic constriction injury (CCI) of the right sciatic nerve, a rat model of neuropathic pain...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#16
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28206989/il-4-mediated-by-hsv-vector-suppresses-morphine-withdrawal-response-and-decreases-tnf%C3%AE-nr2b-and-pc-ebp%C3%AE-in-the-periaqueductal-gray-in-rats
#17
H Yi, T Iida, S Liu, D Ikegami, Q Liu, A Iida, D A Lubarsky, S Hao
Chronic opiates induce the development of physical dependence. Opioid physical dependence characterized by withdrawal symptoms, may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. Elucidation of the mechanisms involved in physical dependence is crucial to developing more effective treatment strategies for opioid dependence. Chronic morphine induces production of proinflammatory cytokines in regional-specific sites of the brain. Interleukin-4 (IL-4) is a prototypical anti-inflammatory cytokine that globally suppresses proinflammatory cytokines...
April 2017: Gene Therapy
https://www.readbyqxmd.com/read/28157809/withdrawal-assessment-tool-1-monitoring-in-picu-a-multicenter-study-on-iatrogenic-withdrawal-syndrome
#18
Angela Amigoni, Maria Cristina Mondardini, Ilaria Vittadello, Federico Zaglia, Emanuele Rossetti, Francesca Vitale, Stefania Ferrario, Fabio Savron, Giancarlo Coffaro, Luca Brugnaro, Roberta Amato, Andrea Wolfler, Linda S Franck
OBJECTIVES: Withdrawal syndrome is an adverse reaction of analgesic and sedative therapy, with a reported occurrence rate between 17% and 57% in critically ill children. Although some factors related to the development of withdrawal syndrome have been identified, there is weak evidence for the effectiveness of preventive and therapeutic strategies. The main aim of this study was to evaluate the frequency of withdrawal syndrome in Italian PICUs, using a validated instrument. We also analyzed differences in patient characteristics, analgesic and sedative treatment, and patients' outcome between patients with and without withdrawal syndrome...
February 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28142305/effects-of-acute-and-repeated-treatment-with-the-biased-mu-opioid-receptor-agonist-trv130-oliceridine-on-measures-of-antinociception-gastrointestinal-function-and-abuse-liability-in-rodents
#19
Ahmad A Altarifi, Bethany David, Karan H Muchhala, Bruce E Blough, Hamid Akbarali, S Stevens Negus
RATIONALE: TRV130 (oliceridine; N-[(3-methoxythiophen-2-yl)methyl]-2-[(9 R)-9-pyridin-2-yl-6-oxaspiro[4.5]decan-9-yl]ethanamine) is a novel mu opioid receptor (MOR) agonist that preferentially activates G-protein versus β-arrestin signaling pathways coupled to MORs. Prevailing evidence suggests that TRV130 and other G-protein-biased MOR agonists may produce therapeutic analgesic effects with reduced adverse effects compared to existing MOR agonists. OBJECTIVES: This study compared the effects of acute and repeated TRV130 administration on measures of antinociception, gastrointestinal function, and abuse liability in rodents...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28134928/blocking-microglial-pannexin-1-channels-alleviates-morphine-withdrawal-in-rodents
#20
Nicole E Burma, Robert P Bonin, Heather Leduc-Pessah, Corey Baimel, Zoe F Cairncross, Michael Mousseau, Jhenkruthi Vijaya Shankara, Patrick L Stemkowski, Dinara Baimoukhametova, Jaideep S Bains, Michael C Antle, Gerald W Zamponi, Catherine M Cahill, Stephanie L Borgland, Yves De Koninck, Tuan Trang
Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal...
March 2017: Nature Medicine
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