- Proteomic data in morphine addiction versus real protein activity: metabolic enzymes. [Journal Article]
- JCJ Cell Biochem 2017 Apr 21
- Drug dependence is an escalating problem worldwide and many efforts are being made to understand the molecular basis of addiction. The morphine model is widely used in these investigations. To date, ...
Drug dependence is an escalating problem worldwide and many efforts are being made to understand the molecular basis of addiction. The morphine model is widely used in these investigations. To date, at least 29 studies exploring the influence of morphine on mammals' proteomes have been published. Among various proteins indicated as up- or down-regulated, the expression changes of enzymes engaged in energy metabolism pathways have often been confirmed. To verify whether proteomics-indicated alterations in enzyme levels reflect changes in their activity, four enzymes: PK, MDH, Complex I, and Complex V were investigated in morphine addiction and abstinence models. After analyses of the rat brain mitochondria fraction in the model of morphine dependence, we found that one of the investigated enzymes (pyruvate kinase) showed statistically significant differences observed between morphine, control and abstinence groups. This article is protected by copyright. All rights reserved.
- Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1) show modestly enhanced alcohol preference and consumption. [Journal Article]
- PlosPLoS One 2017; 12(4):e0174826
- We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this stud...
We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg), and cocaine (10 mg/kg), demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.
- Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish. [Journal Article]
- JEJ Exp Biol 2017 Apr 15; 220(Pt 8):1451-1458
- Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered ...
Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a range of analgesic drugs to determine their efficacy to reduce these responses. This approach aimed to validate larval zebrafish as a reliable replacement for adults as well as providing a high-throughput means of analysing behavioural responses. Zebrafish at 5 days post-fertilization were exposed to known noxious stimuli: acetic acid (0.01%, 0.1% and 0.25%) and citric acid (0.1%, 1% and 5%). The behavioural response of each was recorded and analysed using novel tracking software that measures time spent active in 25 larvae at one time. Subsequently, the efficacy of aspirin, lidocaine, morphine and flunixin as analgesics after exposure to 0.1% acetic acid was tested. Larvae exposed to 0.1% and 0.25% acetic acid spent less time active, whereas those exposed to 0.01% acetic acid and 0.1-5% citric acid showed an increase in swimming activity. Administration of 2.5 mg l(-1) aspirin, 5 mg l(-1) lidocaine and 48 mg l(-1) morphine prevented the behavioural changes induced by acetic acid. These results suggest that larvae respond to a noxious challenge in a similar way to adult zebrafish and other vertebrates and that the effect of nociception on activity can be ameliorated by using analgesics. Therefore, adopting larval zebrafish could represent a direct replacement of a protected adult fish with a non-protected form in pain- and nociception-related research.
- miR-219-5p targets CaMKIIγ to attenuate morphine tolerance in rats. [Journal Article]
- OOncotarget 2017 Mar 08
- Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) ...
Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein kinase II γ (CaMKIIγ) to activate central pain sensitization via N-methyl-D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p attenuates morphine tolerance by targeting CaMKIIγ. We found that the expression of miR-219-5p was decreased significantly after chronic morphine treatment. Overexpression of miR-219-5p by lentivirus injection prevents the development of morphine tolerance. CaMKIIγ, the target gene of miR-219-5p was downregulated by overexpression of miR-219-5p both in vivo and in vitro. Furthermore, we found that lentiviral-mediated miR-219-5p decreased the expression of NMDA receptor subunit 1 (NR1), leading to attenuation of morphine tolerance. Overall, the data demonstrate that miR-219-5p plays a crucial role in alleviating morphine tolerance by inhibiting the CaMKII/NMDA receptor pathway. Overexpression of miR-219-5p may be a potential strategy to ameliorate morphine tolerance.
- Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does affect IL-2/IFN-γ expression of T cells in vitro?: A prospective, randomized, double-blind study. [Journal Article]
- MMedicine (Baltimore) 2017; 96(16):e6639
- CONCLUSIONS: In conclusion, we confirmed that just as morphine, ketamine dose-dependently suppressed IL-2 and IFN-γ of activated T lymphocyte of patients with refractory cancer pain in vitro, but the inhibitory action of low dose ketamine could be neglected.
- Intrathecal Morphine in Spine Surgery: A Meta-analysis of Randomized Controlled Trials. [Journal Article]
- SSpine (Phila Pa 1976) 2017 Apr 18
- CONCLUSIONS: In patients undergoing spine surgery, use of ITM significantly reduced opioid analgesic consumption and VAS pain scores compared to controls within the first 24 hours postoperatively. High-quality, follow-up RCTs with large sample sizes are recommended to determine the potential of supplementary ITM in spine surgery and complete the side effects profile.
- Heroin-related Deaths from the Hennepin County Medical Examiner's Office from 2004 Through 2015. [Journal Article]
- JFJ Forensic Sci 2017 Apr 19
- Over the past two decades, prescription and illicit opioid use has led to changes in public health policy to address the increasing number of opioid-related deaths. The purpose of this study was to r...
Over the past two decades, prescription and illicit opioid use has led to changes in public health policy to address the increasing number of opioid-related deaths. The purpose of this study was to review cases from Hennepin County Medical Examiner's Office between 2004 through 2015 where heroin was listed as a significant contributor or as the cause of death. We identified 322 heroin-related deaths, which were predominantly male (255; 79%). 6-Monoacetylmorphine (6-MAM) median (range) concentrations were as follows: blood (n = 7), 0.010 (0.006-0.078) mg/L; urine (n = 30), 0.359 (0.009-1.75) mg/L; and vitreous humor (n = 31), 0.034 (0.004-0.24) mg/L. Free morphine was measurable in 273 cases and the percent free morphine (range), when grouped by COD, was opioid (n = 124), 28% (2.2%-92%), and mixed drug toxicity (n = 135), 35.3% (1.5%-100%); (p < 0.01). Quantitation of 6-MAM in blood and vitreous humor, along with a free to total morphine ratio >26%, was useful in establishing heroin-related deaths.
- Assessing the survival impact of perioperative opioid consumption in children and adolescents undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. [Journal Article]
- PAPaediatr Anaesth 2017 Apr 17
- CONCLUSIONS: In this retrospective study of children and adolescents who had undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, there was no statistically significant association between opioid consumption and recurrence-free survival or overall survival.
- Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study. [Journal Article]
- HHaemophilia 2017 Apr 16
- CONCLUSIONS: Patients with chronic pain, particularly those with both acute/chronic pain, frequently experience psychological issues, functional disability and reduced HRQoL. Treatment strategies for acute pain (e.g. routine infusions to prevent bleeding) and for chronic pain (e.g. long-acting opioids) may be underused.
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- Risk Factors for Serious Prescription Opioid-Induced Respiratory Depression or Overdose: Comparison of Commercially Insured and Veterans Health Affairs Populations. [Journal Article]
- PMPain Med 2017 Apr 13
- CONCLUSIONS: Risk factor profiles for serious OIRD among US medical users of prescription opioids with private or public health insurance were largely concordant despite substantial differences between the populations in demographics, clinical conditions, health care delivery systems, and clinical practices.