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Sample records for single morphine exposure

  1. A pharmacokinetic-pharmacodynamic model of morphine exposure and subsequent morphine consumption in postoperative pain

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Nyberg, Joakim; Lund, Trine Meldgaard

    2016-01-01

    Purpose To characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation. Methods Dose, formulation and time of morphine administration was available from a published study...... in 63 patients receiving intravenous, oral immediate release or oral controlled release morphine on request after hip surgery. The PK-PD relationship between predicted exposure of morphine and morphine consumption was modeled using repeated time to event (RTTE) modeling in NONMEM. To validate the RTTE...... model, a visual predictive check method was developed with simulated morphine consumption given the exposure of preceding morphine administration. Results The probability of requesting morphine was found to be significantly related to the exposure of morphine as well as night/day. Oral controlled...

  2. Morphine

    African Journals Online (AJOL)

    the use of oral morphine in the palliative care management of HIV/AIDS and cancer. Data was gathered from .... majority of the population of Malawi live in rural areas, often far away from their nearest health facility. ... dependence on the use of substances for their psychic effects, characterised by compulsive use despite ...

  3. Short term morphine exposure in vitro alters proliferation and differentiation of neural progenitor cells and promotes apoptosis via mu receptors.

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    Dafna Willner

    Full Text Available Chronic morphine treatment inhibits neural progenitor cell (NPC progression and negatively effects hippocampal neurogenesis. However, the effect of acute opioid treatment on cell development and its influence on NPC differentiation and proliferation in vitro is unknown. We aim to investigate the effect of a single, short term exposure of morphine on the proliferation, differentiation and apoptosis of NPCs and the mechanism involved.Cell cultures from 14-day mouse embryos were exposed to different concentrations of morphine and its antagonist naloxone for 24 hours and proliferation, differentiation and apoptosis were studied. Proliferating cells were labeled with bromodeoxyuridine (BrdU and cell fate was studied with immunocytochemistry.Cells treated with morphine demonstrated decreased BrdU expression with increased morphine concentrations. Analysis of double-labeled cells showed a decrease in cells co-stained for BrdU with nestin and an increase in cells co-stained with BrdU and neuron-specific class III β-tubuline (TUJ1 in a dose dependent manner. Furthermore, a significant increase in caspase-3 activity was observed in the nestin- positive cells. Addition of naloxone to morphine-treated NPCs reversed the anti-proliferative and pro-apoptotic effects of morphine.Short term morphine exposure induced inhibition of NPC proliferation and increased active caspase-3 expression in a dose dependent manner. Morphine induces neuronal and glial differentiation and decreases the expression of nestin- positive cells. These effects were reversed with the addition of the opioid antagonist naloxone. Our results demonstrate the effects of short term morphine administration on the proliferation and differentiation of NPCs and imply a mu-receptor mechanism in the regulation of NPC survival.

  4. Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

    OpenAIRE

    Matsukizono, Miho; Kamegawa, Mariko; Tanaka, Koichi; Kohra, Shinya; Arizono, Koji; Hamazoe, Yuta; Sugimura, Kazuhisa

    2013-01-01

    An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv) clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg) but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competi...

  5. Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

    Directory of Open Access Journals (Sweden)

    Kazuhisa Sugimura

    2013-02-01

    Full Text Available An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competitive ELISA with M86 and morphine-C-Tg in the absence or presence of varying doses of free morphine and related compounds. IC50 values for opium, morphine, codeine, and heroin were 257 ng/mL, 36.4, 7.3, and 7.4 nM, respectively. Ketamine and cocaine exhibited no competitive binding activity to M86. Thus, we established a phage library-derived scFv, M86, which recognized not only free morphine and codeine as opium components but also heroin. This characteristic of M86 may be useful for developing therapeutic reagents for opiate addiction and as a free morphine-specific antibody probe.

  6. Neonatal Morphine Exposure in Very Preterm Infants – Cerebral Development and Outcomes

    Science.gov (United States)

    Steinhorn, Rachel; McPherson, Chris; Anderson, Peter J; Neil, Jeffrey; Doyle, Lex W; Inder, Terrie

    2015-01-01

    Objective To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood. Study design Observational study of very preterm infants in the Victorian Infant Brain Study cohort. 230 infants born neonatal intensive care unit (NICU) of the Royal Women’s Hospital. 57 (25%) infants received morphine analgesia during their NICU stay at the attending physician’s discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine. Results At term, preterm infants who received morphine had similar rates of grey matter injury to no-morphine infants, but a trend towards smaller cortical volumes in the orbitofrontal (pleft=0.002, pright=0.01) and subgenual (pleft=0.01) regions. At seven years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (p=0.007) than no-morphine children, but at seven years no detrimental impacts of morphine on neurobehavioral outcome were observed. Conclusions Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood. PMID:25919729

  7. The effect of a single dose of morphine on muscle fatigue indices in male rats

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    Sedigheh Amiresmaili

    2016-09-01

    Full Text Available Background and Aim: Endogenous opioids and addictive opiate drugs change many body functions. . Previous studies have referred to the effects of morphine on smooth and pulmonary muscles ., but the  effects of opioids on skeletal muscles is not known well. Thus, the current study aimed at assessing the effect of a single dose of morphine on muscle fatigue in male rats. Materials and Methods: In this experimental study, 40 male Wistar rats weighing 220-270 g were randomly divided into four equal groups: control (the mice were kept in their cages and received food and water, morphine receiving group, fatigue group (the mice in this group were kept running on  a treadmill . for120 minutes at a rate of 20 meters per minute, and morphine plus fatigue group. At the end of the experiments, blood samples were obtained from the corner of their eyes and were sent to the laboratory for measurement of muscle fatigue indexes including lactate dehydrogenase (LDH and creatine phosphokinase (CPK. Results: Administration of morphine to the fatigue group decreased running time compared with the control group (P=0.009. Furthermore, administration of morphine to the fatigue group significantly increased serum levels of LDH (P=0.009 and CPK (P=0.008. Conclusion: The present study showed that administration of a single dose of morphine in rats increases muscle fatigue biomarkers (LDH, CPK.

  8. A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose.

    Science.gov (United States)

    Velez de Mendizabal, Nieves; Jimenez-Mendez, Ricardo; Cooke, Erin; Montgomery, Carolyne J; Dawes, Joy; Rieder, Michael J; Aleksa, Katarina; Koren, Gideon; Jacobo-Cabral, Carlos O; Gonzalez-Ramirez, Rodrigo; Castañeda-Hernandez, Gilberto; Carleton, Bruce C

    2015-10-01

    Currently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination with paracetamol (acetaminophen). Codeine is an opioid, which elicits its analgesic effects via metabolism to morphine and codeine-6-glucuronide. Oral morphine is a feasible alternative for outpatient analgesia; however, the pharmacokinetics of morphine after oral administration have been previously described only sparsely, and there is little information in healthy children. The clinical trial included 40 children from 2 to 6 years of age, with an American Society of Anaesthesiologists physical status classification of 1 or 2, who were undergoing surgical procedures requiring opioid analgesia. Morphine was orally administered prior to surgery in one of three doses: 0.1 mg/kg, 0.2 mg/kg and 0.3 mg/kg. Blood samples were collected for plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations at 30, 60, 90, 120, 180 and 240 min after administration. All analyses were performed with the non-linear mixed-effect modelling software NONMEM version 7.2, using the first-order conditional estimation (FOCE) method. A pharmacokinetic model was developed to simultaneously describe the plasma profiles of morphine and its metabolites M3G and M6G after a single dose of oral morphine in young children (2-6 years of age). The disposition of morphine, M3G and M6G in plasma was best described by a one-compartment model. M3G and M6G metabolite formation was best described by a delay transit compartment, indicating a delay in the appearance of these two major metabolites. This model provides a foundation on which to further evaluate the use of oral morphine and its safety in young children. Longer follow-up time for morphine oral doses and incorporation of

  9. Effect of rat parental morphine exposure on passive avoidance memory and morphine conditioned place preference in male offspring.

    Science.gov (United States)

    Akbarabadi, Ardeshir; Niknamfar, Saba; Vousooghi, Nasim; Sadat-Shirazi, Mitra-Sadat; Toolee, Heidar; Zarrindast, Mohammad-Reza

    2018-02-01

    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. After that, they were let to mate with either an abstinent or control rat. Male offspring's memory was evaluated by step through test. Besides, rewarding effects of morphine were checked with CCP paradigm. Offspring of abstinent animals showed significant memory impairment compared to the control group which was more prominent in the offspring of abstinent females. Conditioning results showed that administration of a high dose of morphine (10mg/kg) that could significantly induce CPP in control rats, was not able to induce similar results in the offspring of morphine abstinent parents; and CPP was much more prominent when it was induced in the offspring of morphine exposed females compared to the progeny of morphine exposed males. It is concluded that parental morphine consumption in adulthood even before mating has destructive effects on memory state of the male offspring and also leads to tolerance to the rewarding effects of morphine. These effects are greater when the morphine consumer parent is the female one. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Wang, Yi-lun; Li, Yu-sheng; Wei, Jie; Li, Hui; Yang, Tuo; Yang, Tu-bao; Lei, Guang-hua

    2015-01-01

    Objectives The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery. Methods Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software. Results Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone. Conclusion The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone. Level of Evidence Level I, meta-analysis of Level I studies. PMID:26474401

  11. Internalizing behaviours in school-age children born very preterm are predicted by neonatal pain and morphine exposure.

    Science.gov (United States)

    Ranger, M; Synnes, A R; Vinall, J; Grunau, R E

    2014-07-01

    Greater neonatal pain is associated with higher internalizing behaviours in very preterm infants at 18 months corrected age, but it is unknown whether this relationship persists to school age. Moreover, it is unclear whether morphine ameliorates or exacerbates the potential influence of neonatal pain/stress on internalizing behaviours. We examined whether neonatal pain-related stress is associated with internalizing behaviours at age 7 years in children born very preterm, and whether morphine affects this relationship. One hundred one children born very preterm (≤32 weeks gestation) were seen at mean age 7.7 years. A parent completed the Parenting Stress Index and Child Behavior Checklist questionnaires. Neonatal pain-related stress (the number of skin-breaking procedures adjusted for clinical factors associated with prematurity) was examined in relation to internalizing behaviour, separately in subjects mechanically ventilated and exposed to both pain and morphine (n = 57) and those never mechanically ventilated, exposed to pain but not morphine (n = 44). In the non-ventilated group, higher skin-breaking procedures (p = 0.037) and parenting stress (p = 0.004) were related to greater internalizing behaviours. In the ventilated group, greater morphine exposure (p = 0.004) was associated with higher child internalizing scores. In very preterm children who undergo mechanical ventilation, judicious use of morphine is important, since morphine may mitigate the negative effects of neonatal pain on nociception but adversely affect internalizing behaviours at school age. Management of procedural pain needs to be addressed in very preterm infants in the neonatal intensive care unit, to prevent long-term effects on child behaviour. © 2013 European Pain Federation - EFIC®

  12. Repeated exposure to morphine alters surface expression of AMPA receptors in the rat medial prefrontal cortex.

    Science.gov (United States)

    Mickiewicz, Amanda L; Napier, T Celeste

    2011-01-01

    Behavioral sensitization describes the intensification of motor activity that results from repeated exposure to drugs of misuse, and the underlying neuronal adaptations are hypothesized to model aspects of the brain changes that occur in humans misusing such drugs. The α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor is an ionotropic glutamate receptor involved in the neuroplasticity that accompanies acute and repeated drug administration. Changing surface expression is one means to regulate AMPA receptor function, and the present study tested the hypothesis that behavioral sensitization to the μ-opioid receptor agonist morphine is accompanied by changes in the subcellular distribution of AMPA receptors in limbic brain regions. To test this hypothesis, we used a protein cross-linking assay to assess cell surface and intracellular levels of GluA1 and GluA2 subunits in the nucleus accumbens, medial prefrontal cortex and ventral pallidum. Repeated morphine treatment decreased surface expression of GluA1 in the medial prefrontal cortex without affecting levels of GluA2. In contrast, surface levels of GluA1 or GluA2 were unchanged in the nucleus accumbens and ventral pallidum, demonstrating that although AMPA receptors in accumbal and pallidal regions are critical mediators of behaviors induced by repeated opiate exposure, these effects are not accompanied by changes in surface expression. The findings reveal that the involvement of AMPA receptor trafficking in opiate-induced behavioral sensitization is relegated to selective regions and that AMPA receptors in the medial prefrontal cortex may be particularly sensitive to these actions. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  13. The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Allahtavakoli

    2012-07-01

    Full Text Available Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Findings. Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. Conclusion. The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine.

  14. Dose-dependent effects of morphine exposure on mRNA and microRNA (miR expression in hippocampus of stressed neonatal mice.

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    Ryan M McAdams

    Full Text Available Morphine is used to sedate critically ill infants to treat painful or stressful conditions associated with intensive care. Whether neonatal morphine exposure affects microRNA (miR expression and thereby alters mRNA regulation is unknown. We tested the hypothesis that repeated morphine treatment in stress-exposed neonatal mice alters hippocampal mRNA and miR expression. C57BL/6 male mice were treated from postnatal day (P 5 to P9 with morphine sulfate at 2 or 5 mg/kg ip twice daily and then exposed to stress consisting of hypoxia (100% N2 1 min and 100% O2 5 min followed by 2h maternal separation. Control mice were untreated and dam-reared. mRNA and miR expression profiling was performed on hippocampal tissues at P9. Overall, 2 and 5 mg/kg morphine treatment altered expression of a total of 150 transcripts (>1.5 fold change, P<0.05 from which 100 unique mRNAs were recognized (21 genes were up- and 79 genes were down-regulated, and 5 mg/kg morphine affected 63 mRNAs exclusively. The most upregulated mRNAs were fidgetin, arginine vasopressin, and resistin-like alpha, and the most down-regulated were defensin beta 11, aquaporin 1, calmodulin-like 4, chloride intracellular channel 6, and claudin 2. Gene Set Enrichment Analysis revealed that morphine treatment affected pathways related to cell cycle, membrane function, signaling, metabolism, cell death, transcriptional regulation, and immune response. Morphine decreased expression of miR-204-5p, miR-455-3p, miR-448-5p, and miR-574-3p. Nine morphine-responsive mRNAs that are involved in neurodevelopment, neurotransmission, and inflammation are predicted targets of the aforementioned differentially expressed miRs. These data establish that morphine produces dose-dependent changes in both hippocampal mRNA and miR expression in stressed neonatal mice. If permanent, morphine-mediated neuroepigenetic effects may affect long-term hippocampal function, and this provides a mechanism for the neonatal morphine

  15. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...

  16. Antiarrhythmic effect of prolonged morphine exposure is accompanied by altered myocardial adenylyl cyclase signaling in rats

    Czech Academy of Sciences Publication Activity Database

    Škrabalová, J.; Neckář, Jan; Hejnová, L.; Bartoňová, I.; Kolář, František; Novotný, J.

    2012-01-01

    Roč. 64, č. 2 (2012), s. 351-359 ISSN 1734-1140 R&D Projects: GA AV ČR(CZ) IAA501110901 Grant - others:Univerzita Karlova(CZ) 429511 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat myocardium * morphine * adenylyl cyclase * G-proteins * arrhythmias Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.965, year: 2012

  17. Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Yang, Ye; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Deng, Zhen-Han; Li, Yu-Sheng; Yang, Tu-Bao; Lei, Guang-Hua

    2017-03-01

    The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. II.

  18. Single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery: a meta-analysis of randomised placebo-controlled studies

    Science.gov (United States)

    Wang, Yi-lun; Zeng, Chao; Xie, Dong-xing; Yang, Ye; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-hua

    2015-01-01

    Objectives To evaluate the efficacy and safety of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery. Design Meta-analysis. Data sources and study eligibility criteria A comprehensive literature search, using Medline (1966–2014), the Cochrane Central Register of Controlled Trials and Embase databases, was conducted to identify randomised placebo-controlled trials that used a combination of single-dose intra-articular bupivacaine and morphine for postoperative pain relief. Results 12 articles were included in this meta-analysis. The mean visual analogue scale (VAS) scores of the bupivacaine plus morphine group were significantly lower than those of the placebo group (weighted mean difference (WMD) −1.75; 95% CI −2.16 to −1.33; pbupivacaine plus morphine group were also significantly lower than those of the placebo group (WMD −1.46; 95% CI −1.63 to −1.29; pbupivacaine plus morphine after knee arthroscopic surgery is effective for pain relief, and its short-term side effects remain similar to saline placebo. PMID:26078306

  19. Influence of renal function on the elimination of morphine and morphine glucuronides

    DEFF Research Database (Denmark)

    Wolff, Jesper; Bigler, Dennis Richard; Christensen, C B

    1988-01-01

    The influence of renal function, measured by 51Cr-EDTA clearance, on morphine and morphine glucuronide kinetics has been studied in 13 patients after a single i.v. injection of morphine. Unconjugated morphine and morphine glucuronides were measured by a sensitive, specific RIA after extraction from...... plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r...

  20. The efficacy of a single dose of pethidine, fentanyl and morphine in treating postanesthesia shivering.

    Science.gov (United States)

    Dabir, Shideh; Jahandideh, Maryam; Abbasinazari, Mohammad; Kouzekanani, Homeyra; Parsa, Tahereh; Radpay, Badiozaman

    2011-10-01

    Postanesthesia shivering is an undesirable event that may induce a variety of adverse consequences including patient discomfort, increased oxygen consumption and wound pain. Thus, its pharmacological treatment should be regarded. The purpose of this study was to compare the efficacy of morphine, fentanyl and pethidine for the treatment of postanesthesia shivering. Fifty patients who developed shivering were treated in a randomized double blinded manner with an intravenous bolus dose of 2 or 4 mg morphine, 25 or 50 mg pethidine, and 50 μg fentanyl. Then, they were monitored for 30 minutes and the shivering suppression grade, the time taken to stop shivering, the shivering cessation time, recurrence of shivering and opioid side effects were evaluated. Core body temperature was measured immediately before, and at 15 and 30 minute after administering the drug. The groups did not differ significantly regarding shivering suppression grade, shivering cessation time, and recurrence of shivering. There was a significant difference in the time taken to stop shivering between groups. Following injection of the drugs, the core temperatures increased in the five groups with statistical difference. All opioids were effective in treating postanesthesia shivering in a similar extent.

  1. Development of Anxiety-Like Behavior via Hippocampal IGF-2 Signaling in the Offspring of Parental Morphine Exposure: Effect of Enriched Environment

    Science.gov (United States)

    Li, Chang-Qi; Luo, Yan-Wei; Bi, Fang-Fang; Cui, Tao-Tao; Song, Ling; Cao, Wen-Yu; Zhang, Jian-Yi; Li, Fang; Xu, Jun-Mei; Hao, Wei; Xing, Xiao-Wei; Zhou, Fiona H; Zhou, Xin-Fu; Dai, Ru-Ping

    2014-01-01

    Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure. PMID:24889368

  2. Deleterious effects of prenatal exposure to morphine on the spatial learning and hippocampal BDNF and long-term potentiation in juvenile rats: Beneficial influences of postnatal treadmill exercise and enriched environment.

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    Ahmadalipour, Ali; Ghodrati-Jaldbakhan, Shahrbanoo; Samaei, Seyed Afshin; Rashidy-Pour, Ali

    2018-01-01

    Prenatal morphine exposure causes a variety of neurobehavioral alterations observed in later life. The present study investigated the effects of postnatal exercise and enriched environment (EE) on alterations in water maze learning and hippocampal long-term potentiation (LTP) and brain derived neurotrophic factor (BDNF) levels induced by exposure to morphine during prenatal period in rats. On gestation days 11-18, pregnant rats were injected twice daily with saline or morphine. Offspring were subjected to postnatal exercise and EE for 30 days and afterward, spatial learning and hippocampal LTP and BDNF levels were investigated. Prenatal morphine-exposure impaired the spatial learning and hippocampal LTP in both male and female offspring. Interestingly, postnatal exercise and EE increased performance in the water maze and improved LTP in both prenatally saline and morphine-exposed male and female rats. Prenatal morphine exposure also caused a reduction in the hippocampal BDNF levels in the female, but not male rats, and postnatal exercise and EE alleviated this deficit. Our results demonstrate that postnatal exercise and EE can improve deficits in water maze learning and hippocampal LTP and BDNF levels caused by prenatal morphine exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    Morphine is a potent opioid analgesic widely used for the treatment of acute pain and for long-term treatment of severe pain. Morphine is a member of the morphinan-framed alkaloids, which are present in the poppy plant. The drug is soluble in water, but its solubility in lipids is poor. In man......) or intrathecal (IT) administration in rats is from 45-800 timer greater than that of morphine, depending on the animal species and the experimental antinociceptive test used. Furthermore, the development of a sensitive high-performance liquid chromatography (HPLC) assay for the quantitative determination...

  4. The effect of prolonged exposure to morphine on canine cerebral 5-HT2A receptors measured with (123)I-R91150 SPECT.

    Science.gov (United States)

    Adriaens, Antita; Polis, Ingeborgh; Vermeire, Simon; Waelbers, Tim; Croubels, Siska; Duchateau, Luc; Van Dorpe, Sylvia; Eersels, Jos; De Spiegeleer, Bart; Peremans, Kathelijne

    2014-07-01

    Down-stream neuronal alterations, including changes in the 5-HT-2A receptor system, play an important role in the etiology and treatment of depression. The present study examined the effect of prolonged opioid treatment on cerebral 5-HT2A receptors. Cerebral 5-HT2A receptor availability was estimated in seven healthy five-year-old female neutered Beagle dogs pre and post 10-day morphine treatment (oral sustained release morphine 20mg twice daily for 10 days) with (123)I-R-91150, a 5-HT2A selective radioligand, and SPECT. 5-HT2A receptor binding indices (BI) for the frontal, parietal, temporal and occipital cortex and the subcortical region were calculated. Statistical analysis was performed using a linear mixed-effect model with treatment as fixed effect and dog as random effect. Morphine treatment significantly (P≤0.05) lowered 5-HT2A BIs in the right and left frontal cortex, the right and left temporal cortex, the right and left parietal cortex, and the subcortical region. The decreased cerebral 5-HT2A receptor availability following prolonged morphine exposure provides further evidence for an interaction between the opioid and serotonergic system. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  5. Morphine dependence in single enteric neurons from the mouse colon requires deletion of β‐arrestin2

    OpenAIRE

    Smith, Tricia H.; Ngwainmbi, Joy; Hashimoto, Atsushi; Dewey, William L.; Akbarali, Hamid I.

    2014-01-01

    Abstract Chronic administration of morphine results in the development of tolerance to the analgesic effects and to inhibition of upper gastrointestinal motility but not to colonic motility, resulting in persistent constipation. In this study we examined the effect of chronic morphine in myenteric neurons from the adult mouse colon. Similar to the ileum, distinct neuronal populations exhibiting afterhyperpolarization (AHP)‐positive and AHP‐negative neurons were identified in the colon. Acute ...

  6. The role of benzodiazepines in breathlessness: a single site, open label pilot of sustained release morphine together with clonazepam.

    Science.gov (United States)

    Allcroft, Peter; Margitanovic, Vera; Greene, Aine; Agar, Meera R; Clark, Katherine; Abernethy, Amy P; Currow, David C

    2013-07-01

    Breathlessness at rest or on minimal exertion despite optimal treatment of underlying cause(s) is distressing and prevalent. Opioids can reduce the intensity of chronic refractory breathlessness and an anxiolytic may be of benefit. This pilot aimed to determine the safety and feasibility of conducting a phase III study on the intensity of breathlessness by adding regular benzodiazepine to low-dose opioid. This is a single site, open label phase II study of the addition of regular clonazepam 0.5 mg nocte orally to Kapanol(R) 10 mg (sustained release morphine sulphate) orally mane together with docusate/sennosides in people with modified Medical Research Council Scale ≥2. Breathlessness intensity on day four was the efficacy outcome. Participants could extend for another 10 days if they achieved >15% reduction over their own baseline breathlessness intensity. Eleven people had trial medication (eight males, median age 78 years (68 to 89); all had COPD; median Karnofsky 70 (50 to 80); six were on long-term home oxygen. Ten people completed day four. One person withdrew because of unsteadiness on day four. Five participants reached the 15% reduction, but only three went on to the extension study, all completing without toxicity. This study was safe, feasible and there appears to be a group who derive benefits comparable to titrated opioids. Given the widespread use of benzodiazepines for the symptomatic treatment of chronic refractory breathlessness and its poor evidence base, there is justification for a definitive phase III study.

  7. Enhanced ability of TRPV1 channels in regulating glutamatergic transmission after repeated morphine exposure in the nucleus accumbens of rat.

    Science.gov (United States)

    Zhang, Haitao; Jia, Dong; Wang, Yuan; Qu, Liang; Wang, Xuelian; Song, Jian; Heng, Lijun; Gao, Guodong

    2017-04-01

    Glutamatergic projections to nucleus accumbens (NAc) drive drug-seeking behaviors during opioids withdrawal. Modulating glutamatergic neurotransmission provides a novel pharmacotherapeutic avenue for treatment of opioids dependence. Great deals of researches have verified that transient receptor potential vanilloid 1 (TRPV1) channels alters synaptic transmitter release and regulate neural plasticity. In the present study, whole-cell patch clamp recordings were adopted to examine the activity of TRPV1 Channels in regulating glutamate-mediated excitatory postsynaptic currents (EPSCs) in NAc of rat during morphine withdrawal for 3days and 3weeks. The data showed that the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and the amplitudes of evoked excitatory postsynaptic currents (eEPSCs) were increased during morphine withdrawal after applied with capsaicin (TRPV1 agonist). Capsaicin decreased the paired pulse ratio (PPR) and increased sEPSCs frequency but not their amplitudes suggesting a presynaptic locus of action during morphine withdrawal. All these effects were fully blocked by the TRPV1 antagonist Capsazepine. Additionally, In the presence of AM251 (CB1 receptor antagonist), depolarization-induced release of endogenous cannabinoids activated TRPV1 channels to enhance glutamatergic neurotransmission during morphine withdrawal. The functional enhancement of TRPV1 Channels in facilitating glutamatergic transmission was not recorded in dorsal striatum. Our findings demonstrate the ability of TRPV1 in regulating excitatory glutamatergic transmission is enhanced during morphine withdrawal in NAc, which would deepen our understanding of glutamatergic modulation during opioids withdrawal. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Morphine exposure and maternal deprivation during the early postnatal period alter neuromotor development and nerve growth factor levels.

    Science.gov (United States)

    de Oliveira, Carla; Scarabelot, Vanessa L; Vercelino, Rafael; Silveira, Natalia P; Adachi, Lauren N S; Regner, Gabriela G; Silva, Lisiane S; de Macedo, Isabel Cristina; de Souza, Andressa; Caumo, Wolnei; Torres, Iraci L S

    2017-12-01

    The objective of this study was to verify whether repeated morphine administration and maternal deprivation in early life alter neurobehavioral development and central nerve growth factor (NGF) levels. A total of 58 male Wistar rat pups were used in our study. From postnatal day 1 (P1), litters were daily deprived of their mother for 3h; this was continued for the first 10days of life. Animals were divided into 5 groups: total control (C), did not receive any intervention; saline (S), received saline solution; morphine (M), received morphine; deprived-saline group (DS), were subjected to maternal deprivation and received saline solution; and deprived-morphine (DM), were subjected to maternal deprivation and received morphine. From P8, newborns received subcutaneous (s.c.) injections of morphine or saline (5μg) once daily for 7days. Righting reflex, negative geotaxis and gait were chosen as postural parameters to evaluate neuromotor reflexes. In the righting reflex test, a delay in the development of animals was evidenced in the M group. Performance of negative geotaxis was slower in the M and DM groups. In the gait test, all groups showed a daily improvement in performance in terms of locomotion frequency. An increased frequency of rearing was observed in the M, DS, and DM groups from P16 to P20. The DM group presented an increase in NGF levels in the brainstem. An increase in cerebral cortex NGF levels in the M, DS, and DM groups was observed as well. Our results suggest that changes in environmental conditions and the disruption of mother-infant interactions during the neonatal period can produce changes in the neurobiology, physiology, and emotional behavior of rats. This finding has important implications for the maternal-neonate interaction needed for normal brain development in newborns. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  9. Morphine decreases enteric neuron excitability via inhibition of sodium channels.

    Directory of Open Access Journals (Sweden)

    Tricia H Smith

    Full Text Available Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a Swiss-Webster mouse myenteric neuron culture and examined their electrophysiological properties by patch-clamp techniques and determined the mechanism for morphine-induced decrease in neuronal excitability. Isolated neurons in culture were confirmed by immunostaining with pan-neuronal marker, β-III tubulin and two populations were identified by calbindin and calretinin staining. Distinct neuronal populations were further identified based on the presence and absence of an afterhyperpolarization (AHP. Cells with AHP expressed greater density of sodium currents. Morphine (3 µM significantly reduced the amplitude of the action potential, increased the threshold for spike generation but did not alter the resting membrane potential. The decrease in excitability resulted from inhibition of sodium currents. In the presence of morphine, the steady-state voltage dependence of Na channels was shifted to the left with almost 50% of channels unavailable for activation from hyperpolarized potentials. During prolonged exposure to morphine (two hours, action potentials recovered, indicative of the development of tolerance in single enteric neurons. These results demonstrate the feasibility of isolating mouse myenteric neurons and establish sodium channel inhibition as a mechanism for morphine-induced decrease in neuronal excitability.

  10. Abuse-related effects of µ-opioid analgesics in an assay of intracranial self-stimulation in rats: modulation by chronic morphine exposure.

    Science.gov (United States)

    Altarifi, Ahmad A; Rice, Kenner C; Negus, S Stevens

    2013-09-01

    Intracranial self-stimulation (ICSS) is an operant procedure in which responding is maintained by electrical brain stimulation. Stimulation frequency can be varied rapidly to maintain a wide range of baseline response rates, and drugs' effects can be evaluated simultaneously on both low ICSS rates maintained by low stimulation frequencies and high ICSS rates maintained by high stimulation frequencies. ICSS 'facilitation' indicates drug-induced increases in low ICSS rates and is often considered an abuse-related effect, whereas ICSS 'depression' indicates decreases in high ICSS rates and may indicate abuse-limiting effects. This study examined the roles of µ-agonist efficacy and of previous µ-agonist exposure as determinants of µ-agonist effects on ICSS in rats with electrodes implanted into the medial forebrain bundle. The high-efficacy, intermediate-efficacy, and low-efficacy µ agonists methadone, fentanyl, and nalbuphine were tested during escalating regimens of morphine exposure (vehicle, 3.2, and 18 mg/kg/day). During vehicle treatment, methadone and fentanyl primarily depressed ICSS, whereas nalbuphine produced weak facilitation that was not dose dependent. Chronic morphine produced tolerance to ICSS depression and increased expression of ICSS facilitation. These results suggest that µ-agonist exposure increases the expression of abuse-related ICSS facilitation by µ agonists with a broad range of efficacies at µ receptors.

  11. Neural mechanisms underlying morphine withdrawal in addicted patients: a review

    Directory of Open Access Journals (Sweden)

    Nima Babhadiashar

    2015-06-01

    Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

  12. Food effects on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules.

    Science.gov (United States)

    Johnson, Franklin; Ciric, Sabrina; Boudriau, Sophie; Swearingen, Dennis; Stauffer, Joseph

    2010-11-01

    Morphine sulfate and naltrexone hydrochloride extended release capsules, indicated for chronic moderate-to-severe pain, contain extended-release morphine pellets with a sequestered naltrexone core. If pellets are tampered by crushing, naltrexone is released to reduce morphine-induced effects that appeal to opioid abusers. The primary objective of this study was to assess single-dose relative bioavailability of morphine when morphine sulfate and naltrexone hydrochloride extended release capsules were taken under fed and fasting conditions and when pellets were sprinkled on apple sauce. This was a single-center, randomized, open-label study in 36 healthy adult volunteers. Subjects took a 100-mg morphine sulfate and naltrexone hydrochloride extended release capsule intact with 240 mL water, under fed and fasted conditions, and when the capsule was opened and pellets were sprinkled over apple sauce and consumed without chewing; each treatment was separated by a 14-day washout. Plasma samples were collected just before dosing through 72 hours postdose for pharmacokinetic analyses of morphine, and through 168 hours postdose for naltrexone and its major metabolite 6-β-naltrexol. Morphine bioavailability was similar for all treatments. There was a lack of sprinkle effect (sprinkle vs. whole, fasted); 90% confidence intervals (CIs) of ratios of log-transformed least squares means for area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) fell within 80%-125% boundaries. For the food effect, 90% CIs were within the boundaries for AUC, but C(max) was reduced and time to C(max) was delayed by 2.5 hours under fed conditions. Naltrexone remained sequestered under all treatment conditions with only trace systemic exposure. Results indicated that morphine sulfate and naltrexone hydrochloride extended release capsules can be administered without regard to meals, and contents can be sprinkled over apple sauce and consumed without chewing by

  13. Detection of codeine, morphine, 6-monoacetylmorphine, and meconin in human umbilical cord tissue: method validation and evidence of in utero heroin exposure.

    Science.gov (United States)

    Jones, Joseph T; Jones, Mary; Jones, Brian; Sulaiman, Kristin; Plate, Charles; Lewis, Douglas

    2015-02-01

    Heroin abuse is a significant public health issue and is on the rise because of the unintended consequences of strengthening controls for nonmedical use of prescription pain killers. Included in this trend is an increase in opiate exposed newborns that are particularly vulnerable to a number of negative health outcomes. After presenting a fully validated liquid chromatography-tandem mass spectrometric method for codeine, morphine, 6-monoacetylmorphine, and meconin, a metabolite of the heroin contaminant noscapine, we compared the outcome of 46 authentic umbilical specimens with the results generated using a previous less sensitive method that did not include meconin. Additionally, we provided a summary of opiate finding from a year-long survey of specimens received into a commercial reference laboratory. The limits of detection for all 4 compounds were 0.1 ng/g, the limit of quantitation was 0.2 ng/g, and the assay was linear from 0.2 to 10.0 ng/g. Of the 46 comparative specimens, this method improved the identification of heroin exposure from 2 to 5, and the year-long survey identified 86 heroin-exposed newborns with 11 of them identified by the sole identification of meconin. This study demonstrated that a more sensitive analytical platform and the inclusion of meconin in the opiates assay improved the ability to distinguish between in utero heroin exposure and maternal administration of codeine or morphine.

  14. Involvement of protein kinase C in the modulation of morphine-induced analgesia and the inhibitory effects of exposure to 60-hz magnetic fields in the land snail, Cepaea nemoralis

    Energy Technology Data Exchange (ETDEWEB)

    Kavaliers, M.; Ossenkopp, K.P. (Univ. of Western Ontario, London (Canada))

    1990-02-26

    One of the more consistent and dramatic effects of exposure to magnetic fields is the attenuation of morphine-induced analgesia. Results of previous studies have implicated alterations in calcium channel functioning and Ca{sup ++} flux in the mediation of these effects. It is generally accepted that Ca{sup ++}-activated-phospholipid-dependent protein kinase (Protein kinase C; PKC) plays an important role in relaying trans-membrane signaling in diverse Ca{sup ++} dependent cellular processes. In experiment 1 we observed that morphine-induced analgesia in the land snail, Cepaea nemoralis, as measured by the latency of an avoidance behavior to a warmed surface, was reduced by the PKC activator, SC-9, and was enhanced by the PKC inhibitors, H-7 and H-9. In contrast, HA-10004, a potent inhibitor of other protein kinases, but only a very weak inhibitor of PKC, had no effect on morphine-induced analgesia. In experiment 2 exposure of snails for 30 minutes to a 1.0 gauss (rms) 60-Hz magnetic field reduced morphine-induced analgesia. This inhibitory effect of the magnetic field was reduced by the PKC inhibitors, H-7 and H-9, and was augmented by the PKC activator SC-9. These results suggest that: (i) PKC is involved in the modulation of morphine-induced analgesia and, (ii) the inhibitory effects of magnetic fields involve PKC.

  15. Effects of environmental enrichment during abstinence in morphine dependent parents on anxiety, depressive-like behaviors and voluntary morphine consumption in rat offspring.

    Science.gov (United States)

    Pooriamehr, Alireza; Sabahi, Parviz; Miladi-Gorji, Hossein

    2017-08-24

    Chronic morphine exposure during puberty increased morphine-induced rewarding effects and sensitization in the next generation. Given the well-known beneficial effects of environmental enrichment on the severity of physical and psychological dependence on morphine, we examined effects of enriched environment during morphine abstinence in morphine dependent parental rats before mating on the anxiety and depressive-like behaviors, and voluntary morphine consumption in their offspring. Paternal and/or maternal rats were injected with bi-daily doses (10mg/kg, 12h intervals) of morphine for 14days followed by rearing in a standard environment (SE) or enriched environment (EE) during 30days of morphine abstinence before mating. The pubertal male and female rat offspring were tested for anxiety (the elevated plus maze- EPM) and depression (sucrose preference test-SPT), and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that EE experience in morphine-dependent both parents result in an increase in the percentage of time spent into open arms/time spent on both arms using EPM in male offspring, higher levels of sucrose preference in female offspring and lower levels of voluntary morphine consumption in male and female offspring. Thus, EE experience in morphine-dependent both parents reduced anxiety, depressive-like behavior and also the voluntary morphine consumption in their offspring during puberty which may prevent the vulnerability of the next generation to drug abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Neonatal morphine enhances nociception and decreases analgesia in young rats.

    Science.gov (United States)

    Zhang, Guo Hua; Sweitzer, Sarah M

    2008-03-14

    The recognition of the impact of neonatal pain experience on subsequent sensory processing has led to the increased advocacy for the use of opioids for pain relief in infants. However, following long-term opioid exposure in intensive care units more than 48% of infants exhibited behaviors indicative of opioid abstinence syndrome, a developmentally equivalent set of behaviors to opioid withdrawal as seen in adults. Little is known about the long-term influence of repeated neonatal morphine exposure on nociception and analgesia. To investigate this, we examined mechanical and thermal nociception on postnatal days 11, 13, 15, 19, 24, 29, 39 and 48 following subcutaneous administration of morphine (3 mg/kg) once daily on postnatal days 1-9. The cumulative morphine dose-response was assessed on postnatal days 20 and 49, and stress-induced analgesia was assessed on postnatal days 29 and 49. Both basal mechanical and thermal nociception in neonatal, morphine-exposed rats were significantly lower than those in saline-exposed, handled-control rats and naive rats until P29. A rightward-shift of cumulative dose-response curves for morphine analgesia upon chronic neonatal morphine was observed both on P20 and P49. The swim stress-induced analgesia was significantly decreased in neonatal morphine-exposed rats on P29, but not on P49. These data indicate that morphine exposure equivalent to the third trimester of gestation produced prolonged pain hypersensitivity, decreased morphine antinociception, and decreased stress-induced analgesia. The present study illustrates the need to examine the long-term influence of prenatal morphine exposure on pain and analgesia in the human pediatric population.

  17. Exploration of central dopamine transporter and D2 receptor in morphine abstinent rats

    International Nuclear Information System (INIS)

    Lin Yansong; Wang Bocheng; Wang Shizhen; Ding Shiyu; Chen Zhengping; Zhang Manda

    2006-01-01

    The experiment was designed to investigate the variation of DAT and D2 receptor in morphine administered and 1,2,3 day abstinent rats. Morphine exposure was induced by repeated morphine (i.p.) treatment for 8 days. Conditioned place preference test was conducted to evaluate the drug seeking behaviour and morphine dependence of rats with morphine exposure. Biodistribution of the imaging agents 125 I-β-CIT and 125 I-IBZM was used to evaluate the central DAT and D2 receptor during morphine exposure and 1,2,3 day's abstinence. Results reveal the following facts. (1) The morphine abstinent rats showed diarrhea and body-shake 1 day after morphine withdrawal. (2) For morphine group, 125 I-β-CIT %ID/g in ST and NAC was higher than that of the 1,2,3 day's abstinent rats and control (P 0.05). (3) 125 I-IBZM %ID/g in ST, NAC and HIP in morphine rats were lower than those of the abstinent and control rats (P 125 I-IBZM %ID/g in ST and NAC gradually increased with the abstinent days. While in ST the %ID/g among the abstinent rats was all lower than that of the control rats, in NAC the %ID/g was still lower in 1 day's abstinent rats (P 0.05), indicating the reduction of hyper-activated DAT and the increase of down-regulatory D2 receptor induced by morphine during morphine withdrawal. Our results confirmed that the dopamine system, especially DAT and D2 receptor in mesolimbic and meso-striatum pathway, has been implicated in morphine treatment. The rewarding properties of morphine and the somatic expression of morphine abstinence were related to changes in mesolimbic and meso-striatum dopaminergic activity. (authors)

  18. Pharmacokinetic evaluation of a sprinkle-dose regimen of a once-daily, extended-release morphine formulation.

    Science.gov (United States)

    Eliot, Lise; Butler, Jackie; Devane, John; Loewen, Gordon

    2002-02-01

    Morphine sulfate extended-release (MSER) uses a drug-delivery technology that allows once-daily dosing. It is possible to open the MSER capsule and sprinkle the contents on soft food, a potentially useful alternative to the intact capsule in patients who have difficulty swallowing. This study compared the bioavailability of MSER and its metabolites morphine-3-glucuronide and morphine-6-glucuronide after administration of MSER in a sprinkle-dose regimen relative to an intact capsule swallowed whole. This was a randomized, open-label, single-dose, crossover study, with a 7-day washout period between the 2 dosing days. Healthy volunteers were randomized to receive an intact 60-mg MSER capsule swallowed whole or the contents of a 60-mg MSER capsule sprinkled on applesauce. Blood samples were collected and analyzed for concentrations of morphine and its active glucuronide metabolites. Pharmacokinetic (PK) parameters were calculated and bioequivalence assessed. Bioequivalence was concluded if the 90% CIs of the ratio of log-transformed values for maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) were within 80% to 125%. Of 30 subjects enrolled, 28 completed the study and were eligible for PK evaluation. Two subjects were withdrawn for reasons unrelated to study treatment. The plasma concentration-time profiles of morphine and its metabolites were superimposable after administration of the 2 regimens. Cmax and total systemic exposure-based on AUC from time 0 to the last quantifiable concentration (AUC(last)) and AUC from time 0 to infinity (AUC(infinity))-were comparable between treatments. The 90% CIs for morphine AUC(last), AUC, and Cmax ratios were 98 to 109, 96 to 106, and 95 to 117, respectively. Similar 90% CIs were obtained for the morphine metabolites. In this study in healthy volunteers, sprinkling the entire contents of an MSER capsule onto applesauce and swallowing without chewing was bioequivalent to swallowing an intact

  19. Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, three-way crossover trial in healthy volunteers.

    Science.gov (United States)

    Johnson, Franklin K; Stark, Jeffrey G; Bieberdorf, Frederick A; Stauffer, Joe

    2010-06-01

    Morphine sulfate/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to mitigate morphine-induced subjective effects, rendering the product less attractive for tampering. The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution. This study also assessed the relative bioavailability of morphine from crushed pellets from MS-sNT capsules and that from the whole, intact product. This single-dose, randomized-sequence, open-label, 3-period, 3-treatment crossover trial was conducted in healthy volunteers. Adults admitted to the study center underwent a 10-hour overnight fast before study drug administration. Each subject received all 3 of the following treatments, 1 per session, separated by a 14-day washout: tampered pellets (crushed for >or=2 minutes with a mortar and pestle) from a 60-mg MS-sNT capsule (60 mg morphine/2.4 mg naltrexone); 60-mg whole, intact MS-sNT capsule; and oral naltrexone HCl (2.4 mg) solution. Plasma concentrations of naltrexone and 6-beta-naltrexol were measured 0 to 168 hours after administration. Morphine pharmaco-kinetics of crushed and whole pellets were determined 0 to 72 hours after administration. The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%. Subjects underwent physical examinations, clinical laboratory tests, and ECG at screening and study

  20. Single-exposure color digital holography

    Science.gov (United States)

    Feng, Shaotong; Wang, Yanhui; Zhu, Zhuqing; Nie, Shouping

    2010-11-01

    In this paper, we report a method for color image reconstruction by recording only one single multi-wavelength hologram. In the recording process, three lasers of different wavelengths emitting in the red, green and blue regions are used for illuminating on the object and the object diffraction fields will arrive at the hologram plane simultaneously. Three reference beams with different spatial angles will interfere with the corresponding object diffraction fields on the hologram plane, respectively. Finally, a series of sub-holograms incoherently overlapped on the CCD to be recorded as a multi-wavelength hologram. Angular division multiplexing is employed to reference beams so that the spatial spectra of the multiple recordings will be separated in the Fourier plane. In the reconstruction process, the multi-wavelength hologram will be Fourier transformed into its Fourier plane, where the spatial spectra of different wavelengths are separated and can be easily extracted by employing frequency filtering. The extracted spectra are used to reconstruct the corresponding monochromatic complex amplitudes, which will be synthesized to reconstruct the color image. For singleexposure recording technique, it is convenient for applications on the real-time image processing fields. However, the quality of the reconstructed images is affected by speckle noise. How to improve the quality of the images needs for further research.

  1. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy

    DEFF Research Database (Denmark)

    Dirks, Jesper; Fredensborg, Birgitte B; Christensen, Dennis

    2002-01-01

    BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central...... neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients...... effects were assessed on a four-point verbal scale 2 and 4 h postoperatively. RESULTS: Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21-33) to 15 (10-19) mg (P

  2. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  3. The Comparison of Intrathecal Morphine and IV Morphine PCA on Pain Control, Patient Satisfaction, Morphine Consumption, and Adverse Effects in Patients Undergoing Reduction Mammoplasty.

    Science.gov (United States)

    Karamese, Mehtap; Akdağ, Osman; Kara, İnci; Yıldıran, Gokce Unal; Tosun, Zekeriya

    2015-01-01

    Following breast reduction procedures, the level of postoperative pain can be severe, and sufficient pain control influences a patient's physiological, immunological, and psychological status. The aim of this study was to examine the use of intrathecal morphine (ITM) in breast reduction surgery with patient-controlled analgesia (PCA). Sixty-two female patients who underwent breast reductions with the same technique participated in this study. The study group (ITM + PCA) included 32 patients; a single shot (0.2 mg) of ITM and intravenous morphine with PCA were administered. In the control group, morphine PCA alone was intravenously administered to 30 patients. Comparisons between the groups of cumulative morphine consumption, visual analog scale scores, and patient satisfaction scores, which were the primary outcome measures, and adverse effects, which were the secondary outcome measures, were conducted. The patients in the 2 groups had similar degrees of pain and satisfaction scores. The study group had lower cumulative morphine consumption (P = .001) than the PCA-only control group; there was no statistically significant difference in adverse effects between the 2 groups. Intrathecal morphine may effectively control pain with lower total morphine consumption following breast reduction surgery.

  4. Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery.

    Science.gov (United States)

    Goot, Benjamin H; Kaufman, Jon; Pan, Zhaoxing; Bourne, David W A; Hickey, Francis; Twite, Mark; Galinkin, Jeffrey; Christians, Uwe; Zuk, Jeannie; da Cruz, Eduardo M

    2018-03-15

    To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome. Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics. A 16-bed cardiac ICU at an university-affiliated hospital. Forty-two patients (20 Down syndrome, 22 controls) were enrolled. None. The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant. This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.

  5. Comparative pharmacokinetics of two modified-release oral morphine formulations (Reliadol® and Kapanol®) and an immediate-release morphine tablet (Morfin 'DAK') in healthy volunteers

    DEFF Research Database (Denmark)

    Bochner, F.; Somogyi, A.A.; Danz, C.

    1999-01-01

    Objective: Reliadol® (Nycomed Denmark A/S) is a new modified-release morphine formulation undergoing clinical evaluation. It consists of a mixture of rapid- and modified-release microencapsulated granules of morphine. The study aims were to investigate the single-dose pharmacokinetics of morphine...

  6. Effects of morphine on brain plasticity.

    Science.gov (United States)

    Beltrán-Campos, V; Silva-Vera, M; García-Campos, M L; Díaz-Cintra, S

    2015-04-01

    Morphine shares with other opiates and drugs of abuse the ability to modify the plasticity of brain areas that regulate the morphology of dendrites and spines, which are the primary sites of excitatory synapses in regions of the brain involved in incentive motivation, rewards, and learning. In this review we discuss the impact of morphine use during the prenatal period of brain development and its long-term consequences in murines, and then link those consequences to similar effects occurring in human neonates and adults. Repeated exposure to morphine as treatment for pain in terminally ill patients produces long-term changes in the density of postsynaptic sites (dendrites and spines) in sensitive areas of the brain, such as the prefrontal cortex, the limbic system (hippocampus, amygdala), and caudate nuclei and nucleus accumbens. This article reviews the cellular mechanisms and receptors involved, primarily dopaminergic and glutamatergic receptors, as well as synaptic plasticity brought about by changes in dendritic spines in these areas. The actions of morphine on both developing and adult brains produce alterations in the plasticity of excitatory postsynaptic sites of the brain areas involved in limbic system functions (reward and learning). Doctors need further studies on plasticity in dendrites and spines and on signaling molecules, such as calcium, in order to improve treatments for addiction. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  7. Morphine tolerance offers protection from radiogenic performance deficits

    International Nuclear Information System (INIS)

    Mickley, G.A.; Stevens, K.E.; Burrows, J.M.; White, G.A.; Gibbs, G.L.

    1983-01-01

    When rats are exposed to a sufficiently large dose of ionizing radiation they exhibit lethargy, hypokinesia, and deficits in performance. These and other behavioral changes parallel those often observed in this species after a large dose of morphine. Since the release of endogenous opiates has been implicated in some stress reactions, we sought to determine if they might play a part in radiogenic behavioral deficits. Rats were trained to criterion on a signaled avoidance task. Some subjects were then implanted with a pellet containing 75 mg of morphine. Other animals received placebo implants. Over a number of days, morphine tolerance was evaluated by measurement of body temperature changes. Prior to 2500 rad 60 Co exposure or sham irradiation, morphine (or placebo) pellets were removed. Twenty-four hours later rats were retested to assess their performance on the avoidance task. Morphine-tolerant subjects performed significantly better than the irradiated placebo-implanted group and no differently than morphine-tolerant/sham-irradiated animals. Morphine tolerance seems to provide a degree of behavioral radiation resistance. These data are consistent with the hypothesis that endogenous opiate hyperexcretion may play some part in the behavioral deficits often observed after irradiation

  8. "Weak" opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky than morphine.

    Science.gov (United States)

    2016-02-01

    So-called weak opioid analgesics are often used to treat severe pain, or when paracetamol or a nonsteroidal anti-inflammatory drug (NSAID) proves inadequate. But are weak opioids any more effective than paracetamol or NSAIDs on nociceptive pain, and are they better tolerated than morphine? To answer these questions, we conducted a review of literature using the standard Prescrire methodology. The potency of codeine and tramadol is strongly influenced by the cytochrome P450 isoenzyme CYP2D6 genotype, which varies widely from one person to another. This explains reports of overdosing or underdosing after administration of standard doses of the two drugs. The potency of morphine and that of buprenorphine, an opioid receptor agonist-antagonist, appears to be independent of CYP2D6 activity. All "weak" opioids can have the same dose-dependent adverse effects as morphine. There is no evidence that, at equivalent analgesic efficacy, weak opioids carry a lower risk of addiction than low-dose morphine. Respiratory depression can occur in ultrarapid metabolisers after brief exposure to standard doses of codeine or tramadol. Similar cases have been reported with dihydrocodeine in patients with renal failure. In addition, tramadol can cause a serotonin syndrome, hypoglycaemia, hyponatraemia and seizures. Several trials have compared different weak opioids in patients with post-operative pain. A single dose of a weak opioid, possibly combined with paracetamol, has greater analgesic efficacy than paracetamol alone but is not more effective than an NSAID alone. There is a dearth of evidence on weak opioids in patients with chronic pain. Available trials fail to show that a weak opioid has markedly superior analgesic efficacy to paracetamol or an NSAID. Sublingual buprenorphine at analgesic doses appears less likely to cause respiratory depression, but it seems to have weak analgesic efficacy. In practice, when opioid therapy is needed, there is no evidence that codeine

  9. Analgesic effect of the electromagnetic resonant frequencies derived from the NMR spectrum of morphine.

    Science.gov (United States)

    Verginadis, Ioannis I; Simos, Yannis V; Velalopoulou, Anastasia P; Vadalouca, Athina N; Kalfakakou, Vicky P; Karkabounas, Spyridon Ch; Evangelou, Angelos M

    2012-12-01

    Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

  10. Effect of local wound infiltration and transversus abdominis plane block on morphine use after laparoscopic colectomy: a nonrandomized, single-blind prospective study.

    Science.gov (United States)

    Park, Jun-Seok; Choi, Gyu-Seog; Kwak, Kyung-Hwa; Jung, Hoon; Jeon, Younghoon; Park, Sungsik; Yeo, Jinseok

    2015-05-01

    Recently, nonopioid-based treatment modalities have been used to improve analgesia and decrease opioid-related side effects after surgery. Transversus abdominis plane (TAP) block and local infiltration of the surgical wound are commonly used multimodal analgesia techniques after abdominal surgery; however, few studies have compared the effectiveness of a TAP block with that of local infiltration of surgical wounds in patients who have undergone laparoscopic colorectal surgery. Sixty patients undergoing laparoscopic colorectal surgery participated in this prospective comparative study. All patients were allocated to 1 of 2 groups as follows: the TAP group or the infiltration group. Patients in the TAP group received bilateral TAP blocks at the end of the surgery. Patients in the infiltration group received local infiltration of anesthetics in the surgical wounds after closure of the peritoneum. All patients received postoperative analgesia with morphine as a patient-controlled analgesia. Opioid consumption and pain scores were recorded at 2, 6, 24, and 48 h after the operation. The characteristics of patients in the TAP group (n = 30) and local infiltration group (n = 29) were comparable. Pain scores while coughing and at rest were not different between the two groups. Postoperative morphine use was significantly reduced in the TAP group compared with that in the local infiltration group at 2-6 h (2.9 ± 1.9 mg versus 4.5 ± 3.2 mg, P = 0.02), 6-24 h (5.5 ± 3.3 mg versus 10.2 ± 8.4 mg, P = 0.00), the first 24 h (16.6 ± 6.6 mg versus 24.0 ± 9.7 mg), and 48 h (23.6 ± 8.2 mg versus 31.8 ± 12.5 mg, P = 0.00). No differences in rescue analgesic use or side effects were noted between the groups. Compared with local anesthetic infiltration, bilateral TAP blocks decreased the cumulative morphine use at 24 h and 48 h postoperatively in patients who had undergone laparoscopic colorectal surgery. Copyright © 2015 Elsevier Inc

  11. Attenuation of morphine tolerance and dependence by thymoquinone in mice

    Directory of Open Access Journals (Sweden)

    Hossein Hosseinzadeh

    2016-01-01

    Full Text Available Objectives: Dependence and tolerance are major restricting factors in the clinical use of opioid analgesics. In the present study, the effects of thymoquinone, the major constituent of Nigella sativa seeds, on morphine dependence and tolerance were investigated in mice. Materials and Methods: Male adult NMRI mice were made tolerant and dependent by repeated injections of morphine (50, 50, and 75 mg/kg, i.p. on 9 a.m., 1 p.m., and 5 p.m., respectively during a 3-day administration schedule. The hot-plate test was used to assess tolerance to the analgesic effects of morphine. Naloxone (2 mg/kg, i.p. was injected to precipitate withdrawal syndrome in order to assess the morphine dependence. To evaluate the effects of thymoquinone on tolerance and dependence to morphine, different single or repeated doses of thymoquinone were administered in mice. Rotarod was used to assess the motor coordination. Results: Administration of single or repeated doses of thymoquinone (20 and 40 mg/kg, i.p. significantly decreased the number of jumps in morphine dependent animals. Repeated administration of thymoquinone (20 and 40 mg/kg, for 3 days and also single injection of thymoquinone (40 mg/kg, on the fourth day attenuated tolerance to the analgesic effect of morphine. None of the thymoquinone doses (10, 20, and 40 mg/kg produced any antinociceptive effects on their own. Motor coordination of animals was impaired by the high dose of thymoquinone (40 mg/kg. Conclusion: Based on these results, it can be concluded that thymoquinone prevents the development of tolerance and dependence to morphine.

  12. Analgesia and pulmonary function after lung surgery: is a single intercostal nerve block plus patient-controlled intravenous morphine as effective as patient-controlled epidural anaesthesia? A randomized non-inferiority clinical trial.

    Science.gov (United States)

    Meierhenrich, R; Hock, D; Kühn, S; Baltes, E; Muehling, B; Muche, R; Georgieff, M; Gorsewski, G

    2011-04-01

    Thoracic epidural anaesthesia (EDA) is regarded as the 'gold standard' for postoperative pain control and restoration of pulmonary function after lung surgery. Easier, less time-consuming, and, perhaps, safer is intercostal nerve block performed under direct vision by the surgeon before closure of the thoracotomy combined with postoperative i.v. patient-controlled analgesia with morphine. We hypothesized that this technique is as effective as thoracic EDA. The study was designed as a single-centre, open labelled, randomized non-inferiority trial. A total of 92 patients undergoing elective lung surgery were randomly assigned to the epidural (n=47) or intercostal group (n=45), and 83 patients completed the study. Pain scores, inspiratory vital capacity, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR) were assessed during the first four postoperative days. Median treatment differences regarding pain scores at rest failed to demonstrate non-inferiority of the intercostal nerve block at the first postoperative day. Patients of the intercostal group reported significantly higher pain scores on coughing during the first and second postoperative days. The epidural group had a significantly higher median FVC, FEV1, and PEFR values on the second postoperative day. No difference was found in pulmonary complications, length of hospital stay, or in-hospital deaths. In patients undergoing lung surgery, single intercostal nerve block plus i.v. patient-controlled analgesia with morphine is not as effective as patient-controlled EDA with respect to pain control and restoration of pulmonary function.

  13. The Neurodevelopmental Impact of Neonatal Morphine Administration

    Directory of Open Access Journals (Sweden)

    Stephanie Attarian

    2014-04-01

    Full Text Available Medical management of newborn infants often necessitates recurrent painful procedures, which may alter nociceptive pathways during a critical developmental period and adversely effect neuropsychological outcomes. To mitigate the effects of repeated painful stimuli, opioid administration for peri-procedural analgesia and ICU (intensive care unit sedation is common in the NICU (neonatal intensive care unit. A growing body of basic and animal evidence suggests potential long-term harm associated with neonatal opioid therapy. Morphine increases apoptosis in human microglial cells, and animal studies demonstrate long-term changes in behavior, brain function, and spatial recognition memory following morphine exposure. This comprehensive review examines existing preclinical and clinical evidence on the long-term impacts of neonatal pain and opioid therapy.

  14. Estimating DPL photomask fabrication load compared with single exposure

    Science.gov (United States)

    Toyama, Nobuhito; Inazuki, Yuichi; Sutou, Takanori; Nagai, Takaharu; Morikawa, Yasutaka; Mohri, Hiroshi; Hayashi, Naoya; Huckabay, Judy A.; Abe, Yoshikuni

    2007-10-01

    DPL (Double Patterning Lithography) has been identified as one of major candidates for 45nm and 32nm HP since ITRS2006update and several reports of the performance or challenges of DPL have been published. DPL requires at least two photomasks with tighter specification of image placement and the difference of mean to target according to ITRS2006update. On the other hand, approximately half of whole features of single layer are written on each photomask and the densest features are split into other photomask in consequence of pitch relaxation for DPL. Then the photomask writing data of two sets for DPL and single data for single exposure are evaluated for photomask fabrication load. The design will be automatically decomposed with EDA tool and OPC will be tuned as DPL or single exposure. Not only number of fractured features but also feasibility study of automatic decomposition will be presented and discussed. The consequences of relaxed pitch on process, inspection, repair, yield, MEEF and cycle time will be discussed with results as available.

  15. The chronic treatment in vivo of salicylate or morphine alters excitatory effects of subsequent salicylate or morphine tests in vitro in hippocampus area CA1.

    Science.gov (United States)

    Sadegh, Mehdi; Fathollahi, Yaghoub; Semnanian, Saeed

    2013-12-05

    The current practical tests were designed to study in vitro interactions in the field potential between salicylate and morphine analgesics in the hippocampus area CA1 taken from morphine-(7 days) or salicylate (6 days)-treated rats. For this, morphine or salicylate was applied in vitro to the hippocampal slices derived from chronically drug-treated or saline-injected rats and drug-induced changes in evoked field potentials of area CA1 were evaluated. Chronic treatment in vivo of morphine or salicylate had no impact on baseline field EPSP and population spikes (PS) but a leftward shift in fEPSP/PS (E/S) curves and an increase in paired pulse ratio at 10 ms IPI were seen. Acute in vitro salicylate produced a durable PS potentiation in morphine-treated group, whereas an increase in PS of all groups was observed after long-term exposure to in vitro salicylate. Acute in vitro morphine caused a stable PS potentiation in control and salicylate treated groups, but not in morphine treated group. A potentiated fEPSP and a greater PS potentiation in salicylate treated group were observed after long-term exposure to in vitro morphine. It is concluded that the chronic treatment in vivo of salicylate or morphine incites lasting changes in the CA1 circuitry, which alters excitatory effects of subsequent salicylate or morphine tests in vitro in a way that an increase in reactivity or tolerance to the acute salicylate or morphine administration was observed. © 2013 Elsevier B.V. All rights reserved.

  16. Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone

    Directory of Open Access Journals (Sweden)

    Atefeh Aminian

    2016-07-01

    Full Text Available Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg, animals received intraperitoneal injections of morphine (5 mg/kg/day and/or naltrexone (20 mg/kg/day, an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy.

  17. Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

    DEFF Research Database (Denmark)

    Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

    2007-01-01

    After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

  18. Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP

    Directory of Open Access Journals (Sweden)

    Michal eBajo

    2014-06-01

    Full Text Available The central amygdala (CeA plays an important role in opioid addiction. Therefore, we examined the effects of naloxone-precipitated morphine withdrawal (WD on GABAergic transmission in rat CeA neurons using whole-cell recordings with naloxone in the bath. The basal frequency of miniature inhibitory postsynaptic currents (mIPSCs increased in CeA neurons from WD compared to placebo rats. Acute morphine (10 M had mixed effects (> 20% change from baseline on mIPSCs in placebo and WD rats. In most CeA neurons (64% from placebo rats, morphine significantly decreased mIPSC frequency and amplitude. In 32% of placebo neurons, morphine significantly increased mIPSC amplitudes but had no effect on mIPSC frequency. In WD rats, acute morphine significantly increased mIPSC frequency but had no effect on mIPSC amplitude in 41% of CeA neurons. In 45% of cells, acute morphine significantly decreased mIPSC frequency and amplitude. Pre-treatment with the cyclic AMP inhibitor (R-adenosine, cyclic 3’,5’-(hydrogenphosphorothioate triethylammonium (RP, prevented acute morphine-induced potentiation of mIPSCs. Pre-treatment of slices with the Gi/o G-protein subunit inhibitor pertussis toxin (PTX did not prevent the acute morphine-induced enhancement or inhibition of mIPSCs. PTX and RP decreased basal mIPSC frequencies and amplitudes only in WD rats. The results suggest that inhibition of GABAergic transmission in the CeA by acute morphine is mediated by PTX-insensitive mechanisms, although PTX-sensitive mechanisms cannot be ruled out for non-morphine responsive cells; by contrast, potentiation of GABAergic transmission is mediated by activated cAMP signaling that also mediates the increased basal GABAergic transmission in WD rats. Our data indicate that during the acute phase of WD, the CeA opioid and GABAergic systems undergo neuroadaptative changes conditioned by a previous chronic morphine exposure and dependence.

  19. Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones.

    Science.gov (United States)

    Rayner, V C; Robinson, I C; Russell, J A

    1988-01-01

    1. Acutely, opioids inhibit oxytocin secretion. To study the responses of oxytocin neurones during chronic opioid exposure, forty-five lactating rats were infused continuously from a subcutaneous osmotically driven mini-pump via a lateral cerebral ventricle with morphine sulphate solution from day 2 post-partum for 5-7 days; the infusion rate was increased 2- or 2.5-fold each 40 h from 10 micrograms/h initially up to 50 micrograms/h; controls were infused with vehicle (1 microliter/h, twenty-eight rats) or were untreated (eight rats). 2. Maternal behaviour was disrupted in 27% of the morphine-treated rats; in rats that remained maternal morphine did not affect body weight or water intake but increased rectal temperature by 0.82 +/- 0.14 degrees C (mean +/- S.E.M.) across the first 4 days. 3. Weight gain of the litters of maternal morphine-treated rats was reduced by 32% during 7 days, predominantly in the first day of treatment when milk transfer was also reduced. Observation of pup behaviour during suckling showed decreased frequency of milk ejections on only the second day of morphine treatment. Plasma concentration of prolactin after 6 days was similar in maternal morphine-treated and control rats, but reduced by 90% in non-maternal morphine-treated rats, indicating normal control of prolactin secretion by suckling in morphine-treated rats. 4. Oxytocin and vasopressin contents, measured by radioimmunoassay, in the supraoptic and paraventricular nuclei and in the neurohypophysis were similar between fourteen maternal morphine-treated, twelve vehicle-treated and eight untreated lactating rats; thus exposure to morphine did not involve increased production and storage of oxytocin. 5. Distribution of [3H]morphine infused intracerebroventricularly into six virgin female rats for 6 days was measured by scintillation counting of tissue extracts. Morphine concentration in the hypothalamus and neurohypophysis was 2.7 and 12.8 micrograms/g, respectively, and in blood

  20. Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones.

    Science.gov (United States)

    Rayner, V C; Robinson, I C; Russell, J A

    1988-02-01

    1. Acutely, opioids inhibit oxytocin secretion. To study the responses of oxytocin neurones during chronic opioid exposure, forty-five lactating rats were infused continuously from a subcutaneous osmotically driven mini-pump via a lateral cerebral ventricle with morphine sulphate solution from day 2 post-partum for 5-7 days; the infusion rate was increased 2- or 2.5-fold each 40 h from 10 micrograms/h initially up to 50 micrograms/h; controls were infused with vehicle (1 microliter/h, twenty-eight rats) or were untreated (eight rats). 2. Maternal behaviour was disrupted in 27% of the morphine-treated rats; in rats that remained maternal morphine did not affect body weight or water intake but increased rectal temperature by 0.82 +/- 0.14 degrees C (mean +/- S.E.M.) across the first 4 days. 3. Weight gain of the litters of maternal morphine-treated rats was reduced by 32% during 7 days, predominantly in the first day of treatment when milk transfer was also reduced. Observation of pup behaviour during suckling showed decreased frequency of milk ejections on only the second day of morphine treatment. Plasma concentration of prolactin after 6 days was similar in maternal morphine-treated and control rats, but reduced by 90% in non-maternal morphine-treated rats, indicating normal control of prolactin secretion by suckling in morphine-treated rats. 4. Oxytocin and vasopressin contents, measured by radioimmunoassay, in the supraoptic and paraventricular nuclei and in the neurohypophysis were similar between fourteen maternal morphine-treated, twelve vehicle-treated and eight untreated lactating rats; thus exposure to morphine did not involve increased production and storage of oxytocin. 5. Distribution of [3H]morphine infused intracerebroventricularly into six virgin female rats for 6 days was measured by scintillation counting of tissue extracts. Morphine concentration in the hypothalamus and neurohypophysis was 2.7 and 12.8 micrograms/g, respectively, and in blood

  1. Morphine: oxycodone interventions in Denmark

    DEFF Research Database (Denmark)

    Munk Mikkelsen, Camilla; Andersen, Stig Ejdrup

    2012-01-01

    , morphine is more cost effective than oxycodone. In primary care, in particular, the price of oxycodone is about 2–3 times higher than that of morphine. Public health insurance in Denmark pays up to 80% of the medication costs for patients in primary care and the regions pays all costs for patients...... in hospital care. On this basis, it is economically very important that drug use in both sectors …...

  2. Morphine-augmented cholescintigraphy enhances duodenogastric reflux

    Energy Technology Data Exchange (ETDEWEB)

    Shih, Wei-Jen; Magoun, S.; Wierzbinski, B.; Ryo, U-Yun [Kentucky Univ., Lexington, KY (United States). Medical Center; Lee, Jong-Kang

    1995-11-01

    Morphine intervention in cholescintigraphy decreases imaging time to diagnose acute cholecystitis. Not infrequently we observe duodenogastric reflux during scintigraphy with and without morphine intervention. To evaluate occurrence of duodenogastric reflux related to morphine, we reviewed 55 patients who underwent cholescintigraphy with (32) and without (23) morphine intervention. Morphine was injected when there was bowel activity with non-visualization of the gallbladder at 60 min. Duodenogastric reflux was identified by the appearance of activity in the area just below or immediately adjacent to the tip of the left hepatic lobe laterally. Among 32 patients with morphine intervention, 19 had acute cholecystitis and 13 chronic cholecystitis. Eleven of 19 (58%) with acute cholecystitis had duodenogastric reflux and 6 of 13 (46%) had duodenogastric reflux in chronic cholecystitis. The total of duodenogastric reflux in the group with morphine injection was 53%. Two patients` duodenogastric reflux occurred before morphine injection and was more apparent after morphine was given. In the without morphine group, 3 had acute cholecystitis and 20 had chronic cholecystitis; 2 (one acute and one chronic cholecystitis) of these 23 (9%) had duodenogastric reflux. Our results indicate: occurrence of duodenogastric reflux in morphine augmented cholescintigraphy is not significantly different in cholecystitis from that in chronic cholecystitis; duodenogastric reflux in morphine augmentation occurs significantly more often than without morphine intervention (p<0.001). We conclude that cholescintigraphy with morphine enhances duodenogastric reflux. The degree of duodenogastric reflux in the acute cholecystitis patients has been more severe than in the chronic cholecystitis patients. (author).

  3. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  4. Photoaffinity labeling of rat liver microsomal morphine UDP-glucuronosyltransferase by ( sup 3 H)flunitrazepam

    Energy Technology Data Exchange (ETDEWEB)

    Thomassin, J.; Tephly, T.R. (Univ. of Iowa, Iowa City (USA))

    1990-09-01

    Benzodiazepines have been shown to competitively inhibit morphine glucuronidation in rat and human hepatic microsomes. Flunitrazepam exerted a potent competitive inhibition of rat hepatic morphine UDP-glucuronosyltransferase (UDPGT) activity (Ki = 130 microM). It has no effect on the activity of p-nitrophenol, 17 beta-hydroxysteroid, 3 alpha-hydroxysteroid, or 4-hydroxybiphenyl UDPGTs. Because flunitrazepam is an effective photoaffinity label for benzodiazepine receptors, studied were performed in solubilized rat hepatic microsomes and with partially purified preparations of morphine UDPGT to determine the enhancement of flunitrazepam inhibition and binding to morphine UDPGT promoted by exposure to UV light. Under UV light, flunitrazepam inhibition was markedly enhanced. UV light exposure also led to a marked increase in binding of (3H)flunitrazepam to microsomal protein, which was protected substantially by preincubation with morphine. Testosterone, androsterone, and UDP-glucuronic acid did not protect against UV-enhanced flunitrazepam binding, and morphine did not reverse flunitrazepam binding once binding had occurred. As morphine UDPGT was purified, a good correlation was found between the increases in specific activity of morphine UDPGT and flunitrazepam binding to protein. Chromatofocusing chromatography showed that flunitrazepam bound only to fractions containing active morphine UDPGT, and no binding to 4-hydroxybiphenyl UDPGT was observed. Fluorography of a sodium dodecyl sulfate-polyacrylamide electrophoresis gel of solubilized hepatic microsomes that had been treated with (3H) flunitrazepam under UV light revealed a band with a monomeric molecular weight between 54,000 and 58,000. This monomeric molecular weight compares favorably with the reported monomeric molecular weight of homogeneous morphine UDPGT (56,000).

  5. The gamma-aminobutyric acid type B (GABAB receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Fu Zhenyu

    2012-07-01

    Full Text Available Abstract Background Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. Methods We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo. Results The present study demonstrated that morphine challenge (3 mg/kg, s.c. obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge. Conclusions Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.

  6. Brain cholinergic involvement during the rapid development of tolerance to morphine

    Science.gov (United States)

    Wahba, Z. Z.; Oriaku, E. T.; Soliman, S. F. A.

    1987-01-01

    The effect of repeated administration of morphine on the activities of the cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in specific brain regions were studied in rats treated with 10 mg/kg morphine for one or two days. Repeated administration of morphine was associated with a decline in the degree of analgesia produced and with a significant increase of AChE activity of the medulla oblongata. A single injection of morphine resulted in a significant decline in ChAT activity in the hypothalamus, cerebellum, and medulla oblongata regions. After two consecutive injections, no decline in ChAT was observed in these regions, while in the cerebral cortex the second administration elicited a significant decline. The results suggest that the development of tolerance to morphine may be mediated through changes in ChAT activity and lend support to the involvement of the central cholinergic system in narcotic tolerance.

  7. Morphine use in cancer surgery

    Directory of Open Access Journals (Sweden)

    Banafsheh eAfsharimani

    2011-08-01

    Full Text Available Morphine is the core of perioperative pain management. However, when it comes to cancer surgery the possibility that this drug might affect tumor recurrence and metastasis has raised concerns. The results of two recent retrospective clinical trials indicated that regional anesthesia/analgesia might be beneficial in prostate and breast cancer surgery. It was proposed that morphine could be responsible for the higher recurrence and mortality rate observed in the general anesthesia/opioid analgesia groups. Nevertheless, the results of several other retrospective studies and one randomized prospective trial failed to confirm any advantage for regional anesthesia/analgesia over general anesthesia and opioid analgesia. Moreover laboratory data on the effect of morphine on cancer are contradictory, ranging from tumor-promoting to anti-tumor effects. Considering that surgical stress and pain promote the recurrence and spread of cancer, choosing a proper analgesic strategy is of high significance. Although the question of whether morphine causes any harm to cancer patients remains unanswered, alternative analgesic regimens could be used concomitant to or instead of morphine to limit its potential adverse effects.

  8. Relationships among morphine metabolism, pain and side effects during long-term treatment

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Christrup, Lona Louring; Sjøgren, Per

    2003-01-01

    The two metabolites of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), have been studied intensively in animals and humans during the past 30 years in order to elucidate their precise action and possible contribution to the desired effects and side effects seen after...... morphine administration. M3G and M6G are formed by morphine glucuronidation, mainly in the liver, and are excreted by the kidneys. The metabolites are found in the cerebrospinal fluid after single as well as multiple doses of morphine. M6G binds to opioid receptors, and animal studies have demonstrated...... of the studies have used lower doses of M6G than of morphine. M3G displays very low affinity for opioid receptors and has no analgesic activity. Animal studies have shown that M3G may antagonize the analgesic effect of morphine and M6G, but no human studies have demonstrated this. M3G has also been connected...

  9. Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression

    Directory of Open Access Journals (Sweden)

    Ru-Yin Tsai

    2016-06-01

    Conclusion: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

  10. Connexin-purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation.

    Science.gov (United States)

    Bhave, Sukhada; Gade, Aravind; Kang, Minho; Hauser, Kurt F; Dewey, William L; Akbarali, Hamid I

    2017-06-01

    Morphine is one of the most widely used drugs for the treatment of pain. However, side effects, including persistent constipation and antinociceptive tolerance, limit its clinical efficacy. Prolonged morphine treatment results in a "leaky" gut, predisposing to colonic inflammation that is facilitated by microbial dysbiosis and associated bacterial translocation. In this study, we examined the role of enteric glia in mediating this secondary inflammatory response to prolonged treatment with morphine. We found that purinergic P2X receptor activity was significantly enhanced in enteric glia that were isolated from mice with long-term morphine treatment ( in vivo ) but not upon direct exposure of glia to morphine ( in vitro ). LPS, a major bacterial product, also increased ATP-induced currents, as well as expression of P2X4, P2X7, IL6, IL-1β mRNA in enteric glia. LPS increased connexin43 (Cx43) expression and enhanced ATP release from enteric glia cells. LPS-induced P2X currents and proinflammatory cytokine mRNA expression were blocked by the Cx43 blockers Gap26 and carbenoxolone. Likewise, colonic inflammation related to prolonged exposure to morphine was significantly attenuated by carbenoxolone (25 mg/kg). Carbenoxolone also prevented gut wall disruption and significantly reduced morphine-induced constipation. These findings imply that enteric glia activation is a significant modulator of morphine-related inflammation and constipation.-Bhave, S., Gade, A., Kang, M., Hauser, K. F., Dewey, W. L., Akbarali, H. I. Connexin-purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation. © FASEB.

  11. Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application on the healthy equine eye.

    Science.gov (United States)

    Gordon, Emma; Stang, Bernadette V; Heidel, Jerry; Poulsen, Keith P; Cebra, Christopher K; Schlipf, John W

    2018-01-19

    To determine if corneal epithelial cell integrity is detrimentally affected by short-term administration of 1.0% morphine sulfate. Additionally, we sought to determine if topical 1.0% morphine applied to the equine cornea would result in ocular or systemic absorption. Six healthy horses. Morphine sulfate (1.0%) was applied topically to one eye every four hours for 72 h before horses were euthanized. Serum samples were collected at varying time points during the study and aqueous and vitreous humor were collected immediately after euthanasia. Morphine quantification in serum, aqueous, and vitreous humor was performed by ELISA. Treated and control corneas were submitted for histopathology. Horses were monitored for adverse ocular and systemic effects throughout the study period. All horses developed mild mucoid ocular discharge in the treated eye. One horse developed a fever during treatment. Morphine was detected in the aqueous humor of the treated eye for all horses with mean ± standard deviation of 165.18 ng/mL ± 87.69 ng/mL. Morphine was detected in vitreous humor of the treated eye of 5 of 6 horses with mean ± standard deviation of 4.87 ± 4.46 ng/mL. Morphine was detected in the serum of 5 of 6 horses at varying time points. Maximum systemic concentration reached in a single horse was 6.98 ng/mL. Corneal histopathology revealed no difference in microscopic appearance between morphine-treated and control corneas. Topical administration of 1.0% morphine sulfate did not appear to cause any significant ocular or systemic adverse effects. Topical ophthalmic morphine application resulted in both ocular and systemic absorption. © 2018 American College of Veterinary Ophthalmologists.

  12. Morphine induces albuminuria by compromising podocyte integrity.

    Directory of Open Access Journals (Sweden)

    Xiqian Lan

    Full Text Available Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD, the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for immunohistochemical studies and Western blot. For in vitro studies, human podocytes were treated with morphine and then probed for the molecular markers of slit diaphragm. Morphine-receiving mice displayed a significant increase in albuminuria and showed effacement of podocyte foot processes. In both in vivo and in vitro studies, the expression of synaptopodin, a molecular marker for podocyte integrity, and the slit diaphragm constituting molecules (SDCM, such as nephrin, podocin, and CD2-associated protein (CD2AP, were decreased in morphine-treated podocytes. In vitro studies indicated that morphine modulated podocyte expression of SDCM through opiate mu (MOR and kappa (KOR receptors. Since morphine also enhanced podocyte oxidative stress, the latter seems to contribute to decreased SDCM expression. In addition, AKT, p38, and JNK pathways were involved in morphine-induced down regulation of SDCM in human podocytes. These findings demonstrate that morphine has the potential to alter the glomerular filtration barrier by compromising the integrity of podocytes.

  13. Effect of linalool on the acquisition and reinstatement of morphine-induced conditioned place preference in mice

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    Narjes Pourtaqi

    2017-04-01

    Full Text Available Objective: The effect of linalool, a terpene alcohol found in many plants, which inhibits NMDA receptors, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP was evaluated in mice.Material and Methods: The effects of different doses of linalool (12.5, 25 and 50 mg/kg, i.p., memantine (20 mg/kg, an NMDA receptor antagonist and saline, in CPP induced by 40 mg/kg of morphine were investigated in mice. In another experiment, a single injection of morphine (10 mg/kg reinstated the place reference following extinction of a place preference induced by morphine (40 mg/kg. Linalool (12.5, 25 and 50 mg/kg, i.p., memantine (20 mg/kg and saline were administrated 30 min before this priming dose of morphine.Results: In the first experiment, linalool (12.5 and 50 mg/kg was able to decrease morphine-induced CPP. In the second part, linalool (25 and 50 mg/kg reduced morphine-induced reinstatement of place preference. Both acquisition and reinstatement of morphine-induced CPP, were considerably decreased by memantine.Conclusion: The present study showed that linalool is able to reduce the acquisition and reinstatement of morphine-induced CPP which might be due tothrough NMDA receptors blocking.

  14. Effect of linalool on the acquisition and reinstatement of morphine-induced conditioned place preference in mice.

    Science.gov (United States)

    Pourtaqi, Narjes; Imenshahidi, Mohsen; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

    2017-01-01

    The effect of linalool, a terpene alcohol found in many plants, which inhibits NMDA receptors, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) was evaluated in mice. The effects of different doses of linalool (12.5, 25 and 50 mg/kg, i.p.), memantine (20 mg/kg, an NMDA receptor antagonist) and saline, in CPP induced by 40 mg/kg of morphine were investigated in mice. In another experiment, a single injection of morphine (10 mg/kg) reinstated the place reference following extinction of a place preference induced by morphine (40 mg/kg). Linalool (12.5, 25 and 50 mg/kg, i.p.), memantine (20 mg/kg) and saline were administrated 30 min before this priming dose of morphine. In the first experiment, linalool (12.5 and 50 mg/kg) was able to decrease morphine-induced CPP. In the second part, linalool (25 and 50 mg/kg) reduced morphine-induced reinstatement of place preference. Both acquisition and reinstatement of morphine-induced CPP, were considerably decreased by memantine. The present study showed that linalool is able to reduce the acquisition and reinstatement of morphine-induced CPP which might be due tothrough NMDA receptors blocking.

  15. An enriched environment reduces the stress level and locomotor activity induced by acute morphine treatment and by saline after chronic morphine treatment in mice.

    Science.gov (United States)

    Xu, Jia; Sun, Jinling; Xue, Zhaoxia; Li, Xinwang

    2014-06-18

    This study investigated the relationships among an enriched environment, stress levels, and drug addiction. Mice were divided randomly into four treatment groups (n=12 each): enriched environment without restraint stress (EN), standard environment without restraint stress (SN), enriched environment with restraint stress (ES), and standard environment with restraint stress (SS). Mice were reared in the respective environment for 45 days. Then, the ES and SS groups were subjected to restraint stress daily (2 h/day) for 14 days, whereas the EN and SN groups were not subjected to restraint stress during this stage. The stress levels of all mice were tested in the elevated plus maze immediately after exposure to restraint stress. After the 2-week stress testing period, mice were administered acute or chronic morphine (5 mg/kg) treatment for 7 days. Then, after a 7-day withdrawal period, the mice were injected with saline (1 ml/kg) or morphine (5 mg/kg) daily for 2 days to observe locomotor activity. The results indicated that the enriched environment reduced the stress and locomotor activity induced by acute morphine administration or saline after chronic morphine treatment. However, the enriched environment did not significantly inhibit locomotor activity induced by morphine challenge. In addition, the stress level did not mediate the effect of the enriched environment on drug-induced locomotor activity after acute or chronic morphine treatment.

  16. Geraniin attenuates Naloxone-Precipitated Morphine Withdrawal and Morphine-Induced Tolerance in Mice

    Directory of Open Access Journals (Sweden)

    Ella Anle Kasanga

    2017-06-01

    Conclusion: Geraniin does not produce any tolerant effects like morphine and also reduced the signs associated with naloxone-precipitated morphine withdrawal in mice. [J Complement Med Res 2017; 6(2.000: 199-205

  17. Tumorigenic responses from single or repeated inhalation exposures to relatively insoluble aerosols of Ce-144

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Mauderly, J.L.; McClellan, R.O.

    1980-01-01

    Human occupational or environmental inhalation exposures may involve repeated or chronic exposures, but most laboratory studies of inhaled radionuclides have involved single exposures. This study was designed to compare the biological effects of repeated inhalation exposures of dogs to a relatively insoluble form of 144 Ce with existing data for singly-exposed dogs that had the same cumulative dose to the lungs two years after exposure. To date, the biological effects observed in these repeatedly-exposed dogs have been substantially different from those seen in singly-exposed dogs, particularly during the first 5 years after the initial exposure. Although pulmonary hemangiosarcoma was the prominent biological effect seen in singly-exposed dogs between 2 and 4 years after exposure, no lung tumors were seen during the 5 years after the first of the repeated exposures. This response plus other clinical observations are discussed in relation to the patterns of dose rate and cumulative dose for the different exposure conditions. (H.K.)

  18. OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings

    Directory of Open Access Journals (Sweden)

    Aline Hajj

    2017-03-01

    Full Text Available Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL. We conducted this study to evaluate the added value of determining some genetic and non-genetic factors to optimize cancer pain treatment. Eighty-nine patients were included in the study for the evaluation of palliative cancer pain management. The regression analysis showed that age, OPRM1 single nucleotide polymorphism (SNP, as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h (given by infusion pump; p = 0.043, 0.029, and <0.001, respectively. The mean doses of morphine decreased with age but increased with the duration of morphine treatment. In addition, patients with AG genotype c.118A>G OPRM1 needed a higher dose of morphine than AA patients. Moreover, metastases, OPRM1 SNP, age, and gender were significantly associated with the QOL in our population. In particular, AA patients for OPRM1 SNP had significantly lower cognitive function than AG patients, a result not previously reported in the literature. These findings could help increase the effectiveness of morphine treatment and enhance the QOL of patients in regards to personalized medicine.

  19. Oral morphine for cancer pain.

    Science.gov (United States)

    Wiffen, Philip J; Wee, Bee; Moore, R Andrew

    2016-04-22

    This is the third updated version of a Cochrane review first published in Issue 4, 2003 of The Cochrane Library and first updated in 2007. Morphine has been used for many years to relieve pain. Oral morphine in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain. To determine the efficacy of oral morphine in relieving cancer pain, and to assess the incidence and severity of adverse events. We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9); MEDLINE (1966 to October 2015); and EMBASE (1974 to October 2015). We also searched ClinicalTrials.gov (1 October 2015). Published randomised controlled trials (RCTs) using placebo or active comparators reporting on the analgesic effect of oral morphine in adults and children with cancer pain. We excluded trials with fewer than 10 participants. One review author extracted data, which were checked by another review author. There were insufficient comparable data for meta-analysis to be undertaken or to produce numbers needed to treat (NNTs) for the analgesic effect. We extracted any available data on the number or proportion of participants with 'no worse than mild pain' or treatment success (very satisfied, or very good or excellent on patient global impression scales). We identified seven new studies in this update. We excluded six, and one study is ongoing so also not included in this update. This review contains a total of 62 included studies, with 4241 participants. Thirty-six studies used a cross-over design ranging from one to 15 days, with the greatest number (11) for seven days for each arm of the trial. Overall we judged the included studies to be at high risk of bias because the methods of randomisation and allocation concealment were poorly reported. The primary outcomes for this review were participant-reported pain and pain relief.Fifteen studies compared oral morphine modified release (Mm

  20. The Role of β-Arrestin2 in the Mechanism of Morphine Tolerance in the Mouse and Guinea Pig Gastrointestinal Tract

    OpenAIRE

    Kang, Minho; Maguma, Hercules T.; Smith, Tricia H.; Ross, Gracious R.; Dewey, William L.; Akbarali, Hamid I.

    2012-01-01

    β-Arrestin2 has been reported to play an essential role in analgesic tolerance. Analgesic tolerance without concomitant tolerance to constipation is a limiting side effect of chronic morphine treatment. Because tolerance to morphine develops in the mouse ileum but not the colon, we therefore examined whether the role of β-arrestin2 in the mechanism of morphine tolerance differs in the ileum and colon. In both guinea pig and mouse, chronic in vitro exposure (2 h, 10 μM) to morphine resulted in...

  1. Place aversion by morphine in offspring born of female morphine administered wistar rats.

    Science.gov (United States)

    Karami, Manizheh; Zarrindast, Mohammad Reza

    2011-01-01

    This research was designed to study sexual differences in place conditioning induced by morphine in offspring born of female Wistar rats mated with drug-naïve males. Mothers were exposed to morphine during the 14(th)-16(th) days of gestational. Control dams were simply saline-injected. Female and male virgin offspring born of morphine-treated or saline-treated mothers were separately housed until become fully matured. A 3-day schedule of an unbiased conditioning procedure was used to the induce conditioning to morphine (2.5-7.5 mg/Kg, SC) in the offspring. According to the results, female offspring born of saline-administered mothers were morphine place-conditioned at lower doses of opioid (2.5 mg/Kg) in comparison to the males. An increase in locomotor activity in the females at 7.5 mg/Kg of opioid was also revealed. In contrast, administration of morphine (2.5-7.5 mg/Kg, SC), induced a significant aversion in either sexes of offspring born of morphine-exposed mothers. Moreover, female offspring of this category acquired more pronounced aversion at higher doses of morphine than males. In addition, a significant morphine-dose effect (7.5 mg/Kg, SC) on locomotor activity of these females' offspring was observed. This study may highlight sex differences in conditioning effects induced by morphine between offspring derived of morphine-treated mothers and those of saline-treated.

  2. The ventral pallidum is critically involved in the development and expression of morphine-induced sensitization.

    Science.gov (United States)

    Mickiewicz, Amanda L; Dallimore, Jeanine E; Napier, T Celeste

    2009-03-01

    Repeated, intermittent exposure to drugs of abuse results in response enhancements to subsequent drug treatments, a phenomenon referred to as sensitization. As persistent neuronal sensitization may contribute to the long-lasting consequences of drug abuse, characterizing the neuroanatomical substrates of sensitization is providing insights into addiction. It is known that the ventral tegmental area (VTA) is necessary for induction, and expression involves the nucleus accumbens (NAc). We reveal here that the ventral pallidum (VP), a brain region reciprocally innervated by the VTA and the NAc, is a critical mediator of opiate-induced behavioral sensitization. Blockade of VP mu-opioid receptors (via intra-VP CTOP injections) negated the ability of systemic administration of the opiate, morphine to induce motor sensitization, and for sensitized rats to subsequently express enhanced responding to a morphine challenge. Intra-VP morphine was sufficient to induce motor sensitization, and this sensitization was expressed following 17 days of withdrawal. Rats with a treatment history of intra-VP morphine demonstrated cross-sensitization to a challenge injection of systemically administered morphine. Conversely, repeated systemic treatments of morphine cross-sensitized to an intra-VP morphine challenge. These results indicate that activation of VP mu-opioid receptors is sufficient to evoke behavioral sensitization and that these receptors are necessary for sensitized responding to systemic morphine. The study pioneers the concept that both development and expression of drug-induced sensitization are regulated by the VP. Thus, the VP is likely an important contributor to neuronal adaptations that underlie addiction.

  3. Tolerance to Morphine Analgesia: Influence of Pain and Method of Morphine Delivery

    Directory of Open Access Journals (Sweden)

    Scott A Chen

    2000-01-01

    Full Text Available Whether some kinds of pain can modify the development of tolerance to morphine analgesia is a controversial issue. Clinically, the development of tolerance is often difficult to establish because many factors can contribute to a decline in analgesic coverage, including disease progression. Basic animal research designed to examine tolerance provides the experimental control necessary to differentiate 'real' tolerance from other variables that can influence morphine analgesia. The present study examines the effects of inflammation induced by complete Freund's adjuvant (CFA on the development of tolerance to morphine analgesia produced by two different methods of morphine delivery - repeated bolus injections and continuous infusion. Male Long-Evans hooded rats were injected with CFA (0.2 mL into the right hind paw under sodium pentobarbital anesthesia or were given anesthesia alone. Starting 24 h later, rats either received an injection of morphine (20 mg/kg, intraperitoneal on four consecutive days or were implanted with a 72 h osmotic minipump that delivered 80 mg/kg morphine over a similar time period. Control animals received saline injections or were implanted with empty minipumps. After 24 h, sensitivity to morphine-induced analgesia was measured by the tail-immersion test (water maintained at 52°C using a cumulative dosing procedure. It was found that CFA attenuated tolerance to the morphine analgesia that was induced by intraperitoneal injections of morphine. In contrast, when morphine was delivered via osmotic minipumps, significant analgesic tolerance was observed in animals that received morphine in the presence of CFA but not in those that received morphine in the absence of CFA. These results show the importance of the method used to deliver morphine in determining the effects of pain on the development of tolerance to morphine analgesia.

  4. Spinal cord thyrotropin releasing hormone receptors of morphine tolerant-dependent and abstinent rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1990-07-01

    The effect of chronic administration of morphine and its withdrawal on the binding of 3H-(3-MeHis2)thyrotropin releasing hormone (3H-MeTRH) to membranes of the spinal cord of the rat was determined. Male Sprague-Dawley rats were implanted with either 6 placebo or 6 morphine pellets (each containing 75-mg morphine base) during a 7-day period. Two sets of animals were used. In one, the pellets were left intact at the time of sacrificing (tolerant-dependent) and in the other, the pellets were removed 16 hours prior to sacrificing (abstinent rats). In placebo-pellet-implanted rats, 3H-MeTRH bound to the spinal cord membranes at a single high affinity binding site with a Bmax of 21.3 +/- 1.6 fmol/mg protein, and an apparent dissociation constant Kd of 4.7 +/- 0.8 nM. In morphine tolerant-dependent or abstinent rats, the binding constants of 3H-MeTRH to spinal cord membranes were unaffected. Previous studies from this laboratory indicate that TRH can inhibit morphine tolerance-dependence and abstinence processes without modifying brain TRH receptors. Together with the present results, it appears that the inhibitory effect of TRH on morphine tolerance-dependence and abstinence is probably not mediated via central TRH receptors but may be due to its interaction with other neurotransmitter systems.

  5. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

    International Nuclear Information System (INIS)

    Bartlett, S.E.; Smith, M.T.; Dood, P.R.

    1994-01-01

    Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of 3 H-MK801 (non-competitive antagonist) and 125 I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of 3 H-muscimol (GABA receptor agonist), 3 H-diazepam and 3 H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA A receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of 3 H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.)

  6. Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, S.E.; Smith, M.T. (Department of Pharmacy, The University of Queensland (Australia)); Dood, P.R. (Clinical Research Centre, Royal Brisbane Hospital Foundation, Brisbane (Australia))

    1994-07-01

    Morphine in high doses and its major metabolite, morphine-3-glucuronide, cause CNS excitation following intrathecal and intracerebroventricular administration by an unknown mechanism. This study investigated whether morphine and morphine-3-glucuronide interact at major excitatory (glutamate), major inhibitory (GABA or glycine), or opioid binding sites. Homogenate binding assays were performed using specific radioligands. At opioid receptors, morphine-3-glucuronide and morphine caused an equipotent sodium shift, consistent with morphine-3-glucuronide behaving as an agonist. This suggests that morphine-3-glucuronide-mediated excitation is not caused by an interaction at opioid receptors. Morphine-3-glucuronide and morphine caused a weak inhibition of the binding of [sup 3]H-MK801 (non-competitive antagonist) and [sup 125]I-ifenprodil (polyamine site antagonist), but at unphysiologically high concentrations. This suggests that CNS excitation would not result from an interaction of morphine-3-glucuronide and high-dose morphine with these sites on the NMDA receptor. Morphine-3-glucuronide and morphine inhibited the binding of [sup 3]H-muscimol (GABA receptor agonist), [sup 3]H-diazepam and [sup 3]H-flunitraxepam (benzodiazepine agonists) binding very weakly, suggesting the excitatory effects of morphine-3-glucuronide and high-dose morphine are not elicited through GABA[sub A] receptors. Morphine-3-glucuronide and high-dose morphine did not prevent re-uptake of glutamate into presynaptic nerve terminals. In addition, morphine-3-glucuronide and morphine did not inhibit the binding of [sup 3]H-strychnine (glycine receptor antagonist) to synaptic membranes prepared from bovine spinal cord. It is concluded that excitation caused by high-dose morphine and morphine-3-glucuronide is not mediated by an interaction with postsynaptic amino acid receptors. (au) (30 refs.).

  7. Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

    Energy Technology Data Exchange (ETDEWEB)

    Bhargava, H.N.; Das, S.

    1986-03-01

    The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

  8. Simultaneous determination of morphine, codeine and 6-acetyl morphine in human urine and blood samples using direct aqueous derivatisation: validation and application to real cases.

    Science.gov (United States)

    Chericoni, S; Stefanelli, F; Iannella, V; Giusiani, M

    2014-02-15

    Opiates play a relevant role in forensic toxicology and their assay in urine or blood is usually performed for example in workplace drug-testing or toxicological investigation of drug impaired driving. The present work describes two new methods for detecting morphine, codeine and 6-monoacethyl morphine in human urine or blood using a single step derivatisation in aqueous phase. Propyl chloroformate is used as the dramatizing agent followed by liquid-liquid extraction and gas-chromatography-mass spectroscopy to detect the derivatives. The methods have been validated both for hydrolysed and unhydrolysed urine. For hydrolysed urine, the LOD and LOQ were 2.5ng/ml and 8.5ng/ml for codeine, and 5.2ng/ml and 15.1ng/ml for morphine, respectively. For unhydrolysed urine, the LOD and LOQ were 3.0ng/ml and 10.1ng/ml for codeine, 2.7ng/ml and 8.1ng/ml for morphine, 0.8ng/ml and 1.5ng/ml for 6-monoacetyl morphine, respectively. In blood, the LOD and LOQ were 0.44ng/ml and 1.46ng/ml for codeine, 0.29ng/ml and 0.98ng/ml for morphine, 0.15ng/ml and 0.51ng/ml for 6-monoacetyl morphine, respectively. The validated methods have been applied to 50 urine samples and 40 blood samples (both positive and negative) and they can be used in routine analyses. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Enduring effects of morphine pellets revealed by conditioned taste aversion.

    Science.gov (United States)

    Manning, F J; Jackson, M C

    1977-03-16

    Morphine pellets (75 mg) were implanted subcutaneously in albino rats. Three days later, following 24 h without water, these rats (Group MSN) were given access to a saccharin solution for 30 min, then injected with naloxone hydrochloride. The classical abstinence signs, including "wet dog shakes"and weight loss, were noted in these subjects, but not in controls given placebo pellets and /or saline injections. In addition, when given an opportunity to drink either saccharine solution or water 24 h later, Group MSN rats drank significantly less saccharin than any of the control groups. Similar drinking patterns were found even when naloxone injection was delayed as long as 3 weeks after pellet implantation, when none of the classical abstinence signs were seen and serum levels of morphine and its metabolites were 100 times lower according to radioimmunoassay. This simple and objective technique is thus more sensitive as a measure of prior morphine exposure than any of the commonly used indices. The continued utility of a dependent-nondependent dichotomy is also examined in light of these and other findings.

  10. Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

    Science.gov (United States)

    Nakhjiri, Elnaz; Saboory, Ehsan; Roshan-Milani, Shiva; Rasmi, Yousef; Khalafkhani, Davod

    2017-03-01

    Stressful events and exposure to opiates during gestation have important effects on the later mental health of the offspring. Anxiety is among the most common mental disorders. The present study aimed to identify effects of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration (PVC) and anxiety behaviors in rats. Pregnant rats were divided into four groups (n = 6, each): saline, morphine, stress + saline and stress + morphine treatment. The stress procedure consisted of restraint twice per day, two hours per session, for three consecutive days starting on day 15 of pregnancy. Rats in the saline and morphine groups received either 0.9% saline or morphine intraperitoneally on the same days. In the morphine/saline + stress groups, rats were exposed to restraint stress and received either morphine or saline intraperitoneally. All offspring were tested in an elevated plus maze (EPM) on postnatal day 90 (n = 6, each sex), and anxiety behaviors of each rat were recorded. Finally, blood samples were collected to determine PVC. Prenatal morphine exposure reduced anxiety-like behaviors. Co-administration of prenatal stress and morphine increased locomotor activity (LA) and PVC. PVC was significantly lower in female offspring of the morphine and morphine + stress groups compared with males in the same group, but the opposite was seen in the saline + stress group. These data emphasize the impact of prenatal stress and morphine on fetal neuroendocrine development, with long-term changes in anxiety-like behaviors and vasopressin secretion. These changes are sex specific, indicating differential impact of prenatal stress and morphine on fetal neuroendocrine system development. Lay Summary Pregnant women are sometimes exposed to stressful and painful conditions which may lead to poor outcomes for offspring. Opiates may provide pain and stress relief to these mothers. In this study, we used an experimental model of

  11. Comparison of radiation exposure during transradial diagnostic coronary angiography with single- or multi-catheters approach.

    Science.gov (United States)

    Plourde, Guillaume; Abdelaal, Eltigani; MacHaalany, Jimmy; Rimac, Goran; Poirier, Yann; Arsenault, Jean; Costerousse, Olivier; Bertrand, Olivier F

    2017-08-01

    To compare radiation exposure during transradial diagnostic coronary angiography (DCA) using standard single- or multi-catheters with different shapes. Transradial DCA can be performed using single- or multi-catheters to canulate left and right coronary ostia. To date, it remains unknown whether there are differences in radiation exposure between the two strategies. From November 2012 to June 2014, 3,410 consecutive patients who underwent transradial DCA were recruited. Groups were based on the initial diagnostic catheter used and were dichotomized between single- and multi-catheters approach. All crossovers were excluded. The multi-catheters approach (Multi) group consisted of Judkins left and right catheters, whereas the single-catheter (Single) group included Amplatz, Barbeau, or Multipurpose catheters. Fluoroscopy time (FT) as a surrogate end-point for total radiation exposure and kerma-area product (KAP; patient radiation exposure) were collected as radiation exposure parameters. A single-catheter strategy was used in 439 patients, while 2,971 patients had a multi-catheters approach. There was no significant difference in FT between groups (2.86 ± 1.48 min for Multi vs. 2.87 ± 1.72 min for Single, P = 0.13). The multi-catheters approach was associated with a significant 15% reduction in KAP (3,599 ± 2,214 cGy · cm 2 vs. 3,073 ± 1,785 cGy · cm 2 , P approach. When pooling all patients, mean FT was 2.86 ± 1.51 min. Mean KAP was 3,141 ± 1,854 cGy · cm 2 . Reference levels in our institution in both groups were below international diagnostic reference levels. Overall both FT and KAP decreased by 15% and 19%, respectively, over the 2-year study period. Compared to a single-catheter approach, a multi-catheters approach with standard Judkins catheters for DCA significantly reduced patient radiation exposure. Whether single catheter designed for DCA by radial approach can further reduce radiation exposure compared to

  12. Morphine

    Science.gov (United States)

    ... and you have a gastrostomy tube (surgically inserted feeding tube), ask your doctor or pharmacist how to ... Remeron); nalbuphine; pentazocine (Talwin); quinidine (in Nuedexta); 5HT3 serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron ( ...

  13. A single exposure to acrolein causes arrhythmogenesis, cardiac electrical dysfunction and decreased heart rate variability in hypertensive rats

    Science.gov (United States)

    Epidemiological studies demonstrate an association between cardiovascular morbidity, arrhythmias, and exposure to air toxicants such as acrolein. We hypothesized that a single exposure to acrolein would increase arrhythmias and cause changes in the electrocardiogram (ECG) of hype...

  14. Blockade of Serotonin 5-HT2AReceptors Suppresses Behavioral Sensitization and Naloxone-Precipitated Withdrawal Symptoms in Morphine-Treated Mice.

    Science.gov (United States)

    Pang, Gang; Wu, Xian; Tao, Xinrong; Mao, Ruoying; Liu, Xueke; Zhang, Yong-Mei; Li, Guangwu; Stackman, Robert W; Dong, Liuyi; Zhang, Gongliang

    2016-01-01

    The increasing prescription of opioids is fueling an epidemic of addiction and overdose deaths. Morphine is a highly addictive drug characterized by a high relapse rate - even after a long period of abstinence. Serotonin (5-HT) neurotransmission participates in the development of morphine dependence, as well as the expression of morphine withdrawal. In this study, we examined the effect of blockade of 5-HT 2A receptors (5-HT 2A Rs) on morphine-induced behavioral sensitization and withdrawal in male mice. 5-HT 2A R antagonist MDL 11,939 (0.5 mg/kg, i.p.) suppressed acute morphine (5.0 mg/kg, s.c.)-induced increase in locomotor activity. Mice received morphine (10 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of morphine (10 mg/kg) was administered to induce the expression of behavioral sensitization. MDL 11,939 (0.5 mg/kg, i.p.) pretreatment suppressed the expression of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. MDL 11,939 (0.5 mg/kg, i.p.) prevented naloxone-precipitated withdrawal in morphine-dependent mice on day 7. Moreover, chronic morphine treatment increased 5-HT 2A R protein level and decreased the phosphorylation of extracellular signal-regulated kinases in the prefrontal cortex. Together, these results by the first time demonstrate that 5-HT 2A Rs modulate opioid dependence and blockade of 5-HT 2A R may represent a novel strategy for the treatment of morphine use disorders. (i)Blockade of 5-HT 2A receptors suppresses the expression of morphine-induced behavioral sensitization.(ii)Blockade of 5-HT 2A receptors suppresses naloxone-precipitated withdrawal in morphine-treated mice.(iii)Chronic morphine exposure induces an increase in 5-HT 2A receptor protein level and a decrease in ERK protein phosphorylation in prefrontal cortex.

  15. Effects of drugs on behavior in rats maintained on morphine, methadone or pentobarbital.

    Science.gov (United States)

    McMillan, D E; McGivney, W T; Hardwick, W C

    1980-10-01

    Dose-effect curves were determined for the effects of drugs on responding under a multiple fixed-ratio 10-response fixed-interval 90-sec schedule of food presentation before and during chronic exposure to drugs in the drinking water. In rats consuming 70 to 90 mg/kg of morphine per day, the dose-effect curves for the rate-decreasing effects of morphine on responding under both schedule components shifted 1/2 log unit to the right, but the dose-effect curves for methadone, pentobarbital and d-amphetamine showed little change. In rats consuming 30 to 55 mg/kg of methadone per day there was little change in the dose-effect curves for the rate-decreasing effects of methadone and d-amphetamine on responding, but the dose-effect curve for morphine shifted 1/2 log unit to the right and the dose-effect curve for pentobarbital shifted upward and to the right. In rats consuming 40 to 50 mg/kg of pentobarbital per day, the dose-effect curve for the rate-decreasing effects of pentobarbital shifted to the right by about 1/4 log unit, and there was a similar but less marked shift to the methadone dose-effect curve to the right. In rats consuming pentobarbital, the morphine dose-effect curve was little changed. These experiments suggest that chronic methadone consumption confers greater tolerance to the effects of morphine on schedule-controlled behavior than it confers upon itself, while chronic morphine consumption confers greater tolerance to its own behavioral effects than it does to those of methadone. There appears to be some reciprocal cross-tolerance between methadone and pentobarbital for schedule-controlled behavior, but not between morphine and pentobarbital.

  16. Proteomic analysis of PKCγ-related proteins in the spinal cord of morphine-tolerant rats.

    Directory of Open Access Journals (Sweden)

    Zongbin Song

    Full Text Available BACKGROUND: Morphine tolerance is a common drawback of chronic morphine exposure, hindering use of this drug. Studies have shown that PKCã may play a key role in the development of morphine tolerance, although the mechanisms are not fully known. METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of morphine tolerance, PKCã knockdown in the spinal cord was successfully carried out using RNA interference (RNAi with lentiviral vector-mediated short hairpin RNA of PKCã (LV-shPKCã. Spinal cords (L4-L5 were obtained surgically from morphine-tolerant (MT rats with and without PKCã knockdown, for comparative proteomic analysis. Total proteins from the spinal cords (L4-L5 were extracted and separated using two-dimensional gel electrophoresis (2DGE; 2D gel images were analyzed with PDQuest software. Seven differential gel-spots were observed with increased spot volume, and 18 spots observed with decreased spot volume. Among these, 13 differentially expressed proteins (DEPs were identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS, comparing between MT rats with and without PKCã knockdown. The DEPs identified have roles in the cytoskeleton, as neurotrophic factors, in oxidative stress, in ion metabolism, in cell signaling, and as chaperones. Three DEPs (GFAP, FSCN and GDNF were validated with Western blot analysis, confirming the DEP data. Furthermore, using immunohistochemical analysis, we reveal for the first time that FSCN is involved in the development of morphine tolerance. CONCLUSIONS/SIGNIFICANCE: These data cast light on the proteins associated with the PKCã activity during morphine tolerance, and hence may contribute to clarification of the mechanisms by which PKCã influences MT.

  17. Review of various liver retraction techniques in single incision laparoscopic surgery for the exposure of hiatus.

    Science.gov (United States)

    Palanivelu, Praveenraj; Patil, Kedar Pratap; Parthasarathi, Ramakrishnan; Viswambharan, Jaiganesh K; Senthilnathan, Palanisami; Palanivelu, Chinnusamy

    2015-01-01

    The main aspect of concern for upper GI procedures has been the retraction of the liver especially large left lobes as commonly encountered in Bariatric surgery. Not doing so would compromise the view of the hiatus, hence theoretically reducing the quality of the surgery and increasing the possibility of complications. The aim of this study was to review the various liver retraction techniques in single incision surgery being done at our institute and analyze them. A retrospective study of the various techniques and a subsequent analysis was made based on advantages and disadvantages of each method. Objectively a quantitative measure of hiatal exposure was done using a scoring system based on the grade of exposure after reviewing the surgical videos. From January 2011 to January 2013 total 104 patients underwent single incision surgery with the various liver retraction techniques with following grades of exposure -liver suspension tube technique with naso gastric tubing (2.11) and with corrugated drain (2.09) needlescopic method (1.2), Umbilical tape sling (1.95), crural stitch method (2.5). Needeloscopic method has the best grade of exposure and is the easiest to start with. The average time to create the liver retraction was 2.8 to 8.6 min.There was no procedure related morbidity or mortality. The mentioned liver retraction techniques are cost effective and easy to learn. We recommend using these techniques to have a good exposure of hiatus, without compromising the safety of surgery in single incision surgery.

  18. Comparison of efficacy of dexketoprofen versus paracetamol on postoperative pain and morphine consumption in laminectomy patients.

    Science.gov (United States)

    Kesimci, Elvin; Gümüş, Tülin; Izdeş, Seval; Sen, Pelin; Kanbak, Orhan

    2011-10-01

    The aim of this prospective randomized, double-blind study was to evaluate the analgesic efficacy and opioid-sparing effects of preemptive single dose of dexketoprofen trometamol in comparison with that of paracetamol or placebo for elective lumbar disc surgery, over a 24-hour (h) investigation period. After institutional approval and informed consent had been obtained, 75 patients scheduled for single level lumbar disc surgery were randomly allocated into three equal groups. Patients received oral dexketoprofen 25 mg (Group D), 500 mg paracetamol (Group P) or placebo tablets (Group C) 30 minutes (min) before induction of standard anesthesia. Patient-controlled analgesia was supplied postoperatively using morphine. Hemodynamics, visual analogue scale (VAS), sedation score, morphine consumption, and side effects were recorded every 15 min in the first hour and at 2, 6 and 24 h after surgery. The mean pain scores were similar among groups (p>0.05). The cumulative (SD) 24-h morphine consumption was 28.1 mg, 40.6 mg, and 43.6 mg for Groups D, P and C, respectively. The amount of morphine use at 2, 6 and 24 h was significantly lower in Group D (p0.05). The study demonstrated that preemptive dexketoprofen trometamol 25 mg is associated with a decrease of up to 35% in morphine consumption compared with placebo over the first 24 h following lumbar disc surgery; however, paracetamol 500 mg did not show the expected opioid-sparing effect comparatively.

  19. The effect of morphine on biliary dynamics

    International Nuclear Information System (INIS)

    Pedersen, S.A.; Oester-Joergensen, E.; Kraglund, K.

    1987-01-01

    The effect of morphine on biliary dynamics was studied by cholescintigraphy with 99m Tc-HIDA. Among 30 normals without morphine injection 3 did not demonstrate intestinal radioactivity after 1 h, whereas all visualized the gallbladder. Eight normals with morphine injection did not demonstrate intestinal radioactivity after 2 h, but all had gallbladder visualization very early. Variables of the time-activity curves from liver areas did not point to impaired uptake or excretion. Morphine-induced increase in resistance to passage from the common duct to the intestines in normals is of a magnitude that forces the total amount of bile to accumulate in the gallbladder. Results from 11 patients after cholecystectomy indicate that the increase in pressure is less than the maximal secretory pressure of the liver. The resorptive capacity and the compliance of the gallbladder enable these events to take place without signs of secondary liver impairment

  20. Neural Circuits via Which Single Prolonged Stress Exposure Leads to Fear Extinction Retention Deficits

    Science.gov (United States)

    Knox, Dayan; Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

    2016-01-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions…

  1. A single exposure to photochemical smog causes airway irritation and cardiac dysrhythmia in mice

    Science.gov (United States)

    The data presented here shows that a single exposure to photochemical smog causes airway irritation and cardiac dysrhythmia in mice. Smog, which is a complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components whi...

  2. A neuropeptide FF agonist blocks the acquisition of conditioned place preference to morphine in C57Bl/6J mice.

    Science.gov (United States)

    Marchand, Stéphane; Betourne, Alexandre; Marty, Virginie; Daumas, Stéphanie; Halley, Hélène; Lassalle, Jean-Michel; Zajac, Jean-Marie; Frances, Bernard

    2006-05-01

    Neuropeptide FF behaves as an opioid-modulating peptide that seems to be involved in morphine tolerance and physical dependence. Nevertheless, the effects of neuropeptide FF agonists on the rewarding properties of morphine remain unknown. C57BL6 mice were conditioned in an unbiased balanced paradigm of conditioned place preference to study the effect of i.c.v. injections of 1DMe (D-Tyr1(NMe)Phe3]NPFF), a stable agonist of the neuropeptide FF system, on the acquisition of place conditioning by morphine or alcohol (ethanol). Morphine (10 mg/kg, i.p.) or ethanol (2 g/kg, i.p.) induced a significant place preference. Injection of 1DMe (1-20 nmol), given 10 min before the i.p. injection of the reinforcing drug during conditioning, inhibited the rewarding effect of morphine but had no effect on the rewarding effect of ethanol. However, a single injection of 1DMe given just before place preference testing was unable to inhibit the rewarding effects of morphine. By itself, 1DMe was inactive but an aversive effect of this agonist could be evidenced if the experimental procedure was biased. These results suggest that neuropeptide FF, injected during conditioning, should influence the development of rewarding effects of morphine and reinforce the hypothesis of strong inhibitory interactions between neuropeptide FF and opioids.

  3. The physiological consequences of varied heat exposure events in adult Myzus persicae: a single prolonged exposure compared to repeated shorter exposures

    Directory of Open Access Journals (Sweden)

    Behnaz Ghaedi

    2016-08-01

    Full Text Available The study of environmental stress tolerance in aphids has primarily been at low temperatures. In these cases, and in the rare cases of high temperature tolerance assessments, all exposures had been during a single stress event. In the present study, we examined the physiological consequences of repeated high temperature exposure with recovery periods between these stress events in Myzus persicae. We subjected individuals to either a single prolonged three hour heating event, or three one hour heating events with a recovery time of 24 h between bouts. Aphids exposed to repeated bouts of high temperatures had more glucose and higher expression of proteins and osmolyte compounds, such as glycerol, compared to the prolonged exposure group. However, aphids exposed to the repeated high temperature treatment had reduced sources of energy such as trehalose and triglyceride compounds than the prolonged exposure group. Recovery time had more physiological costs (based on production of more protein and consumption of more trehalose and triglyceride and benefits (based on production of more osmolytes in repeated high temperature treatments. As aphids are known to respond differently to constant versus ‘natural’ fluctuating temperature regimes, conclusions drawn from constant temperature data sets may be problematic. We suggest future experiments assessing insect responses to thermal stress incorporate a repeated stress and recovery pattern into their methodologies.

  4. The physiological consequences of varied heat exposure events in adult Myzus persicae: a single prolonged exposure compared to repeated shorter exposures

    Science.gov (United States)

    Andrew, Nigel R.

    2016-01-01

    The study of environmental stress tolerance in aphids has primarily been at low temperatures. In these cases, and in the rare cases of high temperature tolerance assessments, all exposures had been during a single stress event. In the present study, we examined the physiological consequences of repeated high temperature exposure with recovery periods between these stress events in Myzus persicae. We subjected individuals to either a single prolonged three hour heating event, or three one hour heating events with a recovery time of 24 h between bouts. Aphids exposed to repeated bouts of high temperatures had more glucose and higher expression of proteins and osmolyte compounds, such as glycerol, compared to the prolonged exposure group. However, aphids exposed to the repeated high temperature treatment had reduced sources of energy such as trehalose and triglyceride compounds than the prolonged exposure group. Recovery time had more physiological costs (based on production of more protein and consumption of more trehalose and triglyceride) and benefits (based on production of more osmolytes) in repeated high temperature treatments. As aphids are known to respond differently to constant versus ‘natural’ fluctuating temperature regimes, conclusions drawn from constant temperature data sets may be problematic. We suggest future experiments assessing insect responses to thermal stress incorporate a repeated stress and recovery pattern into their methodologies. PMID:27547583

  5. Microdialysis evidence that acetylcholine in the nucleus accumbens is involved in morphine withdrawal and its treatment with clonidine.

    Science.gov (United States)

    Rada, P; Pothos, E; Mark, G P; Hoebel, B G

    1991-10-11

    This study used microdialysis to measure changes in extracellular acetylcholine (ACh) content in the nucleus accumbens (NAC) of freely moving rats during acute and chronic morphine treatment, and following naloxone-precipitated withdrawal. Morphine injection (20 mg/kg, i.p.) caused a significant decrease in extracellular ACh which was not apparent after repeated exposure to the opiate for 7 days. Basal recovery of ACh was not altered by chronic morphine treatment. On day 8, after morphine dependence had been established, naloxone caused a large increase in ACh levels accompanied by withdrawal symptoms such as wet dog shakes, diarrhea and teeth-chattering. Pretreatment with clonidine (200 micrograms/kg, i.p.) reduced these withdrawal symptoms and eliminated the ACh response. These results suggest that accumbens ACh is involved in some of the aversive aspects of opiate withdrawal.

  6. Changes in lymphocyte and macrophage subsets due to morphine and ethanol treatment during a retrovirus infection causing murine AIDS

    Energy Technology Data Exchange (ETDEWEB)

    Watson, R.R.; Prabhala, R.H.; Darban, H.R.; Yahya, M.D.; Smith, T.L.

    1988-01-01

    The number of lymphocytes of various subsets were not significantly changed by the ethanol exposure except those showing activation markers which were reduced. The percentage of peripheral blood cells showing markers for macrophage functions and their activation were significantly reduced after binge use of ethanol. Ethanol retarded suppression of cells by retroviral infection. However by 25 weeks of infection there was a 8.6% survival in the ethanol fed mice infected with retrovirus which was much less than virally infected controls. Morphine treatment also increased the percentage of cells with markers for macrophages and activated macrophages in virally infected mice, while suppressing them in uninfected mice. The second and third morphine injection series suppressed lymphocyte T-helper and T-suppressor cells, but not total T cells. However, suppression by morphine was significantly less during retroviral disease than suppression caused by the virus only. At 25 weeks of infection 44.8% of morphine treated, infected mice survived.

  7. Can coadministration of oxycodone and morphine produce analgesic synergy in humans? An experimental cold pain study.

    Science.gov (United States)

    Grach, Michael; Massalha, Wattan; Pud, Dorit; Adler, Rivka; Eisenberg, Elon

    2004-09-01

    The coadministration of subantinociceptive doses of oxycodone with morphine has recently been shown to result in a synergistic antinociceptive effect in rats. The present study was aimed to investigate the possibility that coadministration of morphine and oxycodone can produce a similar synergistic effect in humans exposed to an experimental model of cold pressor test (CPT). The enriched enrollment design was used to exclude 'stoic' and 'placebo responders' in a single-blind fashion. 'Nonstoic', placebo 'nonresponder' female volunteers (n = 30) were randomly assigned to receive 0.5 mg kg(-1) oral morphine sulphate, 0.5 mg kg(-1) oral oxycodone hydrochloride, and the combination of 0.25 mg kg(-1) morphine sulphate with 0.25 mg kg(-1) oxycodone hydrochloride, 1 week apart from each other, in a double-blind crossover design. Latency to pain onset (threshold), pain intensity (VAS), and pain tolerance (time until removal of the hand from the water) were measured six times over a 3-h period, subsequent to the administration of each medication, and were used to assess their antinociceptive effect. The combination produced a significantly higher effect on latency to pain onset than that of morphine alone [difference in mean postbaseline value 2.2; 95% confidence interval (CI) 0.48, 3.9; P = 0.01] but the effect was nonsignificantly smaller that that of oxycodone alone. Similarly, the effect of the combination on pain tolerance was significantly larger than that of morphine alone (combination difference 8.4; 95% CI 2.5, 14.3; P = 0.007), whereas oxycodone alone caused a nonsignificantly larger effect than that of the combination treatment. Comparisons of pain magnitude failed to show any significant differences between the three treatments. These results indicate that at the doses tested, morphine and oxycodone do not produce synergistic antinociceptive effects in healthy humans exposed to the CPT.

  8. Population Pharmacokinetics of Morphine and Morphine-6-Glucuronide following Rectal Administration -A Dose Escalation Study

    DEFF Research Database (Denmark)

    Brokjær, Anne; Kreilgaard, Mads; Olesen, Anne Estrup

    2014-01-01

    cm from the anal verge. A 2 mg morphine hydrochloride dose was administered intravenously as reference. Blood samples were drawn at baseline and at nine time points post dosing. Serum was obtained by centrifugation and assayed for contents of morphine and M6G with a validated high performance liquid...

  9. Bioactivation of morphine-3-propionate, a prodrug of morphine, in tissues from different species

    DEFF Research Database (Denmark)

    Groth, L.; Jørgensen, A.; Steffansen, B.

    1997-01-01

    The bioactivation of the morphine prodrug, morphine-3-propionate, has been evaluated by determination of the first-order hydrolysis rate in different tissue homogenates and blood fractions from various mammal species, including man. The hydrolysis rates were determined in whole blood, serum...

  10. Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence

    Directory of Open Access Journals (Sweden)

    Wen Di

    2012-06-01

    Full Text Available Abstract Background Cholecystokinin octapeptide (CCK-8, the most potent endogenous anti-opioid peptide, has been shown to regulate the processes of morphine dependence. In our previous study, we found that exogenous CCK-8 attenuated naloxone induced withdrawal symptoms. To investigate the precise effect of exogenous CCK-8 and the role of cholecystokinin (CCK 1 and/or 2 receptors in morphine dependence, a SH-SY5Y cell model was employed, in which the μ-opioid receptor, CCK1/2 receptors, and endogenous CCK are co-expressed. Results Forty-eight hours after treating SH-SY5Y cells with morphine (10 μM, naloxone (10 μM induced a cAMP overshoot, indicating that cellular morphine dependence had been induced. The CCK receptor and endogenous CCK were up-regulated after chronic morphine exposure. The CCK2 receptor antagonist (LY-288,513 at 1–10 μM inhibited the naloxone-precipitated cAMP overshoot, but the CCK1 receptor antagonist (L-364,718 did not. Interestingly, CCK-8 (0.1-1 μM, a strong CCK receptor agonist, dose-dependently inhibited the naloxone-precipitated cAMP overshoot in SH-SY5Y cells when co-pretreated with morphine. The L-364,718 significantly blocked the inhibitory effect of exogenous CCK-8 on the cAMP overshoot at 1–10 μM, while the LY-288,513 did not. Therefore, the CCK2 receptor appears to be necessary for low concentrations of endogenous CCK to potentiate morphine dependence in SH-SY5Y cells. An additional inhibitory effect of CCK-8 at higher concentrations appears to involve the CCK1 receptor. Conclusions This study reveals the difference between exogenous CCK-8 and endogenous CCK effects on the development of morphine dependence, and provides the first evidence for the participation of the CCK1 receptor in the inhibitory effects of exogenous CCK-8 on morphine dependence.

  11. The Effect of Ethanol Extract of Aerial Parts of the Mentha piperita in the Acquisition, Tolerance Expression and Dependence to Morphine in Adult Male Mice

    Directory of Open Access Journals (Sweden)

    N Khajeh

    2015-04-01

    Full Text Available Background & aim: Morphine dependence is a compulsive pattern of drug taking, resulting from the positive reinforcement of the rewarding effects of drug taking and the negative reinforcement of withdrawal syndrome that accompanies the cessation of drug taking. The objective of this study was to investigate the effect of ethanol extract of aerial parts of the Mentha piperita in the acquisition, tolerance expression and dependence to morphine in adult male mice Methods: In the present study, 75 NMRI mice were divided into fifiteen groups. The Hot-plate test was used to survey the morphine activity. Morphine was injected (2.5, 5, 10, 20, 40 mg/kg, i.p. twice daily for seven days, except in 8th day in which morphine was administrated at a single dose (50 mg/kg. The extract (50, 75, 100 mg/kg was injected for eight days. The control animals were intact, and sham animals only received morphine. Naloxone was injected (10 mg/kg five hours after the final dose of morphine and the withdrawal signs were recorded during a 30 minute period. The data were expressed as mean values ± SEM and tested, using analysis of one-way ANOVA test. Results: Peppermint extract at doses of 75 and 100 kg significantly improved the tolerance expression and dependence to morphine in animals and significantly reduced the symptoms of withdrawal. Conclusion: Peppermint extract was commuted morphine tolerance and dependence in mice.The plant contained component(s that alleviate morphine withdrawal syndrome. The extract possibly be effective in improving tolerance to morphine.

  12. Effects of casoxin 4 on morphine inhibition of small animal intestinal contractility and gut transit in the mouse

    Directory of Open Access Journals (Sweden)

    Glen S Patten

    2011-02-01

    Full Text Available Glen S Patten1,2, Richard J Head1, Mahinda Y Abeywardena1,21CSIRO Preventative Health National Research Flagship, Adelaide, Australia; 2CSIRO Food and Nutritional Sciences, Adelaide, AustraliaBackground and aims: Chronic opioid analgesia has the debilitating side-effect of constipation in human patients. The major aims of this study were to: 1 characterize the opioid-specific antagonism of morphine-induced inhibition of electrically driven contraction of the small intestine of mice, rats, and guinea pigs; and 2 test if the oral delivery of small milk-derived opioid antagonist peptides could block morphine-induced inhibition of intestinal transit in mice.Methods: Mouse, rat, and guinea pig intact ileal sections were electrically stimulated to contract and inhibited with morphine in vitro. Morphine inhibition was then blocked by opioid subtype antagonists in the mouse and guinea pig. Using a polymeric dye, Poly R-478, the opioid antagonists casoxin 4 and lactoferroxin A were tested orally for blocking activity of morphine inhibition of gut transit in vivo by single or double gavage techniques.Results: The guinea pig tissue was more sensitive to morphine inhibition compared with the mouse or the rat (IC50 [half maximal inhibitory concentration] values as nmol/L ± SEM were 34 ± 3, 230 ± 13, and 310 ± 14 respectively (P < 0.01. The inhibitory influence of opioid agonists (IC50 in electrically driven ileal mouse preparations were DADLE ([D-Ala2, D-Leu5]-enkephalin ≥ met-enkephalin ≥ dynorphin A ≥ DAMGO ([D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin > morphine > morphiceptin as nmol/L 13.9, 17.3, 19.5, 23.3, 230, and 403 respectively. The mouse demonstrated predominantly Κ- and δ-opioid receptor activity with a smaller µ-opioid receptor component. Both mouse and guinea pig tissue were sensitive to casoxin 4 antagonism of morphine inhibition of contraction. In contrast to naloxone, relatively high oral doses of the µ-opioid receptor antagonists

  13. Speckle noise suppression using part of pixels in a single-exposure digital hologram

    Science.gov (United States)

    Leng, Junmin; Zhou, Zhehai; Li, Fubing; Zheng, Qingyu; Liu, Gang

    2017-05-01

    A method is proposed to suppress speckle noise using only part of the pixels in a single-exposure digital hologram. Different holographic patterns are first generated from a single-exposure digital hologram using specially designed binary masks; then, these holographic patterns are reconstructed according to the Fresnel transform. The reconstructed images are superposed and averaged on the intensity to achieve the suppression of speckle noise. The entire denoising process does not need any additional digital holograms or specific requirements for recording a hologram. Theoretical simulation and experiment verification were carried out and confirm that the proposed method is a very convenient and effective way to suppress speckle noise in digital holography. The proposed method has wide applications in holographic imaging, holographic storage, and art display.

  14. Glyphosate accumulation, translocation, and biological effects in Coffea arabica after single and multiple exposures

    DEFF Research Database (Denmark)

    Schrübbers, Lars Christoph; Valverde, Bernal E.; Strobel, Bjarne W.

    2016-01-01

    In perennial crops like coffee, glyphosate drift exposure can occur multiple times during its commercial life span. Due to limited glyphosate degradation in higher plants, a potential accumulation of glyphosate could lead to increased biological effects with increased exposure frequency...... of application, however, was more important regarding biological effects than the number of applications both in the greenhouse and in the field. In the field, berry yield, the most important biological response variable, was reduced 26% by the first out of four sequential applications of glyphosate at 64 g a....... In this study, we investigated glyphosate translocation over time, and its concentration and biological effects after single and multiple simulated spray-drift exposures. Additionally, shikimic acid/glyphosate ratios were used as biomarkers for glyphosate binding to its target enzyme.Four weeks after...

  15. Review of various liver retraction techniques in single incision laparoscopic surgery for the exposure of hiatus

    Directory of Open Access Journals (Sweden)

    Praveenraj Palanivelu

    2015-01-01

    Full Text Available Background: The main aspect of concern for upper GI procedures has been the retraction of the liver especially large left lobes as commonly encountered in Bariatric surgery. Not doing so would compromise the view of the hiatus, hence theoretically reducing the quality of the surgery and increasing the possibility of complications. The aim of this study was to review the various liver retraction techniques in single incision surgery being done at our institute and analyze them. Material and Methods: A retrospective study of the various techniques and a subsequent analysis was made based on advantages and disadvantages of each method. Objectively a quantitative measure of hiatal exposure was done using a scoring system based on the grade of exposure after reviewing the surgical videos. From January 2011 to January 2013 total 104 patients underwent single incision surgery with the various liver retraction techniques with following grades of exposure -liver suspension tube technique with naso gastric tubing (2.11 and with corrugated drain (2.09 needlescopic method (1.2, Umbilical tape sling (1.95, crural stitch method (2.5. Needeloscopic method has the best grade of exposure and is the easiest to start with. The average time to create the liver retraction was 2.8 to 8.6 min.There was no procedure related morbidity or mortality. Conclusions: The mentioned liver retraction techniques are cost effective and easy to learn. We recommend using these techniques to have a good exposure of hiatus, without compromising the safety of surgery in single incision surgery.

  16. Pulmonary Responses of Sprague-Dawley Rats in Single Inhalation Exposure to Graphene Oxide Nanomaterials

    Directory of Open Access Journals (Sweden)

    Sung Gu Han

    2015-01-01

    Full Text Available Graphene is receiving increased attention due to its potential widespread applications in future. However, the health effects of graphene have not yet been well studied. Therefore, this study examined the pulmonary effects of graphene oxide using male Sprague-Dawley rats and a single 6-hour nose-only inhalation technique. Following the exposure, the rats were allowed to recover for 1 day, 7 days, or 14 days. A total of three groups were compared: control (fresh air, low concentration (0.46±0.06 mg/m3, and high concentration (3.76±0.24 mg/m3. The exposure to graphene oxide did not induce significant changes in the body weights, organ weights, and food consumption during the 14 days of recovery time. The microalbumin and lactate dehydrogenase levels in the bronchoalveolar lavage (BAL fluid were not significantly changed due to the exposure. Similarly, total cell count, macrophages, polymorphonuclear leukocytes, and lymphocytes were not significantly altered in the BAL fluid. Plus, the histopathological examination of the rat lungs only showed an uptake of graphene oxide in the alveolar macrophages of the high-concentration group. Therefore, these results demonstrate that the single inhalation exposure to graphene oxide induce minimal toxic responses in rat lungs at the concentrations and time points used in the present study.

  17. Chronic ethanol consumption causes increased glucuronidation of morphine in rabbits.

    Science.gov (United States)

    Narayan, S S; Hayton, W L; Yost, G S

    1991-04-01

    1. Male rabbits were given an i.p. injection of 15 mg/kg morphine and plasma concentrations of morphine and morphine-3-glucuronide (M3G) were simultaneously quantified by h.p.l.c. After 14 days of 10% ethanol in the rabbits' drinking water, a second injection of morphine was administered and plasma concentrations were determined again. 2. Morphine plasma clearance increased significantly by 42% after ethanol treatment. The area under the plasma concentration time curve (AUC) for morphine decreased by 23% while the AUC for the glucuronide increased by 22%. 3. The ratio of the AUCs (glucruonide/morphine) increased by 72%. These results demonstrate that chronic ethanol treatment of rabbits results in increased clearance of morphine after an i.p. dose. The increase in clearance is most likely due to induction of UDP-glucuronosyltransferase isozymes by ethanol.

  18. Morphine induces expression of platelet-derived growth factor in human brain microvascular endothelial cells: implication for vascular permeability.

    Directory of Open Access Journals (Sweden)

    Hongxiu Wen

    Full Text Available Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Morphine, often abused by HIV-infected patients, is known to accelerate neuroinflammation associated with HIV-1 infection. Detailed molecular mechanisms of morphine action however, remain poorly understood. Platelet-derived growth factor (PDGF has been implicated in a number of pathological conditions, primarily due to its potent mitogenic and permeability effects. Whether morphine exposure results in enhanced vascular permeability in brain endothelial cells, likely via induction of PDGF, remains to be established. In the present study, we demonstrated morphine-mediated induction of PDGF-BB in human brain microvascular endothelial cells, an effect that was abrogated by the opioid receptor antagonist-naltrexone. Pharmacological blockade (cell signaling and loss-of-function (Egr-1 approaches demonstrated the role of mitogen-activated protein kinases (MAPKs, PI3K/Akt and the downstream transcription factor Egr-1 respectively, in morphine-mediated induction of PDGF-BB. Functional significance of increased PDGF-BB manifested as increased breach of the endothelial barrier as evidenced by decreased expression of the tight junction protein ZO-1 in an in vitro model system. Understanding the regulation of PDGF expression may provide insights into the development of potential therapeutic targets for intervention of morphine-mediated neuroinflammation.

  19. Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

    Science.gov (United States)

    Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

    2012-01-01

    Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

  20. Effects of sleep deprivation on retrieval and reconsolidation of morphine reward memory in rats.

    Science.gov (United States)

    Shi, Hai-Shui; Luo, Yi-Xiao; Xue, Yan-Xue; Wu, Ping; Zhu, Wei-Li; Ding, Zeng-Bo; Lu, Lin

    2011-04-01

    Relapse induced by exposure to cues associated with drugs of abuse is a major challenge to the treatment of drug addiction. Drug seeking can be inhibited by manipulation of the reconsolidation of drug-related memory. Sleep has been proposed to be involved in various memory processes. However, the role of sleep in drug reward memory is not clear. The present study used conditioned place preference to examine the effects of total sleep deprivation on retrieval and reconsolidation of morphine reward memory in rats. Six-hour total sleep deprivation had no effect on the retrieval of morphine reward memory. However, sleep deprivation from 0-6 h, but not 6-12 h, after re-exposure disrupted the reconsolidation of morphine reward memory. This impairment was not attributable to the formation of an aversive associative memory between the drug-paired context and sleep deprivation. Our findings suggest that sleep plays a critical role in morphine reward memory reconsolidation, and sleep deprivation may be a potential non-pharmacotherapy for the management of relapse associated with drug-related memory. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. An experience with epidural morphine in lumbar surgery patients.

    Science.gov (United States)

    Ozuna, J; Snyder, G

    1987-10-01

    A chart review of the patients who received epidural morphine for lumbar surgery during the first year of implementation of the procedure was conducted. This article reviews the pharmacology and side effects of epidural morphine, describes the procedure of administering epidural morphine, discusses side effects and technical problems encountered, and presents implications for nursing practice.

  2. Nalbuphine added to intrathecal morphine in total knee arthroplasty ...

    African Journals Online (AJOL)

    Introduction: Intrathecal morphine is widely used for postoperative pain control in major orthopaedic surgery. However, its use is associated with frequent side effects. Aim of the work: Aim of the work was to investigate the effects of intrathecal coadministration of nalbuphine with intrathecal morphine on morphine related side ...

  3. Exposure buildup factors for a cobalt-60 point isotropic source for single and two layer slabs

    International Nuclear Information System (INIS)

    Chakarova, R.

    1992-01-01

    Exposure buildup factors for point isotropic cobalt-60 sources are calculated by the Monte Carlo method with statistical errors ranging from 1.5 to 7% for 1-5 mean free paths (mfp) thick water and iron single slabs and for 1 and 2 mfp iron layers followed by water layers 1-5 mfp thick. The computations take into account Compton scattering. The Monte Carlo data for single slab geometries are approximated by Geometric Progression formula. Kalos's formula using the calculated single slab buildup factors may be applied to reproduce the data for two-layered slabs. The presented results and discussion may help when choosing the manner in which the radiation field gamma irradiation units will be described. (author)

  4. No morphine sparing effect of ketamine added to morphine for patient-controlled intravenous analgesia after uterine artery embolization

    DEFF Research Database (Denmark)

    Jensen, Luana Leonora; Handberg, Gitte; Helbo-Hansen, H S

    2008-01-01

    group, n=26) by i.v. patient-controlled analgesia (IV-PCA). Pump settings were bolus dose 1 ml, lockout 10 min, no background infusion. In addition, all patients received diclofenac and acetaminophen for pain relief. Pain scores, morphine consumption and adverse events like nausea, vomiting, itching...... conditions of basal analgesia with acetaminophen and diclofenac, we failed to demonstrate any morphine-sparing effect of IV-PCA ketamine and morphine compared with IV-PCA morphine alone....

  5. B Vitamins Potentiate Acute Morphine Antinociception and Attenuate the Development of Tolerance to Chronic Morphine in Mice.

    Science.gov (United States)

    Deng, Xue-Ting; Han, Yuan; Liu, Wen-Tao; Song, Xue-Jun

    2017-10-01

    Opiate analgesics are the most effective treatments for severe pain, but their clinical utility is often hampered by the development of analgesic tolerance. There are striking similarities between morphine actions and neuropathic pain. We have demonstrated that B vitamins can attenuate neuropathic pain after peripheral nerve injury, sensory neuron inflammation/compression, and transient spinal cord ischemia. Given this similarity, the present study investigated whether B vitamins might be able to modify the antinociceptive effect of morphine as well as morphine tolerance in mice. Cell signaling was assayed by Western blot and immunohistochemistry. Antinociception was assessed in ICR mice using the tail flick. The effects of B vitamins on acute morphine-induced antinociception and chronic morphine tolerance were studied. 1) Co-administration of B vitamins with morphine potentiates acute morphine antinociception. 2) B vitamins attenuate the development of antinociceptive tolerance to chronic morphine administration and inhibit morphine-induced p-NR1, p-PKC in the spinal cord. 3) Morphine induces microglial activation, as evidenced by increased p38 MAPK phosphorylation, IBA1, and IL-1β in the spinal cord, and these changes are inhibited by B vitamins. 4) Treatment of B vitamins alone shows no notable effects on pain threshold and activity of microglia invivo. B vitamins potentiate acute morphine antinociception and attenuate chronic morphine tolerance. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  6. Ultra-low doses of naltrexone or etorphine increase morphine's antinociceptive potency and attenuate tolerance/dependence in mice.

    Science.gov (United States)

    Shen, K F; Crain, S M

    1997-05-23

    In previous studies we showed that low (pM) concentrations of naloxone (NLX), naltrexone (NTX) or etorphine selectively antagonize excitatory, but not inhibitory, opioid receptor-mediated functions in nociceptive types of sensory neurons in culture. Cotreatment of these neurons with pM NTX or etorphine not only results in marked enhancement of the inhibitory potency of acutely applied nM morphine [or other bimodally-acting (inhibitory/excitatory) opioid agonists], but also prevents development of cellular manifestations of tolerance and dependence during chronic exposure to microM morphine. These in vitro studies were confirmed in vivo by demonstrating that acute cotreatment of mice with morphine plus a remarkably low dose of NTX (ca. 10 ng/kg) does, in fact, enhance the antinociceptive potency of morphine, as measured by hot-water tail-flick assays. Furthermore, chronic cotreatment of mice with morphine plus low doses of NTX markedly attenuates development of naloxone-precipitated withdrawal-jumping in physical dependence assays. The present study provides systematic dose-response analyses indicating that NTX elicited optimal enhancement of morphine's antinociceptive potency in mice when co-administered (i.p.) at about 100 ng/kg together with morphine (3 mg/kg). Doses of NTX as low as 1 ng/kg or as high as 1 microg/kg were still effective, but to a lesser degree. Oral administration of NTX in the drinking water of mice was equally effective as i.p. injections in enhancing the antinociceptive potency of acute morphine injections and even more effective in attenuating development of tolerance and NLX-precipitated withdrawal-jumping during chronic cotreatment. Cotreatment with a subanalgesic dose of etorphine (10 ng/kg) was equally effective as NTX in enhancing morphine's antinociceptive potency and attenuating withdrawal-jumping after chronic exposure. These studies provide a rationale for the clinical use of ultra-low-dose NTX or etorphine so as to increase the

  7. Importance of GluA1 subunit-containing AMPA glutamate receptors for morphine state-dependency.

    Directory of Open Access Journals (Sweden)

    Teemu Aitta-aho

    Full Text Available In state-dependency, information retrieval is most efficient when the animal is in the same state as it was during the information acquisition. State-dependency has been implicated in a variety of learning and memory processes, but its mechanisms remain to be resolved. Here, mice deficient in AMPA-type glutamate receptor GluA1 subunits were first conditioned to morphine (10 or 20 mg/kg s.c. during eight sessions over four days using an unbiased procedure, followed by testing for conditioned place preference at morphine states that were the same as or different from the one the mice were conditioned to. In GluA1 wildtype littermate mice the same-state morphine dose produced the greatest expression of place preference, while in the knockout mice no place preference was then detected. Both wildtype and knockout mice expressed moderate morphine-induced place preference when not at the morphine state (saline treatment at the test; in this case, place preference was weaker than that in the same-state test in wildtype mice. No correlation between place preference scores and locomotor activity during testing was found. Additionally, as compared to the controls, the knockout mice showed unchanged sensitization to morphine, morphine drug discrimination and brain regional μ-opioid receptor signal transduction at the G-protein level. However, the knockout mice failed to show increased AMPA/NMDA receptor current ratios in the ventral tegmental area dopamine neurons of midbrain slices after a single injection of morphine (10 mg/kg, s.c., sliced prepared 24 h afterwards, in contrast to the wildtype mice. The results indicate impaired drug-induced state-dependency in GluA1 knockout mice, correlating with impaired opioid-induced glutamate receptor neuroplasticity.

  8. Rifampin reduces oral morphine absorption: a case of transdermal buprenorphine selection based on morphine pharmacokinetics.

    Science.gov (United States)

    Fudin, Jeffrey; Fontenelle, Dania Vanesta; Payne, Annette

    2012-12-01

    A 51-year-old male was referred to the Stratton Veterans Affairs Medical Center Pain Service after hospital admission for endocarditis with a history of heroin use and chronic low back pain. During his hospital stay he experienced a reduction in his serum morphine level ostensibly as a result of concomitant rifampin administration. We hypothesize that diminished absorption was from rifampin-mediated intestinal P-glycoprotein induction, ultimately decreasing serum free morphine and metabolites. The case became more complex in an attempt to balance managed pain, history of substance abuse, completion of antibiotic therapy, and a reasonable pain regimen upon discharge. Ultimately, the patient was titrated onto a buprenorphine transdermal patch, the initiation of which was based on serum free morphine and an extrapolated oral morphine dose by calculation.

  9. Methadone versus morphine for treatment of neonatal abstinence syndrome: a prospective randomized clinical trial.

    Science.gov (United States)

    Brown, M S; Hayes, M J; Thornton, L M

    2015-04-01

    Compare duration of treatment of neonatal abstinence syndrome between methadone and morphine. A prospective, double-masked, randomized trial at a single site. Randomization of methadone or morphine was stratified for maternal treatment with methadone or buprenorphine. Inclusion criteria were (i) maternal treatment with prescribed methadone or buprenorphine, (ii) withdrawal treatment criteria, (iii) adjusted gestational age ⩾35(0/7) weeks and (iv) medically stable. Primary outcome was length of opioid treatment. From January 2011 through October 2012, 78 infants were eligible for the study: 41 methadone-exposed and 37 buprenorphine-exposed. Consent was obtained from 31 mothers, 13/41 (32%) methadone-treated and 18/37 (49%) buprenorphine-treated. Length of opioid treatment was significantly shorter for methadone than morphine treatment, median 14 versus 21 days (P=0.008). Methadone had a shorter length of neonatal withdrawal treatment compared with morphine. Owing to the smaller sample size and single site, a larger randomized study is needed.

  10. Blockade of the Naloxone-induced Aversion in Morphine-conditioned Wistar Rats by L-Arginine Intra-central Amygdala

    Directory of Open Access Journals (Sweden)

    Mahnaz Rahimpour

    2011-03-01

    Full Text Available AbstractObjective(sSingle injection of naloxone, a selective antagonist of morphine, prior to the drug conditioning testing was used to investigate on morphine dependence.Materials and MethodsConditioning to morphine (2.5-10 mg/kg, s.c. was established in adult male Wistar rats (weighing 200-250 g using an unbiased procedure. Nitric oxide agents were microinjected into the central amygdala prior to naloxone-paired place conditioning testing.ResultsThe results showed that morphine produced a significant dose-dependent place preference in animals. Naloxone (0.1-0.4 mg/kg, i.p. injections pre-testing of the response to morphine (7.5 mg/kg, s.c. caused a significant aversion at the higher doses (0.4 mg/kg, i.p.. This response was reversed by microinjection of L-arginine (0.3-3 µg/rat, intra-central amygdala prior to naloxone on the day of the testing. The response to L-arginine was blocked by pre-injection of NG-nitro-L-arginine methyl ester (L-NAME (intra-central amygdala.ConclusionA single injection of naloxone on the test day of morphine place conditioning may simply reveal the occurrence of morphine dependence in rats, and that the nitric oxide in the central amygdala most likely plays a key role in this phenomenon.

  11. Morphine and oxycodone in the management of cancer pain

    International Nuclear Information System (INIS)

    Kalso, E.; Vainio, A.; Rosenberg, P.H.; Mattila, M.J.; Seppaelae, T.

    1990-01-01

    Morphine and oxycodone were administered to ten patients suffering from severe cancer pain in a double-blind cross-over study. The patients titrated themselves pain-free, first intravenously, using a patient-controlled analgesia device, and then orally. Each titration phase lasted for 48 hours. Blood samples were drawn after 36 hr of each administration phase. The plasma levels of morphine, morphine-6- and morphine-3 glucuronides were determined with high performance liquid chromatography (HPLC), whereas the oxycodone samples were assayed with gas chromatography (GC). Twin samples were analyzed for plasma opioid activity with a radioreceptor assay (RRA) using 3 H-dihydromorphien and 3 H-naloxone as radioligands. Adequate analgesia was achieved with both morphine and oxycodone. About 30% more oxycodone was needed intravenously, whereas 25% less oxycodone than morphine was consumed orally. There was a good linear correlation between the morphine concentrations measured with HPLC and RRA. The mean morphine-6-glucuronide to morphine concentration ratio was 2.3 after intravenous and 4.6 after oral administration. Results from RRA indicate that oxycodone in vivo is a potent μ-agonist and that a least part of its analgesic action is mediated by active metabolites. In vitro morphine glucuronides enhanced morphine in displacing radioligands from the opioid receptors, thus suggesting their complex interactions in vivo. (author)

  12. Quantification of dermal exposure to nanoparticles from solid nanocomposites by using single particle ICP-MS

    DEFF Research Database (Denmark)

    Mackevica, Aiga; Olsson, Mikael Emil; Hansen, Steffen Foss

    2016-01-01

    was tested by surface wiping followed by analysis using single particle ICP-MS. The nanoparticles were extracted from the wipes by ultrasonication in deionized water, and this technique was tested to be around 60-100% effective for extracting the particles adsorbed to the wipes. The method was optimized......Engineered nanoparticles are used in various applications due to their unique properties, which has led to their widespread use in consumer products. Silver, titanium and copper-based nanoparticles are few of the most commonly used nanomaterials in consumer products, mainly due to their biocidal...... by spiking the wipes with known amounts of nanoparticles and treating them the same way as the experimental samples. Our preliminary results show that single particle ICP-MS has the potential for quantitatively measuring potential dermal exposure to nanoparticles, and when used in combination with other...

  13. The effect of exposure duration on visual character identification in single, whole and partial report

    DEFF Research Database (Denmark)

    Petersen, Anders; Andersen, Tobias

    2012-01-01

    -Z) was presented at the centre of the screen. Exposure duration was varied from 5 to 210 milliseconds. The letter was followed by a pattern mask. Three subjects each completed 54,080 trials in a 26-Alternative Forced Choice procedure. We compared the exponential, the gamma and the Weibull psychometric functions......, all of these having a temporal offset included, as well as the ex-Gaussian, the log-logistic and finally the squared-logistic, which is a psychometric function we believe have not been described before. The log-logistic and the squared-logistic psychometric function fit well to experimental data...... in both the present study and in a previous study of single-letter identification accuracy. Also, we conducted an experiment to test the ability of the psychometric functions to fit single-letter identification data, at different stimulus contrast levels; also here the same psychometric function prevailed...

  14. Intra-ventral pallidal glutamate antagonists block expression of morphine-induced place preference.

    Science.gov (United States)

    Dallimore, Jeanine E; Mickiewicz, Amanda L; Napier, T Celeste

    2006-10-01

    The role of ionotropic glutamate receptors within the ventral pallidum (VP) in the expression of conditioned place preference (CPP) and motor adaptations to morphine was evaluated. VP-cannulated rats were subjected to 3 days of conditioning in which saline was paired to one distinct chamber in the morning and morphine (8 mg/kg ip or its vehicle) was paired to an alternate chamber in the afternoon. This induced (a) CPP expression in drug-free rats 1 day later, which was blocked by immediate pretreatments with intra-VP injections of a glutamate antagonist cocktail (DL-2-amino-5- phosphonopentanoic acid lithium salt [AP-5] + 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt [CNQX]), and (b) changes in motor function expressed following an acute morphine challenge 18 days later, which were absent if preceded by a 10-day treatment with the glutamate antagonists injected unilaterally once daily in alternating hemispheres. Thus, VP ionotropic glutamate receptors are critical mediators of the expression of place preference and motor adaptations subsequent to repeated morphine exposure.

  15. A Single Neonatal Exposure to BMAA in a Rat Model Produces Neuropathology Consistent with Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Laura Louise Scott

    2017-12-01

    Full Text Available Although cyanobacterial β-N-methylamino-l-alanine (BMAA has been implicated in the development of Alzheimer’s Disease (AD, Parkinson’s Disease (PD and Amyotrophic Lateral Sclerosis (ALS, no BMAA animal model has reproduced all the neuropathology typically associated with these neurodegenerative diseases. We present here a neonatal BMAA model that causes β-amyloid deposition, neurofibrillary tangles of hyper-phosphorylated tau, TDP-43 inclusions, Lewy bodies, microbleeds and microgliosis as well as severe neuronal loss in the hippocampus, striatum, substantia nigra pars compacta, and ventral horn of the spinal cord in rats following a single BMAA exposure. We also report here that BMAA exposure on particularly PND3, but also PND4 and 5, the critical period of neurogenesis in the rodent brain, is substantially more toxic than exposure to BMAA on G14, PND6, 7 and 10 which suggests that BMAA could potentially interfere with neonatal neurogenesis in rats. The observed selective toxicity of BMAA during neurogenesis and, in particular, the observed pattern of neuronal loss observed in BMAA-exposed rats suggest that BMAA elicits its effect by altering dopamine and/or serotonin signaling in rats.

  16. Determination of μ-, δ- and κ-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days: Comparison with animals after 20 days of morphine withdrawal.

    Science.gov (United States)

    Ujcikova, Hana; Hlouskova, Martina; Cechova, Kristina; Stolarova, Katerina; Roubalova, Lenka; Svoboda, Petr

    2017-01-01

    Chronic exposure of mammalian organism to morphine results in adaption to persistent high opioid tone through homeostatic adjustments. Our previous results indicated that in the frontal brain cortex (FBC) of rats exposed to morphine for 10 days, such a compensatory adjustment was detected as large up-regulation of adenylylcyclases I (8-fold) and II (2.5-fold). The other isoforms of AC (III-IX) were unchanged. Importantly, the increase of ACI and ACII was reversible as it disappeared after 20 days of morphine withdrawal. Changes of down-stream signaling molecules such as G proteins and adenylylcyclases should respond to and be preceded by primary changes proceeding at receptor level. Therefore in our present work, we addressed the problem of reversibility of the long-term morphine effects on μ-, δ- and κ-OR protein levels in FBC. Rats were exposed to increasing doses of morphine (10-40 mg/kg) for 10 days and sacrificed either 24 h (group +M10) or 20 days (group +M10/-M20) after the last dose of morphine in parallel with control animals (groups -M10 and -M10/-M20). Post-nuclear supernatant (PNS) fraction was prepared from forebrain cortex, resolved by 1D-SDS-PAGE under non-dissociated (-DTT) and dissociated (+DTT) conditions, and analyzed for the content of μ-, δ- and κ-OR by immunoblotting with C- and N-terminus oriented antibodies. Significant down-regulation of δ-OR form exhibiting Mw ≈ 60 kDa was detected in PNS prepared from both (+M10) and (+M10/-M20) rats. However, the total immunoblot signals of μ-, δ- and κ-OR, respectively, were unchanged. Plasma membrane marker Na, K-ATPase, actin and GAPDH were unaffected by morphine in both types of PNS. Membrane-domain marker caveolin-1 and cholesterol level increased in (+M10) rats and this increase was reversed back to control level in (+M10/-M20) rats. In FBC, prolonged exposure of rats to morphine results in minor (δ-OR) or no change (μ- and κ-OR) of opioid receptor content. The reversible increases

  17. Determination of μ-, δ- and κ-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days: Comparison with animals after 20 days of morphine withdrawal.

    Directory of Open Access Journals (Sweden)

    Hana Ujcikova

    Full Text Available Chronic exposure of mammalian organism to morphine results in adaption to persistent high opioid tone through homeostatic adjustments. Our previous results indicated that in the frontal brain cortex (FBC of rats exposed to morphine for 10 days, such a compensatory adjustment was detected as large up-regulation of adenylylcyclases I (8-fold and II (2.5-fold. The other isoforms of AC (III-IX were unchanged. Importantly, the increase of ACI and ACII was reversible as it disappeared after 20 days of morphine withdrawal. Changes of down-stream signaling molecules such as G proteins and adenylylcyclases should respond to and be preceded by primary changes proceeding at receptor level. Therefore in our present work, we addressed the problem of reversibility of the long-term morphine effects on μ-, δ- and κ-OR protein levels in FBC.Rats were exposed to increasing doses of morphine (10-40 mg/kg for 10 days and sacrificed either 24 h (group +M10 or 20 days (group +M10/-M20 after the last dose of morphine in parallel with control animals (groups -M10 and -M10/-M20. Post-nuclear supernatant (PNS fraction was prepared from forebrain cortex, resolved by 1D-SDS-PAGE under non-dissociated (-DTT and dissociated (+DTT conditions, and analyzed for the content of μ-, δ- and κ-OR by immunoblotting with C- and N-terminus oriented antibodies.Significant down-regulation of δ-OR form exhibiting Mw ≈ 60 kDa was detected in PNS prepared from both (+M10 and (+M10/-M20 rats. However, the total immunoblot signals of μ-, δ- and κ-OR, respectively, were unchanged. Plasma membrane marker Na, K-ATPase, actin and GAPDH were unaffected by morphine in both types of PNS. Membrane-domain marker caveolin-1 and cholesterol level increased in (+M10 rats and this increase was reversed back to control level in (+M10/-M20 rats.In FBC, prolonged exposure of rats to morphine results in minor (δ-OR or no change (μ- and κ-OR of opioid receptor content. The reversible increases

  18. Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats

    NARCIS (Netherlands)

    Alvandi, M.S.; Bourmpoula, M.; Homberg, J.R.; Fathollahi, Y.

    2017-01-01

    Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the

  19. Morphine potentiates neurodegenerative effects of HIV-1 Tat through actions at μ-opioid receptor-expressing glia.

    Science.gov (United States)

    Zou, Shiping; Fitting, Sylvia; Hahn, Yun-Kyung; Welch, Sandra P; El-Hage, Nazira; Hauser, Kurt F; Knapp, Pamela E

    2011-12-01

    Individuals infected with human immunodeficiency virus-1 who abuse opiates can have a higher incidence of virus-associated neuropathology. Human immunodeficiency virus does not infect neurons, but viral proteins such as transactivator of transcription and glycoprotein 120, originating from infected glia, are neurotoxic. Moreover, functional changes in glial cells that enhance inflammation and reduce trophic support are increasingly implicated in human immunodeficiency virus neuropathology. In previous studies, co-exposure with morphine enhanced transactivator of transcription neurotoxicity towards cultured striatal neurons. Since those cultures contained µ-opioid receptor-expressing astroglia and microglia, and since glia are the principal site of infection in the central nervous system, we hypothesized that morphine synergy might be glially mediated. A 60 hour, repeated measures paradigm and multiple co-culture models were used to investigate the cellular basis for opiate-enhanced human immunodeficiency virus neurotoxicity. Morphine co-exposure significantly enhanced transactivator of transcription-induced neuron death when glia were present. Synergistic effects of morphine on transactivator of transcription neurotoxicity were greatest with neuron-glia contact, but also occurred to a lesser extent with glial conditioned medium. Importantly, synergy was lost if glia, but not neurons, lacked µ-opioid receptors, indicating that opiate interactions with human immunodeficiency virus converge at the level of µ-opioid receptor-expressing glia. Morphine enhanced transactivator of transcription-induced inflammatory effectors released by glia, elevating reactive oxygen species, increasing 3-nitrotyrosine production by microglia, and reducing the ability of glia to buffer glutamate. But neuron survival was reduced even more with glial contact than with exposure to conditioned medium, suggesting that noxious elements associated with cell contact augment the toxicity due to

  20. Induction of chronic Fos-related antigens in rat brain by chronic morphine administration.

    Science.gov (United States)

    Nye, H E; Nestler, E J

    1996-04-01

    Previous studies have shown that repeated exposure to cocaine or to several other stimuli induces novel 35-37 kDa Fos-related antigens (chronic Fras) in specific brain regions. Induction of these proteins is associated with prolonged increases in AP-1 DNA binding activity that parallel the long half-life of the chronic Fras in brain. In the current study, we characterized regulation of the chronic Fras in response to prolonged exposure to morphine. After 5 days of morphine treatment, we observed increased levels of the chronic Fras and of AP-1 binding activity in rat striatum and nucleus accumbens, effects that were not seen in most other brain regions that we studied. Concomitant administration of naltrexone, an opioid receptor antagonist, prevented the induction of these proteins. Two-dimensional gel analysis showed that the chronic Fras induced by chronic morphine administration are identical to those induced after chronic cocaine and other treatments. A time course study indicated that chronic Fra induction was first apparent after 3 days of morphine treatment and peaked between 5 and 7 days of treatment in both the striatum and nucleus accumbens. Withdrawal studies demonstrated robust induction of several known acute Fras, including c-Fos, FosB, Fra-1, Fra-2, and delta FosB, at 6 hr after naltrexone precipitation of withdrawal in the striatum, nucleus accumbens, and several other brain regions. Levels of these proteins returned to basal values by 72 hr. In contrast, no further induction of the chronic Fras was evident after 6 hr of withdrawal in the striatum and nucleus accumbens, but levels of the proteins increased beyond their already elevated chronic morphine values after longer periods (72 hr) of withdrawal, even though physical withdrawal symptoms had resolved at this time point. Chronic Fras were also induced after these prolonged withdrawal periods in several other brain regions, where the proteins were not induced by chronic morphine alone. We discuss

  1. Morphine for chronic neuropathic pain in adults.

    Science.gov (United States)

    Cooper, Tess E; Chen, Junqiao; Wiffen, Philip J; Derry, Sheena; Carr, Daniel B; Aldington, Dominic; Cole, Peter; Moore, R Andrew

    2017-05-22

    Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the nervous system. Opioid drugs, including morphine, are commonly used to treat neuropathic pain. Most reviews have examined all opioids together. This review sought evidence specifically for morphine; other opioids are considered in separate reviews. To assess the analgesic efficacy and adverse events of morphine for chronic neuropathic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for randomised controlled trials from inception to February 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. We included randomised, double-blind trials of two weeks' duration or longer, comparing morphine (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment. Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables. We identified five randomised, double-blind, cross-over studies with treatment periods of four to

  2. Intra-articular morphine in horses

    DEFF Research Database (Denmark)

    Lindegaard, Casper

    to a multimodal analgesia protocol. Despite that no research has investigated this issue in horses so far, IA injection of morphine after arthroscopic surgery has become common practice in several veterinary university teaching hospitals in Europe and USA. The aims of this thesis were to investigate the analgesic...... for pharmacological analysis were obtained repeatedly. Pain was evaluated by degree of lameness as well as using a visual analogue scale of pain intensity (VAS) and a composite measure pain scale (CMPS), developed for this purpose. Intra-articular injection of LPS elicited a marked synovitis resulting in lameness...... compared to the same dose administered IV, was demonstrated. In combination with the results of the pharmacologic analysis, this is highly suggestive of a peripherally mediated effect of IA morphine....

  3. Morphine versus oxycodone analgesia after percutaneous kidney stone surgery

    DEFF Research Database (Denmark)

    Pedersen, Katja Venborg; Olesen, Anne Estrup; Drewes, Asbjørn Mohr

    2013-01-01

    According to previous studies oxycodone might have some advantages over morphine in the treatment of visceral pain. This study investigated the opioid consumption (primary outcome), pain relief and side effects (secondary outcomes) of morphine versus oxycodone after percutaneous nephrolithotomy...... using a method where the somatic pain component was minimized. Forty-four adult patients were studied. The patients were randomised to receive either morphine or oxycodone intravenously as postoperative pain treatment. During the first 4 h after surgery the opioid consumption, pain scores and side...... was significantly less frequent with morphine (P = 0.03). In this study morphine and oxycodone produced similar analgesia the first 4 h after surgery but the frequency of nausea was significantly less patient-reported with morphine. The hypothesis that oxycodone would be superior in the treatment of visceral pain...

  4. Utilization of prodrugs to enhance the transdermal absorption of morphine

    DEFF Research Database (Denmark)

    Drustrup, J.; Fullerton, A.; Christrup, Lona Louring

    1991-01-01

    . The esters showed generally a higher water and lipid solubility than morphine and were also much more lipophilic than the parent drug in terms of octanol-buffer partition coefficients. Diffusion experiments in vitro using human skin samples showed that whereas morphine did not penetrate the skin to any...... measurable extent whether applied in the form of saturated solutions in water at pH 7.0 or in isopropyl myristate, the ester prodrugs showed a high penetrating capacity under the same conditions. Steady-state fluxes up to 35 μg morphine/cm per h were observed. For some esters essentially all of the amounts...... penetrated were present in the receptor phase as morphine. The study demonstrates the feasibility of achieving transdermal delivery of morphine based on the ready conversion and the favourable skin penetration properties of morphine esters which in turn are attributed to their combination of adequate water...

  5. Single-exposure visual memory judgments are reflected in inferotemporal cortex

    Science.gov (United States)

    Meyer, Travis

    2018-01-01

    Our visual memory percepts of whether we have encountered specific objects or scenes before are hypothesized to manifest as decrements in neural responses in inferotemporal cortex (IT) with stimulus repetition. To evaluate this proposal, we recorded IT neural responses as two monkeys performed a single-exposure visual memory task designed to measure the rates of forgetting with time. We found that a weighted linear read-out of IT was a better predictor of the monkeys’ forgetting rates and reaction time patterns than a strict instantiation of the repetition suppression hypothesis, expressed as a total spike count scheme. Behavioral predictions could be attributed to visual memory signals that were reflected as repetition suppression and were intermingled with visual selectivity, but only when combined across the most sensitive neurons. PMID:29517485

  6. Single-exposure visual memory judgments are reflected in inferotemporal cortex.

    Science.gov (United States)

    Meyer, Travis; Rust, Nicole

    2018-03-08

    Our visual memory percepts of whether we have encountered specific objects or scenes before are hypothesized to manifest as decrements in neural responses in inferotemporal cortex (IT) with stimulus repetition. To evaluate this proposal, we recorded IT neural responses as two monkeys performed a single-exposure visual memory task designed to measure the rates of forgetting with time. We found that a weighted linear read-out of IT was a better predictor of the monkeys' forgetting rates and reaction time patterns than a strict instantiation of the repetition suppression hypothesis, expressed as a total spike count scheme. Behavioral predictions could be attributed to visual memory signals that were reflected as repetition suppression and were intermingled with visual selectivity, but only when combined across the most sensitive neurons. © 2018, Meyer et al.

  7. Metabolism and pharmacokinetics of morphine in neonates: A review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    Full Text Available Morphine is an agonist of the µ and k receptors, whose activation results in analgesia. Morphine-like agonists act through the µ opioid receptors to cause pain relief, sedation, euphoria and respiratory depression. Morphine is glucuronidated and sulfated at positions 3 and 6; the plasma concentration ratios correlate positively with birth weight, which probably reflects increased liver weight with increasing birth weight. Moreover, morphine clearance correlates positively with gestational age and birth weight. Steady-state morphine plasma concentrations are achieved after 24-48 hours of infusion, but the glucuronide metabolite plasma concentrations do not reach steady state before 60 hours. The morphine-3-glucuronide metabolite has lower clearance, a shorter half-life and a smaller distribution volume compared with the morphine-6 metabolite, which is the most active morphine-like agonist. Ordinary doses cause constipation, urinary retention and respiratory depression. Neonatal pain relief may require a blood level of approximately 120 ng/ml, whereas lower levels (20-40 ng/ml seem adequate for children. A bibliographic search was performed using the PubMed database and the keywords “morphine metabolism neonate” and “morphine pharmacokinetics neonate”. The initial and final cutoff points were January 1990 and September 2015, respectively. The results indicate that morphine is extensively glucuronidated and sulfated at positions 3 and 6, and that the glucuronidation rate is lower in younger neonates compared with older infants. Although much is known about morphine in neonates, further research will be required to ensure that recommended therapeutic doses for analgesia in neonates are evidence based.

  8. Effect of Nebulized Morphine on Dyspnea of Mustard Gas-Exposed Patients: A Double-Blind Randomized Clinical Trial Study

    Directory of Open Access Journals (Sweden)

    Majid Shohrati

    2012-01-01

    Full Text Available Background. Dyspnea is one of the main complaints in a group of COPD patients due to exposure to sulfur mustard (SM and is refractory to conventional therapies. We designed this study to evaluate effectiveness of nebulized morphine in such patients. Materials and Methods. In a double-blind clinical trial study, 40 patients with documented history of exposure to SM were allocated to two groups: group 1 who received 1 mg morphine sulfate diluted by 4 cc normal saline 0.5% using nebulizer once daily for 5 days and group 2 serving as control who received normal saline as placebo. They were visited by pulmonologist 7 times per day to check symptoms and signs and adverse events. Different parameters including patient-scored peak expiratory flow using pick flow meter, visual analogue scale (VAS for dyspnea, global quality of life and cough, and number of respiratory rate, night time awaking for dyspnea and cough have been assessed. Results. The scores of VAS for dyspnea, cough and quality of life and also respiratory rate, heart rate, and night time awaking due to dyspnea and night time awaking due to cough improved significantly after morphine nebulization without any major adverse events. Also pick expiratory flow has been improved significantly after nebulization in each day. Conclusion. Our results showed the clinical benefit of nebulized morphine on respiratory complaints of patients due to exposure to SM without significant side effects.

  9. Biological profile and bioavailability of imidazoline compounds on morphine tolerance modulation.

    Science.gov (United States)

    Caprioli, Giovanni; Mammoli, Valerio; Ricciutelli, Massimo; Sagratini, Gianni; Ubaldi, Massimo; Domi, Esi; Mennuni, Laura; Sabatini, Chiara; Galimberti, Chiara; Ferrari, Flora; Milia, Chiara; Comi, Eleonora; Lanza, Marco; Giannella, Mario; Pigini, Maria; Del Bello, Fabio

    2015-12-15

    Tolerance to opioid administration represents a serious medical alert in different chronic conditions. This study compares the effects of the imidazoline compounds 1, 2, and 3 on morphine tolerance in an animal model of inflammatory pain in the rat. 1, 2, and 3 have been selected in that, although bearing a common scaffold, preferentially bind to α2-adrenoceptors, imidazoline I2 receptors, or both systems, respectively. Such compounds have been tested in vivo by measuring the paw withdrawal threshold to mechanical pressure after complete Freund's adjuvant injection. To determine the ligand levels in rat plasma, an HPLC-mass spectrometry method has been developed. All the compounds significantly reduced the induction of morphine tolerance, showing different potency and duration of action. Indeed, the selective imidazoline I2 receptor interaction (2) restored the analgesic response by maintaining the same time-dependent profile observed after a single morphine administration. Differently, the selective α2C-adrenoceptor activation (1) or the combination between α2C-adrenoceptor activation and imidazoline I2 receptor engagement (3) promoted a change in the temporal profile of morphine analgesia by maintaining a mild but long lasting analgesic effect. Interestingly, the kinetics of compounds in rat plasma supported the pharmacodynamic data. Therefore, this study highlights that both peculiar biological profile and bioavailability of such ligands complement each other to modulate the reduction of morphine tolerance. Based on these observations, 1-3 can be considered useful leads in the design of new drugs able to turn off the undesired tolerance induced by opioids. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Usefulness of MR cholangiopancreatography after intravenous morphine administration

    International Nuclear Information System (INIS)

    Lee, So Jung; Ko, Ji Ho; Cho, Young Duk; Jung, Mi Hee; Yoon, Byung Chull

    2007-01-01

    We wanted to assess the usefulness of MRCP after intravenous morphine administration in the evaluation of the hepatopancreatic pancreatico-biliary ductal system. We studied 15 patients who were suspected of having disease of hepatopancreatic ductal system and they did not have any obstructive lesion on ultrasonography and/or CT. MRCP was acquired before and after morphine administration (0.04 mg/kg, intravenously). Three radiologists scored the quality of the images of the anatomic structures in the hepatopancreatic ductal system. We directly compared the quality of the images obtained with using the two methods and the improvement of the artifacts by pulsatile vascular compression. The MRCP images obtained after intravenous morphine administration were better than those obtained before morphine administration for visualizing the hepatopancreatic ductal system. On direct comparison, the MRCP images obtained after morphine administration were better in 12 cases, equivocal in two cases, and the images before morphine administration were better in only one case. In three patients, MRCP before morphine injection showed signal loss at the duct across the pulsatile hepatic artery. In two of three patients, MRCP after morphine injection showed no signal loss in this ductal area. MRCP after intravenous morphine administration enables physicians to see the hepatopancreatic ductal system significantly better and the artifacts caused by pulsation of the hepatic artery can be avoided

  11. Co-infection of Primary Syphilis and HIV after a Single Exposure - a Case Report

    Directory of Open Access Journals (Sweden)

    Geleki Stamatina

    2015-09-01

    Full Text Available Human immunodeficiency virus type 1- infected patients with syphilis are among the most important transmitters of HIV-1 infection due to biological effects of genital ulcerations, and aggravation due to their continued risky behavior. The association between primary syphilis and acute HIV-1 co-infection is not well documented, and reports on isolated cases are raising special interest and indicate that this double primary co-infection may occur. We present a case of a 31-year-old man with no past medical history who presented with fever, papular rash on the face which lasted for a few days, and a single genital ulcer. He was diagnosed with primary syphilis and primary HIV-1 infection after a single exposure with an infected female sex worker. Male-to-female HIV transmission during vaginal intercourse is significantly more likely than female-to-male HIV transmission. However, high prevalence of sexually transmitted diseases among female sex workers contributed to high HIV transmission probability, as in our case.

  12. Irradiation exposure modulates central opioid functions

    International Nuclear Information System (INIS)

    Dougherty, P.M.; Dafny, N.

    1987-01-01

    Exposure to low doses of gamma irradiation results in the modification of both the antinociceptive properties of morphine and the severity of naloxone-precipitated withdrawal in morphine-dependent rats. To better define the interactions between gamma irradiation and these opiate-mediated phenomena, dose-response studies were undertaken of the effect of irradiation on morphine-induced antinociception, and on the naloxone-precipitated withdrawal syndrome of morphine-dependent rats. In addition, electrophysiologic studies were conducted in rats after irradiation exposure and morphine treatment correlating with the behavioral studies. The observations obtained demonstrated that the antinociceptive effects of morphine as well as naloxone-precipitated withdrawal were modified in a dose-dependent manner by irradiation exposure. In addition, irradiation-induced changes in the evoked responses obtained from four different brain regions demonstrated transient alterations in both baseline and morphine-treated responses that may reflect the alterations observed in the behavioral paradigms. These results suggest that the effects of irradiation on opiate activities resulted from physiologic alterations of central endogenous opioid systems due to alterations manifested within peripheral targets

  13. Irradiation exposure modulates central opioid functions

    Energy Technology Data Exchange (ETDEWEB)

    Dougherty, P.M.; Dafny, N.

    1987-11-01

    Exposure to low doses of gamma irradiation results in the modification of both the antinociceptive properties of morphine and the severity of naloxone-precipitated withdrawal in morphine-dependent rats. To better define the interactions between gamma irradiation and these opiate-mediated phenomena, dose-response studies were undertaken of the effect of irradiation on morphine-induced antinociception, and on the naloxone-precipitated withdrawal syndrome of morphine-dependent rats. In addition, electrophysiologic studies were conducted in rats after irradiation exposure and morphine treatment correlating with the behavioral studies. The observations obtained demonstrated that the antinociceptive effects of morphine as well as naloxone-precipitated withdrawal were modified in a dose-dependent manner by irradiation exposure. In addition, irradiation-induced changes in the evoked responses obtained from four different brain regions demonstrated transient alterations in both baseline and morphine-treated responses that may reflect the alterations observed in the behavioral paradigms. These results suggest that the effects of irradiation on opiate activities resulted from physiologic alterations of central endogenous opioid systems due to alterations manifested within peripheral targets.

  14. Oral morphine prescribing practices in severe cancer pain

    Directory of Open Access Journals (Sweden)

    B Barathi

    2009-01-01

    Full Text Available Background: Nearly one million cancer patients in India need oral morphine for pain relief. Despite doctors prescribing oral morphine in our center, many cancer patients with severe pain found to be not facilitated with adequate pain relief. Aim: This audit was conducted to look at the "oral morphine prescribing practices for severe cancer pain" at a tertiary care hospital. Materials and Methods: Twenty case files of patients, who were admitted with severe cancer pain, and receiving oral morphine were analyzed in pre- and posteducational session. Local standards were set to assess the adequacy of pain relief. Deficiency in achieving analgesia was found in preinterventional audit. A clinical audit was conducted before and after the educational session on oral morphine prescribing. The education for doctors and nurses focused on starting patients on morphine, titration, and administering rescue dose. Then local guidelines on oral morphine prescribing were circulated. And analysis of following factors were done following pre- and posteducational session: Pain intensity at the beginning of treatment, starting dose of morphine, increments in morphine dose, number of rescue doses given, and fall in pain intensity at the end of 1 week. The outcomes were compared with the standards. Results: Preintervention audit showed that only 50% of patients achieved adequate pain relief. Rescue dose was administered in only 20% of patients. While reaudit following the educational session showed that 80% of patients achieved adequate pain relief and 100% received rescue doses. Conclusion: Educational sessions have significant impact on improving oral morphine prescribing practice among doctors and nurses. It was found failing to administer regular as well as rescue doses resulted in inadequate pain relief in patients receiving oral morphine.

  15. Comparison of Morphine, Morphine-Lidocaine, and Morphine-Lidocaine-Ketamine Infusions in Dogs Using an Incision-Induced Pain Model.

    Science.gov (United States)

    Chiavaccini, Ludovica; Claude, Andrew K; Meyer, Robert E

    We aimed to compare antinociceptive effects of IV infusions of morphine (M), morphine-lidocaine (ML), or morphine-lidocaine-ketamine (MLK) combined, in a mild-to-moderate pain model in dogs. Eighteen adult hounds were heavily sedated with IV morphine (0.2 mg/kg) and dexmedetomidine to undergo thoracic skin incisions. After reversal, dogs were randomly assigned to receive loading doses of lidocaine and ketamine (MLK), lidocaine and saline (ML), or equivalent volume of saline (M), followed by 18 hr constant infusions of morphine (0.12 mg/kg/hr), lidocaine (3 mg/kg/hr) and ketamine (0.6 mg/kg/hr); morphine (0.12 mg/kg/hr) and lidocaine (3 mg/kg/hr); or morphine (0.12 mg/kg/hr), respectively. Pain was assessed with Short Form Glasgow Composite Measure Pain Scale and mechanical nociception with von Frey filaments (VFFS). Data were analyzed with linear mixed model on ranks. Independently of treatment, Short Form Glasgow Composite Measure Pain Scale was significantly higher than baseline for 24 hr (p < .0001), while VFFS was significantly lower than baseline for 48 hr post-recovery (p < .0001), with no difference between MLK and M groups. The ML group recorded significantly lower VFFS (p = .02) than the M group for the entire study. In conclusion, there was no significant analgesic difference between MLK and M alone.

  16. Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats.

    Science.gov (United States)

    Lai, Shuhua; Wu, Gangwei; Jiang, Zhixian

    2018-01-01

    Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli. © 2018 The Author(s). Published by S. Karger AG, Basel.

  17. Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats

    Directory of Open Access Journals (Sweden)

    Shuhua Lai

    2018-03-01

    Full Text Available Background/Aims: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD. Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1 is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. Methods: Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. Results: We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4 levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor or LPS-RS (TLR4 antagonist can prevent the development of SPS-induced fear extinction impairment. Conclusion: Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli.

  18. The standardized Withania somnifera Dunal root extract alters basal and morphine-induced opioid receptor gene expression changes in neuroblastoma cells.

    Science.gov (United States)

    Caputi, Francesca Felicia; Acquas, Elio; Kasture, Sanjay; Ruiu, Stefania; Candeletti, Sanzio; Romualdi, Patrizia

    2018-01-10

    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. A range of WSE concentrations was preliminarily tested to evaluate their effects on cell viability. Subsequently, the effects of 5 h exposure to WSE (0.25, 0.50 and 1.00 mg/ml), applied alone and in combination with morphine or naloxone, on MOP and NOP mRNA levels were investigated. Data analysis revealed that morphine decreased MOP and NOP receptor gene expression, whereas naloxone elicited their up-regulation. In addition, pre-treatment with naloxone prevented the morphine-elicited gene expression alterations. Interestingly, WSE was able to: a) alter MOP but not NOP gene expression; b) counteract, at its highest concentration, morphine-induced MOP down-regulation, and c) hamper naloxone-induced MOP and NOP up-regulation. Present in-vitro data disclose novel evidence about the ability of WSE to influence MOP and NOP opioid receptors gene expression in SH-SY5Y cells. Moreover, our findings suggest that the in-vivo modulation of morphine-mediated analgesia by WSE could be related to the hindering of morphine-elicited opioid receptors down-regulation here observed following WSE pre-treatment at its highest concentration.

  19. Head impact exposure measured in a single youth football team during practice drills.

    Science.gov (United States)

    Kelley, Mireille E; Kane, Joeline M; Espeland, Mark A; Miller, Logan E; Powers, Alexander K; Stitzel, Joel D; Urban, Jillian E

    2017-11-01

    OBJECTIVE This study evaluated the frequency, magnitude, and location of head impacts in practice drills within a youth football team to determine how head impact exposure varies among different types of drills. METHODS On-field head impact data were collected from athletes participating in a youth football team for a single season. Each athlete wore a helmet instrumented with a Head Impact Telemetry (HIT) System head acceleration measurement device during all preseason, regular season, and playoff practices. Video was recorded for all practices, and video analysis was performed to verify head impacts and assign each head impact to a specific drill. Eleven drills were identified: dummy/sled tackling, install, special teams, Oklahoma, one-on-one, open-field tackling, passing, position skill work, multiplayer tackle, scrimmage, and tackling drill stations. Generalized linear models were fitted to log-transformed data, and Wald tests were used to assess differences in head accelerations and impact rates. RESULTS A total of 2125 impacts were measured during 30 contact practices in 9 athletes (mean age 11.1 ± 0.6 years, mean mass 44.9 ± 4.1 kg). Open-field tackling had the highest median and 95th percentile linear accelerations (24.7 g and 97.8 g, respectively) and resulted in significantly higher mean head accelerations than several other drills. The multiplayer tackle drill resulted in the highest head impact frequency, with an average of 0.59 impacts per minute per athlete, but the lowest 95th percentile linear accelerations of all drills. The front of the head was the most common impact location for all drills except dummy/sled tackling. CONCLUSIONS Head impact exposure varies significantly in youth football practice drills, with several drills exposing athletes to high-magnitude and/or high-frequency head impacts. These data suggest that further study of practice drills is an important step in developing evidence-based recommendations for modifying or eliminating

  20. Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.

    Science.gov (United States)

    Webster, Lynn R; Smith, Michael D; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M

    2017-09-01

    To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (E max ; primary endpoint) using drug liking visual analog scale (VAS) score, E max using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking E max was significantly lower ( P  <   0.0001) compared with IN morphine ER. Overall drug liking and TDA E max values were significantly lower ( P  <   0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. © 2016 American Academy of Pain Medicine.

  1. Blood-brain distribution of morphine-6-glucuronide in sheep

    DEFF Research Database (Denmark)

    Villesen, H H; Foster, D J R; Upton, R N

    2006-01-01

    At present there are few data regarding the rate and extent of brain-blood partitioning of the opioid active metabolite of morphine, morphine-6-glucuronide (M6G). In this study the cerebral kinetics of M6G were determined, after a short-term intravenous infusion, in chronically instrumented...... conscious sheep....

  2. Peripheral antinociceptive effects of morphine after burn injury

    DEFF Research Database (Denmark)

    Møiniche, S; Dahl, J B; Kehlet, H

    1993-01-01

    In a double-blind study, 2 mg of morphine in saline, or saline only, was given subcutaneously into a second-degree bilateral leg-burn injury in 12 volunteers. Heat-pain thresholds and pressure-pain thresholds were significantly increased by local morphine administration. These results confirm exp...... experimental data demonstrating a peripheral antinociceptive effects of opioids in inflamed tissue....

  3. Peripheral antinociceptive effects of morphine after burn injury

    DEFF Research Database (Denmark)

    Møiniche, S; Dahl, J B; Kehlet, H

    1993-01-01

    In a double-blind study, 2 mg of morphine in saline, or saline only, was given subcutaneously into a second-degree bilateral leg-burn injury in 12 volunteers. Heat-pain thresholds and pressure-pain thresholds were significantly increased by local morphine administration. These results confirm...

  4. Changes in metabolic-related variables during chronic morphine treatment.

    Science.gov (United States)

    Ferenczi, Szilamér; Núñez, Cristina; Pintér-Kübler, Bernadett; Földes, Anna; Martín, Fátima; Márkus, Vera Ladnyánszky; Milanés, M Victoria; Kovács, Krisztina J

    2010-10-01

    To reveal neuroendocrine/neurochemical changes that are responsible for the robust metabolic alterations seen during chronic morphine treatment we followed hormonal-, transcriptional- and behavioral changes during chronic morphine administration in adult male Wistar rats. Animals were implanted with increasing amount of slow release morphine tablets for 8 days. Morphine treated animals gain significantly less weight than placebo implanted controls. This weight loss is due to the dramatic decrease in the food intake and caloric efficiency in the first days of drug administration and to the lasting disregulated feeding pattern. Changes in feeding behavior included increase of diurnal and decrease of nocturnal feeding frequency in morphine treated rats. Significantly less leptin and insulin plasma levels were detected in morphine implanted animals than in placebo implanted controls, while adiponectin and ACTH concentration remain unchanged. Morphine treated rats display an increase of FosB/Delta FosB immunoreactivity at brain sites that have been implicated regulation of food intake and energy expenditure, including hypothalamic arcuate, paraventricular and ventromedial nuclei and in the lateral hypothalamic area as well as in the caudal brainstem. However, morphine-induced long-term metabolic alterations were not accompanied with any significant changes in the expression of anorexigenic neuropeptides POMC and CART in the hypothalamus and in the brainstem. The disregulated feeding pattern was not reflected in changes of orexin transcription, however, a compensatory upregulation was revealed in hypothalamic NPY expression. (c) 2010 Elsevier Ltd. All rights reserved.

  5. Pain management in emergency department: intravenous morphine vs. intravenous acetaminophen

    Directory of Open Access Journals (Sweden)

    Morteza Talebi Doluee

    2015-01-01

    Full Text Available Pain is the most common complaint in emergency department and there are several methods for its control. Among them, pharmaceutical methods are the most effective. Although intravenous morphine has been the most common choice for several years, it has some adverse effects. There are many researches about intravenous acetaminophen as an analgesic agent and it appears that it has good analgesic effects for various types of pain. We searched some electronic resources for clinical trials comparing analgesic effects of intravenous acetaminophen vs. intravenous morphine for acute pain treatment in emergency setting.In two clinical trials, the analgesic effect of intravenous acetaminophen has been compared with intravenous morphine for renal colic. The results revealed no significant difference between analgesic effects of two medications. Another clinical trial revealed that intravenous acetaminophen has acceptable analgesic effects on the post-cesarean section pain when combined with other analgesic medications. One study revealed that administration of intravenous acetaminophen compared to placebo before hysterectomy decreased consumption of morphine via patient-controlled analgesia pump and decreased the side effects. Similarly, another study revealed that the infusion of intravenous acetaminophen vs. placebo after orthopedic surgery decreased the consumption of morphine after the surgery. A clinical trial revealed intravenous acetaminophen provided a level of analgesia comparable to intravenous morphine in isolated limb trauma, while causing less side effects than morphine.It appears that intravenous acetaminophen has good analgesic effects for visceral, traumatic and postoperative pains compare with intravenous morphine.

  6. Effect of Potassium Channel Modulators on Morphine Withdrawal in Mice

    Directory of Open Access Journals (Sweden)

    Vikas Seth

    2010-01-01

    Full Text Available The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K + ATP channel modulators were injected intraperitoneally (i.p. 30 minutes before the naloxone. It was found that a K + ATP channel opener, minoxidil (12.5–50 mg/kg i.p., suppressed the morphine withdrawal significantly. On the other hand, the K + ATP channel blocker glibenclamide (12.5–50 mg/kg i.p. caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K + ATP channels play an important role in the genesis of morphine withdrawal and K + ATP channel openers could be useful in the management of opioid withdrawal. As morphine opens K + ATP channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K + currents.

  7. Development of single-exposure, multidetector neutron spectrometers: the NESCOFI'at'BTF project

    International Nuclear Information System (INIS)

    Bedogni, R.; Esposito, A.; Gentile, A.; Mazzitelli, G.; Buonomo, B.; Gomez-Ros, J.M.; Bortot, D.; Pola, A.; Introini, M.V.

    2014-01-01

    NESCOFI'at'BTF is a 3-y project (2011-13) supported by the Scientific Commission 5 of INFN (Italy). The target is the development of neutron spectrometers similar to the Bonner spheres, in terms of response energy interval and accuracy, but able to determine the neutron spectrum in only one exposure. These devices embed multiple (10 to 30) thermal neutron detectors (TNDs) within a single moderator. Two prototypes, called Spherical Spectrometer (SP 2 ) and cylindrical spectrometer (CYSP), have been set up. Whilst SP 2 has spherical geometry and nearly isotropic response, the CYSP has cylindrical geometry and is intended to be used as a directional spectrometer. Suitable active TNDs will be embedded in the final version of the devices. The resulting instruments could be used as real-time neutron spectrometers in neutron-producing facilities. This communication describes the design criteria, numerical analysis, experimental issues, state-of-the-art and future developments connected with the development of these instruments. Two prototypal single-moderator neutron spectrometers, called SP 2 and CYSP, were designed in the framework of the INFN project NESCOFI'at'BTF. They are intended to be used as isotropic or directional spectrometers, respectively. At present, the SP 2 response matrix was tested with passive detectors, whilst the active version of the instrument is under fabrication. In contrast, the active CYSP is available and its response matrix was partially tested with an Am-Be source, obtaining a very satisfactory agreement. A full test of the CYSP response matrix, using reference neutron fields, is planned before the end of 2013. After the active version of both SP2 and CYSP will be set up and tested, these real-time on-line spectrometers could be replicated and distributed to third-party institutions under collaboration agreement. (authors)

  8. Transient receptor potential cation channel A1 (TRPA1) mediates changes in heart rate variability following a single exposure to acrolein in mice

    Science.gov (United States)

    The data show that a single exposure to acrolein causes autonomic imbalance in mice through the TRPA1 sensor and subsequent cardiac dysfunction. Human and animal studies have shown that short-term air pollution exposure causes...

  9. AMN082, a metabotropic glutamate receptor 7 allosteric agonist, attenuates locomotor sensitization and cross-sensitization induced by cocaine and morphine in mice.

    Science.gov (United States)

    Jenda, M; Gawel, K; Marszalek, M; Komsta, L; Kotlinska, J H

    2015-03-03

    Previous studies have indicated that metabotropic glutamate receptors 7 (mGluR7s) are involved in drug addiction. However, the role of these receptors in drug-induced behavioral sensitization is unknown. The aim of the present study was to determine whether systemic injection of AMN082, a selective mGluR7 allosteric agonist, reduces the cocaine- and morphine-induced hyperactivity and the development and expression of locomotor sensitization, and also affects the reciprocal cross-sensitization to the stimulant effect of cocaine and morphine in mice. AMN082 (1.25-10.0 mg/kg, i.p.) did not have an impact on locomotion of naive mice and did not affect the acute cocaine- or morphine-induced hyperactivity, except the dose of 10 mg/kg that suppressed the locomotor effect of both drugs. Repeated exposure to cocaine or morphine (10 mg/kg, 5× every 3 days) gradually increased locomotion during induction of sensitization and after 4 (cocaine) or 7 day (morphine) withdrawal phase when challenged with cocaine (10 mg/kg, i.p.) or morphine (10 mg/kg, i.p.) on day 17 or 20, respectively. Pretreatment of animals with the lower doses of AMN082 (1.25-5.0 mg/kg, i.p.), 30 min before every cocaine or morphine injection during repeated drug administration or before cocaine or morphine challenge, dose-dependently attenuated the development, as well as the expression of cocaine or morphine locomotor sensitization. AMN082 also inhibited the reciprocal cross-sensitization between these drugs. Prior to administration of MMPIP (10 mg/kg, i.p.), a selective mGluR7 antagonist reversed the inhibitory effect of AMN082 on the development or expression of cocaine or morphine sensitization. These data indicate that AMN082 attenuated the development and expression of cocaine and morphine sensitization, and the reciprocal cross-sensitization via a mechanism that involves mGluR7s. Thus, AMN082 might have therapeutic implications not only in the treatment of cocaine or opioid addiction but also in the

  10. Epidural morphine for postoperative pain relief in children

    DEFF Research Database (Denmark)

    Henneberg, S W; Hole, P; Haas, Inge Madsen De

    1993-01-01

    Epidural morphine for postoperative pain relief is in general use, and has proved to be very efficient in adults. The epidural technique and the use of epidural morphine are much less frequent in children. For 2 years we have prospectively followed 76 children who had epidural morphine...... for postoperative pain relief after major abdominal surgery. The age distribution was from newborn to 13 years, with a median age of 12 months. It was estimated that 94% of the patients had good analgesia for the first 24 postoperative hours and no other opioids were given. The side effects were few, but one case...... the investigation. We observed a change in the sleeping pattern with an increased number of sleep-induced myoclonia during the administration of epidural morphine. In conclusion, the use of epidural morphine in children for postoperative pain relief is very efficient. The minimal effective dose has not been...

  11. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

    Directory of Open Access Journals (Sweden)

    Chen HH

    2015-03-01

    Full Text Available Hwei-Hsien Chen,1,2,* Yao-Chang Chiang,3,4,* Zung Fan Yuan,5,6 Chung-Chih Kuo,5,6 Mei-Dan Lai,2 Tsai-Wei Hung,1 Ing-kang Ho,1,3,4 Shao-Tsu Chen2,7 1Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan; 2Master and PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan; 3Center for Drug Abuse and Addiction, China Medical University Hospital, 4Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 5Master Program in Physiological and Anatomical Medicine, 6Department of Physiology, School of Medicine, Tzu Chi University, 7Department of Psychiatry, Buddhist Tzu Chi General Hospital, Hualien, Taiwan *These authors contributed equally to this work Abstract: Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female

  12. A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients.

    Science.gov (United States)

    Setnik, Beatrice; Roland, Carl L; Goli, Veeraindar; Sommerville, Kenneth; Webster, Lynn

    2013-01-01

    To evaluate whether intact or crushed doses of an extended-release formulation of morphine sulfate surrounding an inner core of sequestered naltrexone (MSN) induces signs and symptoms of withdrawal in opioid-dependent patients. Randomized, double-blind, two-way crossover study. Single center. Fourteen patients with chronic moderate-to-severe noncancer pain receiving opioids were enrolled into the study; six completed the maintenance and treatment phases prior to early study discontinuation for issues with manufacturing; eight discontinued: adverse effects (4), noncompliance (1), patient decision (1), study termination (2). Patients were titrated to a stable dose of MSN (ranging from 30/1.2 to 100/4.0 mg of morphine/naltrexone) that was used in the single-dose crossover evaluation of crushed and intact MSN. Clinical Opiate Withdrawal Scale (COWS). Clinically significant withdrawal (COWS ≥ 13) was observed with rapid onset (≤0.8 hours postdose) in three patients (50 percent) following treatment with crushed MSN at the highest doses administered of ≥60/2.4 mg. Although naltrexone exposure was negligible following exposure to intact MSN, increasing plasma levels of naltrexone and 6-β-naltrexol were associated with COWS score ≥13 in patients who received crushed MSN. COWS ≥ 13 was observed in one patient receiving intact MSN without quantifiable naltrexone concentrations. Crushing the MSN capsule may precipitate moderate-to-severe signs and symptoms of opioid withdrawal in opioid-dependent individuals. The negligible exposure to naltrexone following exposure to intact MSN supports that intact capsules may be taken safely without precipitating withdrawal in opioid-dependent individuals.

  13. A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Lund, Trine Meldgaard; Olesen, Anne Estrup

    2015-01-01

    Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can...

  14. Cytokine Pattern In Sera and Broncho-Alveolar Lavage Six Months After Single Exposure to Sulfur Mustard

    Directory of Open Access Journals (Sweden)

    GHASEM SOLGUE

    2006-07-01

    Full Text Available Background:Cytokines play a major role in both acute and chronic inflammatory processes,including those produced by Sulfur Mustard.This study describes the cytokine level six months after exposure to a single dose of sulfur mustard,defined by IL-1

  15. Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

    NARCIS (Netherlands)

    Mieras, L. (Liesbeth); R. Anthony (Richard); W.H. van Brakel (Wim); Bratschi, M.W. (Martin W.); van den Broek, J. (Jacques); Cambau, E. (Emmanuelle); Cavaliero, A. (Arielle); Kasang, C. (Christa); Perera, G. (Geethal); Reichman, L. (Lee); J.H. Richardus (Jan Hendrik); P. Saunderson (Paul); Steinmann, P. (Peter); Yew, W.W. (Wing Wai)

    2016-01-01

    textabstractPost-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where

  16. A meta-analytic review of the effectiveness of single-layer clothing in preventing exposure from pesticide handling.

    Science.gov (United States)

    Miguelino, Eric S

    2014-01-01

    This review summarizes available information on the penetration of pesticides through single-layer clothing by pesticide handlers and introduces epidemiological and observational studies on pesticide exposure. The data for this report were taken from peer-reviewed articles, publicly available government reports, and publicly available government reviews of registrant-submitted data and information. The arithmetic mean of calculated clothing penetration was obtained for various parts of the body (upper arm, lower arm, chest/torso, back/torso, upper leg, and lower leg) that were exposed to pesticide. The range of pesticide penetration to the various parts of the body through single-layer clothing during mixing, loading, and application (MLA) activities was found to be 6.2% ± 5.7% to 21.4% ± 6.7%, which demonstrates a potential for increased and unintentional pesticide exposures. Based on this evaluation, some accepted default values for protection against pesticide exposure may be overestimated.

  17. Intravenous paracetamol versus dexketoprofen versus morphine in acute mechanical low back pain in the emergency department: a randomised double-blind controlled trial.

    Science.gov (United States)

    Eken, Cenker; Serinken, Mustafa; Elicabuk, Hayri; Uyanik, Emrah; Erdal, Muhammed

    2014-03-01

    The objective of this study was to determine the analgesic efficacy and safety of intravenous, single-dose paracetamol versus dexketoprofen versus morphine in patients presenting with mechanical low back pain (LBP) to the emergency department (ED). This randomised double-blind study compared the efficacy of intravenous 1 gm paracetamol, 50 mg dexketoprofen and 0.1 mg/kg morphine in patients with acute mechanical LBP. Visual analogue scale (VAS) was used for pain measurement at baseline, after 15 and after 30 min. A total of 874 patients were eligible for the study, and 137 of them were included in the final analysis: 46 patients from the paracetamol group, 46 patients in the dexketoprofen group and 45 patients in the morphine group. The mean age of study subjects was 31.5 ± 9.5 years, and 60.6% (n=83) of them were men. The median reduction in VAS score at the 30th minute for the paracetamol group was 65 mm (95% CI 58 to 72), 67 mm (95% CI 60 to 73) for the morphine group and 58 mm (95% CI 50 to 64) for the dexketoprophen group. Although morphine was not superior to paracetamol at 30 min (difference: 3.8 ± 4.9 (95% CI -6 to 14), the difference between morphine and dexketoprofen in reducing pain was 11.2 ± 4.7 (95% CI 2 to 21). At least one adverse effect occurred in 8.7% (n=4) of the cases in the paracetamol group, 15.5% (n=7) of the morphine group, and 8.7% (n=4) of the dexketoprophen group (p=0.482). Intravenous paracetamol, dexketoprofen and morphine are not superior to each other for the treatment of mechanical LBP in ED.

  18. Long-lasting delayed hyperalgesia after chronic restraint stress in rats-effect of morphine administration.

    Science.gov (United States)

    da Silva Torres, Iraci Lucena; Cucco, Simone N S; Bassani, Marcio; Duarte, Marcelo S; Silveira, Patricia P; Vasconcellos, Ana Paula; Tabajara, Angela Sampaio; Dantas, Giovana; Fontella, Fernanda U; Dalmaz, Carla; Ferreira, Maria Beatriz C

    2003-03-01

    Different effects upon the nociceptive response have been observed with exposure to acute and chronic stress in rats. In the present study we repeatedly submitted rats to restraint for 40 days, inducing hyperalgesia using the tail-flick test. A new session of acute stress was applied at the end of 40 days period, and the chronically-stressed animals demonstrated analgesia after forced swimming, but not after restraint. The effect of stress interruption for 14 or 28 days on the nociceptive threshold was then investigated. The basal tail-flick latency remained decreased for at least 28 days (hyperalgesic effect). Following the periods of suspension, the animals were submitted to new session of acute restraint, and stress-induced analgesia was observed only after 28 days of stress interruption. Thus, the mechanisms involved in the long-lasting hyperalgesia presented in this study are not exactly the same as those responsible for the analgesia induced by acute stressors. After 40 days of chronic stress treatment, morphine was injected i.p. (1.0, 5.0 mg/kg or saline). The repeatedly stressed rats displayed decreased morphine effects on nociception compared to unstressed controls. The tolerance of the response to morphine agrees with previous studies suggesting that chronic restraint stress could modify the activity of opioid systems.

  19. Morphine-induced internalization of the L83I mutant of the rat μ-opioid receptor

    Science.gov (United States)

    Cooke, A E; Oldfield, S; Krasel, C; Mundell, S J; Henderson, G; Kelly, E

    2015-01-01

    BACKGROUND AND PURPOSE Naturally occurring single-nucleotide polymorphisms (SNPs) within GPCRs can result in alterations in various pharmacological parameters. Understanding the regulation and function of endocytic trafficking of the μ-opioid receptor (MOP receptor) is of great importance given its implication in the development of opioid tolerance. This study has compared the agonist-dependent trafficking and signalling of L83I, the rat orthologue of a naturally occurring variant of the MOP receptor. EXPERIMENTAL APPROACH Cell surface elisa, confocal microscopy and immunoprecipitation assays were used to characterize the trafficking properties of the MOP-L83I variant in comparison with the wild-type receptor in HEK 293 cells. Functional assays were used to compare the ability of the L83I variant to signal to several downstream pathways. KEY RESULTS Morphine-induced internalization of the L83I MOP receptor was markedly increased in comparison with the wild-type receptor. The altered trafficking of this variant was found to be specific to morphine and was both G-protein receptor kinase- and dynamin-dependent. The enhanced internalization of L83I variant in response to morphine was not due to increased phosphorylation of serine 375, arrestin association or an increased ability to signal. CONCLUSIONS AND IMPLICATIONS These results suggest that morphine promotes a specific conformation of the L83I variant that makes it more liable to internalize in response to morphine, unlike the wild-type receptor that undergoes significantly less morphine-stimulated internalization, providing an example of a ligand-selective biased receptor. The presence of this SNP within an individual may consequently affect the development of tolerance and analgesic responses. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24697554

  20. Differential involvement of D1 and D2 dopamine receptors in the expression of morphine withdrawal signs in rats.

    Science.gov (United States)

    Funada, M.; Shippenberg, T.S.

    1996-10-01

    The role of dopamine (DA) receptors in the expression of opioid dependence was examined by use of an unbiased conditioned place preference paradigm. Male Sprague-Dawley rats were implanted s.c. with two pellets containing placebo or 75mg morphine. Animals received one conditioning session with saline and one with the DA D1 receptor antagonist SCH23390 (0.01-0.05mg, s.c.) or the DA D2 receptor antagonist raclopride (0.25-1.0mg/kg, s.c.). Conditioning sessions were conducted 4 days after pellet implantation. During each of these sessions, physical signs of withdrawal were quantified. In morphine-pelleted animals, the D2 receptor antagonist raclopride produced conditioned place aversions, with a minimum effective dose of 0.5mg/kg. Administration of a higher dose also resulted in wet-dog shakes, ptosis and diarrhea in morphine-pelleted animals. This effect was not observed in response to lower doses of raclopride or in placebo-pelleted animals. The D1 receptor antagonist SCH23390 failed to produce conditioned place aversions in either morphine- or placebo-pelleted animals after single-trial conditioning. This antagonist was also ineffective in producing physical withdrawal signs. After two conditioning sessions with SCH23390, both the morphine- and placebo-pelleted animals exhibited a marked aversion for the SCH23390-paired place. However, there was no difference between groups in the magnitude of this effect. These data demonstrate that the acute blockade of D2 receptors produces aversive effects in opioid-dependent animals and that this effect occurs in the presence of few, if any, prototypic physical withdrawal signs. Furthermore, the inability of a selective D1 receptor antagonist to produce conditioned aversive effects or physical signs of withdrawal suggests an important role of D2 as compared to D1 receptors in the expression of morphine withdrawal signs.

  1. Morphine reduces the threshold of helium preconditioning against myocardial infarction: the role of opioid receptors in rabbits

    Science.gov (United States)

    Pagel, Paul S.; Krolikowski, John G.; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

    2015-01-01

    Objectives Brief, repetitive administration of helium before prolonged coronary artery occlusion and reperfusion protects myocardium against infarction. Opioid receptors mediate the cardioprotective effects of ischemic pre- and postconditioning, but whether these receptors also play a role in helium preconditioning is unknown. We tested the hypotheses that opioid receptors mediate helium preconditioning and that morphine (a μ1-opioid receptor agonist with δ1-opioid agonist properties) lowers the threshold of cardioprotection produced by helium in vivo. Design Randomized, prospective study. Setting University research laboratory. Participants Male New Zealand white rabbits. Interventions Rabbits (n=56) were instrumented for measurement of systemic hemodynamics and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion. In separate experimental groups, rabbits (n=6 or 7 per group) received 0.9% saline (control), one or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture, morphine (0.1 mg/kg, i.v.), or the nonselective opioid antagonist naloxone (6 mg/kg, i.v.) before LAD occlusion. Other groups of rabbits received three cycles of helium or one cycle of helium plus morphine (0.1 mg/kg) in the absence or presence of naloxone (6 mg/kg) before ischemia and reperfusion. Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni’s modification of Student’s t test. Measurements and Main Results Myocardial infarct size was determined using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium reduced myocardial infarct size in an exposure-related manner [36±6 (P>0.05) and 25±4% (P<0.05 versus control) for one and three cycles of helium, respectively; data are mean±SD] compared with control (44±7%). Morphine and naloxone alone did not affect infarct

  2. Cross-sensitization to morphine in cocaine-sensitized rats: behavioral assessments correlate with enhanced responding of ventral pallidal neurons to morphine and glutamate, with diminished effects of GABA.

    Science.gov (United States)

    McDaid, J; Dallimore, J E; Mackie, A R; Mickiewicz, A L; Napier, T C

    2005-06-01

    Common neurobiological substrates contribute to the progressively increased behavioral effects (i.e., sensitization) that occur with repeated intermittent treatments of cocaine and morphine. Consequently, repeated exposure to cocaine can augment responding to morphine (termed cross-sensitization). Drug-induced sensitization in rats may model aspects of the dysfunction in motivation that are imposed by addiction. The ventral pallidum (VP) is involved in motivated behaviors and its function is altered by acute administration of cocaine and morphine, but the effects of repeated drug exposure remain unknown. Targeting this paucity, the present study evaluated electrophysiological changes in the VP of rats exposed to five once-daily cocaine treatments (15 mg/kg i.p.). This regimen also induced behavioral-sensitization that was expressed 3 days later when the rats received either an acute injection of cocaine (15 mg/kg i.p.) or morphine (10 mg/kg i.p.). VP neurons recorded in vivo 3 days after the repeated cocaine treatment regimen demonstrated increased excitatory responding to microiontophoretic applications of morphine and glutamate. The maximal effect (E(max)) was increased without altering potency, suggesting a change in the functional efficacy of the respective receptor systems. This did not represent a potentiation in transmission in general, for the effects of GABA were diminished. The results provide the first evidence for cellular adaptation in the VP after a sensitizing drug treatment paradigm and reveal that cross-sensitization of drug-induced behaviors temporally correlates with changes in VP neuronal responding. These findings advance an emerging theme that alterations in the VP may contribute to the increased motivation for drug seeking that occurs in drug-withdrawn addicts.

  3. Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine.

    Directory of Open Access Journals (Sweden)

    Dusica Bajic

    Full Text Available Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg, a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg.

  4. Effect of Morphine Withdrawal Syndrome on Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Mohammad Allahtavakoli

    2011-01-01

    Full Text Available Objective(sOpioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes.Materials and MethodsAddiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA. Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke.ResultsMorphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05 at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05. ConclusionOur data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

  5. Improvement of buccal delivery of morphine using the prodrug approach

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Jørgensen, A.; Christensen, C.B.

    1997-01-01

    relationship to the lipophilicity of the compounds. In the in vitro studies the optimal permeation was achieved for the prodrug morphine-3-propionate having a log P value of approximately 0.7. In contrast to that optimal in vivo absorption was obtained for the prodrug morphine-3-acetate having a log P value...... Improved by using ester prodrugs with higher lipophilicity than morphine itself. However, the enzymatic stability of the prodrugs in saliva also play an important role for the overall improvement in absorption properties....

  6. Effects of morphine and naloxone on feline colonic transit

    Energy Technology Data Exchange (ETDEWEB)

    Krevsky, B.; Libster, B.; Maurer, A.H.; Chase, B.J.; Fisher, R.S.

    1989-01-01

    The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine cecum and ascending colon transit was accelerated, while at a larger dose morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of the other opioid receptors is inferred.

  7. Intrathecal Administration of Morphine Decreases Persistent Pain after Cesarean Section: A Prospective Observational Study.

    Directory of Open Access Journals (Sweden)

    Kumi Moriyama

    Full Text Available Chronic pain after cesarean section (CS is a serious concern, as it can result in functional disability. We evaluated the prevalence of chronic pain after CS prospectively at a single institution in Japan. We also analyzed perioperative risk factors associated with chronic pain using logistic regression analyses with a backward-stepwise procedure.Patients who underwent elective or emergency CS between May 2012 and May 2014 were recruited. Maternal demographics as well as details of surgery and anesthesia were recorded. An anesthesiologist visited the patients on postoperative day (POD 1 and 2, and assessed their pain with the Prince Henry Pain Scale. To evaluate the prevalence of chronic pain, we contacted patients by sending a questionnaire 3 months post-CS.Among 225 patients who questionnaires, 69 (30.7% of patients complained of persistent pain, although no patient required pain medication. Multivariate analyses identified lighter weight (p = 0.011 and non-intrathecal administration of morphine (p = 0.023 as determinant factors associated with persistent pain at 3 months. The adjusted odds ratio of intrathecal administration of morphine to reduce persistent pain was 0.424, suggesting that intrathecal administration of morphine could decrease chronic pain by 50%. In addition, 51.6% of patients had abnormal wound sensation, suggesting the development of neuropathic pain. Also, 6% of patients with abnormal wound sensation required medication, yet no patients with persistent pain required medication.Although no effect on acute pain was observed, intrathecal administration of morphine significantly decreased chronic pain after CS.

  8. Proteomic analysis of protein composition of rat forebrain cortex exposed to morphine for 10 days; comparison with animals exposed to morphine and subsequently nurtured for 20 days in the absence of this drug

    Czech Academy of Sciences Publication Activity Database

    Ujčíková, Hana; Vošahlíková, Miroslava; Roubalová, Lenka; Svoboda, Petr

    2016-01-01

    Roč. 145, Aug 11 (2016), s. 11-23 ISSN 1874-3919 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP207/12/0919 Institutional support: RVO:67985823 Keywords : morphine * long-term exposure * rat forebrain cortex * post-nuclear supernatant * MALDI-TOF MS/MS * MaxLFQ Subject RIV: CE - Biochemistry Impact factor: 3.914, year: 2016

  9. Single-walled carbon nanotubes toxicity to the freshwater amphipod Hyalella azteca: influence of sediment and exposure duration

    Directory of Open Access Journals (Sweden)

    Messika Revel

    2015-04-01

    Full Text Available Carbon nanomaterials are present in various industrial applications and therefore their release into the environment including freshwater ecosystem is expected to increase. The aim of the present study was to investigate the influence of several parameters on the toxicity of single-walled carbon nanotubes (SWCNT to the freshwater amphipod, Hyalella azteca. The effect of period of exposure, sediment presence and possible impurities released during SWCNT preparation on survival and/or growth of such organism was evaluated. We measured a reduction of survival at concentrations ranging from 10 to 40 mg/L after 96-h exposure, while no mortality was observed with the same concentrations and in the presence of artificial sediment after 14 days of exposure. It is possible that SWCNT are adsorbed on the organic matter from the artificial sediment leading to a decrease of SWCNT bioavailability. The survival and growth toxicity tests revealed a stronger effect at 28 days compared to the 14 days of exposure, and full mortality of organisms at 1000 mg/L for both exposure times. The presence of SWCNT in the gut of survived organisms was observed. The present study demonstrates that the interaction with sediment should be considered when carbon nanotubes toxicity through water exposure is investigated.

  10. The role of CA3-LS-VTA loop in the formation of conditioned place preference induced by context-associated reward memory for morphine.

    Science.gov (United States)

    Jiang, Jin-Xiang; Liu, Huan; Huang, Zhen-Zhen; Cui, Yue; Zhang, Xue-Qin; Zhang, Xiao-Long; Cui, Yu; Xin, Wen-Jun

    2018-01-01

    Addiction-related behaviors, such as conditioned place preference (CPP), require animals to remember an association between environmental cue and drug treatment, and exposure to environmental cue is one of the key contributing factors to relapse. However, how central neural circuit participates in the formation of CPP induced by stimulus of morphine-paired environment remains unknown. In the present study, we found that reexposure to morphine-paired environment significantly increased the activity of hippocampal CA3 neurons, increased the excitability of GABAergic neurons and expression of glutamic acid decarboxylase 65/67 in the caudal lateral septum (LSc) and decreased the activity of GABAergic neurons and GAD65/67 expression in ventral tegmental area (VTA), leading to activation (disinhibition) of dopaminergic neurons. Inactivation of CA3 neurons attenuated GABAergic neurons activity and decreased the upregulation of GAD65/67 in LSc, prevented the dopaminergic neurons activation,and GAD65/67 downregulation in VTA and ameliorated the CPP behavior following exposure to morphine-paired context. Blockade of NMDA receptor in LSc also prevented the upregulation of GAD65/67 in LSc and formation of CPP induced by stimulus of morphine-paired environment. Suppression of GAD activity in LSc also remarkably attenuated the dopaminergic neurons activation and the GAD65/67 downregulation in VTA and prevented the formation of CPP induced by reexposure to morphine-associated context. Collectively, these results, for the first time, illustrated the involvement of neural circuitry of CA3-LSc-VTA, through integration of the contexts and reward information, participated in the reinstatement of CPP induced by exposure to morphine-associated context, which advanced our understanding on neurobiological basis for the context-associated memory and rewarding behavior. © 2016 Society for the Study of Addiction.

  11. Pain-inhibiting inhomogeneous static magnetic field fails to influence locomotor activity and anxiety behavior in mice: no interference between magnetic field- and morphine-treatment.

    Science.gov (United States)

    László, János; Tímár, Júlia; Gyarmati, Zsuzsanna; Fürst, Zsuzsanna; Gyires, Klára

    2009-06-30

    We wanted to demonstrate (i) in the writhing test in mice, whether there was a prolonged analgesic effect induced by an inhomogeneous static magnetic field (SMF) exposure; (ii) whether SMF had an effect on the analgesic effect induced by 0.5mg/kgs.c. administered morphine, on the behavioral patterns, and on the hyperlocomotion-inducing effect of morphine. A magnetic exposure system developed by the present authors was used with peak-to-peak flux densities in the 2-754mT range. The writhing test was used for the assessment of pain. An elevated plus maze and a Conducta System was used for studying the anxiogenic or anxyolitic effect in mice, and the locomotor activity, respectively. We looked for the difference in the number of writhings and in the behavioral patterns between treated (s.c. morphine and/or SMF exposure) and control animals, respectively. (i) The antinociceptive effect could be identified 10-30min following SMF exposition in the writhing test in mice. (ii) SMF failed to affect the morphine-induced antinociception, the behavioral patterns in either type of tests, and the hyperlocomotion-inducing effect of morphine. (i) The long-lasting antinociceptive effect of SMF allows experiments under conditions, when in situ application of the SMF-producing device would be technically difficult or impossible; or where it would disturb the experiments. (ii) The results of behavioral tests with freely moving mice in or in the vicinity of inhomogeneous SMFs are not affected by the SMF in the applied flux density range. (iii) Morphine in treated subjects is not interacting with the inhomogeneous SMFs in the applied flux density range.

  12. Intra-articular morphine in horses

    DEFF Research Database (Denmark)

    Lindegaard, Casper

    Regardless of species, optimal pain management of animals subjected to various painful procedures is of outmost importance for several reasons, including animal welfare considerations, improved convalescence and improved final outcome. One way of improving pain management in horses is through the...... compared to the same dose administered IV, was demonstrated. In combination with the results of the pharmacologic analysis, this is highly suggestive of a peripherally mediated effect of IA morphine.......Regardless of species, optimal pain management of animals subjected to various painful procedures is of outmost importance for several reasons, including animal welfare considerations, improved convalescence and improved final outcome. One way of improving pain management in horses is through...... the principles embodied in "multimodal analgesia". This concept is based on combining various analgesic drugs acting at different levels in the nociceptive pathway, thereby achieving additive and in some situations even synergistic effects of the administered drugs. Consequently, the dose of each drug can...

  13. Single blood-Hg samples can result in exposure misclassification: temporal monitoring within the Japanese community (United States

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    Tsuchiya Ami

    2012-06-01

    Full Text Available Abstract Background The most prominent non-occupational source of exposure to methylmercury is the consumption of fish. In this study we examine a fish consuming population to determine the extent of temporal exposure and investigate the extent to which single time estimates of methylmercury exposure based on blood-Hg concentration can provide reliable estimates of longer-term average exposure. Methods Blood-mercury levels were obtained from a portion of the Arsenic Mercury Intake Biometric Study (AMIBS cohort. Specifically, 56 Japanese women residing in the Puget Sound area of Washington State, US were sampled on three occasions across a one-year period. Results An average of 135 days separated samples, with mean blood-mercury levels for the visits being 5.1, 6.6 and 5.0 μg/l and geometric means being 2.7, 4.5 and 3.1 μg/l. The blood-mercury levels in this group exceed national averages with geometric means for two of the visits being between the 90th and 95th percentiles of nationally observed levels and the lowest geometric mean being between the 75th and 90th percentile. Group means were not significantly different across sampling periods suggesting that exposure of combined subjects remained relatively constant. Comparing intra-individual results over time did not reveal a strong correlation among visits (r = 0.19, 0.50, 0.63 between 1st and 2nd, 2nd and 3rd, and 1st and 3rd sample results, respectively. In comparing blood-mercury levels across two sampling interval combinations (1st and 2nd, 2nd and 3rd, and 1st and 3rd visits, respectively, 58% (n = 34, 53% (n = 31 and 29% (n = 17 of the individuals had at least a 100% difference in blood-Hg levels. Conclusions Point estimates of blood-mercury, when compared with three sample averages, may not reflect temporal variability and individual exposures estimated on the basis of single blood samples should be treated with caution as indicators of long-term exposure

  14. Long-term Morphine-treated Rats are more Sensitive to Antinociceptive Effect of Diclofenac than the Morphine-naive rats

    OpenAIRE

    Akbari, Esmaeil; Mirzaei, Ebrahim; Shahabi Majd, Naghi

    2013-01-01

    This study investigates the effectiveness of the antinociceptive effects of diclofenac, an NSAID, on the nociceptive behavior of morphine-treated rats on formalin test. Rats were treated with morphine-containing drinking water for twenty one days, which induced morphine dependence. The antinociceptive effects of 8, 16, and 32 mg/kg doses of diclofenac were then evaluated and compared with distilled water in a formalin-based model of pain. Diclofenac potentiated pain suppression in morphine-de...

  15. Investigation and analysis of oncologists' knowledge of morphine usage in cancer pain treatment

    Directory of Open Access Journals (Sweden)

    Liu W

    2014-05-01

    Full Text Available Weiran Liu,1,* Shumin Xie,2,* Lin Yue,3,* Jiahao Liu,2 Stephanie Mu-Lian Woo,4 Weilin Liu,2 Adam R Miller,5 Jing Zhang,6 Lijun Huang,7 Lei Zhang8,*1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Anesthesia, Tianjin, People's Republic of China; 2The Xiangya Medical School of Central-South University, Changsha, People's Republic of China; 3Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Outpatient Service, Tianjin, People's Republic of China; 4Harvard University, Cambridge, MA, USA; 5Indiana University School of Medicine, Indianapolis, IN, USA; 6Tianjin Medical University, Tianjin, People's Republic of China; 7Hunan Provincial Tumor Hospital, Department of Lymphoma and Hematology, Changsha, People's Republic of China; 8Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Department of Thoracic Surgery, Tianjin, People's Republic of China *These authors contributed equally to this paperPurpose: To examine oncologists' knowledge of cancer pain and morphine's clinical application in the People's Republic of China. In addition, this study analyzes and discusses the negative factors that currently affect the clinical application of morphine.Patients and methods: A questionnaire survey was given to a random sample of 150 oncologists from Tianjin Medical University Cancer Institute and Hospital. The statistical results were analyzed and processed using SPSS version 21.0 and Matlab version 2012a statistical software. Single-factor analysis of variance, Kruskal–Wallis nonparametric test, and independent samples t-test were adopted to analyze the difference in knowledge scores of morphine usage. The study

  16. Comparison of late effects of single x-ray exposure, chronic tritiated water ingestion, and chronic cesium-137 gamma exposure in mice

    International Nuclear Information System (INIS)

    Carsten, A.L.; Cronkite, E.P.

    1979-01-01

    There is concern over the possible late effects resulting from chronic exposure to tritiated water, a primary by-product of power reactors. We are comparing the genetic and somatic effects of tritiated water ingestion to acute x-ray or chronic cesium-137 gamma-ray exposures. Eight week old mice were maintaned on tritiated water in concentrations of 0.3, 1.0, and 3.0 μCi/ml. Identical animals received cesium-137 gamma exposures equivalent to that from the tritiated water. At 4 week intervals, animals were sacrificed and the hematopoietic stem cell content and cellularity of the bone marrow determined. For comparison of acute and chronic effects, one group of mice received a single whole-body x-ray exposure of 525 rads. The x-irradiated animals showed an immediate sharp decrease in marrow cellularity followed by gradual return to normal levels, with a lifelong reduction in number of marrow stem cells. Animals exposed to the two higher concentrations of tritiated water showed only slight reductions in marrow cellularity, with a lifelong reduction in hematopoietic stem cells in the bone marrow. Comparison of the external gamma exposures to chronic tritiated water ingestion indicates similar patterns. Maintenance of normal cellularity with a reduced number of stem cells in x-rayed animals was shown by tritiated thymidine cytocide to be due to the reduction in number of stem cells in the resting G/sub O/ stage. At this time it is not possible to determine whether there is a significant difference in relative biological effectiveness of tritiated water compared to cesium-137 gamma rays; however, indications are that they are similar

  17. Morphine-assisted cholescintigraphy in the diagnosis of acalculous cholecystitis

    International Nuclear Information System (INIS)

    Sajewicz, Z.; Paradowski, L.; Kowal, A.

    2001-01-01

    Detecting acalculous cholecystitis still causes difficulties. The aim of the study was to assess the usefulness of morphine-assisted cholescintigraphy in the diagnosis of acute and chronic acalculous cholecystitis. Sixteen patients with suspicion of acute or chronic acalculous cholecystitis were examined. in the above mentioned patients choscintigraphy was performed by the intravenous administration of 5 mCi 99mTc-HIDA. None of the patients displayed the gallbladder within 60 min. The intravenous administration of 0.04 mg/kg b.w. morphine did not result in filling a tracer into the gallbladder in 10 patients, which allowed to confirm that acute acalculous cholecystitis. In the remaining 6 patients the morphine induction caused influx of radiotracer into the gallbladder, which allowed to diagnose the chronic acalculous cholecystitis. Morphine-assisted cholescintigraphy turned out to be useful in detecting acute and chronic cholecystitis. (author)

  18. Effects of intravenous morphine on physical examination findings in ...

    African Journals Online (AJOL)

    Conclusion: The study has objectively demonstrated that when compared with placebo judicious administration of I.V morphine provides significant pain reduction without adversely affecting the physical examination findings in patients presenting with acute abdominal pain due to suspected appendicitis.

  19. Morphine in ventilated neonates: Its effects on arterial blood pressure

    NARCIS (Netherlands)

    S.H. Simons (Sinno); D.W.E. Roofthooft (Daniella); M. van Dijk (Monique); R.A. Lingen (Richard); H.J. Duivenvoorden (Hugo); J.N. van den Anker (John); D. Tibboel (Dick)

    2006-01-01

    markdownabstractObjective: To study the effects of continuous morphine infusion on arterial blood pressure in ventilatedneonates. Design: Blinded randomised placebo controlled trial. Setting: Level III neonatal intensive care unit in two centres. Patients: A total of 144 ventilated

  20. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Ghasem Soltani

    2015-10-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  1. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Ghasem Soltani

    2015-09-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  2. Change in the properties of the opiate receptors of the brain under conditions of habituation of rats to morphine

    Energy Technology Data Exchange (ETDEWEB)

    Zaitsev, S.V.; Sergeeva, M.G.; Chichenkov, O.N.; Petrov, V.E.; Varfolomeev, S.D.

    1987-02-20

    The influence of prolonged administration of morphine on the properties of the opiate receptors of the rat brain was investigated. For this purpose they conducted an analysis of the isotherms of binding of labeled ..mu..-, sigma-, and chi-ligands: morphine, D-Ala/sup 2/, D-Leu/sup 5/-enkephalin, and ethylketocyclazocin, with membrane preparations of the brains of rats tolerant to morphine, as well as the control animals. For a quantitative determination of the dissociation constants of the ligand-receptor complexes (K) and the concentration of the reagents ((Q)), they used differential method and the method of simulation modeling. It was shown that the values of K and (Q) for individual animals are subjected to substantial dispersion, whereas the ratios (Q)/K undergo minor individual fluctuations, both in the control group and in the group of rats tolerant to morphine. This permits the ratio (Q)/K to be singled out as one of the main parameters for comparing the properties of opiate receptors of various groups of animals. Using this criterion, as well as the method of simulated modeling, it was shown that the development of tolerance is accompanied by a change in the properties of the delta-receptors (the ratio (Q)/K decreases by a factor of more than two). In contrast to the delta-receptors, no significant influence of the tolerance on the properties of the ..mu..- and chi-receptors, as well as the ultrahigh-affinity ligand binding sites, was detected.

  3. Change in the properties of the opiate receptors of the brain under conditions of habituation of rats to morphine

    International Nuclear Information System (INIS)

    Zaitsev, S.V.; Sergeeva, M.G.; Chichenkov, O.N.; Petrov, V.E.; Varfolomeev, S.D.

    1987-01-01

    The influence of prolonged administration of morphine on the properties of the opiate receptors of the rat brain was investigated. For this purpose they conducted an analysis of the isotherms of binding of labeled μ-, σ-, and chi-ligands: morphine, D-Ala 2 , D-Leu 5 -enkephalin, and ethylketocyclazocin, with membrane preparations of the brains of rats tolerant to morphine, as well as the control animals. For a quantitative determination of the dissociation constants of the ligand-receptor complexes (K) and the concentration of the reagents ([Q]), they used differential method and the method of simulation modeling. It was shown that the values of K and [Q] for individual animals are subjected to substantial dispersion, whereas the ratios [Q]/K undergo minor individual fluctuations, both in the control group and in the group of rats tolerant to morphine. This permits the ratio [Q]/K to be singled out as one of the main parameters for comparing the properties of opiate receptors of various groups of animals. Using this criterion, as well as the method of simulated modeling, it was shown that the development of tolerance is accompanied by a change in the properties of the δ-receptors (the ratio [Q]/K decreases by a factor of more than two). In contrast to the δ-receptors, no significant influence of the tolerance on the properties of the μ- and chi-receptors, as well as the ultrahigh-affinity ligand binding sites, was detected

  4. Cholinergic Synaptic Transmissions Were Altered after Single Sevoflurane Exposure in Drosophila Pupa

    Directory of Open Access Journals (Sweden)

    Rongfa Chen

    2015-01-01

    Full Text Available Purpose. Sevoflurane, one of the most used general anesthetics, is widely used in clinical practice all over the world. Previous studies indicated that sevoflurane could induce neuron apoptosis and neural deficit causing query in the safety of anesthesia using sevoflurane. The present study was designed to investigate the effects of sevoflurane on electrophysiology in Drosophila pupa whose excitatory neurotransmitter is acetylcholine early after sevoflurane exposure using whole brain recording technique. Methods. Wide types of Drosophila (canton-s flies were allocated to control and sevoflurane groups randomly. Sevoflurane groups (1% sevoflurane; 2% sevoflurane; 3% sevoflurane were exposed to sevoflurane and the exposure lasted 5 hours, respectively. All flies were subjected to electrophysiology experiment using patch clamp 24 hours after exposure. Results. The results showed that, 24 hours after sevoflurane exposure, frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs was significantly reduced P<0.05. Furthermore, we explored the underlying mechanism and found that calcium currents density, which partially regulated the frequency of mEPSCs, was significantly reduced after sevoflurane exposure P<0.05. Conclusions. All these suggested that sevoflurane could alter the mEPSCs that are related to synaptic plasticity partially through modulating calcium channel early after sevoflurane exposure.

  5. Cholinergic synaptic transmissions were altered after single sevoflurane exposure in Drosophila pupa.

    Science.gov (United States)

    Chen, Rongfa; Zhang, Tao; Kuang, Liting; Chen, Zhen; Ran, Dongzhi; Niu, Yang; Xu, Kangqing; Gu, Huaiyu

    2015-01-01

    . Sevoflurane, one of the most used general anesthetics, is widely used in clinical practice all over the world. Previous studies indicated that sevoflurane could induce neuron apoptosis and neural deficit causing query in the safety of anesthesia using sevoflurane. The present study was designed to investigate the effects of sevoflurane on electrophysiology in Drosophila pupa whose excitatory neurotransmitter is acetylcholine early after sevoflurane exposure using whole brain recording technique. Wide types of Drosophila (canton-s flies) were allocated to control and sevoflurane groups randomly. Sevoflurane groups (1% sevoflurane; 2% sevoflurane; 3% sevoflurane) were exposed to sevoflurane and the exposure lasted 5 hours, respectively. All flies were subjected to electrophysiology experiment using patch clamp 24 hours after exposure. The results showed that, 24 hours after sevoflurane exposure, frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs) was significantly reduced (P < 0.05). Furthermore, we explored the underlying mechanism and found that calcium currents density, which partially regulated the frequency of mEPSCs, was significantly reduced after sevoflurane exposure (P < 0.05). All these suggested that sevoflurane could alter the mEPSCs that are related to synaptic plasticity partially through modulating calcium channel early after sevoflurane exposure.

  6. Unusual pattern of leukoencephalopathy after morphine sulphate intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Nanan, R.; Stockhausen, H.B. von; Petersen, B. [Children' s Hospital, University of Wuerzburg (Germany); Solymosi, L.; Warmuth-Metz, M. [Department for Neuroradiology, University of Wuerzburg (Germany)

    2000-11-01

    We report a 14-year-old girl with an unusual pattern of leukoencephalopathy after intentional intoxication with morphine sulphate tablets. Toxicological analysis showed exceedingly high levels of morphine and its metabolites. MRI disclosed a leukoencephalopathy with high signal from the centrum semiovale, corpus callosum and cerebellar white matter on T2-weighted images. These findings could be only partially explained by a hypoxic-ischaemic event; neurotoxic effects must be considered in this atypical leukoencephalopathy. (orig.)

  7. Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia.

    Science.gov (United States)

    Gong, Kerui; Jasmin, Luc

    2017-02-01

    It is not uncommon for patients chronically treated with opioids to exhibit opioid-induced hyperalgesia, and this has been widely reported clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small-diameter primary sensory neurons only. Cold allodynia is also a common complaint of patients chronically treated with opioids, yet its molecular mechanisms remain to be understood. Here we present evidence that the cold sensor TRPM8 channel is involved in opioid-induced hyperalgesia. After 7 days of morphine administration, we observed an upregulation of TRPM8 channels using patch clamp recording on sensory neurons and Western blot analysis on dorsal root ganglia. The selective TRPM8 antagonist RQ-00203078 blocked cold hyperalgesia in morphine-treated rats. Also, TRPM8 knockout mice failed to develop cold hyperalgesia after chronic administration of morphine. Our results show that chronic morphine upregulates TRPM8 channels, which is in contrast with the previous finding that acute morphine triggers TRPM8 internalization. Patients receiving chronic opioid are sensitive to cold. We show in mice and rats that sustained morphine administration induces cold hyperalgesia and an upregulation of TRPM8. Knockout or selectively blocking TRPM8 reduces morphine-induced cold hyperalgesia suggesting TRPM8 is regulated by opioids. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  8. Morphine Decreases Enteric Neuron Excitability via Inhibition of Sodium Channels

    OpenAIRE

    Smith, Tricia H.; Grider, John R.; Dewey, William L.; Akbarali, Hamid I.

    2012-01-01

    Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a...

  9. Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats.

    Science.gov (United States)

    Alvandi, Mina Sadighi; Bourmpoula, Maria; Homberg, Judith R; Fathollahi, Yaghoub

    2017-11-01

    Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse. © 2017 Society for the Study of Addiction.

  10. Exposure of Salmonella enterica serovar Typhimurium to high level biocide challenge can select multidrug resistant mutants in a single step.

    Directory of Open Access Journals (Sweden)

    Rebekah N Whitehead

    Full Text Available Biocides are crucial to the prevention of infection by bacteria, particularly with the global emergence of multiply antibiotic resistant strains of many species. Concern has been raised regarding the potential for biocide exposure to select for antibiotic resistance due to common mechanisms of resistance, notably efflux.Salmonella enterica serovar Typhimurium was challenged with 4 biocides of differing modes of action at both low and recommended-use concentration. Flow cytometry was used to investigate the physiological state of the cells after biocide challenge. After 5 hours exposure to biocide, live cells were sorted by FACS and recovered. Cells recovered after an exposure to low concentrations of biocide had antibiotic resistance profiles similar to wild-type cells. Live cells were recovered after exposure to two of the biocides at in-use concentration for 5 hours. These cells were multi-drug resistant and accumulation assays demonstrated an efflux phenotype of these mutants. Gene expression analysis showed that the AcrEF multidrug efflux pump was de-repressed in mutants isolated from high-levels of biocide.These data show that a single exposure to the working concentration of certain biocides can select for mutant Salmonella with efflux mediated multidrug resistance and that flow cytometry is a sensitive tool for identifying biocide tolerant mutants. The propensity for biocides to select for MDR mutants varies and this should be a consideration when designing new biocidal formulations.

  11. Prolonged morphine administration alters protein expression in the rat myocardium

    Directory of Open Access Journals (Sweden)

    Drastichova Zdenka

    2011-11-01

    Full Text Available Abstract Background Morphine is used in clinical practice as a highly effective painkiller as well as the drug of choice for treatment of certain heart diseases. However, there is lack of information about its effect on protein expression in the heart. Therefore, here we aimed to identify the presumed alterations in rat myocardial protein levels after prolonged morphine treatment. Methods Morphine was administered to adult male Wistar rats in high doses (10 mg/kg per day for 10 days. Proteins from the plasma membrane- and mitochondria-enriched fractions or cytosolic proteins isolated from left ventricles were run on 2D gel electrophoresis, scanned and quantified with specific software to reveal differentially expressed proteins. Results Nine proteins were found to show markedly altered expression levels in samples from morphine-treaded rats and these proteins were identified by mass spectrometric analysis. They belong to different cell pathways including signaling, cytoprotective, and structural elements. Conclusions The present identification of several important myocardial proteins altered by prolonged morphine treatment points to global effects of this drug on heart tissue. These findings represent an initial step toward a more complex view on the action of morphine on the heart.

  12. Effect of irradiation on analgesia induced by morphine and endorphin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Lee, Byoung Hun; Hyun, Soung Hee; Chung, Ki Myung [KAERI, Daejeon (Korea, Republic of)

    2003-07-01

    Morphine and endorphin administered intracerebroventricularly (i.c.v.) produce analgesia by activating different descending pain inhibitory systems. Gamma irradiation attenuates the acute analgesic action of i.c.v. injected morphine in mice. This study was done to investigate the effect of-irradiation on the analgesia produced by i.c.v. injected morphine and endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a {sup 60}Co source and the analgesic effects were tested 5, 30, 60, 90 and 180 min after irradiation using the acetic acid-induced writhing test. The analgesic effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for analgesia produced by i.c.v. administration of morphine or endorphin. Irradiation significantly potentiated the analgesia produced by endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results support the hypothesis that morphine and endorphin administered supraspinally produce antinocieception by different neuronal mechanisms.

  13. The effect of morphine on orthodontic tooth movement in rats.

    Science.gov (United States)

    Akhoundi, Mohammad S A; Dehpour, Ahmad Reza; Rashidpour, Mahsa; Alaeddini, Mojgan; Kharazifard, Mohammad Javad; Noroozi, Hassan

    2010-11-01

    To investigate the effect of morphine as an exogenous opioid on orthodontic tooth movement. Naltrexone will be used as an opioid antagonist to confirm the results. Forty rats were randomly divided into four equal groups. The first group received no injection; the second group received daily injections of morphine; the third group received daily naltrexone-morphine injections and the fourth group daily injections of naltrexone-normal saline. The left first maxillary molar in each rat was tipped mesially with a NiTi closed coil spring. The rats were sacrificed after 14 days and the maxillae fixed, sectioned serially and examined histologically. The greatest amount of tooth movement occurred in the Control group and the least amount of tooth movement in the Morphine group. Tooth movement in the Morphine group was significantly different from the other three groups (p 0.05). No statistically significant histological differences were found. Morphine reduced orthodontic tooth movement in rats. This effect was reversed by the opioid antagonist, naltrexone, which had no effect on tooth movement.

  14. Effect of irradiation on analgesia induced by morphine and endorphin

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Lee, Byoung Hun; Hyun, Soung Hee; Chung, Ki Myung

    2003-01-01

    Morphine and endorphin administered intracerebroventricularly (i.c.v.) produce analgesia by activating different descending pain inhibitory systems. Gamma irradiation attenuates the acute analgesic action of i.c.v. injected morphine in mice. This study was done to investigate the effect of-irradiation on the analgesia produced by i.c.v. injected morphine and endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a 60 Co source and the analgesic effects were tested 5, 30, 60, 90 and 180 min after irradiation using the acetic acid-induced writhing test. The analgesic effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for analgesia produced by i.c.v. administration of morphine or endorphin. Irradiation significantly potentiated the analgesia produced by endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results support the hypothesis that morphine and endorphin administered supraspinally produce antinocieception by different neuronal mechanisms

  15. Exposure to plastic surgery during undergraduate medical training: A single-institution review.

    Science.gov (United States)

    Austin, Ryan E; Wanzel, Kyle R

    2015-01-01

    Applications to surgical residency programs have declined over the past decade. Even highly competitive programs, such as plastic surgery, have begun to witness these effects. Studies have shown that early surgical exposure has a positive influence on career selection. To review plastic surgery application trends across Canada, and to further investigate medical student exposure to plastic surgery. To examine plastic surgery application trends, national data from the Canadian Resident Matching Service database were analyzed, comparing 2002 to 2007 with 2008 to 2013. To evaluate plastic surgery exposure, a survey of all undergraduate medical students at the University of Toronto (Toronto, Ontario) during the 2012/2013 academic year was conducted. Comparing 2002 to 2007 and 2008 to 2013, the average number of national plastic surgery training positions nearly doubled, while first-choice applicants decreased by 15.3%. The majority of Canadian academic institutions experienced a decrease in first-choice applicants; 84.7% of survey respondents indicated they had no exposure to plastic surgery during their medical education. Furthermore, 89.7% believed their education had not provided a basic understanding of issues commonly managed by plastic surgeons. The majority of students indicated they receive significantly less plastic surgery teaching than all other surgical subspecialties. More than 44% of students not considering plastic surgery as a career indicated they may be more likely to with increased exposure. If there is a desire to grow the specialty through future generations, recruiting tactics to foster greater interest in plastic surgery must be altered. The present study suggests increased and earlier exposure for medical students is a potential solution.

  16. Exposure to plastic surgery during undergraduate medical training: A single-institution review

    Science.gov (United States)

    Austin, Ryan E; Wanzel, Kyle R

    2015-01-01

    BACKGROUND: Applications to surgical residency programs have declined over the past decade. Even highly competitive programs, such as plastic surgery, have begun to witness these effects. Studies have shown that early surgical exposure has a positive influence on career selection. OBJECTIVE: To review plastic surgery application trends across Canada, and to further investigate medical student exposure to plastic surgery. METHODS: To examine plastic surgery application trends, national data from the Canadian Resident Matching Service database were analyzed, comparing 2002 to 2007 with 2008 to 2013. To evaluate plastic surgery exposure, a survey of all undergraduate medical students at the University of Toronto (Toronto, Ontario) during the 2012/2013 academic year was conducted. RESULTS: Comparing 2002 to 2007 and 2008 to 2013, the average number of national plastic surgery training positions nearly doubled, while first-choice applicants decreased by 15.3%. The majority of Canadian academic institutions experienced a decrease in first-choice applicants; 84.7% of survey respondents indicated they had no exposure to plastic surgery during their medical education. Furthermore, 89.7% believed their education had not provided a basic understanding of issues commonly managed by plastic surgeons. The majority of students indicated they receive significantly less plastic surgery teaching than all other surgical subspecialties. More than 44% of students not considering plastic surgery as a career indicated they may be more likely to with increased exposure. CONCLUSION: If there is a desire to grow the specialty through future generations, recruiting tactics to foster greater interest in plastic surgery must be altered. The present study suggests increased and earlier exposure for medical students is a potential solution. PMID:25821773

  17. Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section: A randomized controlled study.

    Science.gov (United States)

    Weigl, Wojciech; Bieryło, Andrzej; Wielgus, Monika; Krzemień-Wiczyńska, Świetlana; Kołacz, Marcin; Dąbrowski, Michał J

    2017-12-01

    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. This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS. Spinal anesthesia consisted of bupivacaine with either morphine 100 μg (M group), or fentanyl 25 μg and morphine 100 μg (FM group). The frequency of intraoperative pain and pethidine consumption in the 24 hours postoperatively was recorded. Fewer patients in the FM group required additional intraoperative analgesia (P fentanyl and morphine may provide better perioperative analgesia than morphine alone in CS and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after addition of intrathecal fentanyl warrants further investigation using lower doses of fentanyl.

  18. A growth factor attenuates HIV-1 Tat and morphine induced damage to human neurons: implication in HIV/AIDS-drug abuse cases.

    Directory of Open Access Journals (Sweden)

    Shaily Malik

    2011-03-01

    Full Text Available The neuropathological abnormalities of human immunodeficiency virus (HIV-1 patients abusing illicit drugs suggest extensive interactions between the two agents, thereby leading to increased rate of progression to neurodegeneration. The role of HIV-1 transactivating protein, Tat has been elucidated in mediating neuronal damage via apoptosis, a hallmark of HIV-associated dementia (HAD, however the underlying mechanisms involved in enhanced neurodegeneration by illicit drugs remain elusive. In this study, we demonstrated that morphine enhances HIV-Tat induced toxicity in human neurons and neuroblastoma cells. Enhanced toxicity by Tat and morphine was accompanied by increased numbers of TUNEL positive apoptotic neurons, elevated caspase-3 levels and decreased ratio of anti- and pro-apoptotic proteins, Bcl2/Bax. Tat and morphine together elicited high levels of reactive oxygen species that were NADPH dependent. Significant alterations in mitochondrial membrane homeostasis were also observed with co-exposure of these agents. Extensive studies of mitogen activated protein kinase (MAPK signaling pathways revealed the involvement of c-Jun N-terminal kinase (JNK and extracellular signal-regulated kinase-1/2 (ERK1/2 pathways in enhanced toxicity of Tat and morphine. In addition to this, we found that pre-treatment of cells with platelet derived growth factor (PDGF-BB protected neurons from HIV-Tat and morphine induced damage. PDGF-BB alleviated ROS production, maintained mitochondrial membrane potential, decreased caspase-3 activation and hence protected the cells from undergoing apoptosis. PDGF-BB mediated protection against Tat and morphine involved the phosphatidylinositol-3 kinase (PI3K pathway, as specific inhibitor of PI3K abrogated the protection conferred by PDGF-BB. This study demonstrates the mechanism of enhanced toxicity in human neurons subjected to co-exposure of HIV protein Tat and morphine, thus implying its importance in HIV positive drug

  19. [History of opium poppy and morphine].

    Science.gov (United States)

    Norn, Svend; Kruse, Poul R; Kruse, Edith

    2005-01-01

    Opium has been known for millennia to relieve pain and its use for surgical analgesia has been recorded for several centuries. The Sumerian clay tablet (about 2100 BC) is considered to be the world's oldest recorded list of medical prescriptions. It is believed by some scholars that the opium poppy is referred to on the tablet. Some objects from the ancient Greek Minoan culture may also suggest the knowledge of the poppy. A goddess from about 1500 BC shows her hair adorned probably with poppy-capsules and her closed eyes disclose sedation. Also juglets probably imitating the poppy-capsules were found in that period in both Cyprus and Egypt. The first authentic reference to the milky juice of the poppy we find by Theophrastus at the beginning of the third century BC. In the first century the opium poppy and opium was known by Dioscorides, Pliny and Celsus and later on by Galen. Celsus suggests the use of opium before surgery and Dioscorides recommended patients should take mandrake (contains scopolamine and atropine) mixed with wine, before limb amputation. The Arabic physicians used opium very extensively and about 1000 AD it was recommended by Avicenna especially in diarrhoea and diseases of the eye. Polypharmacy, including a mixture of nonsensical medications were often used. Fortunately for both patients and physicians many of the preparations contained opium. The goal was a panacea for all diseases. A famous and expensive panacea was theriaca containing up to sixty drugs including opium. Simplified preparations of opium such as tinctura opii were used up to about 2000 in Denmark. In the early 1800s sciences developed and Sertürner isolated morphine from opium and was the founder of alkaloid research. A more safe and standardized effect was obtained by the pure opium. Several morphine-like drugs have been synthesized to minimize adverse effects and abuse potential. Opioid receptors were identified and characterized in binding assays and their localization

  20. Exposure-based cognitive behavioral therapy for irritable bowel syndrome. A single-case experimental design across 13 subjects.

    Science.gov (United States)

    Boersma, Katja; Ljótsson, Brjánn; Edebol-Carlman, Hanna; Schrooten, Martien; Linton, Steven J; Brummer, Robert J

    2016-11-01

    Irritable bowel syndrome (IBS) is a highly prevalent disorder with a significant impact on quality of life. The presence of psychological symptoms in IBS patients such as catastrophic worry and behavioral avoidance suggests the possible efficacy of cognitive behavioral interventions. Exposure-based cognitive behavioral therapy (CBT) has proven to be a promising approach but has only been investigated in a few studies and mainly via the Internet. Therefore, the aims of this study were to extend and replicate previous findings and to evaluate whether an individual, face-to-face, exposure-based CBT leads to improvement in gastrointestinal symptoms, pain catastrophizing, avoidance behavior and quality of life in IBS patients. Thirteen patients with IBS according to Rome III criteria participated in a single-case experimental study using a five-week baseline and a subsequent twelve-session intervention phase focusing on psycho-education, mindfulness and in vivo exposure. Standardized measurement of gastrointestinal symptoms, pain catastrophizing, avoidance behavior and quality of life was conducted weekly during baseline as well as intervention phase and at six-month follow-up. Results showed that over 70% of patients improved significantly on gastrointestinal symptoms, pain catastrophizing, and quality of life. Effects on avoidance behavior were modest. These results strengthen and extend earlier findings and provide further support for the efficacy of exposure-based strategies for IBS.

  1. Wide-field time-correlated single photon counting (TCSPC) microscopy with time resolution below the frame exposure time

    Energy Technology Data Exchange (ETDEWEB)

    Hirvonen, Liisa M. [Department of Physics, King' s College London, Strand, London WC2R 2LS (United Kingdom); Petrášek, Zdeněk [Max Planck Institute of Biochemistry, Department of Cellular and Molecular Biophysics, Am Klopferspitz 18, D-82152 Martinsried (Germany); Suhling, Klaus, E-mail: klaus.suhling@kcl.ac.uk [Department of Physics, King' s College London, Strand, London WC2R 2LS (United Kingdom)

    2015-07-01

    Fast frame rate CMOS cameras in combination with photon counting intensifiers can be used for fluorescence imaging with single photon sensitivity at kHz frame rates. We show here how the phosphor decay of the image intensifier can be exploited for accurate timing of photon arrival well below the camera exposure time. This is achieved by taking ratios of the intensity of the photon events in two subsequent frames, and effectively allows wide-field TCSPC. This technique was used for measuring decays of ruthenium compound Ru(dpp) with lifetimes as low as 1 μs with 18.5 μs frame exposure time, including in living HeLa cells, using around 0.1 μW excitation power. We speculate that by using an image intensifier with a faster phosphor decay to match a higher camera frame rate, photon arrival time measurements on the nanosecond time scale could well be possible.

  2. Time-dependent inhibition of Na+/K+-ATPase induced by single and simultaneous exposure to lead and cadmium

    Science.gov (United States)

    Vasić, V.; Kojić, D.; Krinulović, K.; Čolović, M.; Vujačić, A.; Stojić, D.

    2007-09-01

    Time-dependent interactions of Na+/K+-ATPase, isolated from rat brain synaptic plasma membranes (SPMs), with Cd2+ and Pb2+ ions in a single exposure and in a mixture were investigated in vitro. The interference of the enzyme with these metal ions was studied as a function of different protein concentrations and exposure time. The aim of the work was to investigate the possibility of selective recognition of Cd2+ and Pb2+ ions in a mixture, on the basis of the different rates of their protein-ligand interactions. Decreasing protein concentration increased the sensitivity of Na+/K+-ATPase toward both metals. The selectivity in protein-ligand interactions was obtained by variation of preincubation time (incubation before starting the enzymatic reaction).

  3. Response of cardiac autonomic modulation after a single exposure to musical auditory stimulation.

    Science.gov (United States)

    Ferreira, Lucas L; Vanderlei, Luiz Carlos M; Guida, Heraldo L; de Abreu, Luiz Carlos; Garner, David M; Vanderlei, Franciele M; Ferreira, Celso; Valenti, Vitor E

    2015-01-01

    The acute effects after exposure to different styles of music on cardiac autonomic modulation assessed through heart rate variability (HRV) analysis have not yet been well elucidated. We aimed to investigate the recovery response of cardiac autonomic modulation in women after exposure to musical auditory stimulation of different styles. The study was conducted on 30 healthy women aged between 18 years and 30 years. We did not include subjects having previous experience with musical instruments and those who had an affinity for music styles. The volunteers remained at rest for 10 min and were exposed to classical baroque (64-84 dB) and heavy metal (75-84 dB) music for 10 min, and their HRV was evaluated for 30 min after music cessation. We analyzed the following HRV indices: Standard deviation of normal-to-normal (SDNN) intervals, root mean square of successive differences (RMSSD), percentage of normal-to-normal 50 (pNN50), low frequency (LF), high frequency (HF), and LF/HF ratio. SDNN, LF in absolute units (ms 2 ) and normalized (nu), and LF/HF ratio increased while HF index (nu) decreased after exposure to classical baroque music. Regarding the heavy metal music style, it was observed that there were increases in SDNN, RMSSD, pNN50, and LF (ms 2 ) after the musical stimulation. In conclusion, the recovery response of cardiac autonomic modulation after exposure to auditory stimulation with music featured an increased global activity of both systems for the two musical styles, with a cardiac sympathetic modulation for classical baroque music and a cardiac vagal tone for the heavy metal style.

  4. Cholinergic Synaptic Transmissions Were Altered after Single Sevoflurane Exposure in Drosophila Pupa

    OpenAIRE

    Chen, Rongfa; Zhang, Tao; Kuang, Liting; Chen, Zhen; Ran, Dongzhi; Niu, Yang; Xu, Kangqing; Gu, Huaiyu

    2015-01-01

    Purpose. Sevoflurane, one of the most used general anesthetics, is widely used in clinical practice all over the world. Previous studies indicated that sevoflurane could induce neuron apoptosis and neural deficit causing query in the safety of anesthesia using sevoflurane. The present study was designed to investigate the effects of sevoflurane on electrophysiology in Drosophila pupa whose excitatory neurotransmitter is acetylcholine early after sevoflurane exposure using whole brain recordin...

  5. Intrathecal morphine is superior to intravenous PCA in patients undergoing minimally invasive cardiac surgery

    Directory of Open Access Journals (Sweden)

    Chirojit Mukherjee

    2012-01-01

    Full Text Available Aim of our study was to evaluate the beneficial effect of low dose intrathecal morphine on postoperative analgesia, over the use of intravenous patient controlled anesthesia (PCA, in patients undergoing fast track anesthesia during minimally invasive cardiac surgical procedures. A randomized controlled trial was undertaken after approval from local ethical committee. Written informed consent was obtained from 61 patients receiving mitral or tricuspid or both surgical valve repair in minimal invasive technique. Patients were assigned randomly to 2 groups. Group 1 received general anesthesia and intravenous patient controlled analgesia (PCA pump with Piritramide (GA group. Group 2 received a single shot of intrathecal morphine (1.5 μg/kg body weight prior to the administration of general anesthesia (ITM group. Site of puncture was confined to lumbar (L1-2 or L2-3 intrathecal space. The amount of intravenous piritramide used in post anesthesia care unit (PACU and the first postoperative day was defined as primary end point. Secondary end points included: time for tracheal extubation, pain and sedation scores in PACU upto third postoperative day. For statistical analysis Mann-Whitney-U Test and Fishers exact test (SPSS were used. We found that the demand for intravenous opioids in PACU was significantly reduced in ITM group (P <0.001. Pain scores were significantly decreased in ITM group until second postoperative day (P <0.01. There was no time delay for tracheal extubation in ITM group, and sedation scores did not differ in either group. We conclude that low dose single shot intrathecal morphine provides adequate postoperative analgesia, reduces the intravenous opioid consumption during the early postoperative period and does not defer early extubation.

  6. The effects of a single memantine treatment on behavioral alterations associated with binge alcohol exposure in neonatal rats.

    Science.gov (United States)

    Idrus, Nirelia M; McGough, Nancy N H; Spinetta, Michael J; Thomas, Jennifer D; Riley, Edward P

    2011-01-01

    The third trimester in human fetal development represents a critical time of brain maturation referred to as the "brain growth spurt". This period occurs in rats postnatally, and exposure to ethanol during this time can increase the risk of impairments on a variety of cognitive and motor tasks. It has been proposed that one potential mechanism for the teratogenic effects of ethanol is NMDA receptor-mediated excitotoxicity during periods of ethanol withdrawal. In neonatal rats, antagonism of NMDA receptors during ethanol withdrawal, with drugs such as MK-801 and eliprodil, has been shown to mitigate some of the behavioral deficits induced by developmental ethanol exposure. The current study examined whether memantine, an NMDA receptor antagonist and a drug used clinically in Alzheimer's patients, would attenuate impairments associated with binge ethanol exposure in neonatal rats. On postnatal day 6, rats were exposed to 6 g/kg ethanol via intubation with controls receiving an isocaloric maltose dextrin solution. Twenty-one hours following the ethanol binge, rats received intraperitoneal injections of memantine at 0, 10, 15, or 20 mg/kg. Ethanol's teratogenic effects were assessed using multiple behavioral tasks: open field activity, parallel bars and spatial discrimination reversal learning. Ethanol-treated rats were overactive in the open field and were impaired on both reversal learning and motor performance. Administration of 15 or 20 mg/kg memantine during withdrawal significantly attenuated ethanol's adverse effects on motor coordination, but did not significantly alter activity levels or improve the spatial learning deficits associated with neonatal alcohol exposure. These results indicate that a single memantine administration during ethanol withdrawal can mitigate motor impairments but not spatial learning impairments or overactivity observed following a binge ethanol exposure during development in the rat. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Steady-state kinetics and dynamics of morphine in cancer patients

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Sjøgren, P; Jensen, N H

    1999-01-01

    Eighteen patients suffering from chronic pain due to cancer completed a balanced, double-blind, double-dummy, two period cross-over trial comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, after...... administration of morphine given as controlled-release (CR) tablets (every 12 h) and immediate-release (IR) tablets (every 6 h). The same total daily dose of morphine was given in both study periods. Patients received both test formulations for 4 days and on the final day of each period, peripheral venous blood...... samples for analysis of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were obtained. Pain intensity, sedation, and continuous reaction time (CRT) were assessed. No significant differences could be demonstrated in AUC/dose, Cmin, Cmax or fluctuation index values between the two treatments...

  8. Effect of linalool on morphine tolerance and dependence in mice.

    Science.gov (United States)

    Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Hosseini, Mohammadreza; Razavi, Bibi Marjan

    2012-09-01

    Linalool, a terpene alcohol, has been shown to interact with the opioid system and N-methyl-D-aspartate (NMDA) receptor. Therefore, the effect of linalool on morphine dependence and tolerance was studied. Dependence and tolerance were induced in mice using subcutaneous morphine injections, three times a day (50, 50 and 75 mg/kg /day) for 3 days. To evaluate the effect of agents on the induction of morphine dependence and tolerance, linalool (50, 75 and 100 mg/kg), clonidine (positive control), alpha-2 receptor agonist, (0.1 mg/kg), memantine, NMDA receptor antagonist (positive control), (30 mg/kg) and saline were injected intraperitoneally three times a day for 3 days. To determine the expression of morphine dependence and tolerance, all compounds were injected once intraperitoneally on the day of experiment. The effect of linalool and other agents on dependence were evaluated by counting the number of jumps (induced by naloxone 5 mg/kg). The tolerance was evaluated by the tail-flick test. The results showed that linalool in the induction and expression phase increased the nociception threshold. Linalool (48% and 95.6% at doses 75 and 100 mg/kg, respectively), clonidine and memantine reduced the severity of withdrawal signs in the induction and expression phases. This study indicated that linalool has a significant effect on morphine tolerance and dependence. This effect may be mediated partially through the inhibition of NMDA receptors. Copyright © 2012 John Wiley & Sons, Ltd.

  9. The significance of the adenosinergic system in morphine dependence

    Directory of Open Access Journals (Sweden)

    Lupina Malgorzata

    2015-09-01

    Full Text Available Addiction is a chronic and recurrent disease. In its pathology, neuroadaptive changes within the dopaminergic pathways inside the mesolimbic system play a predominant role. Of note, the manner in which various neurotransmitters act on their receptors, may modulate the addictive process. Adenosine, an important neuromodulator in the central nervous system, is able to modify the opioid dependence, doing so mainly by its activity on the adenosine A1 and A2A receptors. In the present manuscript, the actual state of knowledge on the relationships between adenosinergic receptors and opioid dependence has been described. Various literature data on the involvement of adenosine ligands, mainly in the signs of morphine withdrawal, as well as morphine-induced sensitization, were also collected. Additionally, in this paper, some important interactions between adenosine and other neurotransmitters (e.g. dopamine, glutamate are described. It is put forward that these connections are the major mechanism of involvement of the adenosinergic system in morphine addiction. The repeatedly confirmed effectiveness of adenosine ligands in morphine dependence, as seen in various experimental protocols, suggests that adenosine ligands may be useful tools for developing new strategies for attenuating morphine dependence.

  10. Single-exposure two-dimensional superresolution in digital holography using a vertical cavity surface-emitting laser source array.

    Science.gov (United States)

    Granero, Luis; Zalevsky, Zeev; Micó, Vicente

    2011-04-01

    We present a new implementation capable of producing two-dimensional (2D) superresolution (SR) imaging in a single exposure by aperture synthesis in digital lensless Fourier holography when using angular multiplexing provided by a vertical cavity surface-emitting laser source array. The system performs the recording in a single CCD snapshot of a multiplexed hologram coming from the incoherent addition of multiple subholograms, where each contains information about a different 2D spatial frequency band of the object's spectrum. Thus, a set of nonoverlapping bandpass images of the input object can be recovered by Fourier transformation (FT) of the multiplexed hologram. The SR is obtained by coherent addition of the information contained in each bandpass image while generating an enlarged synthetic aperture. Experimental results demonstrate improvement in resolution and image quality.

  11. Single shot damage mechanism of Mo/Si multilayer optics under intense pulsed XUV-exposures

    NARCIS (Netherlands)

    Khorsand, A.R.; Sobierajski, R.; Louis, Eric; Bruijn, S.; Gleeson, A.; van de Kruijs, Robbert Wilhelmus Elisabeth; Gullikson, E.M.; Bijkerk, Frederik

    2010-01-01

    We investigated single shot damage of Mo/Si multilayer coatings exposed to the intense fs XUV radiation at the Free-electron LASer facility in Hamburg - FLASH. The interaction process was studied in situ by XUV reflectometry, time resolved optical microscopy, and “post-mortem” by

  12. DNA damage in rats after a single oral exposure to diesel exhaust particles

    DEFF Research Database (Denmark)

    Danielsen, Pernille Høgh; Risom, Lotte; Wallin, Håkan

    2008-01-01

    The gastrointestinal route of exposure to particulate matter is important because particles are ingested via contaminated foods and inhaled particles are swallowed when removed from the airways by the mucociliary clearance system. We investigated the effect of an intragastric administration by oral...... gavage of diesel exhaust particles (DEP) in terms of DNA damage, oxidative stress and DNA repair in colon epithelial cells, liver, and lung of rats. Eight rats per group were exposed to Standard Reference Material 2975 at 0.064 or 0.64 mg/kg bodyweight for 6 and 24 h. Increased levels of 8-oxo-7...

  13. Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury

    International Nuclear Information System (INIS)

    He, Haiyan; Huh, Jin; Wang, Huihua; Kang, Yi; Lou, Jianshi; Xu, Zhelong

    2016-01-01

    Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2 h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (ΔΨm) were measured. Morphine reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ΔΨm at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine reduced

  14. Single walled carbon nanotube reactivity and cytotoxicity following extended aqueous exposure

    International Nuclear Information System (INIS)

    Panessa-Warren, Barbara J.; Maye, Mathew M.; Warren, John B.; Crosson, Kenya M.

    2009-01-01

    Globally carbon nanoparticles are increasingly utilized, yet it is not known if these nanoparticles pose a threat to the environment or human health. This investigation examined 'as-prepared', and acid cleaned carbon nanoparticle physicochemical characteristics (by FTIR, TEM, FESEM, UV-VIS and X-ray microanalysis), and whether these characteristics changed following 2.5-7 yr exposure to pH neutral saline or fresh water. To determine if these aqueous aged nanotubes were cytotoxic, these nanotubes were incubated with human epithelial monolayers and analyzed for cell viability (vital staining) and ultrastructural nanoparticle binding/localization (TEM, FESEM). The presence of Ni and Y catalyst, was less damaging to cells than CNT lattice surface oxidation. Extended fresh water storage of oxidized CNTs did not reduce surface reactive groups, nor lessen cell membrane destruction or cell death. However storing oxidized CNTs in saline or NOM significantly reduced CNT-induced cell membrane damage and increased cell survival to control levels. - Oxidized SWCNTs in pH neutral fresh and saline water showed no reduction in surface oxidation with time, yet exposure of these nanotubes to saline and NOM reduced human cell toxicity markedly

  15. Epidural steroids, epidural morphine and epidural steroids combined with morphine in the treatment of post-laminectomy syndrome.

    Science.gov (United States)

    Rocco, A G; Frank, E; Kaul, A F; Lipson, S J; Gallo, J P

    1989-03-01

    Epidural morphine injection followed by a steroid has been reported to be effective for the post-laminectomy pain ('failed back') syndrome. This double-blind, parallel study was undertaken to evaluate that mode of therapy. Twenty-two patients who had undergone at least one prior laminectomy, who were still symptomatic, were randomized to receive 50 mg of lidocaine epidurally with: (a) 75 mg triamcinolone diacetate (TR); or (b) 8 mg of preservative-free morphine (MP); or (c) both (TR and MP), at 1 month intervals for 3 consecutive months. The spinal interspace identified with the patients' pain complaint was the site of injection. For each treatment, patients were admitted to the Clinical Research Center for 24 h and their condition continuously monitored with a pulse oximeter and apnea monitor. Five to 7 patients in each group had pain relief for less than 1 month. No patient given morphine had pain relief for more than 1 month. Life-threatening ventilatory depression occurred in the group given triamcinolone and morphine. The use of morphine alone or combined with slow release triamcinolone does not appear to be appropriate for the treatment of the post-laminectomy pain syndrome.

  16. Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material.

    Science.gov (United States)

    Maynard, Andrew D; Baron, Paul A; Foley, Michael; Shvedova, Anna A; Kisin, Elena R; Castranova, Vincent

    2004-01-09

    Carbon nanotubes represent a relatively recently discovered allotrope of carbon that exhibits unique properties. While commercial interest in the material is leading to the development of mass production and handling facilities, little is known of the risk associated with exposure. In a two-part study, preliminary investigations have been carried out into the potential exposure routes and toxicity of single-walled carbon nanotube material (SWCNT)--a specific form of the allotrope. The material is characterized by bundles of fibrous carbon molecules that may be a few nanometers in diameter, but micrometers in length. The two production processes investigated use-transition metal catalysts, leading to the inclusion of nanometer-scale metallic particles within unrefined SWCNT material. A laboratory-based study was undertaken to evaluate the physical nature of the aerosol formed from SWCNT during mechanical agitation. This was complemented by a field study in which airborne and dermal exposure to SWCNT was investigated while handling unrefined material. Although laboratory studies indicated that with sufficient agitation, unrefined SWCNT material can release fine particles into the air, concentrations generated while handling material in the field were very low. Estimates of the airborne concentration of nanotube material generated during handling suggest that concentrations were lower than 53 microg/m(3) in all cases. Glove deposits of SWCNT during handling were estimated at between 0.2 mg and 6 mg per hand.

  17. Safety of pain control with morphine: new (and old) aspects of ...

    African Journals Online (AJOL)

    Background: A 26-year-old, 59 kg female was administered morphine 10 mg during tonsillectomy, and 5 mg in the recovery room. She died 5 hours after the operation. Hypoxic cerebral injury, arising from morphine side-effects, was pronounced the cause of death, in spite of morphine being undetectable in blood. Recent ...

  18. Recommended use of morphine in neonates, infants and children based on a literature review

    DEFF Research Database (Denmark)

    Kart, T; Christrup, Lona Louring; Rasmussen, M

    1997-01-01

    The indication for morphine use is primarily pain, but also a combined analgesic and sedative effect may be the rationale behind morphine administration. Paediatric morphine regimens have been reported for children with postoperative pain, pain related to cancer, sickle cell crisis pain, burns...

  19. Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

    Science.gov (United States)

    Perrine, Shane A; Eagle, Andrew L; George, Sophie A; Mulo, Kostika; Kohler, Robert J; Gerard, Justin; Harutyunyan, Arman; Hool, Steven M; Susick, Laura L; Schneider, Brandy L; Ghoddoussi, Farhad; Galloway, Matthew P; Liberzon, Israel; Conti, Alana C

    2016-04-15

    Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo-pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex

  20. Mechanical impedance of the sitting human body in single-axis compared to multi-axis whole-body vibration exposure.

    Science.gov (United States)

    Holmlund, P; Lundström, R

    2001-01-01

    The study was aimed to investigate the mechanical impedance of the sitting human body and to compare data obtained in laboratory single-axis investigations with multi-axis data from in vehicle measurements. The experiments were performed in a laboratory for single-axis measurements. The multi-axis exposure was generated with an eight-seat minibus where the rear seats had been replaced with a rigid one. The subjects in the multi-axis experiment all participated in the single-axis experiments. There are quite a few investigations in the literature describing the human response to single-axis exposure. The response from the human body can be expected to be affected by multi-axis input in a different way than from a single-axis exposure. The present knowledge of the effect of multiple axis exposure is very limited. The measurements were performed using a specially designed force and accelerometer plate. This plate was placed between the subject and the hard seat. Outcome shows a clear difference between mechanical impedance for multi-axis exposure compared to single-axis. This is especially clear in the x-direction where the difference is very large. The conclusion is that it seems unlikely that single-axis mechanical impedance data can be directly transferred to a multi-axis environment. This is due to the force cross-talk between different directions.

  1. Stability of Fentanyl Citrate, Hydromorphone Hydrochloride, Ketamine Hydrochloride, Midazolam, Morphine Sulfate, and Pentobarbital Sodium in Polypropylene Syringes

    OpenAIRE

    Anderson, Collin; MacKay, Mark

    2015-01-01

    Purpose: Determine the stability of fentanyl 10 mcg/mL in 0.9% sodium chloride, fentanyl 10 mcg/mL in 5% dextrose, fentanyl 50 mcg/mL, hydromorphone 100 mcg/mL in 0.9% sodium chloride, ketamine 10 mg/mL, midazolam 0.4 mg/mL in 5% dextrose, midazolam 5 mg/mL, morphine 1 mg/mL in 0.9% sodium chloride, morphine 1 mg/mL in 5% dextrose, and pentobarbital 50 mg/mL when stored as single drug entities at room temperature in polypropylene syringes. Methods: Four 5 mL samples of each drug and concentra...

  2. Interest Rate Demands and Television Viewing-Is a Single Exposure More Influential Than Routine Viewing?

    Science.gov (United States)

    Hetsroni, Amir; Reizer, Abira; Ben Zion, Uri

    2017-04-01

    This study examined the impact of media consumption, and particularly exposure to television, on decisions regarding interest rate demands. One hundred and fifty-four participants were randomly divided into two groups: in the manipulation group, participants were exposed to a news clip about an Iranian nuclear attack on Israel, whereas in the control group, the participants were not exposed to the film. Both groups filled a questionnaires regarding their interest rate requirements in different situations, their media conception behaviors, and demographic questionnaires. Frequent routine viewing increased the interest rate demands only among participants in the manipulation group, but the manipulation itself did not have a significant effect on interest rate demands. The results are explained in terms of cultivation theory.

  3. Single inhalation exposure to 90SrCl2 in the Beagle dog: early hematological effects

    International Nuclear Information System (INIS)

    Gillett, N.; Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; Rebar, A.H.; McClellan, R.O.

    1985-01-01

    Young adult Beagle dogs were exposed once to aerosols containing 90 SrCl 2 to obtain initial body burdens ranging from 2.5 to 250 uCi 90 Sr/kg body weight and subsequently observed throughout their life span. All of the dogs are now dead. The primary cause of death over the entire length of the study was radiation-induced osteosarcomas. However, six dogs died at less than 30 days after exposure as a result of a radiation-induced bone marrow aplasia. Review of hematological parameters of all dogs showed a similar, consistent, and often dramatic pancytopenia in those animals having a long-term retained burden of greater than 10 uCi 90 Sr/kg. The hematologic changes were similar to those seen in people exposed to high doses of whole body external radiation. 4 references, 1 figure, 1 table

  4. Single exposure to disclaimers on airbrushed thin ideal images increases negative thought accessibility.

    Science.gov (United States)

    Selimbegović, Leila; Chatard, Armand

    2015-01-01

    Disclaimers on airbrushed thin ideal images can attract attention to the thin ideal standard promoted by the advertisements, which can be damaging rather than helpful. In this study, 48 female college students were exposed to a thin ideal image including a disclaimer, a neutral sentence, or nothing. Two weeks and two months after this, they were again exposed to the same image but with no accompanying text in any of the conditions. Negative thought accessibility was assessed three times, after each exposure to the thin-ideal image, using reaction time measures. Participants randomly assigned to the disclaimer condition systematically showed greater accessibility of negative thoughts than those in the other two conditions, irrespective of the time of measurement. These results suggest that disclaimers on airbrushed images may have some counter-productive effects by accentuating the problems that they precisely aim to address. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Biological fate of a single administration of 191Pt in rats following different routes of exposure

    International Nuclear Information System (INIS)

    Moore, W. Jr.; Hysell, D.; Crocker, W.; Stara, J.

    1975-01-01

    The retention, tissue distribution, and excretion of 191 Pt in adult rats was determined following oral, intravenous (IV), and intratracheal administration. The highest retention was obtained following IV dosing, and lowest retention (less than 0.5 percent) occurred after oral dosing. Tissues containing the highest concentrations of 191 Pt following IV administration were the kidney, adrenal, spleen, and liver. Following a single oral dose, almost all of the 191 Pt was excreted in the feces due to nonabsorption, whereas after IV dosing, similar quantities were excreted in both the urine and feces. Following IV dosing of pregnant rats, 191 Pt was found in all the fetuses; however, the amount was small

  6. Bioactivation of morphine-3-propionate, a prodrug of morphine, in tissues from different species

    DEFF Research Database (Denmark)

    Groth, L.; Jørgensen, A.; Steffansen, B.

    1997-01-01

    and plasma from rat, rabbit and man, in serum from pig, in liver, kidney, brain, buccal mucosa, muscle and skin homogenate from rat, rabbit and pig and in skin homogenate from man. Within the same species there was no difference in the enzymatic activity in whole blood, serum and plasma. Comparing...... the enzymatic activity in blood fractions from the various species, the activity was higher in man followed by rabbit, rat and pig, respectively. The enzymatic activity in the tissue homogenates was general highest in liver followed by kidney, brain, buccal mucosa, muscle and skin. The tissue homogenate from...... rabbit had higher enzymatic activity than those from rat, which again showed higher activity than those from pig. Comparison of the Michaelis-Menten parameters, K(m) and V(max), obtained using pig and rat serum respectively, suggested that morphine-3-propionate has a lower affinity for enzymes present...

  7. Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer.

    Science.gov (United States)

    Slutsker, L; Hoesly, F C; Miller, L; Williams, L P; Watson, J C; Fleming, D W

    1990-07-11

    Although eosinophilia-myalgia syndrome has been linked to use of tryptophan, it has been unclear whether tryptophan itself or a contaminant causes illness. In Oregon, we compared the brand and source of tryptophan used by 58 patients with eosinophilia-myalgia syndrome with the brand and source of tryptophan used by 30 asymptomatic controls identified through a random telephone survey and 63 asymptomatic controls who contacted the Oregon Health Division voluntarily. Although a single brand/retail lot of tryptophan was statistically associated with the development of eosinophilia-myalgia syndrome, there was no common importer, wholesaler, tablet maker, encapsulator, or distributor. However, 45 (98%) of 46 cases had taken a product made by one manufacturer, compared with three (30%) of 10 telephone survey controls and 15 (48%) of 31 volunteer controls. Retail lots of tryptophan from this manufacturer that were associated with cases were significantly more likely to have been produced from January through June 1989 than lots from this manufacturer that were taken by controls. These findings indicate that the recent epidemic of eosinophilia-myalgia syndrome was caused by a contaminant or an alteration in a subset of tryptophan manufactured by a single company in Japan shortly before the outbreak began.

  8. Subanaesthetic ketamine spares postoperative morphine and controls pain better than standard morphine does alone in orthopaedic-oncological patients.

    Science.gov (United States)

    Kollender, Yehuda; Bickels, Jacob; Stocki, Daniel; Maruoani, Nissim; Chazan, Shoshana; Nirkin, Alexander; Meller, Isaac; Weinbroum, Avi A

    2008-05-01

    Postoperative pain in patients with bone and soft tissue cancer is different from that of other surgical patients due to the severity of the pain generated during surgery and because many of them have already been in pain preoperatively. The search for optimal intravenous pharmacologic management for this population is an ongoing one. We conducted a 10-month prospective, randomised, double blind study to compare the effects of a standard morphine dose to a 35%-lower dose plus a subanaesthetic dose of ketamine for postoperative pain control in patients undergoing bone and soft tissue cancer surgery under standardised general anaesthesia. After extubation, when objectively awake (>or=5/10 on a 0-10 visual analogue scale (VAS)) and complaining of pain (>or=5/10 VAS), patients were connected to an intravenous patient-controlled analgesia (IV-PCA) device that delivered 1.5 mg morphine/bolus (MO group) or 1 mg morphine+5mg ketamine/bolus (MK group), with a 7 min lockout time. Rescue intramuscular diclofenac 75 mg was available Q4/day. Follow-up lasted 96 h. Fifty-seven patients (24 males, aged 18-74 years) completed the study. Pain scores were lower in the MK group compared to the MO patients, although MO patients (n=29) used 32.9+/-24.9 mg/patient morphine during the first 24 postoperative h compared to 14.6+/-11.4 mg/patient (Pphysiotherapy score was 35% higher for the MK patients (P<0.05). No patient had hallucinations. Postoperative nausea and vomiting rates were higher in the MO group. The use of subanaesthetic ketamine plus 2/3 the standard dose of morphine following bone and tissue resections results in 1) lower and more stable pain score, 2) approximately 60% morphine sparing effect, 3) a shorter period of postoperative IV-PCA dependence. Such therapy is also associated with better early physical performance.

  9. Role of delta-opioid receptors in mediating the aversive stimulus effects of morphine withdrawal in the rat.

    Science.gov (United States)

    Funada, M; Schutz, C G; Shippenberg, T S

    1996-04-04

    An unbiased place preference conditioning procedure was used to examine the role of delta-opioid receptors in mediating the aversive effects of opioid withdrawal. Rats were implanted s.c. with two pellets each containing placebo or 75 mg morphine. Single-trial conditioning sessions with saline and the opioid receptor antagonists naloxone (0.001-1.0 mg/kg, s.c.), naltrindole (0.01-3.0 mg/kg, s.c.) or naltriben (0.01-3.0 mg/kg, s.c.) commenced 4 days later. During these conditioning sessions, physical signs of withdrawal were also quantified. Tests of conditioning were conducted on day 5. Naloxone in doses of 0.01-1.0 mg/kg produced significant conditioned place aversions in morphine-implanted animals. A dose of 0.01 mg/kg produced few physical withdrawal signs whereas higher doses resulted in marked wet dog shakes, body weight loss ptosis and diarrhea. No such effects were observed in control (placebo-implanted) animals. Administration of the selective delta-opioid receptor antagonists naltrindole and naltriben produced dose-related place aversions in morphine-implanted animals. The magnitude of these effects did not differ from that observed with naloxone. The minimum effective doses of naltrindole and naltriben were 0.1 mg/kg. Doses of 0.1-1.0 mg/kg produced few, if any, somatic signs of withdrawal whereas higher doses of these antagonists only produced diarrhea and wet-dog shakes. Other withdrawal signs were absent. In contrast to the opioid receptor antagonists tested, the dopamine D1 receptor antagonist SCH23390 failed to produced conditioned place aversions or physical signs of withdrawal in morphine-pelleted animals. These data demonstrate that the selective blockade of either delta- or mu-opioid receptors is sufficient to induce conditioned aversive effects in morphine-dependent animals. They also indicate that physical symptoms associated with precipitated morphine withdrawal differ depending upon the opioid receptor antagonist employed.

  10. Effect of BCNU on mouse skin and spinal cord in single drug and radiation exposures

    International Nuclear Information System (INIS)

    Lelieveld, P.; Brown, J.M.; Goffinet, D.R.; Schoeppel, S.L.; Scoles, M.

    1979-01-01

    We set out to determine whether any interaction occurs between BCNU and radiation for the mouse skin and spinal cord. Single doses of BCNU of 10, 20, or 30 mg/kg were injected intraperitoneally as a function of time before or after irradiation of the foot or spinal cord of anesthesized C3H mice. Enhancement of the radiation skin reaction (dose enhancement factor = 1.3) was seen when BCNU (30 mg/kg) was given 1 day, 6 hr, and 2 hr prior to irradiation of the foot with 2,500 rad, and a larger DEF of 1.6 was observed when BCNU was given immediately before the radiation dose. However, with a different mouse strain (BALB/c) not anesthetized at the time of irradiation, no significant enhancement following a dose of 20 mg/kg BCNU was observed. Experiments are in progress to determine the cause of these differences. BCNU (10 mg/kg) was given 24 hr or immediately prior to various single doses of radiation to a 12 mm segment of the mouse spinal cord (T/sub 11-12/ to L/sub 1-2/), and the subsequent myelitis was scored monthly. The addition of BCNU to irradiation did not accelerate the development of myelitis, not the ultimate proportion of animals developing hind limb paralysis: the 50% myelitis dose at 10 months (MD/sub 50/10/sub mo/) values for irradiation alone, BCNU at the time of irradiation and 24 hr before were 3,722, 3,795 and 3,853 rad, respectively

  11. Recommended use of morphine in neonates, infants and children based on a literature review

    DEFF Research Database (Denmark)

    Kart, T; Christrup, Lona Louring; Rasmussen, M

    1997-01-01

    The indication for morphine use is primarily pain, but also a combined analgesic and sedative effect may be the rationale behind morphine administration. Paediatric morphine regimens have been reported for children with postoperative pain, pain related to cancer, sickle cell crisis pain, burns...... not seem to be more susceptible to respiratory depression than older children. Despite shortcomings in the knowledge of the pharmacodynamics of morphine, it can be considered safe to administer morphine to neonates, infants or children. Initial regimens has been calculated from the pharmacokinetic...

  12. [Effects of morphine, butorphanol and levomethadone in different doses on thermal nociceptive thresholds in horses].

    Science.gov (United States)

    Dönselmann Im Sande, Paula; Hopster, Klaus; Kästner, Sabine

    2017-04-19

    Various opioids are available for use in equine medicine. Studies directly comparing their analgesic effects and side effects are rare. Therefore, the aim of this study was to compare the antinociceptive effect and the duration of analgesia of two different doses of morphine, butorphanol and levomethadone in horses. Eight adult, healthy horses were used for this randomized, placebo-controlled, blinded cross-over trail. Each horse received placebo (P = 0.9% saline) and morphine (M 0.1  = 0.1 mg/kg; M 0.2  = 0.2 mg/kg), butorphanol (B 0.1  = 0.1 mg/kg; B 0.2  = 0.2 mg/kg) and levomethadone (L 0.1  = 0.1 mg/kg; L 0.2  = 0.2 mg/kg) in a low and a high dose and with a wash-out period of 14 days. Thermal thresholds were determined by incremental contact heat applied to the skin at the withers. Single stimulations were performed 15 minutes prior and 10, 30, 60, 90, 120, 180, 240, 300, 360, 420, 540 and 1350 minutes after treatment. Threshold values, gastrointestinal auscultation score and horses' behavior were recorded. Data were analyzed with analysis of variance for repeated measurements (p thermal thresholds did not reach significance. Thermal threshold increased significantly in the groups M 0.2 , B 0.1 , B 0.2 , L 0.1 and L 0.2 for 240, 90, 90, 60 and 300 minutes, respectively. Behavioural changes, increased locomotion and decreased bowel sounds as well as delayed time until defecation were noticed in all groups. Levomethadone induced a dose-dependent increase and prolongation of analgesia, whereas with butorphanol there was no difference between dosages regarding duration and intensity of analgesia. Morphine provided detectable analgesia only in the high dose of 0.2 mg/kg. Levomethadone and morphine in the low dose (0.1 mg/kg) produced only minor and short lived anti-nociception and further studies are necessary to give a profound dose recommendation for the use of these drugs in horses.

  13. Pulmonary exposure to single-walled carbon nanotubes does not affect the early immune response against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Swedin Linda

    2012-05-01

    Full Text Available Abstract Background Single-walled carbon nanotubes (SWCNT trigger pronounced inflammation and fibrosis in the lungs of mice following administration via pharyngeal aspiration or inhalation. Human exposure to SWCNT in an occupational setting may occur in conjunction with infections and this could yield enhanced or suppressed responses to the offending agent. Here, we studied whether the sequential exposure to SWCNT via pharyngeal aspiration and infection of mice with the ubiquitous intracellular parasite Toxoplasma gondii would impact on the immune response of the host against the parasite. Methods C57BL/6 mice were pre-exposed by pharyngeal administration of SWCNT (80 + 80 μg/mouse for two consecutive days followed by intravenous injection with either 1x103 or 1x104 green fluorescence protein and luciferase-expressing T. gondii tachyzoites. The dissemination of T. gondii was monitored by in vivo bioluminescence imaging in real time for 7 days and by plaque formation. The inflammatory response was analysed in bronchoalveolar lavage (BAL fluid, and by assessment of morphological changes and immune responses in lung and spleen. Results There were no differences in parasite distribution between mice only inoculated with T. gondii or those mice pre-exposed for 2 days to SWCNT before parasite inoculum. Lung and spleen histology and inflammation markers in BAL fluid reflected the effects of SWCNT exposure and T. gondii injection, respectively. We also noted that CD11c positive dendritic cells but not F4/80 positive macrophages retained SWCNT in the lungs 9 days after pharyngeal aspiration. However, co-localization of T. gondii with CD11c or F4/80 positive cells could not be observed in lungs or spleen. Pre-exposure to SWCNT did not affect the splenocyte response to T. gondii. Conclusions Taken together, our data indicate that pre-exposure to SWCNT does not enhance or suppress the early immune response to T. gondii in mice.

  14. An Investigation of Modifying Effects of Metallothionein Single-Nucleotide Polymorphisms on the Association between Mercury Exposure and Biomarker Levels

    Science.gov (United States)

    Wang, Yi; Goodrich, Jaclyn M.; Gillespie, Brenda; Werner, Robert; Basu, Niladri

    2012-01-01

    Background: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. Objective: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure–biomarker relationships. Methods: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methylmercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. Results: The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the U.S. general population (0.95 μg/L and 0.47 μg/g, respectively). The mean estimated daily MeHg intake was 0.084 μg/kg/day (range, 0–0.98 μg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 μg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270837) AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1M TC and CC genotypes (n = 15), respectively. Conclusion: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general

  15. Morphine sparing effect of low dose ketamine during patient ...

    African Journals Online (AJOL)

    Measurements: Morphine consumption, visual analogue pain score (VAPS), pulse oximetry oxygen saturation (SpO2), respiratory rate (RR), verbal descriptive sedation score (VDSS), nausea, pruritis, dreaming, and hallucinations were recorded at 1, 4, 24 and 48 hours. Equivalence of the two groups was assessed by ...

  16. Rectal absorption of morphine from controlled release suppositories

    NARCIS (Netherlands)

    Moolenaar, Frits; Meyler, Pim; Frijlink, Erik; Jauw, Tjoe Hang; Visser, Jan; Proost, Johannes

    1995-01-01

    The absorption profiles and bioavailability of morphine in human volunteers (n = 13) were described after oral administration of MS Contin tablets and rectal administration of a newly developed controlled release suppository. By manipulating the viscosity of fatty suppository base an entirely

  17. Enhanced analgesic effect of morphine-nimodipine combination ...

    Indian Academy of Sciences (India)

    Unknown

    varying in a linear manner with the frequency of action potentials. The influx, in turn, leads to release of various neurotransmitters that diffuse across the synaptic cleft to the postsynaptic membrane and binds to their specific receptors. Morphine is the drug of choice for treatment of chronic pain (McCarberg and Barkin 2001).

  18. Pattern of morphine prescription by doctors in a Nigeria tertiary ...

    African Journals Online (AJOL)

    Results: The results showed that more than half (51.7%) of all morphine prescriptions were from the Radiation Oncology Department, while the newly created Day Care Hospice Unit accounted for 31.8% of the prescriptions. No prescriptions were seen from the Labor ward. Only 1.1% of all the prescriptions conformed to ...

  19. The measurement of morphine in the hair of heroin abusers.

    Science.gov (United States)

    George, S; Braithwaite, R A

    1997-07-01

    Several techniques have been described for the determination of morphine in hair as a method of monitoring past heroin use. However, although some of the techniques [notably radioimmunoassay (RIA)] may appear relatively simple to perform, any results obtained must be interpreted with caution. In this study, hair specimens from four known heroin abusers were sectionally analysed by a specific RIA for morphine. Prior to analysis, all hair sections were cleaned to remove any possible surface contamination. Five different hair digestion procedures were evaluated to determine the most effective method that could be used to liberate morphine from hair. The greatest analytical recovery was obtained by incubation with 1.0 M sodium hydroxide for 18 h at 55 degrees C, neutralization with 1.0 M hydrochloric acid, and pH adjustment with 0.1 M phosphate buffer (pH 7.0). The morphine concentrations detected in the hair specimens ranged from 0.5 to 13.2 ng/mg of hair. It was also found that the use of shorter length segments (e.g. 1 cm length) gave a clearer, more detailed picture of the historic pattern of heroin use in the four subjects studied.

  20. Nalbuphine added to intrathecal morphine in total knee arthroplasty ...

    African Journals Online (AJOL)

    Moustafa Abdelaziz Moustafa

    2012-03-02

    Mar 2, 2012 ... delayed respiratory depression.3 These side effects may lead to patient discomfort and prolonged hospital .... No evidence of respiratory depression was detected in any patient during the study period. .... Michelet P, Guervilly C, Helaine A. Adding ketamine to morphine for patient-controlled analgesia after ...

  1. Morphine more fine? Its effects in critically ill newborns

    NARCIS (Netherlands)

    S.H.P. Simons (Sinno)

    2004-01-01

    textabstractThe pharmacist Sertürner first isolated morphine from opium in 1803 and named it after Morpheus, the god of dreams in Greco-Roman mythology. Ever since, it has been one of the most frequently used drugs to relieve pain, for a variety of age groups. In our days, however, there is still

  2. Modulation of dopaminergic neurotransmission by morphine in the rat

    NARCIS (Netherlands)

    P. Moleman (Peter)

    1977-01-01

    textabstractThe pleasant effects of opium were already known 6000 years ago and opium has been used for medical purposes for at least 3500 years. Opium, and its r.1ain constituent morphine, evoke a feeling of well-being and always relieve pain of any origin, in other words, a perfect analgesic and

  3. Rayzon® matches morphine after laparotomy in women

    African Journals Online (AJOL)

    Adele

    for up to 12 hours, or until rescue medication was requested. In addi- tion, the general safety was evaluated continuously, and a Global. Evaluation of Study Medication was provided by the women at the conclusion of the study. ... RAYZON® 40 mg IM provides pain relief equivalent to morphine. 12 mg IM but with longer ...

  4. Evaluation of the single radiosensitivity in patients subjected to medical exposure that show severe skin reactions

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Vallerga, M.B.; Portas, M.; Perez, M.R.

    2006-01-01

    The Burnt Hospital of the Buenos Aires City Government (HQGCBA) it is a hospital of reference of the Net of Medical Responses in Radiological Emergencies of the Argentine Republic. In the mark of an agreement among the HQGCBA and the Authority Regulatory Nuclear (ARN), it is in execution a study protocol for the one boarding diagnoses and therapeutic of radioinduced cutaneous leisure. They exist individual variations that can condition the response to the ionizing radiations (IR), so much in accidental exposures as having programmed (radiotherapy, radiology interventionist). In this context, the individual radiosensitivity is evaluated in the patients signed up in this protocol that presented sharp or late cutaneous reactions, with grades of severity 3-4 (approaches EORTC/RTOG). The capacity of repair of the DNA was evaluated in outlying blood lymphocytes irradiated in vitro (2 Gy, gamma of Co-60) by means of the micronucleus techniques and comet essay in alkaline conditions. In this work two cases in those that is applied this study protocol, the therapeutic answer and its correlate with the discoveries of the radiosensitivity tests is presented. Case 1: patient of feminine sex, subjected to external radiotherapy by a breast infiltrating ductal carcinoma; developed sharp cutaneous radiotoxicity grade 3 (confluent humid epithelitis) that motivate the interruption of the treatment. Case 2: patient of masculine sex, subjected to a coronary angioplasty (interventionist radiology); developed late cutaneous radiotoxicity grade 4 (ulceration in dorsal region). Both patients were treated with topical trolamine associated to systemic administration of pentoxiphiline and antioxidants. The therapeutic answer is evaluated by means of clinical pursuit, photographic serial register and complementary exams (thermography and ultrasonography of high frequency). In the case 1 the answer was very favorable, with precocious local improvement and complete remission of symptoms and

  5. Shifts in the metabolic function of a benthic estuarine microbial community following a single pulse exposure to silver nanoparticles

    International Nuclear Information System (INIS)

    Echavarri-Bravo, Virginia; Paterson, Lynn; Aspray, Thomas J.; Porter, Joanne S.; Winson, Michael K.; Thornton, Barry; Hartl, Mark G.J.

    2015-01-01

    The increasing use of silver nanoparticles (AgNPs) as a biocidal agent and their potential accumulation in sediments may threaten non-target natural environmental bacterial communities. In this study a microcosm approach was established to investigate the effects of well characterized OECD AgNPs (NM-300) on the function of the bacterial community inhabiting marine estuarine sediments (salinity 31‰). The results showed that a single pulse of NM-300 AgNPs (1 mg L −1 ) that led to sediment concentrations below 6 mg Ag kg −1 dry weight inhibited the bacterial utilization of environmentally relevant carbon substrates. As a result, the functional diversity changed, but recovered after 120 h under the experimental conditions. This microcosm study suggests that AgNPs under environmentally relevant experimental conditions can negatively affect bacterial function and provides an insight into the understanding of the bacterial community response and resilience to AgNPs exposure, important for informing relevant regulatory measures. - Highlights: • AgNPs affected the bacterial community function in estuarine marine sediments. • AgNPs inhibited the bacterial utilization of environmentally relevant substrates. • Heterotrophic bacterial groups showed resilience to AgNPs after 120 h exposure. • AgNPs did not affect the bacterial community structure in sediments. - AgNPs inhibited the bacterial utilization of environmentally relevant substrates and caused temporary shifts in the bacterial functional diversity in marine estuarine sediments

  6. Effects of single and combined exposures to copper and benzotriazole on Eisenia fetida.

    Science.gov (United States)

    Xing, Yanshuai; Luo, Jinghan; Zhang, Junjie; Li, Bing; Gong, Xinying; Liu, Zhen; Liu, Chunguang

    2017-11-01

    Benzotriazole (BTR), an emerging class of environmental pollutant, is widely used in industrial applications and household dishwashing agents. Despite the reported toxicity of BTR to aquatic organisms, little is known about its effects on terrestrial invertebrates. Copper (Cu) accumulates in agricultural soils receiving urban waste products, fertilizers, fungicides, and urban sewage. In this study, two different types of bioassays (acute toxicity test and behavioral toxicity test) were performed to evaluate the toxicity of Cu and BTR, both singly and together, on the earthworm (Eisenia fetida) in artificial soil. The results of avoidance behaviour tests showed that the EC 50,48 h values for Cu and BTR were 1.47 and 0.46 mmol kg -1 , respectively. The results of the acute toxicity tests showed that the LC 50,7 d and LC 50,14 d of Cu in earthworms were 9.19 and 5.28 mmol kg -1 , respectively, and the LC 50,7 d and LC 50,14 d of BTR were 2.43 and 1.76 mmol kg -1 , respectively. Toxicity analysis demonstrated that the binary BTR and Cu mixture had predominantly antagonistic effects on the avoidance behaviour and survival of earthworms. The Cu 2+ activities and mortality of earthworms decreased significantly with increasing concentrations of BTR, while the solid-liquid distribution coefficient of Cu increased. These results indicated that the presence of BTR can reduce the toxicity as well as the bioavailability of Cu in soil with both BTR and Cu. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Sex-dependent influences of morphine and its metabolites on pain sensitivity in the rat.

    Science.gov (United States)

    Doyle, H H; Murphy, A Z

    2018-04-01

    Preclinical studies report that the effective dose for morphine is approximately 2-fold higher in females than males. Following systemic administration, morphine is metabolized via Phase II glucuronidation in the liver and brain into two active metabolites: morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), each possessing distinct pharmacological profiles. M6G binds to μ opioid receptors and acts as a potent analgesic. In contrast, M3G binds to toll-like receptor 4 (TLR4), initiating a neuroinflammatory response that directly opposes the analgesic effects of morphine and M6G. M3G serum concentrations are 2-fold higher in females than males, however, sex-specific effects of morphine metabolites on analgesia and glial activation in vivo remain unknown. The present studies test the hypothesis that increased M3G, and subsequent TLR4-mediated activation of glia, is a primary mechanism driving the attenuated response to morphine in females. We demonstrate that intra-PAG M6G results in a greater analgesic response in females than morphine alone. M6G analgesia was reversed with co-administration of (-)-naloxone, but not (+)-naloxone, suggesting that this effect is μ opioid receptor mediated. In contrast, intra-PAG administration of M3G significantly attenuated the analgesic effects of systemic morphine in males only, increasing the 50% effective dose of morphine two-fold (5.0 vs 10.3mg/kg) and eliminating the previously observed sex difference. An increase in IL-1β, IL-6 and TNF was observed in females following intra-PAG morphine or M6G. In males, only IL-1β levels increased following morphine. Changes in cytokine levels following M3G were limited to TNF in females. Together, these data implicate sex differences in morphine metabolism, specifically M3G, as a contributing factor in the attenuated response to morphine observed in females. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Retrospective analysis of the financial break-even point for intrathecal morphine pump use in Korea.

    Science.gov (United States)

    Kim, Eun Kyoung; Shin, Ji Yeon; Castañeda, Anyela Marcela; Lee, Seung Jae; Yoon, Hyun Kyu; Kim, Yong Chul; Moon, Jee Youn

    2017-10-01

    The high cost of intrathecal morphine pump (ITMP) implantation may be the main obstacle to its use. Since July 2014, the Korean national health insurance (NHI) program began paying 50% of the ITMP implantation cost in select refractory chronic pain patients. The aims of this study were to investigate the financial break-even point and patients' satisfaction in patients with ITMP treatment after the initiation of the NHI reimbursement. We collected data retrospectively or via direct phone calls to patients who underwent ITMP implantation at a single university-based tertiary hospital between July 2014 and May 2016. Pain severity, changes in the morphine equivalent daily dosage (MEDD), any adverse events, and patients' satisfaction were determined. We calculated the financial break-even point of ITMP implantation via investigating the patient's actual medical costs and insurance information. During the studied period, 23 patients received ITMP implantation, and 20 patients were included in our study. Scores on an 11-point numeric rating scale (NRS) for pain were significantly reduced compared to the baseline value ( P break-even point was 28 months for ITMP treatment after the NHI reimbursement policy. ITMP provided effective chronic pain management with improved satisfaction and reasonable financial break-even point of 28 months with 50% financial coverage by NHI program.

  9. Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.

    Directory of Open Access Journals (Sweden)

    Theresa Alexandra Mattioli

    Full Text Available The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4. Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (- naloxone, an opioid receptor antagonist, and (+ naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence.

  10. Influence of fentanyl and morphine on intestinal circulation

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of 86 Rb and 9-micron spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O 2 up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation

  11. Influence of fentanyl and morphine on intestinal circulation

    Energy Technology Data Exchange (ETDEWEB)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-06-01

    The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of /sup 86/Rb and 9-micron spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O/sub 2/up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.

  12. Morphine as first medication for treatment of cancer pain

    Directory of Open Access Journals (Sweden)

    Beatriz C. Nunes

    2014-07-01

    Full Text Available BACKGROUND AND OBJECTIVES: the medications used according to the recommendation of the World Health Organization do not promote pain relief in a number of patients with cancer pain. The aim of this study was to evaluate the use of morphine as first medication for the treatment of moderate cancer pain in patients with advanced and/or metastatic disease, as an option to the recommendations of the World Health Organization analgesic ladder. METHOD: sixty patients without opioid therapy, with >18 years of age, were randomized into two groups. G1 patients received medication according to the analgesic ladder and started treatment with non-opioids in the first, weak opioids in the second, and strong opioids in the third step; G2 patients received morphine as first analgesic medication. The efficacy and tolerability of initial use of morphine were evaluated every two weeks for three months. RESULTS: the groups were similar with respect to demographic data. There was no significant difference between the groups regarding pain intensity, quality of life, physical capacity, satisfaction with treatment, need for complementation and dose of morphine. In G1 there was a higher incidence of nausea (p = 0.0088, drowsiness (p = 0.0005, constipation (p = 0.0071 and dizziness (p = 0.0376 in the second visit and drowsiness (p = 0.05 in the third. CONCLUSIONS: the use of morphine as first medication for pain treatment did not promote better analgesic effect than the ladder recommended by World Health Organization, with higher incidence of adverse effects.

  13. Oral Morphine Consumption Reduces Lens Development in Rat Embryos

    Directory of Open Access Journals (Sweden)

    Hossein Bahadoran

    2012-07-01

    Full Text Available Objective: Consumption of morphine, during pregnancy, in addition to inducing defects in the mother’s nervous system function, caused defects or delays in the formation and evolution of embryonic visual system. In the present study, changes in lens development was assessed in embryos exposed in utero to morphine. Material and Methods: Female Wistar rats (250-300 g were mated with male rats and pregnancy was determined by sperm observation in vaginal smear. This day was considered as embryonic day zero (E0. The females were then divided randomly into the experimental and the control groups. The control group received tap water and the experimental group received morphine (0.05 mg/ml in their water. On embryonic day 13 ( E13, blood samples were collected from the retro-orbital sinus of all animals for plasma corticosterone detection. On embryonic day 17(E17, the animals were killed by an overdose of chloroform and the embryos were taken out surgically. The embryos were fixed in 10% formalin for 30 days. At this time, the head of the embryos were removed for tissue processing and Hematoxylin- Eosin (H&E staining. The samples were evaluated using light microscope and MOTIC software. Results: Our data indicated that plasma corticosterone level was dramatically increased and the lens was thinner in the experimental group. (Although the proliferation of lens cells increased in the experiment group but that lens had delay in removing the proliferated and elongation cells with abnormal density in the lateral part of the lens in compare with control group. I have no idea what the authors are stating here. Moreover, the opening of the eyelids was delayed in the off springs of the mothers who received morphine. Conclusions: This study showed that morphine consumption during pregnancy leads to defects in fetal visual system development, particularly in the lens, and eyelids.

  14. Delayed extinction and stronger drug-primed reinstatement of methamphetamine seeking in rats prenatally exposed to morphine.

    Science.gov (United States)

    Shen, Ying-Ling; Chen, Shao-Tsu; Chan, Tzu-Yi; Hung, Tsai-Wei; Tao, Pao-Luh; Liao, Ruey-Ming; Chan, Ming-Huan; Chen, Hwei-Hsien

    2016-02-01

    Prenatal morphine (PM) affects the development of brain reward system and cognitive function. The present study aimed to determine whether PM exposure increases the vulnerability to MA addiction. Pregnant Sprague-Dawley rats were administered saline or morphine during embryonic days 3-20. The acquisition, extinction and reinstatement of methamphetamine (MA) conditioned place preference (CPP) and intravenous self-administration (SA) paradigms were assessed in the male adult offspring. There was no difference in the acquisition and expression of MA CPP between saline- and PM-exposed rats, whereas PM-exposed rats exhibited slower extinction and greater MA priming-induced reinstatement of drug-seeking behavior than controls. Similarly, MA SA under progressive ratio and fixed ratio schedules was not affected by PM exposure, but PM-exposed rats required more extinction sessions to reach the extinction criteria and displayed more severe MA priming-, but not cue-induced, reinstatement. Such alterations in extinction and reinstatement were not present when PM-exposed rats were tested in an equivalent paradigm assessing operant responding for food pellets. Our results demonstrate that PM exposure did not affect the association memory formation during acquisition of MA CPP or SA, but impaired extinction learning and increased MA-primed reinstatement in both tasks. These findings suggest that the offspring of women using morphine or heroin during pregnancy might predict persistent MA seeking during extinction and enhanced propensity to MA relapse although they might not be more susceptible to the reinforcing effect of MA during initiation of drug use. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Effect of Short-term Forced Exercise on Naloxone Induced Withdrawal Symptoms in Morphine Addicted Male Rats

    Directory of Open Access Journals (Sweden)

    KH Saadipour

    2008-01-01

    Full Text Available ABSTRACT: Introduction & Objective: Opioid dependence has been causing limitation in usage of morphine and other opioid drugs in pain control. The aim of this study was to assess the effect of short-term forced exercise on withdrawal syndrome in morphine addicted male rats. Materials & Methods: This experimental study was done in the physiology research center of Ahwas Jondishapour University of Medical Sciences. Twenty four young male Wistar rats, weighing 200-300gr, were randomly divided into four groups: no addiction and no exercise, no addiction and exercise, addiction and no exercise and addiction and exercise. The exercise groups underwent treadmill forced exercise for ten days. The first five days morphine was administrated (ip twice daily with increasing dose (5، 10، 20، 40, 50 mg/kg to addicted groups. Also single dose (50mg/kg of morphine was administrated to them on the 10th day of exercise. After administration of naloxone hydrochloride the withdrawal symptoms were evaluated for 5 minutes. The findings of this study were analyzed by SPSS software and One- way ANOVA (Tukey test. Results: The findings of this study showed that the withdrawal symptoms was elevated in exercise and addicted groups in comparison with control group (p<0.05 , p<0.01. However, most of withdrawal symptoms decreased in addicted and exercise group in comparison with addicted and no exercise group (p<0.01, p<0.001. Conclusion: The exercise could increase endogenous opioid and withdrawal symptoms in animals but reduce withdrawal symptoms in addicted and exercise groups compared to addicted and no exercise group. Its mechanism might be related to down regulation and low sensitivity of opioid receptors

  16. Effect of increased exposure times on amount of residual monomer released from single-step self-etch adhesives.

    Science.gov (United States)

    Altunsoy, Mustafa; Botsali, Murat Selim; Tosun, Gonca; Yasar, Ahmet

    2015-10-16

    The aim of this study was to evaluate the effect of increased exposure times on the amount of residual Bis-GMA, TEGDMA, HEMA and UDMA released from single-step self-etch adhesive systems. Two adhesive systems were used. The adhesives were applied to bovine dentin surface according to the manufacturer's instructions and were polymerized using an LED curing unit for 10, 20 and 40 seconds (n = 5). After polymerization, the specimens were stored in 75% ethanol-water solution (6 mL). Residual monomers (Bis-GMA, TEGDMA, UDMA and HEMA) that were eluted from the adhesives (after 10 minutes, 1 hour, 1 day, 7 days and 30 days) were analyzed by high-performance liquid chromatography (HPLC). The data were analyzed using 1-way analysis of variance and Tukey HSD tests. Among the time periods, the highest amount of released residual monomers from adhesives was observed in the 10th minute. There were statistically significant differences regarding released Bis-GMA, UDMA, HEMA and TEGDMA between the adhesive systems (p<0.05). There were no significant differences among the 10, 20 and 40 second polymerization times according to their effect on residual monomer release from adhesives (p>0.05). Increasing the polymerization time did not have an effect on residual monomer release from single-step self-etch adhesives.

  17. Long-term morphine delivery via slow release morphine pellets or osmotic pumps: Plasma concentration, analgesia, and naloxone-precipitated withdrawal.

    Science.gov (United States)

    McLane, Virginia D; Bergquist, Ivy; Cormier, James; Barlow, Deborah J; Houseknecht, Karen L; Bilsky, Edward J; Cao, Ling

    2017-09-15

    Slow-release morphine sulfate pellets and osmotic pumps are common routes of chronic morphine delivery in mouse models, but direct comparisons of these drug delivery systems are lacking. In this study, we assessed the efficacy of slow-release pellets versus osmotic pumps in delivering morphine to adult mice. Male C57BL/6NCr mice (8weeksold) were implanted subcutaneously with slow-release pellets (25mg morphine sulfate) or osmotic pumps (64mg/mL, 1.0μL/h). Plasma morphine concentrations were quantified via LC-MS/MS, analgesic efficacy was determined by tail flick assay, and dependence was assessed with naloxone-precipitated withdrawal behaviors (jumping) and physiological effects (excretion, weight loss). Morphine pellets delivered significantly higher plasma drug concentrations compared to osmotic pumps, which were limited by the solubility of the morphine sulfate and pump volume/flow rate. Within 96h post-implantation, plasma morphine concentrations were indistinguishable in pellet vs. pump-treated samples. While osmotic pump did not have an antinociceptive effect in the tail flick assay, pumps and pellets induced comparable dependence symptoms (naloxone-precipitated jumping behavior) from 24-72h post-implantation. In this study, we compared slow-release morphine pellets to osmotic minipumps for morphine delivery in mice. We found that osmotic pumps and subcutaneous morphine sulfate pellets yielded significantly different pharmacokinetics over a 7-day period, and as a result significantly different antinociceptive efficacy. Nonetheless, both delivery methods induced dependence as measured by naloxone-precipitated withdrawal. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Reflections on: "A general role for adaptations in G-Proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function".

    Science.gov (United States)

    Nestler, Eric J

    2016-08-15

    In 1991 we demonstrated that chronic morphine exposure increased levels of adenylyl cyclase and protein kinase A (PKA) in several regions of the rat central nervous system as inferred from measures of enzyme activity in crude extracts (Terwilliger et al., 1991). These findings led us to hypothesize that a concerted upregulation of the cAMP pathway is a general mechanism of opiate tolerance and dependence. Moreover, in the same study we showed similar induction of adenylyl cyclase and PKA activity in nucleus accumbens (NAc) in response to chronic administration of cocaine, but not of several non-abused psychoactive drugs. Morphine and cocaine also induced equivalent changes in inhibitory G protein subunits in this brain region. We thus extended our hypothesis to suggest that, particularly within brain reward regions such as NAc, cAMP pathway upregulation represents a common mechanism of reward tolerance and dependence shared by several classes of drugs of abuse. Research since that time, by many laboratories, has provided substantial support for these hypotheses. Specifically, opiates in several CNS regions including NAc, and cocaine more selectively in NAc, induce expression of certain adenylyl cyclase isoforms and PKA subunits via the transcription factor, CREB, and these transcriptional adaptations serve a homeostatic function to oppose drug action. In certain brain regions, such as locus coeruleus, these adaptations mediate aspects of physical opiate dependence and withdrawal, whereas in NAc they mediate reward tolerance and dependence that drives increased drug self-administration. This work has had important implications for understanding the molecular basis of addiction. "A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function". Previous studies have shown that chronic morphine increases levels of the G-protein subunits Giα and Goα, adenylate cyclase, cyclic AMP

  19. Proteomic analysis of post-nuclear supernatant fraction and percoll-purified membranes prepared from brain cortex of rats exposed to increasing doses of morphine

    Czech Academy of Sciences Publication Activity Database

    Ujčíková, Hana; Eckhardt, Adam; Kagan, Dmytro; Roubalová, Lenka; Svoboda, Petr

    2014-01-01

    Roč. 12, Feb 14 (2014), s. 11 ISSN 1477-5956 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : morphine * long-term exposure * rat brain cortex * isolated plasma membranes * post-nuclear supernatant * 2D electrophoresis Subject RIV: CE - Biochemistry Impact factor: 1.725, year: 2014

  20. Memory Impairment and Reduced Exploratory Behavior in Mice after Administration of Systemic Morphine

    Directory of Open Access Journals (Sweden)

    Junichi Kitanaka

    2015-01-01

    Full Text Available In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p. induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg or β-funaltrexamine (5 mg/kg but not by norbinaltorphimine (5 mg/kg or naltrindole (5 mg/kg, suggesting that the morphine-induced spatial memory impairment was mediated predominantly by jl-opioid receptors (MOPs. Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM in mice treated with morphine (15 mg/kg or scopolamine (1 mg/kg, but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg, in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety.

  1. Effects of berberine on acquisition and reinstatement of morphine-induced conditioned place preference in mice

    Directory of Open Access Journals (Sweden)

    Faezeh Vahdati Hassani

    2016-03-01

    Full Text Available Objective: It has been shown that berberine, a major component of Berberis vulgaris extract, modulates the activity of several neurotransmitter systems including dopamine (Da and N-methyl-D-aspartate (NMDA contributing to rewarding and reinforcing effects of morphine. Drug craving and relapsing even after a long time of abstinence therapy are the most important problems of addiction. In the present study, we investigated the alleviating effects of berberine on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP in mice. Materials and Methods: In male NMRI mice, the acquisition of CPP was established by 40 mg/kg of morphine sulphate injection and extinguished after the extinction training and reinstated by a 10 mg/kg injection of morphine.  The effects of different doses of berberine (5, 10, and 20 mg/kg on the acquisition and reinstatement induced by morphine were evaluated in a conditioned place preference test. Results: The results showed that intraperitoneal administration of berberine (5, 10, and 20 mg/kg did not induce conditioned appetitive or aversive effects. Injection of berberine (10 and 20 mg/kg 2 h before the morphine administration reduced acquisition of morphine-induced CPP. In addition, same doses of berberine significantly prevented the reinstatement of morphine-induced CPP. Conclusion: These results suggest that berberine can reduce the acquisition and reinstatement of morphine-induced conditioned place preference and may be useful in treatment of morphine addiction.

  2. Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

    Directory of Open Access Journals (Sweden)

    MIKI TSUJITA

    2007-01-01

    Full Text Available Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2. In the other experiment, apneic threshold PaC0(2 was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit

  3. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    International Nuclear Information System (INIS)

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-01-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-[ 14 C]xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in 14 CO 2 excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an α 2 -adrenergic agonist

  4. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-04-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

  5. Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine

    Directory of Open Access Journals (Sweden)

    Rodríguez-Muñoz María

    2009-03-01

    Full Text Available Abstract Background Although the systemic administration of cannabinoids produces antinociception, their chronic use leads to analgesic tolerance as well as cross-tolerance to morphine. These effects are mediated by cannabinoids binding to peripheral, spinal and supraspinal CB1 and CB2 receptors, making it difficult to determine the relevance of each receptor type to these phenomena. However, in the brain, the CB1 receptors (CB1Rs are expressed at high levels in neurons, whereas the expression of CB2Rs is marginal. Thus, CB1Rs mediate the effects of smoked cannabis and are also implicated in emotional behaviors. We have analyzed the production of supraspinal analgesia and the development of tolerance at CB1Rs by the direct injection of a series of cannabinoids into the brain. The influence of the activation of CB1Rs on supraspinal analgesia evoked by morphine was also evaluated. Results Intracerebroventricular (icv administration of cannabinoid receptor agonists, WIN55,212-2, ACEA or methanandamide, generated a dose-dependent analgesia. Notably, a single administration of these compounds brought about profound analgesic tolerance that lasted for more than 14 days. This decrease in the effect of cannabinoid receptor agonists was not mediated by depletion of CB1Rs or the loss of regulated G proteins, but, nevertheless, it was accompanied by reduced morphine analgesia. On the other hand, acute morphine administration produced tolerance that lasted only 3 days and did not affect the CB1R. We found that both neural mu-opioid receptors (MORs and CB1Rs interact with the HINT1-RGSZ module, thereby regulating pertussis toxin-insensitive Gz proteins. In mice with reduced levels of these Gz proteins, the CB1R agonists produced no such desensitization or morphine cross-tolerance. On the other hand, experimental enhancement of Gz signaling enabled an acute icv administration of morphine to produce a long-lasting tolerance at MORs that persisted for more than

  6. Changes in n-hexane toxicokinetics in short-term single exposure due to co-exposure to methyl ethyl ketone in volunteers.

    Science.gov (United States)

    Shibata, Eiji; Johanson, Gunnar; Löf, Agneta; Ernstgård, Lena; Gullstrand, Elisabeth; Sigvardsson, Karl

    2002-08-01

    Animal studies demonstrate that the formation of the neurotoxic metabolite, 2,5-hexanedione (HD) decreases during co-exposure to methyl ethyl ketone (MEK). The aim of the present study was to describe the influence of co-exposure to MEK on n-hexane toxicokinetics in humans. Four healthy male volunteers were exposed, on different occasions, to three different combinations of vapor of these solvents, namely: 50 ppm n-hexane alone, and in combination with 100 and 200 ppm MEK, for 2 h during light physical exercise (50 W). Arterialized capillary blood, venous blood, and urine were sampled at scheduled intervals before, during, and up to 24 h after the onset of the exposure. HD in venous blood and urine was analyzed by gas chromatography with electron capture detector after derivatization with O-(pentafluorobenzyl) hydroxylamine. Serum HD decreased with increasing exposure to MEK at 2 h after the onset of the exposure, from an average concentration of 2.2 micromol/l in the n-hexane-alone condition to 1.2 and 0.44 micromol/l in the 100 and 200-ppm MEK conditions, respectively. The area under the concentration-time curve of HD in venous blood and the concentration of HD at 2 and 4 h after the end of exposure decreased with increasing MEK. These results suggest that combined exposure to MEK and n-hexane at occupationally realistic levels depresses the metabolism of n-hexane in a dose-dependent fashion. The internal exposure to the toxic metabolite of n-hexane decreased with co-exposure to MEK in a dose-dependent fashion. Estimation of external exposure by HD in serum or urine could be confounded by the co-exposure to MEK.

  7. Effects of prenatal exposure to single-wall carbon nanotubes on reproductive performance and neurodevelopment in mice.

    Science.gov (United States)

    Ivani, Saeed; Karimi, Isaac; Tabatabaei, Seyed Reza Fatemi; Syedmoradi, Leila

    2016-07-01

    Carbon nanotubes with extraordinary properties may become a novel drug and gene delivery tool in nanomedicine; however, insufficient information is available regarding their biosafety. Therefore, this work was performed to study the effect of prenatal exposure of single-walled carbon nanotubes (SWCNTs) on reproductive and neurobehavioral endpoints in mice. Thirty pregnant female mice were assigned to three groups (n = 10 for each group). The two treated groups were injected intraperitoneally (i.p.) with 1 or 10 mg/kg body weight (b.w.) of SWCNTs suspended in 1 ml of phosphate buffer saline (PBS) on gestational days 0 and 3. The control group was injected i.p. with an equal volume of PBS. The neurobehavioral ontogeny of pups was evaluated using a modified Fox battery. A decrease in litter size on postnatal day 2 was observed in the group treated with 10 mg/kg b.w. of SWCNTs whereas no significant differences between groups were observed in any other parameters. The behavioral development of pups did not show significant differences during growth except for the surface righting reflex, which showed significant delay compared to control in the group treated with 1 mg/kg b.w. SWCNTs. Moreover, exposed offspring (10 mg/kg b.w. SWCNTs) displayed enhanced anxiety in the elevated plus maze; however, other ethological analysis (Morris water maze and open field test) did not show behavioral changes in the experimental groups. In conclusion, the present results demonstrated small changes in offspring sensory and motor development following exposure to SWCNTs and support the idea that SWCNT risk assessment merits further investigation. © The Author(s) 2014.

  8. Interactions of "ultra-low" doses of naltrexone and morphine in mature and young male and female rats.

    Science.gov (United States)

    Hamann, Scott R; Malik, Hammad; Sloan, Jewell W; Wala, Elzbieta P

    2004-01-01

    Sex and age influence morphine analgesia in humans and animals. Mature rats show greater morphine analgesia in males than in females. Ultra-low doses of naltrexone enhance morphine analgesia. In mature rats (18-22 weeks), naltrexone (0.002-2.0 mg/kg)-morphine (2 mg/kg) cotreatment enhanced morphine analgesia in females, an effect inversely related to naltrexone dose. Conversely, in mature male rats, naltrexone tended to decrease morphine analgesia with increasing dose. In young rats (8-10 weeks), morphine analgesia was unrelated to sex and in both sexes the naltrexone-morphine interaction was negligible. These data show that dose, age, and sex alter the naltrexone-morphine interaction in rats.

  9. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

    Science.gov (United States)

    Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

    2015-01-01

    Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

  10. Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Foster, David John Richard; Upton, Richard Neil

    2015-01-01

    The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomized, double......-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30 mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin...... and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model...

  11. Analgesia induced by morphine microinjected into the nucleus raphe magnus: effects on tonic pain.

    Science.gov (United States)

    Dualé, Christian; Sierralta, Fernando; Dallel, Radhouane

    2007-07-01

    One of the possible sites of action of the analgesic effect of morphine is the Nucleus Raphe Magnus, as morphine injected into this structure induces analgesia in transient pain models. In order to test if morphine in the Nucleus Raphe Magnus is also analgesic in a tonic pain model, 5 microg of morphine or saline (control) were microinjected into the Nucleus Raphe Magnus of the rat. Analgesic effects were assessed following nociceptive stimulation using transient heating of the tail (phasic pain) and subcutaneous orofacial injection of 1.5 % formalin (tonic pain). While morphine was strongly analgesic for the tail-flick response (p Magnus is not the exclusive site of action of morphine-induced analgesia in clinical conditions.

  12. Modulation of ethanol-intake by morphine: Evidence for a central site of action

    Energy Technology Data Exchange (ETDEWEB)

    Wild, K.D.; Reid, L.D. (Rensselaer Polytechnic Institute, Troy, NY (USA))

    1990-01-01

    Previous studies have shown that subcutaneous administration of low doses of morphine increase, while subcutaneous naloxone decreases, ethanol-intake in rats. However, the site of action of morphine modulation of ethanol-intake remains unclear. In an attempt to elucidate this issue, seven graded doses of morphine were given intracerebroventricularly to rats 15 min prior to an opportunity to consume water and sweetened alcoholic beverage for 2 hr. Two lower doses of intracerebroventricular morphine reliably increased ethanol-intake, while higher doses decreased intake of water. Preference ratios were reliably increased by morphine doses of 1 {mu}g and higher. The present data provide support for a central site of morphine modulation of ethanol-intake.

  13. Population pharmacokinetic modelling of morphine, gabapentin and their combination in the rat

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Gabel-Jensen, Charlotte

    2016-01-01

    Purpose The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co......-administration of the two drugs leads to modifications of their pharmacokinetic profiles. Methods The pharmacokinetics of morphine, morphine-3-glucuronide and gabapentin were characterised in rats following subcutaneous injections of morphine, gabapentin or their combination. Non-linear mixed effects modelling was applied...... to describe the pharmacokinetics of the compounds and possible interactions. Results The plasma-concentration-time profiles of morphine and gabapentin were best described using a three- and a one-compartment disposition model respectively. Dose dependencies were found for morphine absorption rate...

  14. Anthropometry-corrected exposure modeling as a method to improve trunk posture assessment with a single inclinometer.

    Science.gov (United States)

    Van Driel, Robin; Trask, Catherine; Johnson, Peter W; Callaghan, Jack P; Koehoorn, Mieke; Teschke, Kay

    2013-01-01

    Measuring trunk posture in the workplace commonly involves subjective observation or self-report methods or the use of costly and time-consuming motion analysis systems (current gold standard). This work compared trunk inclination measurements using a simple data-logging inclinometer with trunk flexion measurements using a motion analysis system, and evaluated adding measures of subject anthropometry to exposure prediction models to improve the agreement between the two methods. Simulated lifting tasks (n=36) were performed by eight participants, and trunk postures were simultaneously measured with each method. There were significant differences between the two methods, with the inclinometer initially explaining 47% of the variance in the motion analysis measurements. However, adding one key anthropometric parameter (lower arm length) to the inclinometer-based trunk flexion prediction model reduced the differences between the two systems and accounted for 79% of the motion analysis method's variance. Although caution must be applied when generalizing lower-arm length as a correction factor, the overall strategy of anthropometric modeling is a novel contribution. In this lifting-based study, by accounting for subject anthropometry, a single, simple data-logging inclinometer shows promise for trunk posture measurement and may have utility in larger-scale field studies where similar types of tasks are performed.

  15. Comparative bioavailability of a morphine suppository given rectally and in a colostomy

    DEFF Research Database (Denmark)

    Højsted, J; Rubeck-Petersen, K; Rask, H

    1990-01-01

    In eight patients with a colostomy, plasma morphine levels were followed for 8 h after administration of 20 mg morphine chloride as a suppository, first rectally and after at least 48 h via the colostomy. The bioavailability after administration in the colostomy showed very great variation...... higher plasma concentrations after colostomy application than after rectal administration. It is concluded that administration of morphine suppositories in a colostomy cannot be recommended....

  16. Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats

    OpenAIRE

    Milne Brian; Mattioli Theresa-Alexandra M; Cahill Catherine M

    2010-01-01

    Abstract Background The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate t...

  17. The effects of morphine and methylnaltrexone on gastrointestinal pain in healthy male participants

    DEFF Research Database (Denmark)

    Brokjaer, A; Olesen, A E; Christrup, L L

    2015-01-01

    rectum, or (iii) 12 mg MNTX given subcutaneously before 30 mg rectal morphine. At baseline and after drug administration peripheral and central effects of the drugs were assessed by experimental pain to the skin, muscle, rectum and pupillometry. KEY RESULTS: Compared to placebo there was no local effect...... of morphine on mechanical rectal distension. In contrast, an increase in tolerated volume was seen following MNTX/morphine administration (p manifested as an increase in mechanical muscle pressure thresholds (both p...

  18. Intravenous Paracetamol Decreases Requirements of Morphine in Very Preterm Infants.

    Science.gov (United States)

    Härmä, Antti; Aikio, Outi; Hallman, Mikko; Saarela, Timo

    2016-01-01

    To determine whether intravenous paracetamol therapy is effective in pain therapy in premature infants. From June 2009 to December 2011, 108 infants born very low gestational age (neonatal intensive care unit period. Pain symptoms were screened using pain scale scoring Neonatal Infant Acute Pain Assessment Scale. The number of apneas during the neonatal intensive care unit stay, and ventilation days per patient, were calculated. The mean (SD) total number of paracetamol doses per patient was 16.9 (11.7), and the postnatal age for the first dose was 13.3 (13.8) hours. Infants in the paracetamol group needed significantly fewer morphine doses per patient than the comparisons, 1.78 (4.56) doses vs 4.35 (11.53), P = .044. The exposed had lower cumulative morphine dosage 0.17 (0.45) mg/kg vs 0.37 (0.96) mg/kg, P = .047. There were no differences in the Neonatal Infant Acute Pain Assessment Scale scores, or the numbers of apneas, or ventilation days. There was no evidence of adverse events including hepatic toxicity. The need for morphine decreased significantly after the introduction of paracetamol for the VLGA infants. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Degradation of morphine in opium poppy processing waste composting.

    Science.gov (United States)

    Wang, Yin Quan; Zhang, Jin Lin; Schuchardt, Frank; Wang, Yan

    2014-09-01

    To investigate morphine degradation and optimize turning frequency in opium poppy processing waste composting, a pilot scale windrow composting trial was run for 55 days. Four treatments were designed as without turning (A1), every 5 days turning (A2), every 10 days turning (A3) and every 15 days turning (A4). During composting, a range of physicochemical parameters including the residual morphine degradation, temperature, pH, and the contents of total C, total N, total P and total K were investigated. For all treatments, the residual morphine content decreased below the detection limit and reached the safety standards after day 30 of composting, the longest duration of high temperature (⩾50 °C) was observed in A3, pH increased 16.9-17.54%, total carbon content decreased 15.5-22.5%, C/N ratio reduced from 46 to 26, and the content of total phosphorus and total potassium increased slightly. The final compost obtained by a mixture of all four piles was up to 55.3% of organic matter, 3.3% of total nutrient (N, P2O5 and K2O) and 7.6 of pH. A turning frequency of every ten days for a windrow composting of opium poppy processing waste is recommended to produce homogenous compost. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Morphine analgesia and cerebral opiate receptors: a developmental study

    International Nuclear Information System (INIS)

    Auguy-Valette, A.; Pontonnier, G.; Cros, J.; Gouarderes, C.; Gout, R.

    1978-01-01

    Development of the analgesic response to morphine and ontogenesis of central opiate receptors were analyzed in rats 5 to 120 days old. The analgesic effect of morphine increased until day 15, after which it decreased to reach a plateau at about day 30. With phenoperidine, on the other hand, the analgesic effect increased until day 15, remained constant between day 15 and day 30 after which it decreased slowly. The ratio of the amounts of morphine in blood over those in brain increased about 3 fold between day 15 and day 30. Opiate receptors were detected in the brain of newborn rats; stereospecific binding of [ 3 H]-naloxone at 10 and 50 nM indicated the presence of low and high affinity binding sites. The number of [ 3 H]-naloxone binding sites increased rapidly during the second and third week after birth. Their affinity for several opiates remained constant throughout development. These results indicate that the analgesic activity of opiates varies with age: until day 15, the analgesic effect of opiates increases in parallel with the number of opiate brain receptors. Then, the formation of the blood brain barrier introduces an additional step in the regulation of opiate activity. (author)

  1. Transient receptor potential cation channel A1 (TRPA1) mediates decrements in cardiac mechanical function and dysrhythmia caused by a single air pollution exposure in mice

    Science.gov (United States)

    This work, which will be presented at SOT 2014, demonstrates that a single exposure to either ozone or acrolein causes decrements in cardiac function and altered electrical activity (i.e. arrhythmia). The results suggest that this effect is mediated by the airway sensor TRPA1. ...

  2. Pulmonary exposure to particles from diesel exhaust, urban dust or single-walled carbon nanotubes and oxidatively damaged DNA and vascular function in apoE(-/-)mice

    DEFF Research Database (Denmark)

    Vesterdal, Lise K; Jantzen, Kim; Sheykhzade, Majid

    2012-01-01

    Abstract This study compared the oxidative stress level and vasomotor dysfunction after exposure to urban dust, diesel exhaust particles (DEP) or single-walled carbon nanotubes (SWCNT). DEP and SWCNT increased the production of reactive oxygen species (ROS) in cultured endothelial cells and acell......Abstract This study compared the oxidative stress level and vasomotor dysfunction after exposure to urban dust, diesel exhaust particles (DEP) or single-walled carbon nanotubes (SWCNT). DEP and SWCNT increased the production of reactive oxygen species (ROS) in cultured endothelial cells...... and acellullarly, whereas the exposure to urban dust did not generate ROS. ApoE(-/-) mice, which were exposed twice to 0.5 mg/kg of the particles by intratracheal instillation, had unaltered acetylcholine-elicited vasorelaxation in aorta segments. There was unaltered pulmonary expression level of Vcam-1, Icam-1...... instillation of the same particles had no effect on biomarkers of pulmonary oxidative stress and dilatory dysfunction in the aorta....

  3. Topical application of morphine for wound healing and analgesia in patients with oral lichen planus: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Zaslansky, Ruth; Schramm, Cynthia; Stein, Christoph; Güthoff, Claas; Schmidt-Westhausen, Andrea Maria

    2018-01-01

    The objective of this study was to investigate the effect of topical morphine on erosive/ulcerative lesions in patients with oral lichen planus (OLP). Previous studies reported on an enhanced remission of skin wounds when morphine was applied topically. This was single-center, prospective, double-blind, placebo-controlled, randomized, multi-arm (3), phase II study (RCT). Patients diagnosed with erosive and/or ulcerative OLP applied 0.2 or 0.4 mg morphine dissolved in glycerine, three times a day for 5 days. The primary outcome was the extent of healing. Secondary outcomes were as follows: (1) effect on pain, (2) presence and severity of opioid-related central and local side effects, (3) whether patients required 'rescue medication' for treatment of pain, and (4) total intake of test substance. A total of 123 patients were screened for eligibility, 45 patients were recruited into the study, and 43 completed it. Patients applied a solution of either placebo or 0.2 or 0.4% morphine in groups of n = 12, n = 15, and n = 16, respectively. Extent of healing was similar in the three groups. Severity of pain was minor pre-treatment and throughout the course of the study. Only minor adverse events were reported (dry mouth, burning sensation). Morphine did not enhance wound healing compared to placebo-treated patients. Healing was observed in all groups, which may be attributed to an effect of glycerine or to the natural course of the disease. Patients experienced only mild levels of pain, rendering the model insensitive for assessing pain. OLP is a chronic disease and current treatment options are limited. Healing occurred in all three study groups, an effect we attribute to the carrier.

  4. Role of music in morphine rewarding effects in mice using conditioned place preference method.

    Science.gov (United States)

    Tavakoli, Farnaz; Hoseini, Seyed Ebrahim; Mokhtari, Mokhtar; Vahdati, Akbar; Razmi, Nematollah; Vessal, Mahmood

    2012-01-01

    This research aims at studying the neuroendocrine effects of music on creating morphine dependence in mice using conditioned place preference (CPP). The mice treated with 10 mg/kg morphine subcutaneously, fast music and slow music. Morphine was used to create dependence. In order to recognize the morphine rewarding effects, CPP technique was used. In the conditioning stage that lasted for 8 days, different groups of mice, after receiving the treatment were randomly placed in compartment for 30 minutes. The post-conditioning stage included the fourth day, the ninth day, the 12th day and the 16th day. Comparing place preference between morphine group and the control group, a significant increase (pmusic group compared with morphine group alone. In addition morphine + alone in the rain music group demonstrated a significantly increased conditioned place preference (pmusic acts as a positive pleasant emotion increasing the dopaminergic activity in the Nucleus Accumbens (NAc) and Ventral Tegmental Area (VTA) and through associated learning mechanisms of reward-related behavior increases morphine addiction. However, taxi girl music may act as unpleasant experiences producing negative emotions and reducing morphine addiction.

  5. Effects of endurance, resistance, and concurrent exercise on learning and memory after morphine withdrawal in rats.

    Science.gov (United States)

    Zarrinkalam, Ebrahim; Heidarianpour, Ali; Salehi, Iraj; Ranjbar, Kamal; Komaki, Alireza

    2016-07-15

    Continuous morphine consumption contributes to the development of cognitive disorders. This work investigates the impacts of different types of exercise on learning and memory in morphine-dependent rats. Forty morphine-dependent rats were randomly divided into five groups: sedentary-dependent (Sed-D), endurance exercise-dependent (En-D), strength exercise-dependent (St-D), and combined (concurrent) exercise-dependent (Co-D). Healthy rats were used as controls (Con). After 10weeks of regular exercise (endurance, strength, and concurrent; each five days per week), spatial and aversive learning and memory were assessed using the Morris water maze and shuttle box tests. The results showed that morphine addiction contributes to deficits in spatial learning and memory. Furthermore, each form of exercise training restored spatial learning and memory performance in morphine-dependent rats to levels similar to those of healthy controls. Aversive learning and memory during the acquisition phase were not affected by morphine addiction or exercise, but were significantly decreased by morphine dependence. Only concurrent training returned the time spent in the dark compartment in the shuttle box test to control levels. These findings show that different types of exercise exert similar effects on spatial learning and memory, but show distinct effects on aversive learning and memory. Further, morphine dependence-induced deficits in cognitive function were blocked by exercise. Therefore, different exercise regimens may represent practical treatment methods for cognitive and behavioral impairments associated with morphine-related disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Effects of ketamine and magnesium on morphine induced tolerance and dependence in mice

    Directory of Open Access Journals (Sweden)

    Bohlul Habibi Asl

    2005-05-01

    Full Text Available The goal of this study was to evaluate the effects of ketamine and magnesium on prevention of development of morphine tolerance and dependence in mice. In this study different groups of mice received morphine (50 mg/kg, sc + (saline 10ml/kg, morphine (50 mg/kg, sc + ketamine (25,50 or 75mg/kg, ip, morphine (50 mg/kg, sc + magnesium (10,20 or 40 mg/kg, ip, morphine (50 mg/kg, sc +ketamine (25 mg/kg, ip + magnesium (10 mg/kg, ip] once a day for four days. Tolerance was assessed by administration of morphine (9 mg/kg, ip and using hot plate test on fifth day. Withdrawal symptoms were assessed by administration of naloxone (4 mg/kg, ip two hours after co-administration of morphine with either ketamine or magnesium. It was found that pretreatment with ketamine or magnesium decreased the degree of tolerance and dependence. Additionally, co-administration of ketamine and magnesium before morphine administration decreased the tolerance and dependence significantly. From these results it may be concluded that administration of ketamine or magnesium alone or together could prevent the development of tolerance and dependence to the analgesic effects of morphine. These effects may be related to the N-Methyl-DAspartate (NMDA receptor antagonist behavior of ketamine and the ability of magnesium to block the Ca channel of NMDA receptors.

  7. Microinjection of Orexin-A into the Locus Coeruleus Area Induces Morphine Withdrawal Behaviors in Morphine Independent Rats

    Directory of Open Access Journals (Sweden)

    Hosin Azizi

    2012-02-01

    Full Text Available Introduction: Orexin neuropeptide has a role in opioid withdrawal behaviors. Orexin-expressing neurons that are present in the hypothalamic nuclei send dense projections to the Locus Coeruleus (LC. Withdrawal syndrome is temporally associated with hyperactivity of LC neurons. LC neurons do not show withdrawal-induced hyperactivity in brain slices from morphine-dependent rats. Thus, it has been suggested that the increase in LC neuronal activity seen in vivo is mediated by extrinsic factors. Therefore, this study was carried out to find whether LC microinjection of orexin-A can induce withdrawal behaviors. Method: Adult male Wistar rats were used in this study. Intra-LC microinjection of orexin-A or orexin-A vehicle was performed one week after LC cannulation. Thereafter, somatic signs of withdrawal were evaluated during a period of 25 min.Findings: Orexin-A induced several signs of morphine withdrawal. Conclusion: It may be concluded that orexin at LC acts as an extrinsic factor in the expression of morphine withdrawal syndrome.

  8. Cell and Tissue Damage after Skin Exposure to Ionizing Radiation: Short- and Long-Term Effects after a Single and Fractional Doses.

    Science.gov (United States)

    Kinoshita, Kahori; Ishimine, Hisako; Shiraishi, Kenshiro; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Kanayama, Koji; Mineda, Kazuhide; Mashiko, Takanobu; Feng, Jingwei; Nakagawa, Keiichi; Kurisaki, Akira; Itami, Satoshi; Yoshimura, Kotaro

    2014-01-01

    Ionizing radiation is often used to treat progressive neoplasms. However, the consequences of long-term radiation exposure to healthy skin tissue are poorly understood. We aimed to evaluate the short- and long-term radiation damage to healthy skin of the same irradiation given either as single or fractional doses. C57BL/J6 mice were randomly assigned to one of three groups: a control and two exposure groups (5 Gy ×2 or 10 Gy ×1). The inguinal area was irradiated (6-MeV beam) 1 week after depilation in the treatment groups. Skin samples were evaluated macroscopically and histologically for up to 6 months after the final exposure. After anagen hair follicle injury by irradiation, hair cycling resumed in both groups, but hair graying was observed in the 10 Gy ×1 group but not in the 5 Gy ×2 group, suggesting the dose of each fractional exposure is more relevant to melanocyte stem cell damage than the total dose. On the other hand, in the long term, the fractional double exposures induced more severe atrophy and capillary reduction in the dermis and subcutis, suggesting fractional exposure may cause more depletion of tissue stem cells and endothelial cells in the tissue. Thus, our results indicated that there were differences between the degrees of damage that occurred as a result of a single exposure compared with fractional exposures to ionizing radiation: the former induces more severe acute injury to the skin with irreversible depigmentation of hairs, while the latter induces long-term damage to the dermis and subcutis. © 2015 S. Karger AG, Basel.

  9. Music therapy inhibits morphine-seeking behavior via GABA receptor and attenuates anxiety-like behavior induced by extinction from chronic morphine use.

    Science.gov (United States)

    Kim, Ki Jin; Lee, Sang Nam; Lee, Bong Hyo

    2018-05-01

    Morphine is a representative pain killer. However, repeated use tends to induce addiction. Music therapy has been gaining interest as a useful type of therapy for neuropsychiatric diseases. The present study examined whether Korean traditional music (KT) could suppress morphine-seeking behavior and anxiety-like behavior induced by extinction from chronic morphine use and additionally investigated a possible neuronal mechanism. Male Sprague-Dawley rats were trained to intravenously self-administer morphine hydrochloride (1.0 mg/kg) using a fixed ratio 1 schedule in daily 2 h session during 3 weeks. After training, rats who established baseline (variation less than 20% of the mean of infusion for 3 consecutive days) underwent extinction. Music was played twice a day during extinction. In the second experiment, the selective antagonists of GABA A and GABA B receptors were treated before the last playing to investigate the neuronal mechanism focusing on the GABA receptor pathway. Another experiment of elevated plus maze was performed to investigate whether music therapy has an anxiolytic effect at the extinction phase. KT but not other music (Indian road or rock music) reduced morphine-seeking behavior induced by a priming challenge with morphine. And, this effect was blocked by the GABA receptor antagonists. In addition, KT showed anxiolytic effects against withdrawal from morphine. Results of this study suggest that KT suppresses morphine-seeking behavior via GABA receptor pathway. In addition, KT showed to have anxiolytic effects, suggesting it has bi-directional effects on morphine. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Different regional gray matter loss in recent onset PTSD and non PTSD after a single prolonged trauma exposure.

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    Yunchun Chen

    Full Text Available OBJECTIVE: Gray matter loss in the limbic structures was found in recent onset post traumatic stress disorder (PTSD patients. In the present study, we measured regional gray matter volume in trauma survivors to verify the hypothesis that stress may cause different regional gray matter loss in trauma survivors with and without recent onset PTSD. METHOD: High resolution T1-weighted magnetic resonance imaging (MRI were obtained from coal mine flood disaster survivors with (n = 10 and without (n = 10 recent onset PTSD and 20 no trauma exposed normal controls. The voxel-based morphometry (VBM method was used to measure the regional gray matter volume in three groups, the correlations of PTSD symptom severities with the gray matter volume in trauma survivors were also analyzed by multiple regression. RESULTS: Compared with normal controls, recent onset PTSD patients had smaller gray matter volume in left dorsal anterior cingulate cortex (ACC, and non PTSD subjects had smaller gray matter volume in the right pulvinar and left pallidum. The gray matter volume of the trauma survivors correlated negatively with CAPS scores in the right frontal lobe, left anterior and middle cingulate cortex, bilateral cuneus cortex, right middle occipital lobe, while in the recent onset PTSD, the gray matter volume correlated negatively with CAPS scores in bilateral superior medial frontal lobe and right ACC. CONCLUSION: The present study identified gray matter loss in different regions in recent onset PTSD and non PTSD after a single prolonged trauma exposure. The gray matter volume of left dorsal ACC associated with the development of PTSD, while the gray matter volume of right pulvinar and left pallidum associated with the response to the severe stress. The atrophy of the frontal and limbic cortices predicts the symptom severities of the PTSD.

  11. Bioavailability study of arsenic and mercury in traditional Chinese medicines (TCM) using an animal model after a single dose exposure.

    Science.gov (United States)

    Tinggi, Ujang; Sadler, Ross; Ng, Jack; Noller, Barry; Seawright, Alan

    2016-04-01

    Traditional Chinese medicines (TCM) are increasingly being used as alternative medicines in many countries, and this has caused concern because of adverse health effects from toxic metal bioavailability such as mercury (Hg) and arsenic (As). The aim of this study was to investigate the bioavailability of As and Hg from TCM after a single exposure dose using an animal model of female Sprague-Dawley rats. The rats were divided into 6 groups which included four groups treated with sodium arsenite (NaAsO2), arsenic sulfide (As2S3), mercuric chloride (HgCl2), mercuric sulfide (HgS), and two groups treated with TCM containing high Hg or As (Liu Shen Wan: As 7.7-9.1% and Hg 1.4-5.0%; Niuhang Jie du Pian: As 6.2-7.9% and Hg <0.001%). The samples of urine, faeces, kidney and liver were collected for analysis and histological assay. The results indicated that relatively low levels of As and Hg from these TCM were retained in liver and kidney tissues. The levels of As in these tissues after TCM treatment were consistent with the levels from the As sulphide treated group. With the exception of the mercuric chloride treated group, the levels of Hg in urine from other groups were very low, and high levels of As and Hg from TCM were excreted in faeces. The study showed poor bioavailability of As and Hg from TCM as indicated by low relative bioavailability of As (0.60-1.10%) and Hg (<0.001%). Histopathological examination of rat kidney and liver tissues did not show toxic effects from TCM. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  12. Effect of filtration on morphine and particle content of injections prepared from slow-release oral morphine tablets

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    Brandon Susan

    2009-12-01

    Full Text Available Abstract Background Injections of mixtures prepared from crushed tablets contain insoluble particles which can cause embolisms and other complications. Although many particles can be removed by filtration, many injecting drug users do not filter due to availability, cost or performance of filters, and also due to concerns that some of the dose will be lost. Methods Injection solutions were prepared from slow-release morphine tablets (MS Contin® replicating methods used by injecting drug users. Contaminating particles were counted by microscopy and morphine content analysed by liquid chromatography before and after filtration. Results Unfiltered tablet extracts contained tens of millions of particles with a range in sizes from 400 μm. Cigarette filters removed most of the larger particles (> 50 μm but the smaller particles remained. Commercial syringe filters (0.45 and 0.22 μm produced a dramatic reduction in particles but tended to block unless used after a cigarette filter. Morphine was retained by all filters but could be recovered by following the filtration with one or two 1 ml washes. The combined use of a cigarette filter then 0.22 μm filter, with rinses, enabled recovery of 90% of the extracted morphine in a solution which was essentially free of tablet-derived particles. Conclusions Apart from overdose and addiction itself, the harmful consequences of injecting morphine tablets come from the insoluble particles from the tablets and microbial contamination. These harmful components can be substantially reduced by passing the injection through a sterilizing (0.22 μm filter. To prevent the filter from blocking, a preliminary coarse filter (such as a cigarette filter should be used first. The filters retain some of the dose, but this can be recovered by following filtration with one or two rinses with 1 ml water. Although filtration can reduce the non-pharmacological harmful consequences of injecting tablets, this remains an unsafe

  13. Influence of bile acid derivates on morphine analgesic effect in mice

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    Vasović Velibor

    2014-01-01

    Full Text Available Background/Aim. It is known that bile acids improve the absorption, bioavailability and pharmacodynamic characteristics of some drugs. Morphine analgesia is produced by activation of opioid receptors within the central nervous system (CNS at both spinal and supraspinal levels. Since a morphine molecule contains 3 polar groups and therefore hard to transfer through the blood-brain barrier, the aim of the study was to examine the potential influence of bile acids derivates, namely sodium salt of monoketocholic acid (MKH-Na and methyl ester of monoketocholic acid (MKH-Me, on analgesic effect of morphine. Methods. White male mice of NMRI-Haan strain, with body weight of 20-24 g, were used in this study. The analgesic effect of morphine (administered by subcutaneous and intramuscular route in a dose of 2 mg/kg, with and without pretreatment with MKH-Na (4 mg/kg and MKH-Me (4 mg/kg was estimated by the hot plate method. Results. Administration of MKH-Me prior to subcutaneous administration of morphine increased the morphine analgesic effect but the increase was not statistically significant. At the same time administration of MKH-Na did not affect morphine analgesic effect. The analgesic effect of morphine increased when administered intramuscularly 20 min after MKH-Me administration. When compared with the group of animals treated only with morphine, a statistically significant increase in analgesic effect was detected 10, 30, 40 and 50 min after morphine administration (p < 0.05. Pretreatment with MKH-Na did not affect morphine analgesic effect. Conclusion. According to the results of this study it can be presumed that after intramuscular morphine administration methyl ester of monoketocholic acid increases morphine transport into the central nervous system and consequently the analgesic effect, as well. Further research on bile acids-morphine interaction both in vitro and in vivo is necessary to completely elucidate the mechanism of this

  14. Oral Morphine Use in South India: A Population-Based Study

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    M.R. Rajagopal

    2017-12-01

    Full Text Available Purpose: Access to opioids for pain control is recognized as an urgent issue in low- and middle-income countries. Here we report temporal and regional trends in morphine use in Kerala, India. Methods: Oral morphine use data for the State of Kerala (2012 to 2015 was used to describe temporal trends, regional variation, and provider characteristics. Total morphine use was calculated for each district of Kerala to derive an annual per capita use rate (milligrams per capita. Each provider was classified as government, private, nongovernment organization (NGO, or NGO partnership. Results: Oral morphine use for Kerala was 1.32 mg/capita and increased over the study period 27% (from 1.23 mg/capita to 1.56 mg/capita. There was substantial variation in morphine use across districts (range, 0.49 mg/capita to 2.97 mg/capita; six-fold difference. This variation increased over time (19-fold difference in 2015. In 2015, 31% of morphine providers (51 of 167 were government institutions; they delivered 48% of total morphine in Kerala. Corresponding data for other providers are private institutions, 23% of centers and 13% of morphine; NGOs, 41% of centers and 34% of morphine; and NGO partnerships, 5% of centers and 4% of morphine. From 2012 to 2015, the total number of centers increased by 35%, from 124 to 167. Conclusion: Oral morphine use has increased over time in Kerala but remains substantially lower than estimated need. There is significant geographic variation of use. Efforts are needed to improve palliative care in Kerala and to reduce regional disparities in access to opioids.

  15. Oral Morphine Use in South India: A Population-Based Study.

    Science.gov (United States)

    Rajagopal, M R; Karim, Safiya; Booth, Christopher M

    2017-12-01

    Purpose Access to opioids for pain control is recognized as an urgent issue in low- and middle-income countries. Here we report temporal and regional trends in morphine use in Kerala, India. Methods Oral morphine use data for the State of Kerala (2012 to 2015) was used to describe temporal trends, regional variation, and provider characteristics. Total morphine use was calculated for each district of Kerala to derive an annual per capita use rate (milligrams per capita). Each provider was classified as government, private, nongovernment organization (NGO), or NGO partnership. Results Oral morphine use for Kerala was 1.32 mg/capita and increased over the study period 27% (from 1.23 mg/capita to 1.56 mg/capita). There was substantial variation in morphine use across districts (range, 0.49 mg/capita to 2.97 mg/capita; six-fold difference). This variation increased over time (19-fold difference in 2015). In 2015, 31% of morphine providers (51 of 167) were government institutions; they delivered 48% of total morphine in Kerala. Corresponding data for other providers are private institutions, 23% of centers and 13% of morphine; NGOs, 41% of centers and 34% of morphine; and NGO partnerships, 5% of centers and 4% of morphine. From 2012 to 2015, the total number of centers increased by 35%, from 124 to 167. Conclusion Oral morphine use has increased over time in Kerala but remains substantially lower than estimated need. There is significant geographic variation of use. Efforts are needed to improve palliative care in Kerala and to reduce regional disparities in access to opioids.

  16. Intracoerulear microinjection of orexin-A induces morphine withdrawal-like signs in rats.

    Science.gov (United States)

    Ghaemi-Jandabi, Masoumeh; Azizi, Hossein; Ahmadi-Soleimani, S Mohammad; Semnanian, Saeed

    2017-04-01

    Orexin (hypocretin) neuropeptides play a pivotal role in expression of opioid withdrawal signs. Hypothalamic orexinergic neurons provide dense afferents for the nucleus locus coeruleus (LC). Somatic signs of opioid withdrawal are associated with the enhanced activity of LC neurons. In addition, intra-LC administration of orexin-A leads to the hyperactivity of LC neurons. The present study was an attempt to investigate whether intra-LC microinjection of orexin-A induces morphine withdrawal-like signs in both morphine dependent and control rats. To end this, adult male Wistar rats weighing 250-300g were used. For induction of morphine dependence, animals received morphine sulfate subcutaneously (10mg/kg, s.c.) at an interval of 12h for 9days. On day 10, intra-LC orexin injection (100μM, 200nl) was carried out two hours after last morphine administration. Morphine withdrawal-like signs were assessed in a transparent Plexiglas test chamber (30cm diameter, 50cm height) for 25min. Orexin-A microinjection induced some morphine withdrawal-like signs in both morphine dependent (chewing, scratching, rearing, teeth chattering, wet-dog shake and paw tremor) and control (chewing, scratching, rearing, sniffing, wet-dog shake and head tremor) rats. Furthermore, microinjection of SB-334867, a selective orexin type-1 receptor antagonist before orexin-A significantly suppressed orexin-induced morphine withdrawal-like signs. It seems that orexin-A, via increasing the activity of LC neurons, mediates the induction of some morphine withdrawal-like signs independent of morphine dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Perinatal protein deprivation facilitates morphine cross-sensitization to cocaine and enhances ΔFosB expression in adult rats.

    Science.gov (United States)

    Perondi, María Cecilia; Gutiérrez, María Cecilia; Valdomero, Analía; Cuadra, Gabriel Ricardo

    2017-08-30

    Previous studies have indicated that neural changes induced by early nutritional insult cause an altered response to pharmacological treatments, including addictive drugs. This study evaluates the influence of perinatal protein malnutrition in developing cross-sensitization to cocaine-induced rewarding effects in animals pre-exposed to morphine. Different groups of well-nourished (C-rats) and protein-deprived animals (D-rats) were treated twice a day for three days with increasing doses of morphine or with saline. After 3days, the incentive motivational effects of cocaine were assessed in a Conditioned Place Preference paradigm in both groups. In saline pre-treated animals, dose-response curves to cocaine revealed a conditioning effect in D-rats at doses of 5, 7.5 and 10mg/kg, while this effect was observed in C-rats only with 10 and 15mg/kg. Furthermore, when animals of both groups were pre-treated with escalating doses of morphine, cross-sensitization to the conditioning effect of cocaine was elicited only in D-rats with low doses of cocaine (5 and 7.5mg/kg). In contrast, under the same experimental conditions, C-rats show no cross-sensitization. To correlate this differential rewarding response with a molecular substrate linked to the behavioral changes observed after repeated drug exposure, ΔFosB expression was assessed in different brain regions. D-rats showed a significant increase in this transcription factor in the nucleus accumbens, amygdala and medial prefrontal cortex. These results demonstrated that perinatal protein deprivation facilitates rewarding effects and the development of cross-sensitization to cocaine, which correlates with an upregulation of ΔFosB in brain areas related to the reward circuitry. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine.

    Science.gov (United States)

    Chi, Benjamin H; Sinkala, Moses; Stringer, Elizabeth M; Cantrell, Ronald A; Mtonga, Velepi; Bulterys, Marc; Zulu, Isaac; Kankasa, Chipepo; Wilfert, Catherine; Weidle, Paul J; Vermund, Sten H; Stringer, Jeffrey S A

    2007-05-11

    To determine whether prior exposure to single-dose nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) is associated with attenuated CD4 cell response, death, or clinical treatment failure in women starting antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTI). Open cohort evaluation of outcomes for women in program sites across Zambia. HIV treatment was provided according to Zambian/World Health Organization guidelines. Peripartum NVP exposure status was known for 6740 women initiating NNRTI-containing ART, of whom 751 (11%) reported prior use of NVP for PMTCT. There was no significant difference in mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60) months. Multivariable analyses showed no significant differences in mortality [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215 cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7). Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes, highlighting the importance of ART screening and initiation early in pregnancy.

  19. Intravenous Morphine vs Intravenous Ketofol for Treating Renal Colic; a Randomized Controlled Trial

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    Gholamreza Faridaalaee

    2016-08-01

    Full Text Available Introduction: The main purpose of emergency department (ED management for renal colic  is prompt pain relief. The present study aimed to compare the analgesic effects of intravenus (IV ketofol with morphine in management of ketorolac persistent renal colic. Methods: This study is a single blind randomized, clinical trial, on patients who were presented to ED with renal colic, whose pain was resistant to 30 mg IV ketorolac. The patients were randomly assigned to either IV morphine (0.1 mg/kg or IV ketofol (0.75 mg/kg propofol and 0.75 mg/kg and the measures of treatment efficacy were compared between the groups after 5 and 10 minutes. Results: 90 patients with mean age of 38.01 ± 9.78 years were randomly divided into 2 groups of 45 (66.7% male. Treatment failure rate was significantly lower in ketofol group after 5 (20% vs 62.2%, p < 0.001 and 10 minutes (11.1% vs 44.4%, p < 0.001. ARR and NNT for ketofol after 5 miutes were 42.22% (95% CI: 23.86 – 60.59 and 3 (95% CI: 1.7 - 4.2, respectively. After 10 minutes, these measures reached 33.33 (95% CI:16.16 – 50.51 and 4 (95% CI: 2.0 - 6.2, respectively. NNH and ARI for hallucination or agitation were 12 (95%CI: 5.8 - 174.2 and 8.89% (0.57 - 17.20, respectively. Conclusion: The results of the present study, showed the significant superiority of ketofol (NNT at 5 minute = 3 and NNT at 10 minute = 4  in ketorolac resistant renal colic pain management. However, its NNH of 12, could limit its routine application in ED for this purpose.

  20. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of

  1. Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Adams, M.L.; Morris, D.L.; Dewey, W.L.

    1986-03-05

    ..beta..-endorphin, (met)enkephalin, and (leu)enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO/sub 4/ or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. ..beta..-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; (met)enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; (leu)-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs.

  2. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

    Science.gov (United States)

    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  3. Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

    International Nuclear Information System (INIS)

    Adams, M.L.; Morris, D.L.; Dewey, W.L.

    1986-01-01

    β-endorphin, [met]enkephalin, and [leu]enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO 4 or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. β-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; [met]enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; [leu]-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs

  4. Comparison of transversus abdominis plane block vs spinal morphine for pain relief after Caesarean section.

    LENUS (Irish Health Repository)

    McMorrow, R C N

    2011-05-01

    Transversus abdominis plane (TAP) block is an alternative to spinal morphine for analgesia after Caesarean section but there are few data on its comparative efficacy. We compared the analgesic efficacy of the TAP block with and without spinal morphine after Caesarean section in a prospective, randomized, double-blinded placebo-controlled trial.

  5. Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation.

    Science.gov (United States)

    Chen, Ming; Zhao, Yanfang; Yang, Hualan; Luan, Wenjie; Song, Jiaojiao; Cui, Dongyang; Dong, Yi; Lai, Bin; Ma, Lan; Zheng, Ping

    2015-07-24

    One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.

  6. Aspects of intrathecal morphine for postoperative pain relief in major orthopedic surgery

    NARCIS (Netherlands)

    Slappendel, Robert

    2000-01-01

    The optimal site to administer opioids e.g. morphine is as close as possible to the opiate receptor site (spinal cord) by the intrathecal route, as it is the place of effectiveness. To improve the clinical effectiveness of intrathecal morphine two strategies are proposed: 1. to lower the

  7. Effects of extremely low frequency electromagnetic fields on morphine analgesia and tolerance in rats.

    Science.gov (United States)

    Ozdemir, Ercan; Demirkazik, Ayse; Gursoy, Sinan; Taskıran, Ahmet S; Kilinc, Olca; Arslan, Gokhan

    2017-10-01

    Several studies have demonstrated that the electromagnetic fields produce analgesic activity. The aim of this study was to investigate the effects of extremely low frequency (ELF) electromagnetic fields (EMF) on morphine analgesia and tolerance in rats. In the study, 78 adult male Wistar albino rats (approximately 240 ± 12 g) were used. The application of 50 Hz magnetic field, each day the same times for 30 minutes for 15 days, and a total of four times every 15 minute intervals. To constitute morphine tolerance, high dose of morphine (50 mg/kg) were administered for 3 days in rats and tolerance was evaluated on day 4. Prior to analgesia tests, the effective dose (5 mg/kg) of morphine was injected into rats. In the statistical analyzes of the data, analysis of variance (two-way ANOVA) was used and the multiple comparison determined by Tukey tests. The maximum analgesic effect of the 5 mT magnetic field was determined on 7 days. Administration of morphine (5 mg/kg) in rats exposed to a magnetic field, the analgesic effect was significantly higher compared to the morphine group (p application of ELF-EMFs to rats increases the morphine analgesia and reduces morphine tolerance.

  8. Effects of morphine on replication of herpes simplex virus type 1 and 2

    African Journals Online (AJOL)

    Several drugs are being used in treatment of HSV (Herpesviridae) infection in human but still introducing an effective safe drug is desirable. We investigated the inhibitory effect of morphine on replication of HSV in vitro. The results indicated that a concentration of up to 200 ìg/ml morphine had a limited effect on Vero cell ...

  9. Amperometric morphine sensing using a molecularly imprinted polymer-modified electrode

    International Nuclear Information System (INIS)

    Yeh, W.-M.; Ho, K.-C.

    2005-01-01

    This study incorporates morphine into a molecularly imprinted polymer (MIP) for the amperometric detection of morphine. The polymer, poly(3,4-ethylenedioxythiophene), PEDOT, is an electroactive film that catalyzes morphine oxidation and lowers the oxidization potential on an indium tin oxide (ITO) electrode. The MIP-PEDOT modified electrode is prepared by electropolymerizing PEDOT onto an ITO electrode in a 0.1 M LiClO 4 solution with template addition (morphine). After template molecule extraction, the oxidizing current of the MIP-PEDOT modified electrode is measured in a 0.1 M KCl solution (pH = 5.3) at 0.75 V (versus Ag/AgCl/sat'd KCl) with the morphine concentration varying in the 0.1-5 mM range. A linear range, displaying the relationship between steady-state currents and morphine concentrations, from 0.1 to 1 mM, is obtained. The proposed amperometric sensor could be used for morphine detection with a sensitivity of 91.86 μA/cm 2 per mM. A detection limit of 0.2 mM at a signal-to-noise ratio of 3 is achieved. Moreover, the proposed method can discriminate between morphine and its analogs, such as codeine

  10. Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants.

    NARCIS (Netherlands)

    Velden, A.A.E.M. van der; Hopman, J.C.W.; Klaessens, J.H.G.M.; Feuth, A.B.; Sengers, R.C.A.; Liem, K.D.

    2006-01-01

    BACKGROUND: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. OBJECTIVES: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. METHODS: 11 patients (GA 26.6-33.0 weeks, BW

  11. Relationships among morphine metabolism, pain and side effects during long-term treatment

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Christrup, Lona Louring; Sjøgren, Per

    2003-01-01

    found evidence for a contributory effect of M6G to the overall effects observed after morphine administration. Several studies have demonstrated that administration of M6G is accompanied by fewer and a milder degree of opioid-like side effects than observed after morphine administration, but most...

  12. Dendrosomal nanocurcumin prevents morphine self-administration behavior in rats despite CA1 damage.

    Science.gov (United States)

    Noroozi, Jalaleden; Hassanpour-Ezatti, Majid; Alaei, Hojjat A

    2017-12-01

    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. Pretreatment with both doses of DNC markedly suppressed morphine intake. Morphine self-administration resulted in a 71% reduction in the number of hippocampal CA1 neurons. DNC (5 mg/kg) pretreatment only marginally improved (by 22%) neuronal loss in this area. The data suggest that the effect of DNC on morphine self-administration is largely independent of the CA1 area. A functional restoration and regulation of reward circuit activity by DNC may reduce the motivation for morphine despite CA1 damage.

  13. Morphine Protects Spinal Cord Astrocytes from Glutamate-Induced Apoptosis via Reducing Endoplasmic Reticulum Stress

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    Chao Zhang

    2016-10-01

    Full Text Available Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS. Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.

  14. High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors

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    Messlinger Karl

    2009-04-01

    Full Text Available Abstract Background Morphine and its derivatives are key drugs in pain control. Despite its well-known analgesic properties morphine at high concentrations may be proalgesic. Particularly, short-lasting painful sensations have been reported upon dermal application of morphine. To study a possible involvement of TRP receptors in the pro-nociceptive effects of morphine (0.3 – 10 mM, two models of nociception were employed using C57BL/6 mice and genetically related TRPV1 and TRPA1 knockout animals, which were crossed and generated double knockouts. Hindpaw skin flaps were used to investigate the release of calcitonin gene-related peptide indicative of nociceptive activation. Results Morphine induced release of calcitonin gene-related peptide and sensitized the release evoked by heat or the TRPA1 agonist acrolein. Morphine activated HEK293t cells transfected with TRPV1 or TRPA1. Activation of C57BL/6 mouse dorsal root ganglion neurons in culture was investigated with calcium imaging. Morphine induced a dose-dependent rise in intracellular calcium in neurons from wild-type animals. In neurons from TRPV1 and TRPA1 knockout animals activation by morphine was markedly reduced, in the TRPV1/A1 double knockout animals this morphine effect was abrogated. Naloxone induced an increase in calcium levels similar to morphine. The responses to both morphine and naloxone were sensitized by bradykinin. Conclusion Nociceptor activation and sensitization by morphine is conveyed by TRPV1 and TRPA1.

  15. Pharmacological consequences of long-term morphine treatment in patients with cancer and chronic non-malignant pain

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Sjøgren, Per; Hansen, Steen Honoré

    2004-01-01

    In patients with pain of malignant origin morphine may be administered in high and often increasing doses during extended periods of time. In patients with chronic pain of non-malignant origin morphine may be an important remedy, and in these cases the goal is to keep the morphine dose stable. Th...

  16. Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J; Hansen, B L

    1992-01-01

    In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after...... elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during...... mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough...

  17. Delayed postoperative gastric emptying following intrathecal morphine and intrathecal bupivacaine.

    LENUS (Irish Health Repository)

    Lydon, A M

    2012-02-03

    PURPOSE: A decrease in the rate of gastric emptying can delay resumption of enteral feeding, alter bioavailability of orally administered drugs, and result in larger residual gastric volumes, increasing the risk of nausea and vomiting. We compared the effects of 1) intrathecal bupivacaine (17.5 mg) and 2) the combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine (17.5 mg) on the rate of gastric emptying in patients undergoing elective hip arthroplasty. METHODS: Twenty four fasting ASA 1-3 patients were randomly assigned, in a double blind manner, to receive intrathecal hyperbaric bupivacaine (17.5 mg), either alone (group 1), or followed by intrathecal morphine (0.6 mg) (group 2). Gastric emptying was measured (using an acetaminophen absorption technique), twice in each patient; preoperatively, and approximately one hour postoperatively. Gastric emptying parameters are: AUC (area under the plasma acetaminophen concentration time curve), maximum plasma acetaminophen concentration (Cmax), and time to Cmax (tCmax), analyzed using paired Student\\'s t tests. RESULTS: Gastric emptying rates were reduced in both group 1 (AUC = 14.98 (3.8) and 11.05 (4.6) pre- and postoperatively, respectively) and group 2 (AUC = 13.93 (3.59) and 6.4 (3.42) pre- and postoperatively, respectively); the magnitude of the reduction was greater in group 2 [AUC (P = 0.04), Cmax (P = 0.05), tCmax (P = 0.13)]. CONCLUSION: The combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine (17.5 mg) delays gastric emptying postoperatively.

  18. Therapeutic suggestion has not effect on postoperative morphine requirements.

    Science.gov (United States)

    van der Laan, W H; van Leeuwen, B L; Sebel, P S; Winograd, E; Baumann, P; Bonke, B

    1996-01-01

    This study was designed to confirm the effect of therapeutic intraoperative auditory suggestion on recovery from anesthesia, to establish the effect of preoperative suggestion, and to assess implicit memory for intraoperative information using an indirect memory task. Sixty consenting unpremedicated patients scheduled for elective gynecologic surgery were randomly divided into three equal groups: Group 1 received a tape of therapeutic suggestions preoperatively, and the story of Robinson Crusoe intraoperatively; Group 2 heard the story of Peter Pan preoperatively and therapeutic suggestions intraoperatively; Group 3 heard the Crusoe story preoperatively and the Peter Pan story intraoperatively. A standardized anesthetic technique was used with fentanyl, propofol, isoflurane, and nitrous oxide. After surgery, all patients received patient-controlled analgesia (PCA) with a standardized regimen. In the 24 h postsurgery, morphine use was recorded every 6 h and at 24 h an indirect memory test (free association) was used to test for memory of the stories. Anxiety scores were measured before surgery and at 6 and 24 h postsurgery. There were no significant differences between groups for postoperative morphine use, pain or nausea scores, anxiety scores, or days spent in hospital after surgery. Seven of 20 patients who heard the Pan story intraoperative gave a positive association with the word "Hook," whereas 2 of 20 who did not hear the story gave such an association. Indirect memory for the Pan story was established using confidence interval (CI) analysis. (The 95% CI for difference in proportion did not include zero). No indirect memory for the Crusoe story could be demonstrated. This study did not confirm previous work which suggested that positive therapeutic auditory suggestions, played intraoperatively, reduced PCA morphine requirements. In contrast, a positive implicit memory effect was found for a story presented intraoperatively.

  19. Morphine deteriorates spatial memory in sodium salicylate treated rats.

    Science.gov (United States)

    Sadegh, Mehdi; Fathollahi, Yaghoub; Naghdi, Nasser; Semnanian, Saeed

    2013-03-15

    Tolerance and cross-tolerance for the effects of morphine (M) and sodium salicylate on nociception and learning were examined. The anti-nociceptive effects were measured by using the classic tail flick (TF) and hot plate (HP) tests and learning was measured with the Morris water maze (MWM). Tolerance or cross-tolerance was induced by daily injection (i.p.) of morphine sulfate (10mg/kg for 7 days) or sodium salicylate (300 mg/kg for 6 days). The injection of sodium salicylate increased both TF and HP latencies. This anti-nociceptive effect was progressively decreased across six injections and tolerance to sodium salicylate was developed. When M was injected to sodium salicylate-tolerant rats, a weakened anti-nociceptive effect was seen, indicating cross-tolerance to M. Acute treatment with M also increased TF latency. This anti-nociceptive effect was successively decreased across seven injections and tolerance to M was developed. When sodium salicylate was injected to M-tolerant rats, a diminished anti-nociceptive effect was seen, indicating cross-tolerance to sodium salicylate. Acute M impaired water maze performance, while chronic M and sodium salicylate had no effects on MWM performance. However, when M was injected to rats that had received sodium salicylate after each training trial for 7 days, these rats spent less time in target quadrant as compared to M and saline groups. It is concluded that chronic sodium salicylate induces tolerance to anti-nociceptive effects of M and vice versa. Also chronic salicylate may produce lasting metaplastic changes in brain mechanisms behind spatial learning and memory, which can be visualized in cross-sensitization to morphine. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  20. Dwarf mutant of Papaver somniferum with high morphine content

    International Nuclear Information System (INIS)

    Chauhan, S.P.; Patra, N.K.; Srivastava, H.K.

    1987-01-01

    Opium poppy, Papaver somniferum L. is an important medicinal plant known for its morphine, codeine, and thebaine alkaloids. This Institute had earlier released two latex opium yielding poppy varieties, Shyama and Shweta, which are now cultivated by the farmers under the supervision of the Narcotic Department of the Government of India. However, both these varieties became susceptible to downy mildew (Peronospora arborescens). Lodging due to heavy capsule weight is another problem affecting latex yield. With these problems in mind, we undertook mutation breeding on the above mentioned two varieties employing gamma rays (5 kR, 15 kR, 20 kR) and EMS (0.2%, 0.4%, 0.6%) and combined mutagens (5 kR + 0.2% EMS, 5 kR + 0.4% EMS and 5 kR + 0.6% EMS). M 1 from the treated seeds (405 plants) was raised in winter 1984-85. M 2 generation of 13,500 plants (i.e. 270 M 1 progenies x 50 plants) was raised in winter 1985/86. A dwarf mutant with high morphine content was identified in M 2 from the variety Shweta treated with 5 kR + 0.4% EMS. The mutant differs by its dwarf stature, compact leaf arrangements, multilocular capsules, increased capsule number, and small capsule size. The mutant is under testing for its superior morphine production. It may be used as dwarf gene source in hybridization for improving lodging resistance. This mutant is a novel type, which was not available in our germplasm collection

  1. Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine

    Directory of Open Access Journals (Sweden)

    Robin W. Rockhold

    2002-10-01

    Full Text Available Abstract: The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP, an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v. infusion of morphine (26 nmol/μl/h for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, dermally, initially, 3 days prior to initiation of i.c.v. morphine infusion and again on the first day of infusion. Withdrawal was precipitated after 3 days of infusion by administering an opioid antagonist, naloxone (48 nmol/5 μl, i.c.v.. Twelve of 23 MP-treated rats exhibited signs of acetylcholinesterase inhibitor intoxication (mild tremors and showed reduced spontaneous locomotor activity (tested by an open field test, prior to naloxone. The brain cholinesterase activity in these 12 rats was 13% of levels in control rats. Eleven rats that did not show toxic signs, exhibited cholinesterase activities that were 20% of control (not significant versus toxic group. The group that showed signs of MP intoxication exhibited a significantly lower incidence of opioid withdrawal jumping, rearing and wet dog shakes compared with the non-toxic group. No differences between quantal withdrawal signs (ptosis, penis-licking, and vocalization were noted between the two groups. The results suggest that toxic inhibition of acetylcholinesterase non-specifically reduces locomotor activity and may obscure certain behavioral signs of withdrawal from opioid dependence. This indicates that caution should be used in interpreting a direct involvement of acetylcholinesterase inhibition in preventing opioid dependence.

  2. Paradoxical effects of the opioid antagonist naltrexone on morphine analgesia, tolerance, and reward in rats.

    Science.gov (United States)

    Powell, Kelly J; Abul-Husn, Noura S; Jhamandas, Asha; Olmstead, Mary C; Beninger, Richard J; Jhamandas, Khem

    2002-02-01

    Opioid agonists such as morphine have been found to exert excitatory and inhibitory receptor-mediated effects at low and high doses, respectively. Ultra-low doses of opioid antagonists (naloxone and naltrexone), which selectively inhibit the excitatory effects, have been reported to augment systemic morphine analgesia and inhibit the development of tolerance/physical dependence. This study investigated the site of action of the paradoxical effects of naltrexone and the generality of this effect. The potential of ultra-low doses of naltrexone to influence morphine-induced analgesia was investigated in tests of nociception. Administration of intrathecal (0.05 and 0.1 ng) or systemic (10 ng/kg i.p.) naltrexone augmented the antinociception produced by an acute submaximal dose of intrathecal (5 microg) or systemic (7.5 mg/kg i.p.) morphine in the tail-flick test. Chronic intrathecal (0.005 and 0.05 ng) or systemic (10 ng/kg) naltrexone combined with morphine (15 microg i.t.; 15 mg/kg i.p.) over a 7-day period inhibited the decline in morphine antinociception and prevented the loss of morphine potency. In animals rendered tolerant to intrathecal (15 microg) or systemic (15 mg/kg) morphine, administration of naltrexone (0.05 ng i.t.; 10 and 50 ng/kg i.p.) significantly restored the antinociceptive effect and potency of morphine. Thus, in ultra-low doses, naltrexone paradoxically enhances morphine analgesia and inhibits or reverses tolerance through a spinal action. The potential of naltrexone to influence morphine-induced reward was also investigated using a place preference paradigm. Systemic administration of ultra-low doses of naltrexone (16.7, 20.0, and 25.0 ng/kg) with morphine (1.0 mg/kg) extended the duration of the morphine-induced conditioned place preference. These effects of naltrexone on morphine-induced reward may have implications for chronic treatment with agonist-antagonist combinations.

  3. Combined intra-articular glucocorticoid, bupivacaine and morphine reduces pain and convalescence after diagnostic knee arthroscopy

    DEFF Research Database (Denmark)

    Rasmussen, Sten; Lorentzen, Jan S; Larsen, Allan S

    2002-01-01

    We studied the effect of intra-articullar saline vs. bupivacaine + morphine or bupivacaine morphine + methylprednisolone after diagnostic knee arthroscopy. In a double-blind randomized study, 60 patients undergoing diagnostic knee arthroscopy without a therapeutic procedure were allocated to groups...... receiving intra-articular saline, intra-articular bupivacaine 150 mg + morphine 4 mg or the same dose of bupivacaine + morphine + intra-articular methylprednisolone 40 mg at the end of arthroscopy during general anesthesia. All patients were instructed to resume normal activities immediately after...... the procedure. Pain during movement and walking, leg muscle force and joint effusion, use of crutches and duration of sick leave were assessed. A combination of bupivacaine and morphine reduced pain, duration of immobilization and of convalescence. The addition of methylprednisolone further reduced pain, use...

  4. Steady-state kinetics and dynamics of morphine in cancer patients

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Sjøgren, P; Jensen, N H

    1999-01-01

    Eighteen patients suffering from chronic pain due to cancer completed a balanced, double-blind, double-dummy, two period cross-over trial comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, after...... to analgesia and side effects, and there was no difference in the patients' overall impression of the two treatments. More important, there was no difference between the Tmax and the time to peak sedation after administration of IR tablets (P = 0.63). However, due to the relatively small number of patients...... administration of morphine given as controlled-release (CR) tablets (every 12 h) and immediate-release (IR) tablets (every 6 h). The same total daily dose of morphine was given in both study periods. Patients received both test formulations for 4 days and on the final day of each period, peripheral venous blood...

  5. Comparison of analgesic effects of intra-articular tenoxicam and morphine in anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Guler, Gulen; Karaoglu, Sinan; Velibasoglu, Hediye; Ramazanogullari, Nesrin; Boyaci, Adem

    2002-07-01

    This study compared the analgesic effect of intra-articular injection of tenoxicam with that of morphine on postoperative pain after anterior cruciate ligament (ACL) reconstruction. Forty-two patients undergoing arthroscopically ACL reconstructions using hamstring tendons underwent the same anesthetic protocol. The patients were randomized to receive 25 ml normal saline, 20 mg tenoxicam in 25 ml normal saline, or 2 mg morphine in 25 ml normal saline. Postoperative pain was assessed using a visual analogue scale and measuring analgesic requirements. We found both that both intra-articular tenoxicam and intra-articular morphine provided better analgesia than that in the control group. Although pain scores were similar between tenoxicam and morphine groups 30 min postoperative, the analgesic requirements in with tenoxicam were significantly lower than those with morphine group 3-6 h postoperatively.

  6. Successful management of a difficult cancer pain patient by appropriate adjuvant and morphine titration

    Directory of Open Access Journals (Sweden)

    Shiv PS Rana

    2011-01-01

    Full Text Available Morphine has been used for many years to relieve cancer pain. Oral morphine (in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain. The dose of oral morphine is titrated up to achieve adequate relief from pain with minimal side effects. Antidepressant and anticonvulsant drugs, when used in addition to conventional analgesics, give excellent relief from cancer pain. Most cancer pain responds to pharmacological measures with oral morphine but some pain like neuropathic and bony pain, pain in children and elderly age group, and advanced malignancy pain are very difficult to treat. Here, we report the management of a similar patient of severe cancer pain and the difficulty that we came across during dose titration of oral morphine and adjuvant analgesic.

  7. Mechanisms of adaptation from a multiple to a single step recovery strategy following repeated exposure to forward loss of balance in older adults.

    Directory of Open Access Journals (Sweden)

    Christopher P Carty

    Full Text Available When released from an initial, static, forward lean angle and instructed to recover with a single step, some older adults are able to meet the task requirements, whereas others either stumble or fall. The purpose of the present study was to use the concept of margin of stability (MoS to investigate balance recovery responses in the anterior-posterior direction exhibited by older single steppers, multiple steppers and those that are able to adapt from multiple to single steps following exposure to repeated forward loss of balance. One hundred and fifty-one healthy, community dwelling, older adults, aged 65-80 years, participated in the study. Participants performed four trials of the balance recovery task from each of three initial lean angles. Balance recovery responses in the anterior-posterior direction were quantified at three events; cable release (CR, toe-off (TO and foot contact (FC, for trials performed at the intermediate lean angle. MoS was computed as the anterior-posterior distance between the forward boundary of the Base of Support (BoS and the vertical projection of the velocity adjusted centre of mass position (XCoM. Approximately one-third of participants adapted from a multiple to a single step recovery strategy following repeated exposure to the task. MoS at FC for the single and multiple step trials in the adaptation group were intermediate between the exclusively single step group and the exclusively multiple step group, with the single step trials having a significant, 3.7 times higher MoS at FC than the multiple step trials. Consistent with differences between single and multiple steppers, adaptation from multiple to single steps was attributed to an increased BoS at FC, a reduced XCoM at FC and an increased rate of BoS displacement from TO to FC. Adaptations occurred within a single test session and suggest older adults that are close to the threshold of successful recovery can rapidly improve dynamic stability following

  8. The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice.

    Science.gov (United States)

    Zhu, Lin; Xue, Junyi; Xia, Qingsu; Fu, Peter P; Lin, Ge

    2017-02-01

    Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and the most common poisonous plants affecting livestock, wildlife, and humans. Our previous studies demonstrated that PA-derived DNA adducts can potentially be a common biological biomarker of PA-induced liver tumor formation. In order to validate the use of these PA-derived DNA adducts as a biomarker, it is necessary to understand the basic kinetics of the PA-derived DNA adducts formed in vivo. In this study, we studied the dose-dependent response and kinetics of PA-derived DNA adduct formation and removal in male ICR mice orally administered with a single dose (40 mg/kg) or multiple doses (10 mg/kg/day) of retrorsine, a representative carcinogenic PA. In the single-dose exposure, the PA-derived DNA adducts exhibited dose-dependent linearity and persisted for up to 4 weeks. The removal of the adducts following a single-dose exposure to retrorsine was biphasic with half-lives of 9 h (t 1/2α ) and 301 h (~12.5 days, t 1/2β ). In the 8-week multiple exposure study, a marked accumulation of PA-derived DNA adducts without attaining a steady state was observed. The removal of adducts after the multiple exposure also demonstrated a biphasic pattern but with much extended half-lives of 176 h (~7.33 days, t 1/2α ) and 1736 h (~72.3 days, t 1/2β ). The lifetime of PA-derived DNA adducts was more than 8 weeks following the multiple-dose treatment. The significant persistence of PA-derived DNA adducts in vivo supports their role in serving as a biomarker of PA exposure.

  9. Transcriptional profiling of C57 and DBA strains of mice in the absence and presence of morphine

    Directory of Open Access Journals (Sweden)

    Golden Greg T

    2007-03-01

    Full Text Available Abstract Background The mouse C57BL/6 (C57 and DBA/2J (DBA inbred strains differ substantially in many aspects of their response to drugs of abuse. The development of microarray analyses represents a genome-wide method for measuring differences across strains, focusing on expression differences. In the current study, we carried out microarray analysis in C57 and DBA mice in the nucleus accumbens of drug-naïve and morphine-treated animals. Results We identified mRNAs with altered expression between the two strains. We validated the mRNA expression changes of several such mRNAs, including Gnb1, which has been observed to be regulated by several drugs of abuse. In addition, we validated alterations in the enzyme activity of one mRNA product, catechol-O-methyltransferase (Comt. Data mining of expression and behavioral data indicates that both Gnb1 and Comt expression correlate with aspects of drug response in C57/DBA recombinant inbred strains. Pathway analysis was carried out to identify pathways showing significant alterations as a result of treatment and/or due to strain differences. These analyses identified axon guidance genes, particularly the semaphorins, as showing altered expression in the presence of morphine, and plasticity genes as showing altered expression across strains. Pathway analysis of genes showing strain by treatment interaction suggest that the phosphatidylinositol signaling pathway may represent an important difference between the strains as related to morphine exposure. Conclusion mRNAs with differing expression between the two strains could potentially contribute to strain-specific responses to drugs of abuse. One such mRNA is Comt and we hypothesize that altered expression of Comt may represent a potential mechanism for regulating the effect of, and response to, multiple substances of abuse. Similarly, a role for Gnb1 in responses to multiple drugs of abuse is supported by expression data from our study and from other

  10. Ghrelin and endocannabinoids participation in morphine-induced effects in the rat nucleus accumbens.

    Science.gov (United States)

    Sustkova-Fiserova, Magdalena; Jerabek, Pavel; Havlickova, Tereza; Syslova, Kamila; Kacer, Petr

    2016-02-01

    In addition to dopamine, endocannabinoids are thought to participate in neural reward mechanisms of opioids. Number of recent studies suggests crucial involvement of ghrelin in some addictive drugs effects. Our previous results showed that ghrelin participates in morphine-induced changes in the mesolimbic dopaminergic system associated with reward processing. The goal of the present study was to test whether the growth hormone secretagogue receptor (GHS-R1A) antagonist JMV2959 was able to influence morphine-induced effects on anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) in the nucleus accumbens shell (NACSh). We used in vivo microdialysis to determine changes in levels of AEA and 2-AG in the NACSh in rats following (i) an acute morphine dose (5, 10 mg/kg s.c.) with and without JMV2959 pretreatment (3, 6 mg/kg i.p.) or (ii) a morphine challenge dose (5 mg/kg s.c.) with and without JMV2959 (3, 6 mg/kg i.p.) pretreatment, administered during abstinence following repeated doses of morphine (5 days, 10-40 mg/kg). Co-administration of ghrelin (40 ug/kg i.p.) was used to verify the ghrelin mechanisms involvement. Pretreatment with JMV2959 significantly and dose-dependently reversed morphine-induced anandamide increases in the NACSh in both the acute and longer-term models, resulting in a significant AEA decrease. JMV2959 significantly intensified acute morphine-induced decreases in accumbens 2-AG levels and attenuated morphine challenge-induced 2-AG decreases. JMV2959 pretreatment significantly reduced concurrent morphine challenge-induced behavioral sensitization. JMV2959 pretreatment effects were abolished by co-administration of ghrelin. Our results indicate significant involvement of ghrelin signaling in morphine-induced endocannabinoid changes in the NACSh.

  11. Does neonatal morphine use affect neuropsychological outcomes at 8 to 9 years of age?

    Science.gov (United States)

    de Graaf, Joke; van Lingen, Richard A; Valkenburg, Abraham J; Weisglas-Kuperus, Nynke; Groot Jebbink, Liesbeth; Wijnberg-Williams, Barbara; Anand, Kanwaljeet J S; Tibboel, Dick; van Dijk, Monique

    2013-03-01

    Morphine is widely used to treat severe pain in neonatal intensive care unit patients. Animal studies suggest adverse long-term side effects of neonatal morphine, but a follow-up study of 5-year-old children who participated in a morphine-placebo controlled trial as newborns found no such effects on the child's general functioning. This study indicated that morphine may negatively affect response inhibition, a domain of executive functions. Therefore, we performed a second follow-up study in the same population at the age of 8 to 9 years, focused on the child's general functioning in terms of intelligence, visual motor integration, and behavior and on executive functions. Children in the morphine group showed significantly less externalizing problems according to the parents but more internalizing behavior according to the teachers, but only after adjustment for intelligence quotient (IQ), potential confounders using a propensity score, and additional open-label morphine. Morphine-treated children showed significantly fewer problems with executive functions in daily life as rated by parents for the subscales inhibition and organization of materials and for planning/organizing as rated by the teachers. After adjustment for IQ and the propensity score, executive functioning as rated by the parents remained statistically significantly better in the morphine-treated group. The influence of the additional morphine given was not of a significant influence for any of the outcome variables. Overall, the present study demonstrates that continuous morphine infusion of 10 μg/kg/h during the neonatal period does not harm general functioning and may even have a positive influence on executive functions at 8 to 9 years. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. Morphine and Codeine in Oral Fluid after Controlled Poppy Seed Administration

    Science.gov (United States)

    Concheiro, Marta; Newmeyer, Matthew N.; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A.; Huestis, Marilyn A.

    2014-01-01

    Opiates are an important drug class in drug testing programs. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only 2 addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45g raw poppy seed doses, each containing 15.7mg morphine and 3.1mg codeine, 8h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography tandem mass spectrometry (1μg/L morphine and codeine limits of quantification). Specimens (n=459) were collected before and up to 32h after the first dose. All specimens screened positive 0.5h after dosing and remained positive for 0.5-13h at Draeger 20μg/L morphine cutoff. Maximum OF morphine and codeine concentrations (Cmax) were 177 and 32.6μg/L, with times to Cmax (Tmax) of 0.5-1h and 0.5-2.5h post-dose, respectively. Windows of detection after the second dose extended at least 24h for morphine and to 18h for codeine. After both doses, the last morphine positive OF result was 1h with 40μg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cutoff, and 0.5h with 95μg/L cutoff, recently recommended by the Driving Under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1h after ingestion of 15.7mg of morphine in raw poppy seeds, depending upon the cutoff employed. PMID:25345619

  13. Patient-controlled analgesia in the pediatric population: morphine versus hydromorphone

    Science.gov (United States)

    DiGiusto, Matthew; Bhalla, Tarun; Martin, David; Foerschler, Derek; Jones, Megan J; Tobias, Joseph D

    2014-01-01

    Objective Patient controlled analgesia (PCA) is commonly used to provide analgesia following surgical procedures in the pediatric population. Morphine and hydromorphone remain the most commonly used opioids for PCA. Although both are effective, adverse effects may occur. When these adverse effects are unremitting or severe, opioid rotation may be required. In this study, we retrospectively evaluated PCA use, the adverse effect profile, and the frequency of opioid rotation. Methods This retrospective study was performed at Nationwide Children’s Hospital (Columbus, OH). The hospital’s electronic registry was queried for PCA use delivering either morphine or hydromorphone from January 1, 2008 to December 31, 2010. Results A total of 514 patients were identified, that met study entry criteria. Of the 514 cases, 298 (56.2%) were initially started on morphine and 225 (43.8%) were initially started on hydromorphone. There were a total of 26 (5.1%) opioid changes in the cohort of 514 patients. Of the 26 switches, 23 of 298 (7.7%) were from morphine to hydromorphone, and 3 of 225 (1.3%) were from hydromorphone to morphine (P=0.0008). Of the 17 morphine-to-hydromorphone switches with adverse effects, pruritus (64.7%), and inadequate pain control (47.1%) were the most common side effects. The most common side effect resulting in a hydromorphone-to-morphine switch was nausea (66.7%). Conclusion PCA switches from morphine-to-hydromorphone (88.5%) were more common than vice-versa (11.5%). The most common reasons for morphine-to-hydromorphone switch were pruritus and inadequate pain control. These data suggest that a prospective study is necessary to determine the side effect differences between morphine and hydromorphone in pediatric PCA. PMID:25152630

  14. Inhibition of tolerance to spinal morphine antinociception by low doses of opioid receptor antagonists.

    Science.gov (United States)

    McNaull, Benjamin; Trang, Tuan; Sutak, Maaja; Jhamandas, Khem

    2007-04-10

    Ultra-low doses of opioid receptor antagonists inhibit development of chronic spinal morphine tolerance. As this phenomenon mechanistically resembles acute tolerance, the present study examined actions of opioid receptor antagonists on acute spinal morphine tolerance. In adult rats, administration of three intrathecal injections of morphine (15 microg) at 90 min intervals produced a significant decline of the antinociceptive effect and loss of agonist potency in both the tail-flick and paw-pressure tests. These reduced responses, indicative of acute tolerance, were blocked by co-injection of morphine (15 microg) with naltrexone (NTX, 0.05 ng), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTAP, 0.001 ng), naltrindole (0.06 ng), or nor-binaltorphimine (0.1 ng). Repeated injections of CTAP, naltrindole, or nor-binaltorphimine without morphine elicited a delayed weak antinociceptive response which was blocked by a high dose of naltrexone (2 microg). In another set of experiments, administration of low dose spinal (0.05 ng) or systemic (0.01 microg/kg) morphine produced a sustained thermal hyperalgesia. This response was blocked by opioid receptor antagonists at doses inhibiting development of acute morphine tolerance. Lastly, an acute spinal injection of morphine (15 microg) with naltrexone (0.05 ng) produced a sustained analgesic response; this was antagonized by adenosine receptor antagonist, 8-phenyltheophylline (3 microg). The results show that ultra-low doses of opioid receptor antagonists block acute tolerance to morphine. This effect may result from blockade of opioid excitatory effects that produce a latent hyperalgesia that then contributes to induction of tolerance. The sustained antinociception produced by combination of morphine with an opioid receptor antagonist shows dependency on the adenosine receptor activity.

  15. CCR5 mediates HIV-1 Tat-induced neuroinflammation and influences morphine tolerance, dependence, and reward.

    Science.gov (United States)

    Gonek, Maciej; McLane, Virginia D; Stevens, David L; Lippold, Kumiko; Akbarali, Hamid I; Knapp, Pamela E; Dewey, William L; Hauser, Kurt F; Paris, Jason J

    2017-11-13

    The HIV-1 regulatory protein, trans-activator of transcription (Tat), interacts with opioids to potentiate neuroinflammation and neurodegeneration within the CNS. These effects may involve the C-C chemokine receptor type 5 (CCR5); however, the behavioral contribution of CCR5 on Tat/opioid interactions is not known. Using a transgenic murine model that expresses HIV-1 Tat protein in a GFAP-regulated, doxycycline-inducible manner, we assessed morphine tolerance, dependence, and reward. To assess the influence of CCR5 on these effects, mice were pretreated with oral vehicle or the CCR5 antagonist, maraviroc, prior to morphine administration. We found that HIV-1 Tat expression significantly attenuated the antinociceptive potency of acute morphine (2-64 mg/kg, i.p.) in non-tolerant mice. Consistent with this, Tat attenuated withdrawal symptoms among morphine-tolerant mice. Pretreatment with maraviroc blocked the effects of Tat, reinstating morphine potency in non-tolerant mice and restoring withdrawal symptomology in morphine-tolerant mice. Twenty-four hours following morphine administration, HIV-1 Tat significantly potentiated (∼3.5-fold) morphine-conditioned place preference and maraviroc further potentiated these effects (∼5.7-fold). Maraviroc exerted no measurable behavioral effects on its own. Protein array analyses revealed only minor changes to cytokine profiles when morphine was administered acutely or repeatedly; however, 24 h post morphine administration, the expression of several cytokines was greatly increased, including endogenous CCR5 chemokine ligands (CCL3, CCL4, and CCL5), as well as CCL2. Tat further elevated levels of several cytokines and maraviroc pretreatment attenuated these effects. These data demonstrate that CCR5 mediates key aspects of HIV-1 Tat-induced alterations in the antinociceptive potency and rewarding properties of opioids. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Assessment of a von Frey device for evaluation of the antinociceptive effects of morphine and its application in pharmacodynamic modeling of morphine in dogs.

    Science.gov (United States)

    KuKanich, Butch; Lascelles, B Duncan X; Papich, Mark G

    2005-09-01

    To assess the use of a von Frey device as a mechanical nociceptive stimulus for evaluation of the antinociceptive effects of morphine in dogs and its potential application in the pharmacodynamic modeling of morphine in that species. 6 healthy Beagles. von Frey thresholds were measured in all dogs before and at intervals after they received no treatment (control dogs) and i.v. administration of morphine sulfate (1 mg/kg; treated dogs) in a crossover study. The von Frey device consisted of a rigid tip (0.5 mm in diameter) and an electronic load cell; the operator was unaware of recorded measurements. Application of the von Frey device was simple and well tolerated by all dogs and caused no apparent tissue damage. No significant changes in thresholds were detected in the control dogs at 8 hourly measurements, indicating a lack of acquired tolerance, learned aversion, or local hyperalgesia. When assessed as a group, treated dogs had significantly high thresholds for 4 hours following morphine administration, compared with baseline values; individually, thresholds decreased to baseline values within (mean +/- SE) 2.8 +/- 0.6 hours. The maximal effect (change from baseline values) was 213 +/- 43%, and the plasma morphine concentration to achieve 50% maximal effect was 13.92 +/- 2.39 ng/mL. Data suggest that, in dogs, evaluation of the antinociceptive effect and pharmacodynamic modeling of a dose of morphine sulfate (1 mg/kg, i.v.) can be successfully achieved by use of a von Frey device.

  17. A single exposure to acrolein desensitizes baroreflex responsiveness and increases cardiac arrhythmias in normotensive and hypertensive rats

    Science.gov (United States)

    Background – Short-term exposure to air pollutants has been linked to acute cardiovascular morbidity and mortality. Even in the absence of overt symptoms, pollutants can cause subtle disruptions of internal regulatory mechanisms, which maintain homeostatic balance, thereby reduci...

  18. Attenuation of morphine withdrawal signs, blood cortisol and glucose level with forced exercise in comparison with clonidine

    Directory of Open Access Journals (Sweden)

    Majid Motaghinejad

    2014-01-01

    Full Text Available Background: Morphine withdrawal usually results in undesired outcomes , despite partial benefits of alternative medication such as methadone, because of the lack of mental sedation during the withdrawal period, may not lead to the desired result. In this study, forced exercise by treadmill is used to manage morphine dependence in animal model. Materials and Methods: Forty adult male mice were divided into 5 groups, from which 4 groups became dependent by increasing daily doses of morphine for 6 days (20-45 mg/kg, SC. Afterwards, the animals were treated for 21 days by either of the following protocol: Positive control (dependent received once daily 45 mg/kg of morphine sulfate (SC for 21 day, group under treatment by clonidine (0.4 mg/kg, SC for 21 day group under treatment by forced exercise by treadmill for 21 day, group under treatment by combination of clonidine (0.4 mg/kg, SC and forced exercise by treadmill for 21day and the negative control group(independent received saline injection like other groups. Each of this administration was injected at 8 AM. Finally, in the test day (day 28, all animals received a single dose of naloxone (3 mg/kg, SC at 8 AM and then were observed for withdrawal signs, and Total Withdrawal Score (TWS was determined as described previously. After withdrawal sign evaluation for evaluation of stress level of dependent mice, blood cortisol and glucose level were measured in non-fasting situations well. Results: This study showed that TWS significantly decreased in all treatment groups in comparison with positive control group (P < 0.001. Moreover, blood cortisol and glucose level significantly decreased in group under treatment by clonidine (0.4 mg/kg and group under treatment by combination of clonidine (0.4 mg/kg and forced exercise by treadmill groups in comparison with control positive (dependent (P < 0.05. Conclusion: This study suggested that forced exercise can be useful as adjunct therapy in dependent people

  19. Effect of Exposure Type and Timing of Injuries in Division I College Football: A 4-year Single Program Analysis.

    Science.gov (United States)

    Krill, Michael K; Borchers, James R; Hoffman, Joshua T; Tatarski, Rachel L; Hewett, Timothy E

    2017-02-01

    Football players compete with a high risk of injury due to the sport. With the recent efforts to improve safety, the National Collegiate Athletic Association (NCAA) established new terminology to clearly define exposure types and reduce the number of high contact exposures. To compare football injury rates (IR) with a focus on game versus practice, time in season of injury, mechanism of injury and utilizing recent exposure types defined by the NCAA (live contact, full-pads and non-contact). Licensed medical professionals monitored a college football program regular season from 2012-2015. Each injury was classified by timing of the injury, mechanism of injury, and whether it occurred in game or practice. Player attendance and type of exposure (non-contact, full-pad or live contact, which involves live tackling to the ground and/or full-speed blocking and can occur in full-pad or half-pad ('shell') equipment) was documented. IR were calculated per 1000 athlete-exposures (AE). Mid-exact P tests compared rates between variables. The game IR was over three times as high as the practice IR (p injuries observed occurred from a contact mechanism (IR: 2.508/1000 AE). The highest IR during the fall football season occurred in the pre-season at 5.769/1000 AE. Overall IR observed in this cohort were lower than prior studies published before recent NCAA rule changes and guideline implementation to improve athlete safety. Athletes in this cohort were at significantly increased risk of injury from live contact exposures.

  20. Single-centre experience of radiation exposure in acute surgical patients: assessment of therapeutic impact and future recommendations.

    Science.gov (United States)

    Fitzmaurice, Gerard J; Brown, Robin; Cranley, Brian; Conlon, Enda F; Todd, R Alan J; O'Donnell, Mark E

    2010-09-01

    Radiological investigations have become a key adjunct in patient management and consequently radiation exposure to patients is increasing. The study objectives were to examine the use of radiological investigations in the management of acute surgical patients and to assess whether a guideline-based radiation exposure risk/benefit analysis can aid in the choice of radiological investigation used. A prospective observational study was completed over a 12-week period from April to July 2008 for all acute surgical admissions. Data recorded included demographics, clinical presentation, differential diagnosis, investigations, surgical interventions, and final clinical outcome. The use of radiological investigative modalities as an adjunct to clinical assessment was then evaluated against The Royal College of Radiologists (RCR) guidelines. A total of 380 acute surgical admissions (M = 174, F = 185, children = 21) were assessed during the study period. Seven hundred thirty-four radiological investigations were performed with a mean of 1.93 investigations per patient. Based on the RCR guidelines, 680 (92.6%) radiological investigations were warranted and included 142 CT scans (19.3%), 129 chest X-rays (17.6%), and 85 abdominal X-rays (11.6%). Clinically, radiological imaging complemented surgical management in 326 patients (85.8%) and the management plan remained unchanged for the remaining 54 patients (14.2%). This accounted for an average radiation dose of 4.18 millisievert (mSv) per patient or 626 days of background radiation exposure. CT imaging was responsible for the majority of the radiation exposure, with a total of 1310 mSv (82.6%) of the total radiation exposure being attributed to CT imaging in 20.8% of acute admissions. Subgroup analysis demonstrated that 92.8% of the CT scans performed were appropriate. Radiation exposure was generally low for the majority of acute surgical admissions. However, it is recommended that CT imaging requests be evaluated carefully

  1. Single and Combined Exposure to Zinc- and Copper-Containing Welding Fumes Lead to Asymptomatic Systemic Inflammation.

    Science.gov (United States)

    Markert, Agnieszka; Baumann, Ralf; Gerhards, Benjamin; Gube, Monika; Kossack, Veronika; Kraus, Thomas; Brand, Peter

    2016-02-01

    Recently, it has been shown that exposure to welding fumes containing both zinc and copper leads to asymptomatic systemic inflammation in humans as shown by an increase of blood C-reactive protein. In the present study, it was investigated which metal is responsible for this effect. Fifteen healthy male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc. For each exposure blood C-reactive protein increased. Copper- and zinc-containing welding fumes are able to induce systemic inflammation.

  2. Morphine Biosynthesis in Opium Poppy Involves Two Cell Types: Sieve Elements and Laticifers[W][OPEN

    Science.gov (United States)

    Onoyovwe, Akpevwe; Hagel, Jillian M.; Chen, Xue; Khan, Morgan F.; Schriemer, David C.; Facchini, Peter J.

    2013-01-01

    Immunofluorescence labeling and shotgun proteomics were used to establish the cell type–specific localization of morphine biosynthesis in opium poppy (Papaver somniferum). Polyclonal antibodies for each of six enzymes involved in converting (R)-reticuline to morphine detected corresponding antigens in sieve elements of the phloem, as described previously for all upstream enzymes transforming (S)-norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole-stem and latex total protein extracts generated 2031 and 830 distinct protein families, respectively. Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex. Salutaridine synthase was detected in the whole stem, but not in the latex subproteome. The final three enzymes converting thebaine to morphine were among the most abundant active latex proteins despite a limited occurrence in laticifers suggested by immunofluorescence labeling. Multiple charge isoforms of two key O-demethylases in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine biosynthesis appears to occur only in sieve elements, whereas conversion of thebaine to morphine is predominant in adjacent laticifers, which contain morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun proteomics has substantially resolved the cellular localization of morphine biosynthesis in opium poppy. PMID:24104569

  3. Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray

    Science.gov (United States)

    Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.

    2014-01-01

    Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060

  4. Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats

    Directory of Open Access Journals (Sweden)

    Milne Brian

    2010-04-01

    Full Text Available Abstract Background The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Results Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Conclusion Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of

  5. Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.

    Science.gov (United States)

    Mattioli, Theresa-Alexandra M; Milne, Brian; Cahill, Catherine M

    2010-04-16

    The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone

  6. Amperometric detection of morphine based on poly(3,4-ethylenedioxythiophene) immobilized molecularly imprinted polymer particles prepared by precipitation polymerization

    International Nuclear Information System (INIS)

    Ho, K.-C.; Yeh, W.-M.; Tung, T.-S.; Liao, J.-Y.

    2005-01-01

    Molecular imprinting is a novel technique used for chiral separation, artificial antibodies, sensors, and assays. Typically, molecular imprinted polymers (MIPs) are monoliths with irregular shapes. However, microspherical shapes with more uniform size can be obtained by the method of precipitation polymerization, which offers a higher active surface area by manipulating its compositions. In this study, MIP particles for the target molecule, morphine, were synthesized using a precipitation polymerization method that is more facile than the previous one that produced a thermally polymerized bulk. The conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), was utilized to immobilize the MIP particles onto the indium tin oxide (ITO) glass as a MIP/PEDOT-modified electrode. The sensitivity for the MIP/PEDOT-modified electrode with MIP particles was 41.63 μA/cm 2 mM, which is more sensitive than that with non-MIP particles or that of a single PEDOT film with no incorporated particles in detecting morphine ranging from 0.1 to 2 mM. The detection limit was 0.3 mM (S/N = 3). In addition, we presented that the modified electrode can discriminate codeine that plays an interfering species

  7. Stability of Fentanyl Citrate, Hydromorphone Hydrochloride, Ketamine Hydrochloride, Midazolam, Morphine Sulfate, and Pentobarbital Sodium in Polypropylene Syringes.

    Science.gov (United States)

    Anderson, Collin; MacKay, Mark

    2015-12-16

    Determine the stability of fentanyl 10 mcg/mL in 0.9% sodium chloride, fentanyl 10 mcg/mL in 5% dextrose, fentanyl 50 mcg/mL, hydromorphone 100 mcg/mL in 0.9% sodium chloride, ketamine 10 mg/mL, midazolam 0.4 mg/mL in 5% dextrose, midazolam 5 mg/mL, morphine 1 mg/mL in 0.9% sodium chloride, morphine 1 mg/mL in 5% dextrose, and pentobarbital 50 mg/mL when stored as single drug entities at room temperature in polypropylene syringes. Four 5 mL samples of each drug and concentration were prepared in 10 mL polypropylene syringes. The samples were stored at ambient room temperature in a locked cabinet. Triplicate determinations of drug concentration for each sample were performed initially, on day 50 or 51, and on day 100 using high-performance liquid chromatography with diode-array detection. With the exception of the hydromorphone 100 mcg/mL dilution, all compounds were found to contain greater than 95% of their initial concentration remaining at 100 days. Each sample remained clear and colorless when visually inspected.

  8. Prolonged increase of cis-urocanic acid levels in human skin and urine after single total-body ultraviolet exposures

    NARCIS (Netherlands)

    Kammeyer, A.; Pavel, S.; Asghar, S. S.; Bos, J. D.; Teunissen, M. B.

    1997-01-01

    Cis-urocanic acid (cis-UCA), a mediator of immunosuppression, is formed from trans-UCA upon UV-exposure of the skin. This study describes a liquid chromatographic method for the simultaneous quantification of cis- and trans-UCA in skin, urine and plasma of nonirradiated volunteers. It also describes

  9. Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D liver microtissue model

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Løhr, Mille; Roursgaard, Martin

    2014-01-01

    BackgroundThe liver has a crucial role in metabolic homeostasis as well as being the principal detoxification centre of the body, removing xenobiotics and waste products which could potentially include some nanomaterials (NM). With the ever increasing public and occupational exposure associated w...

  10. Morphine-induced MOR-1X and ASF/SF2 Expressions Are Independent of Transcriptional Regulation: Implications for MOR-1X Signaling.

    Science.gov (United States)

    Regan, Patrick M; Sariyer, Ilker K; Langford, T Dianne; Datta, Prasun K; Khalili, Kamel

    2016-07-01

    Recently, multiple μ-opioid receptor (MOR) isoforms have been identified that originate from a single gene, OPRM1; however, both their regulation and their functional significance are poorly characterized. The objectives of this study were to decipher, first, the regulation of alternatively spliced μ-opioid receptor isoforms and the spliceosome components that determine splicing specificity and, second, the signaling pathways utilized by particular isoforms both constitutively and following agonist binding. Our studies demonstrated that the expression of a particular splice variant, MOR-1X, was up-regulated by morphine, and this coincided with an increase in the essential splicing factor ASF/SF2. Structural comparison of this isoform to the prototypical variant MOR-1 revealed that the unique distal portion of the C-terminal domain contains additional phosphorylation sites, whereas functional comparison found distinct signaling differences, particularly in the ERK and p90 RSK pathways. Additionally, MOR-1X expression significantly reduced Bax expression and mitochondrial dehydrogenase activity, suggesting a unique functional consequence for MOR-1X specific signaling. Collectively, these findings suggest that alternative splicing of the MOR is altered by exogenous opioids, such as morphine, and that individual isoforms, such as MOR-1X, mediate unique signal transduction with distinct functional consequence. Furthermore, we have identified for the first time a potential mechanism that involves the essential splicing factor ASF/SF2 through which morphine regulates splicing specificity of the MOR encoding gene, OPRM1. © 2015 Wiley Periodicals, Inc.

  11. The efficacy of paracetamol versus tenoxicam on postoperative pain and morphine consumption after abdominal hysterectomy: a placebo-controlled, randomized study.

    Science.gov (United States)

    Gunusen, I; Karaman, S; Acar, A; Sargin, A; Firat, V

    2012-01-01

    The purpose of this study was to determine the analgesic efficacy and side-effects of paracetamol and tenoxicam in comparison with placebo in patients with postoperative pain after elective abdominal hysterectomy. A total of 120 patients were randomly divided into three groups to receive either paracetamol 1 g, tenoxicam 20 mg or placebo intravenously at the end of surgery, and then morphine was administered by a patient-controlled analgesia device postoperatively. Tenoxicam was associated with lower pain scores at the 2nd, 4th, 6th and 24th hour postoperatively. Total morphine consumption was 44.8 +/- 17.4 mg, 64.6 +/- 19.6 mg, 69.2 +/- 22.1 (tenoxicam, paracetamol and placebo group, respectively) and there was a significant difference in the tenoxicam group compared with the other two groups (p < 0.05). Side-effects except for nausea were similar. A single dose of 20 mg tenoxicam provided effective analgesia and reduced total morphine consumption in comparison with paracetamol and placebo after abdominal hysterectomy.

  12. Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain

    DEFF Research Database (Denmark)

    Carstensen, M.; Møller, Ann

    2010-01-01

    In experimental trials, ketamine has been shown to reduce hyperalgesia, prevent opioid tolerance, and lower morphine consumption. Clinical trials have found contradictory results. We performed a review of randomized, double-blinded clinical trials of ketamine added to opioid in i.v. patient...... for i.v. PCA was superior to i.v. PCA opioid alone. The combination allows a significant reduction in pain score, cumulative morphine consumption, and postoperative desaturation. The benefit of adding ketamine to morphine in i.v. PCA for orthopaedic or abdominal surgery remains unclear. Owing to huge...

  13. [Study of Lavoisier morphine chlorhydrate stability in different active perfusion systems after reconstitution in different solvents].

    Science.gov (United States)

    Truelle-Hugon, B; Tourrette, G; Couineaux, B; Gache-Charrette, C

    1997-01-01

    The stability of morphine chlorhydrate injectable solutions with no preservative used for drug delivery system (PCA) was investigated. Many concentrations of morphine chlorhydrate were prepared using different solvents and in several containers: PCA cartridges and plastic syringes stored at 37 degrees C. Assays of drug substance and of degradation products were determined at different time within 14 days. In such conditions, morphine chlorhydrate solutions were stable: degradation products were quantitated less than the usual normal i.e. 2% of the theoric concentration of the drug.

  14. Combined intra-articular glucocorticoid, bupivacaine and morphine reduces pain and convalescence after diagnostic knee arthroscopy

    DEFF Research Database (Denmark)

    Rasmussen, Sten; Lorentzen, Jan S; Larsen, Allan S

    2002-01-01

    We studied the effect of intra-articullar saline vs. bupivacaine + morphine or bupivacaine morphine + methylprednisolone after diagnostic knee arthroscopy. In a double-blind randomized study, 60 patients undergoing diagnostic knee arthroscopy without a therapeutic procedure were allocated to groups...... the procedure. Pain during movement and walking, leg muscle force and joint effusion, use of crutches and duration of sick leave were assessed. A combination of bupivacaine and morphine reduced pain, duration of immobilization and of convalescence. The addition of methylprednisolone further reduced pain, use...

  15. Tolerance to the anticonvulsant effect of morphine in mice: blockage by ultra-low dose naltrexone.

    Science.gov (United States)

    Roshanpour, Maryam; Ghasemi, Mehdi; Riazi, Kiarash; Rafiei-Tabatabaei, Neda; Ghahremani, Mohammad Hossein; Dehpour, Ahmad Reza

    2009-02-01

    The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a mouse model of clonic seizures induced by pentylenetetrazole, and whether ultra-low doses of the opioid receptor antagonist naltrexone which selectively block G(s) opioid receptors were capable of preventing the observed tolerance. The results showed that the morphine anticonvulsant effect could be subject to tolerance after repeated administration. Both the development and expression of tolerance were inhibited by ultra-low doses of naltrexone, suggesting the possible involvement of G(s)-coupled opioid receptors in the development of tolerance to the anticonvulsant effect of morphine.

  16. Radiation-induced transformation of SV40-immortalized human thyroid epithelial cells by single and fractionated exposure to γ-irradiation in vitro

    International Nuclear Information System (INIS)

    Riches, A.C.; Herceg, Z.; Bryant, P.E.; Wynford-Thomas, D.

    1994-01-01

    Radiation-induced transformation of a human thyroid epithelial cell line (HTori-3) has been investigated following exposure to single and fractionated doses of γ-irradiation. The human epithelial cells were irradiated in vitro and following passaging, transplanted to the athymic nude mouse. Following a single exposure to γ-irradiation in the range 0.5-4Gy, 22 tumours were observed in 45 recipients and following three equal fractions in the range 0.5-4Gy per fraction, 18 tumours were observed in 31 recipients. Tumours were undifferentiated carcinomas and were observed from 7 to 20 weeks after transplantation. They occurred after similar radiation doses to those received by the children in the Belarus region of Ukraine, who developed thyroid tumours. The number of tumours observed, in each group receiving cells irradiated with a single dose of γ-irradiation in the range 0.5-4 Gy, was similar. Cell lines were established from some tumours and the tumorigenicity confirmed by retransplantation. These tumour cell lines were more radiosensitive than the human thyroid epithelial cell line they were derived from. This indicates that transformed cells were not being selected from a subpopulation within the parent cell line but that radiation-induced transformants were being induced de novo. The human origin of the tumours was established by karyotyping, immunocytochemical demonstration of human epithelial cytokeratins and p53 analysis. DNA fingerprinting confirmed that the tumours were derived from the original cell line. (author)

  17. Dynamic changes of peripheral blood T-lymphocyte DNA-Synthesis in rabbits after fractionated and single exposure to 60Co-γ rays

    International Nuclear Information System (INIS)

    Wang Zongwu; Chen Tiehe; Yu Zhijie; Han Ling; Pan Yusha; Su Fuqiang

    1988-01-01

    The experiments in 59 rabbits γ-irradiated with doses of 0, 0.5, 1.0, 2.0, and 3.0 Gy in fractional and single exposure to 60 Co-γ rays were reported, respectively · Dynamics of the changes of DNA-Synthesis in T-lymphocytes of peripheral blood was obserced during 29 days after γ-irradiation. Marked inhibition in DNA-synthesis was found on 1st day after irradiation. Recovery was observed in 3rd day after irradiation. The levels of DNA-synthesis before irradiation was recovered on 7th day after exposure for all groups. For fractionated irradiation, however, an increase, rather than a decrese, of DNA-synthesis was in the group of 1.0 Gy

  18. 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.

    Science.gov (United States)

    Sadeghzadeh, Fatemeh; Babapour, Vahab; Haghparast, Abbas

    2017-04-01

    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). Subcutaneous (sc) injection of morphine (5 mg kg -1 ) was used daily during a 3-day conditioning phase. After a 24-hr "off" period following achievement of extinction criterion, rats were tested for FD- and priming-induced reinstatement of morphine CPP by an ineffective (0.5 mg kg -1 , sc) and priming (1 mg kg -1 , sc) dose of morphine, respectively. In the next experiments, animals received different doses of intra-accumbal Sulpiride (0.25, 1, and 4 µg/0.5 µL saline) bilaterally and were subsequently tested for morphine reinstatement. Our findings indicated that the 24-hr FD facilitated reinstatement of morphine CPP. Furthermore, the D2-like receptor antagonist attenuated the ineffective morphine dose+ FD- and priming-induced reinstatement of morphine CPP dose-dependently. Also, contribution of D2-like receptors in mediation of the ineffective morphine dose+ FD-induced reinstatement of CPP was greater than morphine priming-induced reinstatement of CPP. The role of dopaminergic system in morphine reinstatement through a neural pathway in the NAc provides the evidence that D2-like receptor antagonist can be useful therapeutic targets for reinstatement of morphine CPP. © 2016 Wiley Periodicals, Inc.

  19. A review of common methods to convert morphine to methadone

    Directory of Open Access Journals (Sweden)

    Eric Wong

    2013-01-01

    Full Text Available When dosed appropriately on carefully chosen patients, methadone can be a very safe and effective choice in managing chronic pain. Many authors have discussed important issues surrounding patient selection, drug interactions, screening for QTc prolongation and monitoring. This article will focus on the dosing dilemma that exists after the patient is deemed an appropriate candidate for methadone and a conversion is necessary from another opioid. Despite many publications dedicated to addressing this challenging topic, there is no consensus on the most appropriate method for converting an opioid regimen to methadone. Given the lack of concrete guidance, clinicians in a community setting are likely to be faced with an increased challenge if there are no available pain specialists to provide clinical support. Common methods for converting morphine to methadone will be reviewed and two clinical patient scenarios used to illustrate the outcomes of applying the methods.

  20. Metal accumulation and antioxidant defenses in the freshwater fish Carassius auratus in response to single and combined exposure to cadmium and hydroxylated multi-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Ruijuan; Wang, Xinghao; Wang, Zunyao, E-mail: wangzun315cn@163.com; Wei, Zhongbo; Wang, Liansheng

    2014-06-30

    Highlights: • Cd and OH-MWCNTs have a synergistic effect on Carassius auratus. • OH-MWCNTs significantly increased Cd accumulation in liver after 12 d exposure. • Co-exposure to Cd and OH-MWCNTs evoked severe hepatic oxidative stress. - Abstract: The effects of cadmium, hydroxylated multi-walled carbon nanotubes, and their mixture on metal accumulation and antioxidant defenses were studied using the goldfish Carassius auratus as the test organism. The fish were exposed to 0.1 mg/L Cd, 0.5 mg/L OH-MWCNTs, or 0.1 mg/L Cd + 0.5 mg/L OH-MWCNTs for 3 and 12 days. Then, the Cd concentration was determined in the gill, liver and muscle. Moreover, hepatic antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase), glutathione level and malondialdehyde content were also measured. A continuous accumulation of Cd was observed throughout the experimental period. Cd accumulation in tissues occurred in the following order: gill > liver > muscle at 3 days and liver > gill > muscle at 12 days. The concentrations of Cd in the livers of fish exposed to the combination of Cd + OH-MWCNTs were significantly higher than those in fish exposed to either single chemical after 12 d of exposure. Meanwhile, the mixture evoked severe oxidative stress in the exposed fish, as indicated by significant inhibition of SOD, CAT and GPx activity, a remarkable decrease in GSH level, and simultaneous elevation of MDA content. These results suggested that the effect of the combined factors on metal accumulation and oxidative stress biomarkers was more obvious than that of single factors at longer exposure durations.

  1. Production of Mouse Monoclonal Antibody against Morphine without Cross Reactivity with Heroin

    Directory of Open Access Journals (Sweden)

    S Kashaninan

    2014-12-01

    Conclusion: The study findings revealed that the produced antibody against morphine was comparable with other antibodies for specificity and affinity; therefore it is usable in design of diagnostic immunoassay in biologic fluids.

  2. The effects of peripheral injection of Matricaria Chamomilla extract on morphine withdrawal syndrome in rats

    Directory of Open Access Journals (Sweden)

    mohammad hosein Esmaeili

    2013-08-01

    Conclusion: These results suggest that, the intra-peritoneal injection of MC extract can reduces effectively morphine withdrawal syndrome in rats. Therefore it is necessary to study its effect on humans and also identify its effective components.

  3. Effect of morphine on biliary dynamics. A scintigraphic study with /sup 99m/Tc-HIDA

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, S.A.; Oester-Joergensen, E.; Kraglund, K.

    1987-01-01

    The effect of morphine on biliary dynamics was studied by cholescintigraphy with /sup 99m/Tc-HIDA. Among 30 normals without morphine injection 3 did not demonstrate intestinal radioactivity after 1 h, whereas all visualized the gallbladder. Eight normals with morphine injection did not demonstrate intestinal radioactivity after 2 h, but all had gallbladder visualization very early. Variables of the time-activity curves from liver areas did not point to impaired uptake or excretion. Morphine-induced increase in resistance to passage from the common duct to the intestines in normals is of a magnitude that forces the total amount of bile to accumulate in the gallbladder. Results from 11 patients after cholecystectomy indicate that the increase in pressure is less than the maximal secretory pressure of the liver. The resorptive capacity and the compliance of the gallbladder enable these events to take place without signs of secondary liver impairment.

  4. Acute generalized exanthematous pustulosis caused by morphine, confirmed by positive patch test and lymphocyte transformation test

    NARCIS (Netherlands)

    Kardaun, Sylvia H.; de Monchy, Jan G.

    Morphine, an opium alkaloid, frequently causes side effects such as hyperhidrosis and facial flushing, but serious cutaneous adverse drug reactions are seldom observed. Best known are Urticaria, erythema, and pruritus; sometimes pseudoallergic anaphylactoid reactions, and blisters are reported.

  5. Objective markers of the analgesic response to morphine in experimental pain research

    DEFF Research Database (Denmark)

    Brokjær, Anne; Olesen, Anne Estrup; Kreilgaard, Mads

    2015-01-01

    INTRODUCTION: In experimental pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect...... placebo or 30mg rectal morphine at two separate sessions. At baseline and several time points after drug administration, the central effects of morphine were assessed by experimental muscle pain, pupil diameter, prolactin concentration and resting EEG. RESULTS: Morphine increased tolerance to muscle pain...... of morphine on three objective pharmacodynamic markers (pupil diameter, prolactin concentration and resting electroencephalography (EEG)) and compare the changes from placebo with subjective analgesia on experimental muscle pain for convergent validation. METHODS: Fifteen healthy male participants received...

  6. Morphine Decreases Social Interaction of Adult Male Rats, While THC Does Not Affect It

    Czech Academy of Sciences Publication Activity Database

    Šlamberová, R.; Mikulecká, Anna; Macúchová, E.; Hrebíčková, I.; Ševčíková, M.; Nohejlová, K.; Pometlová, M.

    2016-01-01

    Roč. 65, Suppl.5 (2016), S547-S555 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : social behavior * opioids * morphine * cannabinoids * THC * male rats Subject RIV: FH - Neurology Impact factor: 1.461, year: 2016

  7. Blood pH and brain uptake of /sup 14/C-morphine

    Energy Technology Data Exchange (ETDEWEB)

    Schulman, D.S.; Kaufman, J.J.; Eisenstein, M.M.; Rapoport, S.I.

    1984-11-01

    /sup 14/C-Morphine was injected iv in control awake rats or in rats subjected to metabolic alkalosis or acidosis. Ten minutes later, radioactivity was determined within each of seven brain regions, after correction was made for intravascular tracer. In each region, parenchymal radioactivity was correlated positively and significantly (P less than 0.05) with arterial blood pH. Brain radioactivity was twofold to threefold greater in alkalotic rats (mean pH . 7.62) than in acidotic rats (mean pH . 7.16). The results are consistent with the pH-partition hypothesis for drug entry into the brain and indicate that morphine uptake can be increased by elevating the fraction of lipid-soluble uncharged morphine base in blood, by means of alkalosis. The observations may account for an exaggerated morphine-induced analgesia in alkalotic patients.

  8. Comparative hazard identification by a single dose lung exposure of zinc oxide and silver nanomaterials in mice

    DEFF Research Database (Denmark)

    Gosens, Ilse; Kermanizadeh, Ali; Jacobsen, Nicklas Raun

    2015-01-01

    O) and a triethoxycaprylylsilane functionalised ZnO NM suspended in water with 2% mouse serum were examined 24 hours following a single intratracheal instillation (I.T.). An acute pulmonary inflammation was noted (marked by a polymorphonuclear neutrophil influx) with cell damage (LDH and total protein) in broncho-alveolar lavage...

  9. Preconceptional paternal glycidamide exposure affects embryonic gene expression: Single embryo gene expression study following in vitro fertilization

    Czech Academy of Sciences Publication Activity Database

    Brevik, A.; Rusňáková, Vendula; Duale, N.; Slagsvold, H.H.; Olsen, A.-K.; Storeng, R.; Kubista, Mikael; Brunborg, G.; Lindeman, B.

    2011-01-01

    Roč. 32, č. 4 (2011), s. 463-471 ISSN 0890-6238 R&D Projects: GA AV ČR(CZ) IAA500520809 Institutional research plan: CEZ:AV0Z50520701 Keywords : Single-cell gene expression * Glycidamide * Acrylamide Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.226, year: 2011

  10. Effect of extradural morphine on somatosensory evoked potentials to dermatomal stimulation

    DEFF Research Database (Denmark)

    Lund, C; Selmar, P; Hansen, O B

    1987-01-01

    The effect of the extradural (L2-3) administration of morphine 6 mg on early (less than 0.5 s) somatosensory evoked cortical potentials (SEP) to electrical stimulation of the L1- and S1-dermatomes was examined in eight patients. Extradural morphine did not influence SEP amplitude. SEP latency did...... not change, except for a minor increase in the latencies of the onset and the P2 components following S1 stimulation....

  11. Molecular interactions between selected sodium salts of bile acids and morphine hydrochloride.

    Science.gov (United States)

    Poša, Mihalj; Csanádi, János; Kövér, Katalin E; Guzsvány, Valéria; Batta, Gyula

    2012-06-01

    The objective of this study was to understand the prolonged analgesic action of morphine hydrochloride observed in the presence of sodium 12-oxochenodeoxycholanate. Based on literature, this phenomenon may be due to the formation of aggregates in the cell between the molecules of bile acids and morphine. In addition to the sodium 12-oxochenodeoxycholanate, the present investigation also included salts of cholic and 7-oxodeoxycholic acids. Saturation transfer difference NMR experiments showed that morphine binds to the bile acid molecule close to the aromatic protons H1 and H2 provided that the concentration of the bile acid salt approaches the critical micellar concentration (CMC). The spin-lattice relaxation times (T(1)) of the affected protons decrease significantly in the presence of micellar solutions of the bile acid salts, and the most pronounced change in T(1) was observed for sodium 7-oxodeoxycholate. Diffusion-ordered NMR experiments suggested that morphine hydrochloride can interact only with sodium 7-oxochenodeoxycholate. It can be supposed that the molecular ratio of sodium 7-oxodeoxycholate and morphine hydrochloride in the mixed micelle is 2:1. The CMC values of mixed micelles do not differ from the CMC values of the micelle constituents, which suggests that the binding of morphine hydrochloride does not perturb the hydrophobic domain of the bile acid molecule. In the presence of bile acids, the transfer rate constant (k(12)) of morphine hydrochloride from the buffered aqueous solution to chloroform (model of the cell membrane) shows a decrease. A significant decrease of the k(12) was also observed in the presence of micellar solutions. Kinetic measurements indicated that, in addition to micellar interaction between morphine hydrochloride and sodium salts of bile acids, a complex may also be formed in chloroform via hydrogen bonds formed between the drug and bile acid molecules. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Predicting morphine related side effects in the ED: An international cohort study.

    Science.gov (United States)

    Bounes, Vincent; Charriton-Dadone, Béatrice; Levraut, Jacques; Delangue, Cyril; Carpentier, Françoise; Mary-Chalon, Stéphanie; Houze-Cerfon, Vanessa; Sommet, Agnès; Houze-Cerfon, Charles-Henri; Ganetsky, Michael

    2017-04-01

    Morphine is the reference treatment for severe acute pain in an emergency department. The purpose of this study was to describe and analyse opioid-related ADRs (adverse drug reactions) in a large cohort of emergency department patients, and to identify predictive factors for those ADRs. In this prospective, observational, pharmaco-epidemiological international cohort study, all patients aged 18years or older who were treated with morphine were enrolled. The study was done in 23 emergency departments in the US and France. Baseline numerical rating scale score and initial and total doses of morphine titration were recorded. Logistic regression analysis was used to study the effects of demographic, clinical and medical history covariates on the occurrence of opioid-induced ADRs within 6h after treatment. A total of 1128 patients were included over 10months. Median baseline initial pain scores were 8/10 (7-10) versus 3/10 (1-4) after morphine administration. Median titration duration was 10min (IQR, 1-30). The occurrence of opioid-induced ADRs was 25% and 2% were serious. Patients experienced mainly nausea and drowsiness. Medical history of travel sickness (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.01-2.86) and history of nausea or vomiting post morphine (OR, 3.86; 95% CI, 2.29-6.51) were independent predictors of morphine related ADRs. Serious morphine related ADRs are rare and unpredictable. Prophylactic antiemetic therapy could be proposed to patients with history of travel sickness and history of nausea or vomiting in a postoperative setting or after morphine administration. Copyright © 2016. Published by Elsevier Inc.

  13. Comparison of Intravenous Morphine Versus Paracetamol in Sciatica: A Randomized Placebo Controlled Trial.

    Science.gov (United States)

    Serinken, Mustafa; Eken, Cenker; Gungor, Faruk; Emet, Mucahit; Al, Behcet

    2016-06-01

    The objective was to compare intravenous morphine and intravenous acetaminophen (paracetamol) for pain treatment in patients presenting to the emergency department with sciatica. Patients, between the ages of 21 and 65 years, suffering from pain in the sciatic nerve distribution and a positive straight leg-raise test composed the study population. Study patients were assigned to one of three intravenous interventions: morphine (0.1 mg/kg), acetaminophen (1 g), or placebo. Physicians, nurses, and patients were blinded to the study drug. Changes in pain intensity were measured at 15 and 30 minutes using a visual analog scale. Rescue drug (fentanyl) use and adverse effects were also recorded. Three-hundred patients were randomized. The median change in pain intensity between treatment arms at 30 minutes were as follows: morphine versus acetaminophen 25 mm (95% confidence interval [CI] = 20 to 29 mm), morphine versus placebo 41 mm (95% CI = 37 to 45 mm), and acetaminophen versus placebo 16 mm (95% CI = 12 to 20 mm). Eighty percent of the patients in the placebo group (95% CI = 63.0% to 99%), 18% of the patients in the acetaminophen group (95% CI = 10.7% to 28.5%), and 6% of those in the morphine group (95% CI = 2.0% to 13.2%) required a rescue drug. Adverse effects were similar between the morphine and acetaminophen groups. Morphine and acetaminophen are both effective for treating sciatica at 30 minutes. However, morphine is superior to acetaminophen. © 2016 by the Society for Academic Emergency Medicine.

  14. Morphine alters the circulating proteolytic profile in mice: functional consequences on cellular migration and invasion.

    Science.gov (United States)

    Xie, Nan; Khabbazi, Samira; Nassar, Zeyad D; Gregory, Kye; Vithanage, Tharindu; Anand-Apte, Bela; Cabot, Peter J; Sturgess, David; Shaw, Paul N; Parat, Marie-Odile

    2017-12-01

    Opioids modulate the tumor microenvironment with potential functional consequences for tumor growth and metastasis. We evaluated the effects of morphine administration on the circulating proteolytic profile of tumor-free mice. Serum from morphine-treated (1 or 10 mg/kg, i.p. every 12 h) or saline-treated mice was collected at different time points and tested ex vivo in endothelial, lymphatic endothelial, and breast cancer cell migration assays. Serum from mice that were treated with 10 mg/kg morphine for 3 d displayed reduced chemotactic potential for endothelial and breast cancer cells, and elicited reduced cancer cell invasion through reconstituted basement membrane compared with serum from saline controls. This was associated with decreased circulating matrix metalloproteinase 9 (MMP-9) and increased circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) and TIMP-3/4 as assessed by zymography and reverse zymography. By using quantitative RT-PCR, we confirmed morphine-induced alterations in MMP-9 and TIMP expression and identified organs, including the liver and spleen, in which these changes originated. Pharmacologic inhibition of MMP-9 abrogated the difference in chemotactic attraction between serum from saline-treated and morphine-treated mice, which indicated that reduced proteolytic ability mediated the decreased migration toward serum from morphine-treated mice. This novel mechanism may enable morphine administration to promote an environment that is less conducive to tumor growth, invasion, and metastasis.-Xie, N., Khabbazi, S., Nassar, Z. D., Gregory, K., Vithanage, T., Anand-Apte, B., Cabot, P. J., Sturgess, D., Shaw, P. N., Parat, M.-O. Morphine alters the circulating proteolytic profile in mice: functional consequences on cellular migration and invasion. © FASEB.

  15. Subjective perception of cocaine reward in mice assessed by a single exposure place preference (sePP) paradigm

    DEFF Research Database (Denmark)

    Runegaard, Annika H.; Jensen, Kathrine Louise; Dencker, Ditte

    2017-01-01

    Background The potential of abused drugs to induce addiction and compulsive drug-related behavior is associated with their ability to alter dopamine signaling. Dopamine plays a key role in reward signaling and it has been of great interest to investigate how various drugs of abuse alter reward....... The sePP protocol allows further dissection of the mechanism and influence of initial cocaine exposure on subsequent drug-related behaviors by including extinction and reinstatement. The lack of sePP in female mice may reflect a biologically relevant sex difference in the initial subjective perception...

  16. Nurses' perceptions and experiences regarding Morphine usage in burn pain management.

    Science.gov (United States)

    Bayuo, J; Agbenorku, P

    2015-06-01

    Morphine, a classical example of opioid has been described as one of the analgesics of choice for burn pain management but there have been reports of under utilization of the medication and subsequent poor pain management. Nurses have a pivotal role in successful burn pain management and should therefore possess positive perception as well as strong knowledge base of pain care. In light of this realization, this study sought to investigate the perception and experiences of nurses working in the burns unit possess towards the medication. Purposive sampling approach was used to select twenty (20) nurses. Descriptive and themed content analysis approaches were used to analyze data. Mean years in general nursing practice and practice in the burns unit were obtained as 7.4 and 3.4 years respectively. Results indicate that nurses have a clear understanding of the intensity of burn pain but perception towards morphine was mixed and some respondents were unsure about some of the pertinent facts of morphine and thus, would prefer other medications such as paracetamol, diclofenac and pethidine. Addiction to the medication and morphine causing death were major themes identified. The resultant effect of these perception and experiences imply and confirm the under usage of morphine. It is therefore recommended that nurses within the burn unit be taken through training modules on the suitability of morphine in burn pain management. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  17. Formulation development and stability testing of oral morphine solution utilizing preformulation approach.

    Science.gov (United States)

    Preechagoon, Detpon; Sumyai, Viroj; Tontisirin, Khanittha; Aumpon, Sirikul; Pongjanyakul, Thaned

    2005-08-18

    Prefomulation approach utilizing the fractional-ordered randomized blocked design was employed for the formulation development and stability testing of morphine solution. Factors expecting to affect the stability of morphine were evaluated, i.e., vehicle, antioxidant, chelating agent, and pH of the solution. Eight formulations of a possible 16 were prepared according to the block design. The stability of the preparations was tested after 35 days of storage. The data of preformulation study were used for formulation development. The presence of glycerin and ethylenediamine-tetraacetic acid in the formulation, and the pH of the solution adjusted to 4, stabilized morphine. The concentration of morphine decreased drastically in the formulations containing sodium metabisulfite, and those pH adjusted to 6. After 35 days, only 65% of morphine was found in the formulation containing sodium metabisulfite and pH adjusted to 6. The results of preformulation study were used for preparing oral morphine preparations. Samples were kept in amber glass bottles and stored at 4 degrees C and 25 degrees C/75% RH for 13 months. No precipitation of the four formulations was detected. Only a decrease of odor and a small increase of pH value of the preparations (preformulation approach. They were stable more than 13 months when stored at 4 degrees C and 25 degrees C/75% RH.

  18. Morphine enhances the release of 3H-purines from rat brain cerebral cortical prisms

    International Nuclear Information System (INIS)

    Wu, P.H.; Phillis, J.W.; Yuen, H.

    1982-01-01

    In vitro experiments have shown that 3 H-purines can be released from 3 H-adenosine preloaded rat brain cortical prisms by a KCl-evoked depolarization. The KCl-evoked release of 3 H-purines is dependent on the concentration of KCl present in the superfusate. At concentrations of 10(-7) approximately 10(-5)M morphine did not influence the basal release of 3 H-purines from the prisms, although it enhanced the KCl-evoked release of 3 H-purines. The enhancement of KCl-evoked 3 H-purine release by morphine was concentration-dependent and was antagonized by naloxone, suggesting the involvement of opiate receptors. Uptake studies with rat brain cerebral cortical synaptosomes show that morphine is a very weak inhibitor of adenosine uptake. Comparisons with dipyridamole, a potent inhibitor of adenosine uptake, suggest that this low level of inhibition of the uptake did not contribute significantly to the release of 3 H-purine by morphine seen in our experiments. It is therefore suggested that morphine enhances KCl-evoked 3 H-purine release by an interaction with opiate receptors and that the resultant increase in extracellular purine (adenosine) levels may account for some of the actions of morphine

  19. Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

    Directory of Open Access Journals (Sweden)

    Pichili Vijaya Bhaskar Reddy

    2012-01-01

    Full Text Available HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB. Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population.

  20. Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats.

    Science.gov (United States)

    Wen, D; Sun, D; Zang, G; Hao, L; Liu, X; Yu, F; Ma, C; Cong, B

    2014-09-26

    Cholecystokinin octapeptide (CCK-8), a brain-gut peptide, plays an important role in several opioid addictive behaviors. We previously reported that CCK-8 attenuated the expression and reinstatement of morphine-induced conditioned place preference. The possible effects of CCK-8 on the negative affective components of drug abstinence are not clear. There are no studies evaluating the effect of CCK-8 on emotional symptoms, such as anxiety, in morphine-withdrawal animals. We investigated the effects of CCK-8 on the anxiety-like behavior in morphine-withdrawal rats using an elevated plus-maze. Morphine withdrawal elicited time-dependent anxiety-like behaviors with peak effects on day 10 (5 days after induction of morphine dependence). Treatment with CCK-8 (0.1 and 1 μg, i.c.v.) blocked this anxiety in a dose-dependent fashion. A CCK1 receptor antagonist (L-364,718, 10 μg, i.c.v.) blocked the effect of CCK-8. Mu-opioid receptor antagonism with CTAP (10 μg, i.c.v.) decreased the 'anxiolytic' effect. CCK-8 inhibited anxiety-like behaviors in morphine-withdrawal rats by up-regulating endogenous opioids via the CCK1 receptor in rats. This study clearly identifies a distinct function of CCK-8 and a potential medication target of central CCK1 receptors for drugs aimed at ameliorating drug addiction. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Microglia: A Promising Target for Treating Neuropathic and Postoperative Pain, and Morphine Tolerance

    Directory of Open Access Journals (Sweden)

    Yeong-Ray Wen

    2011-08-01

    Full Text Available Management of chronic pain, such as nerve-injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer, is a real clinical challenge. Major surgeries, such as breast and thoracic surgery, leg amputation, and coronary artery bypass surgery, also lead to chronic pain in 10–50% of individuals after acute postoperative pain, partly due to surgery-induced nerve injury. Current treatments mainly focus on blocking neurotransmission in the pain pathway and have only resulted in limited success. Ironically, chronic opioid exposure might lead to paradoxical pain. Development of effective therapeutic strategies requires a better understanding of cellular mechanisms underlying the pathogenesis of neuropathic pain. Progress in pain research points to an important role of microglial cells in the development of chronic pain. Spinal cord microglia are strongly activated after nerve injury, surgical incision, and chronic opioid exposure. Increasing evidence suggests that, under all these conditions, the activated microglia not only exhibit increased expression of microglial markers CD 11 b and Iba 1, but also display elevated phosphorylation of p38 mitogen-activated protein kinase. Inhibition of spinal cord p38 has been shown to attenuate neuropathic and postoperative pain, as well as morphine-induced antinociceptive tolerance. Activation of p38 in spinal microglia results in increased synthesis and release of the neurotrophin brain-derived neurotrophic factor and the proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α. These microglia-released mediators can powerfully modulate spinal cord synaptic transmission, leading to increased excitability of dorsal horn neurons, that is, central sensitization, partly via suppressing inhibitory synaptic transmission. Here, we review studies that support the pronociceptive role of microglia in conditions of neuropathic and postoperative pain and opioid

  2. Detection of simulated pulmonary nodules by single-exposure dual-energy computed radiography of the chest: effect of a computer-aided diagnosis system (Part 2)

    International Nuclear Information System (INIS)

    Kido, Shoji; Kuriyama, Keiko; Kuroda, Chikazumi; Nakamura, Hironobu; Ito, Wataru; Shimura, Kazuo; Kato, Hisatoyo

    2002-01-01

    Objective: To evaluate the performance of the computer-aided diagnosis (CAD) scheme on the detection of pulmonary nodules (PNs) in single-exposure dual-energy subtraction computed radiography (CR) images of the chest, and to evaluate the effect of this CAD scheme on radiologists' detectabilities. Methods and material: We compared the detectability by the CAD scheme with the detectability by 12 observers by using conventional CR (C-CR) and bone-subtracted CR (BS-CR) images of 25 chest phantoms with a low-contrast nylon nodule. Results: Both in the CAD scheme and for the observers, the detectability of BS-CR images was superior to that of C-CR images (P<0.005). The detection performance of the CAD scheme was equal to that of the observers. The nodules detected by the CAD did not necessarily coincide with those by the observers. Thus, if observers can use the results of the CAD system as a 'second opinion', their detectabilities increase. Conclusion: The CAD system for detection of PNs in the single-exposure dual-energy subtraction method is promising for improving radiologists' detectabilities of PNs

  3. Resistance and aerobic exercise protects against acute endothelial impairment induced by a single exposure to hypertension during exertion

    OpenAIRE

    Phillips, Shane A.; Das, Emon; Wang, Jingli; Pritchard, Kirkwood; Gutterman, David D.

    2011-01-01

    Resistance and aerobic exercise is recommended for cardiovascular health and disease prevention. However, the accompanying increase in arterial pressure during resistance exercise may be detrimental to vascular health. This study tests the vascular benefits of aerobic compared with resistance exercise on preventing impaired vascular function induced by a single weight lifting session that is associated with acute hypertension. Healthy, lean sedentary (SED) subjects, weight lifters, runners (>...

  4. A single exposure to alcohol during brain development induces microencephaly and neuronal losses in genetically susceptible mice, but not in wild type mice.

    Science.gov (United States)

    de Licona, Hannah Klein; Karacay, Bahri; Mahoney, Jo; McDonald, Elizabeth; Luang, Thirath; Bonthius, Daniel J

    2009-05-01

    Maternal alcohol abuse during pregnancy can damage the fetal brain and lead to fetal alcohol syndrome (FAS). Despite public warnings discouraging alcohol use during pregnancy, many pregnant women continue to drink intermittently because they do not believe that occasional exposures to alcohol can be harmful to a fetus. However, because of genetic differences, some fetuses are much more susceptible than others to alcohol-induced brain injury. Thus, a relatively low quantity of alcohol that may be innocuous to most fetuses could damage a genetically susceptible fetus. Neuronal nitric oxide synthase (nNOS) can protect developing mouse neurons against alcohol toxicity by synthesizing neuroprotective nitric oxide. This study examined whether a single exposure to alcohol, which causes no evident injury in wild type mice, can damage the brains of mice genetically deficient for nNOS (nNOS-/- mice). Wild type and nNOS-/- mice received intraperitoneal injections of alcohol (0.0, 2.2, or 4.4mg/g body weight) either as a single dose on postnatal day (PD) 4 or as repeated daily doses over PD4-9. Brain volumes and neuronal numbers within the hippocampus and cerebral cortex were determined on PD10. Alcohol exposure on PD4-9 restricted brain growth and caused neuronal death in both strains of mice, but the severity of microencephaly and neuronal loss were more severe in the nNOS-/- mice than in wild type. The 4.4 mg/g alcohol dose administered on PD4 alone caused significant neuronal loss and microencephaly in the nNOS-/- mice, while this same dose caused no evident injury in the wild type mice. Thus, during development, a single exposure to alcohol can injure a genetically vulnerable brain, while it leaves a wild type brain unaffected. Since the genes that confer alcohol resistance and vulnerability in developing humans are unknown, any particular human fetus is potentially vulnerable. Thus, women should be counseled to consume no alcohol during pregnancy.

  5. Incubation Period and Early Natural History Events of the Acute Form of Paracoccidioidomycosis: Lessons from Patients with a Single Paracoccidioides spp. Exposure.

    Science.gov (United States)

    Buccheri, Renata; Khoury, Zarifa; Barata, Luis Carlos Barradas; Benard, Gil

    2016-06-01

    Several aspects of the natural history of paracoccidioidomycosis are still poorly understood. Different from the most prevalent, chronic form of the disease, the acute form represents a continuum from the initial respiratory infection to the full-blown disease, thus providing an opportunity to elucidate the pathogenesis of the early phase of this mycosis. We describe, for the first time, two patients with a single time point exposure to Paracoccidioides spp., for whom we were able to determine the time lapsed between exposure to the fungus Paracoccidioides spp. and the onset of signs and symptoms. In case 1, the pulmonary infection was unapparent, and the first manifestations of the acute/subacute form of the disease presented 4 months after Paracoccidioides spp. In case 2, self-limited, non-specific respiratory and systemic symptoms presented 45 days after infection. Thus, our patients confirm that, within a few weeks of infection, Paracoccidioides spp. affects the pulmonary lymphatic system and initially causes no or mild-to-moderate self-limited symptoms, eventually causing abnormalities on a chest X-ray, all of which spontaneously subside. These cases provide some insight into the natural history of this mycosis, the extent of the host exposure to the fungus, and the determination of its incubation period.

  6. Chronic morphine treatment attenuates cell growth of human BT474 breast cancer cells by rearrangement of the ErbB signalling network.

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    Inka Regine Weingaertner

    Full Text Available There is increasing evidence that opioid analgesics may interfere with tumour growth. It is currently thought that these effects are mediated by transactivation of receptor tyrosine kinase (RTK-controlled ERK1/2 and Akt signalling. The growth of many breast cancer cells is dependent on hyperactive ErbB receptor networks and one of the most successful approaches in antineoplastic therapy during the last decade was the development of ErbB-targeted therapies. However, the response rates of single therapies are often poor and resistance mechanisms evolve rapidly. To date there is no information about the ability of opioid analgesics to interfere with the growth of ErbB-driven cancers.Here we demonstrate that ErbB2 overexpressing BT474 human breast cancer cells carry fully functional endogenous µ-opioid receptors. Most interestingly, the acute opioid effects on basal and Heregulin-stimulated ERK1/2 and Akt phosphorylation changed considerably during chronic Morphine treatment. Investigation of the underlying mechanism by the use of protein kinase inhibitors and co-immunoprecipitation studies revealed that chronic Morphine treatment results in rearrangement of the ErbB signalling network leading to dissociation of ERK1/2 from Akt signalling and a switch from ErbB1/ErbB3 to ErbB1/ErbB2-dependent cell growth. In chronically Morphine-treated cells Heregulin-stimulated ERK1/2 signalling is redirected via a newly established PI3K- and metalloproteinase-dependent feedback loop. Together, these alterations result in apoptosis of BT474 cells. A similar switch in Heregulin-stimulated ERK1/2 signalling from an ErbB2-independent to an ErbB2-, PI3K- and metalloproteinase-dependent mechanism was also observed in κ-opioid receptor expressing SKBR3 human mammary adenocarcinoma cells.The present data demonstrate that the ErbB receptor network of human breast cancer cells represents a target for chronic Morphine treatment. Rearrangement of ErbB signalling by chronic

  7. Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis.

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    Chen, Yanhua; Qin, Yi; Li, Li; Chen, Jing; Zhang, Xu; Xie, Yubo

    2017-10-01

    Morphine is widely used for relieving cancer pain in patients with advanced cancer. However, whether morphine can suppress or promote the progression of cancer in breast cancer patients receiving morphine analgesia remains unclear. Therefore, we used an in vitro model treated with morphine and naloxone to investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells were cultured with different concentrations (0.01 to 10 µM) of morphine at 12th, 24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In addition, cell proliferation was conducted by colony formation assay. In this study, we have found that morphine (0.01 to 10 µM) could significantly reduce the cell vitality, growth and colony formation rate of MCF-7 cells, which has a certain relationship with cell cycle progression arrested at the G0/G1 and G2/M phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not reverse these effects, which indicates that the inhibition of MCF-7 breast cancer cell growth and proliferation by morphine could be its independent effect, not associated with opioid receptors. Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be unable to promote the progression of cancer in breast cancer patients receiving morphine analgesia.

  8. Synergistic Effects of Citalopram and Morphine in the Renal Colic Pain Relief; a Randomized Clinical Trial

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    Mehrdad Esmailian

    2014-03-01

    Full Text Available Introduction: Although the synergistic effects of opioids and other analgesic drugs such as non-steroidal anti-inflammatory drugs (NSAIDs have been established in relieving acute pain due to renal calculi, no studies today have evaluated the concomitant administration of opiates and other drugs with analgesic effects, such as serotonin re-uptake inhibitors. Considering the high prevalence of renal colic, the present study was carried out to compare the effect of concomitant prescription of morphine and a placebo with that of morphine and citalopram on the management of acute pain due to renal calculi. Methods: The present double-blind randomized clinical trial was carried out from October 2012 to March 2013 in the Al-Zahra educational Hospital in Isfahan, Iran. A total of 90 patients with acute renal colic pain were randomly divided into two groups of 45 subjects. The subjects in one group received morphine/ placebo and another one morphine/citalopram. The patients’ pain severity was determined by visual analogue scale (VAS before and 20 minutes after administration of medications. In case of persistent pain the second or even third dose was administered and the pain severity was once again determined. Data were analyzed with STATA 11.0 using chi-squared, two-way ANOVA, Bonferroni post hoc test, and log rank test. Results: The decrease in pain severity in the morphine/citalopram group was significantly compared to the morphine/placebo group and the time before administration of the medications (p<0.001. In contrast, administration of morphine/placebo did not have a significant effect on pain severity at this interval (p=0.32. Kaplan-Meier curve showed that the first injection was successful in relieving pain in 15 (33.3% and 26 (57.8% subjects in the morphine/placebo and morphine/citalopram groups, respectively. The second injection of these medications resulted in therapeutic success in 35 (87.8% and 42 (95.6% subjects in the above groups

  9. Patient-controlled analgesia in the pediatric population: morphine versus hydromorphone

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    DiGiusto M

    2014-08-01

    Full Text Available Matthew DiGiusto,2 Tarun Bhalla,1 David Martin,1 Derek Foerschler,3 Megan J Jones,2 Joseph D Tobias1 1Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital and the Ohio State University, 2The Ohio State School of Medicine, 3Department of Anesthesiology, The Ohio State University, Columbus, OH, USA Objective: Patient controlled analgesia (PCA is commonly used to provide analgesia following surgical procedures in the pediatric population. Morphine and hydromorphone remain the most commonly used opioids for PCA. Although both are effective, adverse effects may occur. When these adverse effects are unremitting or severe, opioid rotation may be required. In this study, we retrospectively evaluated PCA use, the adverse effect profile, and the frequency of opioid rotation. Methods: This retrospective study was performed at Nationwide Children’s Hospital (Columbus, OH. The hospital's electronic registry was queried for PCA use delivering either morphine or hydromorphone from January 1, 2008 to December 31, 2010. Results: A total of 514 patients were identified, that met study entry criteria. Of the 514 cases, 298 (56.2% were initially started on morphine and 225 (43.8% were initially started on hydromorphone. There were a total of 26 (5.1% opioid changes in the cohort of 514 patients. Of the 26 switches, 23 of 298 (7.7% were from morphine to hydromorphone, and 3 of 225 (1.3% were from hydromorphone to morphine (P=0.0008. Of the 17 morphine-to-hydromorphone switches with adverse effects, pruritus (64.7%, and inadequate pain control (47.1% were the most common side effects. The most common side effect resulting in a hydromorphone-to-morphine switch was nausea (66.7%. Conclusion: PCA switches from morphine-to-hydromorphone (88.5% were more common than vice-versa (11.5%. The most common reasons for morphine-to-hydromorphone switch were pruritus and inadequate pain control. These data suggest that a prospective study is necessary

  10. The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors.

    Science.gov (United States)

    Rezayof, A; Khajehpour, L; Zarrindast, M R

    2009-05-05

    The current study was conducted to examine the involvement of muscarinic acetylcholine receptors of the amygdala in morphine-induced state-dependent memory retrieval. Male Wistar rats implanted bilaterally with cannulas in the amygdala were submitted to a step-through type passive avoidance task, and tested 24 h after training to measure step-through latency. Post-training s.c. administration of morphine at the doses of 5 and 7.5 mg/kg impaired the memory on the test day, which was restored when the same doses of morphine were used as a pre-test drug. This phenomenon is well known as morphine-induced state-dependent memory retrieval. Bilateral microinjection of the non-selective muscarinic acetylcholine receptor agonist, pilocarpine (0.25 and 0.5 microg/side), into the amygdala with an ineffective dose of morphine (0.5 mg/kg s.c.) significantly improved the memory retrieval and mimicked the effects of pre-test administration of a higher dose of morphine. It should be noted that in the animals that received saline after training and tested following intra-amygdala administration of pilocarpine (0.125, 0.25 and 0.5 microg/side) and those which received post-training morphine (7.5 mg/kg s.c.) and pre-test intra-amygdala microinjection of the same doses of pilocarpine, no significant change was observed in the step-through latencies. On the other hand, pre-test intra-amygdala microinjection of a selective muscarinic acetylcholine receptor antagonist scopolamine (0.125 and 0.25 microg/side) inhibited morphine-induced state-dependent memory retrieval. In addition, no significant changes were seen in memory retrieval of the animals trained before saline treatment and tested following intra-amygdala microinjection of the same doses of scopolamine (0.0625, 0.125 and 0.25 microg/side). Bilateral microinjection of scopolamine into the amygdala reversed the pilocarpine-induced potentiation of the morphine response. In view of the known actions of the drugs used, the present

  11. Resistance and aerobic exercise protects against acute endothelial impairment induced by a single exposure to hypertension during exertion.

    Science.gov (United States)

    Phillips, Shane A; Das, Emon; Wang, Jingli; Pritchard, Kirkwood; Gutterman, David D

    2011-04-01

    Resistance and aerobic exercise is recommended for cardiovascular health and disease prevention. However, the accompanying increase in arterial pressure during resistance exercise may be detrimental to vascular health. This study tests the vascular benefits of aerobic compared with resistance exercise on preventing impaired vascular function induced by a single weight lifting session that is associated with acute hypertension. Healthy, lean sedentary (SED) subjects, weight lifters, runners (>15 miles/wk), and cross trainers (chronic aerobic and resistance exercisers), underwent a single progressive leg press weight lifting session with blood pressure measurements. Brachial artery flow-mediated vasodilation (FMD; an index of arterial endothelial function) was determined using ultrasonography immediately before and after weight lifting. Sublingual nitroglycerin (0.4 mg) was used to determine endothelium-independent dilation after weight lifting. All subjects were normotensive with similar blood pressure responses during exercise. Baseline FMD was lower in runners (5.4 ± 0.5%; n = 13) and cross trainers (4.44 ± 0.3%; n = 13) vs. SED (8.5 ± 0.8%; n = 13; P = 0.037). Brachial FMD improved in conditioned weight lifters (to 8.8 ± 0.9%; P = 0.007) and runners (to 7.6 ± 0.6%; P weight lifting in resistance and aerobic athletes. Resistance and aerobic exercise may confer similar protection against acute vascular insults such as exertional hypertension.

  12. Age-related postoperative morphine requirements in children following major surgery--an assessment using patient-controlled analgesia (PCA)

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Henneberg, Steen Winther; Hole, P

    1996-01-01

    To investigate if small children require less morphine for postoperative analgesia than do older children and adolescents we analysed the morphine consumption pattern of 28 consecutive children on intravenous patient-controlled analgesia (PCA) following major surgery. The median age-specific morp......To investigate if small children require less morphine for postoperative analgesia than do older children and adolescents we analysed the morphine consumption pattern of 28 consecutive children on intravenous patient-controlled analgesia (PCA) following major surgery. The median age...

  13. Involvement of chemokine CXCL11 in the development of morphine tolerance in rats with cancer-induced bone pain.

    Science.gov (United States)

    Guo, Genhua; Peng, Yawen; Xiong, Bingrui; Liu, Daiqiang; Bu, Huilian; Tian, Xuebi; Yang, Hui; Wu, Zhen; Cao, Fei; Gao, Feng

    2017-05-01

    Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXC chemokine 11 (CXCL11) in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer-induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We found that the level of CXCL11 in lumbar spinal cord was increased during the development of morphine tolerance in cancer-induced bone pain rats. Meanwhile, CXCL11 was co-localized with markers of astrocytes and neurons in the spinal cord. Inhibition of CXCL11 by neutralizing antibodies could remarkably attenuate the degree of morphine tolerance and decrease the activation of astrocytes. Moreover, blocking astrocyte activation by d, l-Fluorocitric acid could distinctly alleviate morphine tolerance and reduce the expression of CXCL11. Finally, morphine stimulation could induce the release of CXCL11 by cultured astrocytes and neurons in vitro. In summary, our results provide evidence that spinal CXCL11 plays a powerful modulatory role in the development of morphine tolerance through cross-talking between astrocytes and neurons. Read the Review series "Pain". © 2016 International Society for Neurochemistry.

  14. Single Exposure of Human Oral Mucosa Fibroblasts to Ultraviolet B Radiation Reduces Proliferation and Induces COX-2 Expression and Activation

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    Y Boza

    2010-12-01

    Full Text Available The lip vermillion constitutes a transition tissue, between oral mucosa and skin, where oral mucosal cells from epithelial and connective tissue compartments are exposed to ultraviolet (UV sunlight. Fibroblasts are abundant resident cells of the connective tissue which are key regulators of extracellular matrix composition, as well as, epithelial and endothelial cell function. UVB light, an inherent component of sunlight, causes several alterations in skin fibroblasts, including premature senescence and increased cyclooxygenase (COX-2 expression. To assess if UVB irradiation had similar effects on fibroblasts derived from human oral mucosa (HOM, primary cultures of HOM fibroblasts were irradiated with a single dose of 30 or 60 mJ/cm²of UVB light or sham-irradiated. Fibroblast proliferation was assessed from 3 to 48 hrs after UVB-irradiation utilizing [³H]-thymidine incorporation and MTT assays. In addition, COX-2 mRNA expression was detected by RT-PCR, and PGE2 production was assessed using enzyme immunoassay from 0.5 to 24 hrs after UVB-irradiation. The results showed a significant decrease in proliferation of UVB-irradiated HOM fibroblasts as compared to controls as measured by both [³H]-thymidine incorporation and MTT assays (p<0.001. HOM fibroblasts had increased COX-2 mRNA expression at 0.5 and 12 hrs after irradiation, and PGE2 production was elevated at 12 and 24 hrs post-irradiation as compared to controls (p<0.05. The results showed an inhibitory effect of a single dose of UVB irradiation on HOM fibroblast proliferation with an increase in COX-2 expression and activation. Therefore, photodamaged fibroblasts may play and important role in the pathogenesis of UV-induced lesions of the lip.

  15. Role of Estrogen on Prevention of Morphine Addiction in Ovarectomized Female Rats

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    A Rafati

    2008-04-01

    Full Text Available ABSTRACT: Introduction & Objective: Evidence indicates that the biological response and the causes of drug abuse may be different between women and men. These sex differences in drug abuse may be due to socio-cultural factors or biological (hormonal differences. Estrogen is one of the hormones which involves in dopamine release in striatum and nucleus accumbency and also is one of the most important neurotransmitters in central nervous system which has critical role in morphine addiction. So, in this study we survey the role of estrogen on dependency and tendency to morphine in rat as a factor of sex differences in addiction. Materials & Methods: This experimental study was carried out in Yazd University of Medical Sciences. Behavioral changes like morphine craving was evaluated by self-administration as a criterion for tendency and for assessment of dependency. we evaluated withdrawal syndrome sings (e.g. jumping, wet dog shaking, etc in control group (ovarectomized female rats receiving morphine sulfate solution and test group (ovarectomized female rats, pretreated with estradiol benzoate before receiving daily morphine sulfate solution. Data obtained were analyzed by SPSS software, using T-test analysis Results: Results showed that although pretreatment with estradiol in test group might lead to a significant decline in withdrawal syndrome sings in comparison with control group, differences in morphine craving as a criterion for tendency was not significant between the two groups. Conclusion: According to our findings, it seems that estrogen, through central mechanisms and its effect on brain dopaminergic system, reduces the physical dependency to morphine.

  16. Quantification of the Pharmacodynamic Interaction of Morphine and Gabapentin Using a Response Surface Approach.

    Science.gov (United States)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Gabel-Jensen, Charlotte; Kreilgaard, Mads; Heegaard, Anne-Marie; Lund, Trine Meldgaard

    2017-11-01

    The combination of morphine and gabapentin has shown to be promising for managing postoperative pain but finding the right dose for the combination has proven to be a challenge. The purpose of this study was to quantitatively characterize the pharmacodynamic interaction between the two drugs and to identify the optimal concentration-effect relationship of the combination. Information regarding plasma concentrations and von Frey withdrawal thresholds following incisional surgery on Sprague Dawley rats, after administration of morphine, gabapentin, or their combination was available from published studies. The combined pharmacodynamic effect of morphine and gabapentin was analyzed and linked to drug plasma concentrations via a response surface approach using non-linear mixed-effect modeling. Full reversal of withdrawal thresholds for the pain stimulation to presurgery values was estimated at morphine plasma concentration of 435.1 ng/mL. Co-administration of up to 40 μg/mL of gabapentin led to a reduction of the needed morphine concentration down to 307.5 ng/mL (~ 29% reduction). Combination of concentration ranges of gabapentin between 20 and 40 μg/mL with any morphine concentrations between 100 and 600 ng/mL were found to lead up to 50% increased effect relatively to the effect attained by morphine alone. This study highlights the importance of finding the right combination in multimodal analgesia and demonstrates the usefulness of the response surface approach for the study of pharmacodynamic interactions. The proposed pharmacokinetic-pharmacodynamic model may provide the basis for a rational clinical trial design with the aim to identify the optimal dose combination ratios in humans.

  17. Comparison of effects of preoperatively administered lornoxicam and tenoxicam on morphine consumption after laparoscopic cholecystectomy.

    Science.gov (United States)

    Kocaayan, E; Ozkardeşler, S; Ozzeybek, D; Bayindir, S; Akan, M

    2007-08-01

    The efficacy, tolerability and the morphine-sparing effects of lornoxicam were compared with those of tenoxicam when used preoperatively in patients undergoing laparoscopic cholecystectomy. In this prospective, double-blind study, 60 ASA I-II patients undergoing laparoscopic cholecystectomy were randomized equally to receive intravenous tenoxicam 40 mg (Group T) or lornoxicam 16 mg (Group L), preemptively. Three patients withdrew from the study, so 57 patients were included in the analysis. In the postoperative period, the first morphine demand times, pain scores, side-effects and cumulative morphine consumptions were evaluated during the first 24 h. The patient characteristics data and the duration of surgery were similar between two groups, except for body weights (P = 0.002). The first morphine demand time was significantly longer in Group L (P = 0.037), but the pain levels did not differ. The mean pain scores were higher in Group T in the 15 min (P = 0.036), 1 h (P = 0.020), 2 h (P = 0.001) and 4 h (P = 0.0042) after extubation. A statistically significant difference between two groups was found in calculated cumulative morphine consumptions per kilogram in the 15 min (P = 0.037), 30 min (P = 0.016), and 1 h (P = 0.004) and 2 h (P = 0.013) between two groups. There was no difference in the severity of nausea but 13 patients in Group T and five patients in Group L had vomiting (P = 0.018). Patient satisfaction was similar in the two groups. Preoperatively administered lornoxicam 16 mg significantly prolonged the first morphine demand time, reduced postoperative morphine consumption during the first 4 h and caused significantly fewer adverse effects when compared with tenoxicam after laparoscopic cholecystectomy.

  18. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems

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    Elham A. Afify

    2017-11-01

    Full Text Available 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. The study revealed that propranolol (0.25–20 mg/Kg, IP administration did not produce analgesia in mice. However, 10 mg/Kg propranolol, enhanced the antinociceptive effect of sub-analgesic doses of morphine (0.2, 1, and 2 mg/Kg, IP in the three nociceptive tests. It also shifted the dose response curve of morphine to the left. The combined effect of propranolol and morphine was attenuated by haloperidol (D2 receptor antagonist, 1.5 mg/Kg, IP, and bicuculline (GABAA receptor antagonist, 2 mg/Kg, IP. Repeated daily administration of propranolol (10 mg/Kg, IP did not alter the nociceptive responses in the three pain tests, but it significantly potentiated morphine-induced antinociception in the hot plate, acetic acid-evoked writhing, and in the second phase of formalin tests. Together, the data suggest that a cross-talk exists between the opioidergic and adrenergic systems and implicate dopamine and GABA systems in this synergistic effect of morphine-propranolol combination. Propranolol may serve as an adjuvant therapy to potentiate the effect of opioid analgesics.

  19. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

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    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-03-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting /sup 3/H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities.

  20. Effect of Genistein on reproductive parameter and serum nitric oxide levels in morphine-treated mice

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    Cyrus Jalili

    2016-02-01

    Full Text Available Background: The predominant phytoestrogen in soy and derived products is the isoflavone Genistein. Genistein has antioxidant properties. Morphine is a main psychoactive chemical in opium that can increase the generation of free radicals and therefore it could adversely affects the spermatogenesis. Objective: The main goal was to investigate whether the Genistein could protect morphine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone and nitric oxide in blood serum. Materials and Methods: In this study, various doses of Genistein (0, 1, 2, and 3 mg/kg and Genistein plus morphine (0, 1, 2, and 3 mg/kg were administered interaperitoneally to 48 male mice for 30 consequent days. These mice were randomly assigned to 8 groups (n=6 and sperm parameters (sperm cells viability, count, motility and morphology, testis weight and histology, testosterone hormone (ELISA method, FSH and LH hormones (immunoradiometry and serum nitric oxide (griess assay were analyzed and compared. Results: The results indicated that morphine administration significantly decreased testosterone (0.03 ng/mg LH and FSH level, histological parameters, count, viability (55.3%, morphology and motility of sperm cells (1%, testis weight (0.08 gr and increase nitric oxide compared to saline group (p=0.00. However, administration of Genistein and Genistein plus morphine significantly boosted motility, morphology, count, viability of sperm cells, seminiferous tubules diameter, germinal thickness, testosterone, LH and FSH while decrease nitric oxide level in all groups compared to morphine group (p<0.025. Conclusion: It seems that Genistein administration could increase the quality of spermatozoa and prevent morphine- induced adverse effects on sperm parameters.

  1. Blockade of dorsal hippocampal orexin-1 receptors impaired morphine-induced state-dependent learning.

    Science.gov (United States)

    Farahmandfar, Maryam; Kadivar, Mehdi; Rastipisheh, Sareh

    2016-12-01

    Behavioral abnormalities associated with opiate addiction include memory and learning deficits, which are the result of some alterations in the neuromodulatory systems. Recently, orexin has shown to influence drug addiction neural circuitry, specifically in mediating reward-related perception and memory. To explore the possible interaction of orexinergic and opioidergic system on modulation of learning and memory, we have investigated the effects of intra-dorsal hippocampal (intra-CA1) administration of orexin-1 receptor agonist and the competitive orexin-1 antagonist, SB-334867, on morphine-induced memory impairment by using step-down passive avoidance task in mice. Pre-training injection of morphine (5mg/kg, i.p.) impaired memory, which was restored when 24h later the same dose of the drug was administered. Pre-test administration of orexin-1 (0.5, 5 and 50pmol, intra-CA1) had not a significant effect on the retention latency compared to the saline-treated animals, but it restored the memory impairment induced by pre-training morphine (5mg/kg, i.p.). Pre-test administration of SB-334867 (10, 20 and 40nmol, intra-CA1) by itself decreased the retention latencies of passive avoidance task. Co-administration of orexin-1 (0.5, 5 and 50pmol, intra-CA1) and morphine (1mg/kg, i.p.) on the test day induced morphine state-dependent memory. Conversely, pre-test injection of SB-334867 (10, 20 and 40nmol, intra-CA1) inhibited the orexin-1-induced potentiation of morphine state-dependent learning on the test day. It is concluded that dorsal hippocampal orexin-1 receptors may be involved, at least in part, in morphine state-dependent learning in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Withania somnifera root extract prolongs analgesia and suppresses hyperalgesia in mice treated with morphine.

    Science.gov (United States)

    Orrù, Alessandro; Marchese, Giorgio; Casu, Gianluca; Casu, Maria Antonietta; Kasture, Sanjay; Cottiglia, Filippo; Acquas, Elio; Mascia, Maria Paola; Anzani, Nicola; Ruiu, Stefania

    2014-04-15

    Previous studies demonstrated that Withania somnifera Dunal (WS), a safe medicinal plant, prevents the development of tolerance to the analgesic effect of morphine. In the present study, we investigated whether WS extract (WSE) (100 mg/kg, i.p.) may also modulate the analgesic effect induced by acute morphine administration (2.5, 5, 10 mg/kg, s.c.) in the tail-flick and in the hot plate tests, and if it may prevent the development of 2.5 mg/kg morphine-induced rebound hyperalgesia in the low intensity tail-flick test. Further, to characterize the receptor(s) involved in these effects, we studied, by receptor-binding assay, the affinity of WSE for opioid (μ, δ, k), cannabinoid (CB1, CB2), glutamatergic (NMDA), GABAergic (GABAA, GABAB), serotoninergic (5HT2A) and adrenergic (α2) receptors. The results demonstrated that (i) WSE alone failed to alter basal nociceptive threshold in both tests, (ii) WSE pre-treatment significantly protracted the antinociceptive effect induced by 5 and 10 mg/kg of morphine only in tail-flick test, (iii) WSE pre-treatment prevented morphine-induced hyperalgesia in the low intensity tail-flick test, and (iv) WSE exhibited a high affinity for the GABAA and moderate affinity for GABAB, NMDA and δ opioid receptors. WSE prolongs morphine-induced analgesia and suppresses the development of morphine-induced rebound hyperalgesia probably through involvement of GABAA, GABAB, NMDA and δ opioid receptors. This study suggests the therapeutic potential of WSE as a valuable adjuvant agent in opioid-sparing therapies. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J; Hansen, B L

    1992-01-01

    elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during...

  4. Reconstruction of the anterior cruciate ligament: comparison of analgesia using intrathecal morphine, intra-articular morphine and intra-articular levobupivacaine

    Directory of Open Access Journals (Sweden)

    Leandro Queiroz Pinheiro

    2015-06-01

    Full Text Available OBJECTIVE: To compare the analgesic effect of intra-articular administration of morphine and levobupivacaine (separately or in combination with intrathecal administration of morphine in patients undergoing anterior cruciate ligament (ACL reconstruction using autologous grafts from the patellar tendon.METHODS: This was a retrospective analysis on data gathered from the medical files of 60 patients aged 20 to 50 years who underwent knee video arthroscopy for ACL reconstruction. The patients were divided into four groups of 15 individuals (A, B, C and D according to the agent administered into the joint and around the incision: 20 mL of saline solution with 5 mg of morphine in A; 20 mL of 0.5% levobupivacaine solution in B; 10 mL of solution with 2.5 mg of morphine plus 10 mL of 0.5% levobupivacaine solution in C; and morphine administered intrathecally in D.RESULTS: All the groups presented low pain scores during the first 12 h after the surgery. Groups B and C presented significantly greater pain scores than shown by group D (control, 24 h after the surgery. There was no statistical difference in pain scores between group A and group D.CONCLUSION: The patients in group A presented analgesia comparable to that of the patients in group D, whereas the procedure of group C was no capable of reproducing the analgesic effect observed in group D, as observed 24 h after the surgery. Further studies are needed in order to show the exact mechanism of action, along with the ideal dose and concentration for applying opioids to joints.

  5. Hediste diversicolor as bioindicator of pharmaceutical pollution: Results from single and combined exposure to carbamazepine and caffeine.

    Science.gov (United States)

    Pires, Adília; Almeida, Ângela; Calisto, Vânia; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Soares, Amadeu M V M; Figueira, Etelvina; Freitas, Rosa

    2016-10-01

    Several environmental stressors have been identified as key and/or emerging drivers of habitat change that could significantly influence marine near-shore ecosystems. These include increasing discharges of pharmaceutical contaminants into the aquatic coastal systems. Pharmaceutical drugs are often detected in aquatic environments but still information on their toxicity impacts on inhabiting species is scarce, especially when acting in combination. Furthermore, almost no information is available on the impacts of pharmaceuticals in polychaetes, often the most abundant taxon in benthic communities and commonly used as indicator species of environmental conditions. Therefore, the present study aimed to evaluate the biochemical alterations induced in the polychaete Hediste diversicolor, from a low contaminated area at the Ria de Aveiro lagoon (Portugal), by the antiepileptic drug carbamazepine (0.0 - control, 0.3, 3.0, 6.0 and 9.0μg/L) and the stimulant caffeine (0.0 - control, 0.5, 3.0, and 18.0μg/L), acting alone and in combination (0.3 CBZ+0.5 CAF and 6.0 CBZ+3.0 CAF). Glutathione S-transferases (GSTs), superoxide dismutase (SOD) and catalase (CAT) activities was determined in Hediste diversicolor from each condition. Lipid peroxidation (LPO), glutathione reduced and oxidized (GSH and GSSG), glycogen and electron transport system (ETS) were also measured. The results obtained clearly revealed that both drugs induced oxidative stress in H. diversicolor, shown by the increase on LPO levels and decrease on total glutathione and GSH/GSSG ratio with the increase of exposure concentrations. Furthermore, the present findings demonstrated that polychaetes biotransformation capacity as well as antioxidant defense mechanisms were not sufficiently efficient to fight against the excess of reactive oxygen species (ROS) leading to LPO when organisms were exposed to both drugs. Our results also demonstrated that polychaetes tended to decrease the activity of ETS when exposed to

  6. Reverse of Acute and Chronic Morphine Tolerance by Lithocholic Acid via Down-regulating UGT2B7

    Directory of Open Access Journals (Sweden)

    Zizhao Yang

    2016-11-01

    Full Text Available Lithocholic acid (LCA deposited in human livers always induces drastic pains which need analgesic drug, like morphine to release. Our research showed that LCA can effectively inhibit uridine 5'-diphospho-glucuronosyltransferase 2B7 (UGT2B7 in morphine tolerance-like human normal liver cells, HL-7702, then increase μ-opioid receptor (MOR and calcium-calmodulin dependent protein kinase IIα (CaMKIIα expression. In vivo assay, UGT2B7 was significantly repressed in the livers of acute or chronic morphine tolerance mice pretreated with LCA (10, 50 and 100 mg/kg, p.o.. To investigate the connections between LCA function performance and changes of UGT2B7 enzymatic activity in mice livers, two morphine metabolites, morphine-3-glucuronide (M3G and morphine-6-glucuronide (M6G were quantified by solid phase extraction (SPE-HPLC-MS/MS. The result indicated no matter in acute or chronic morphine tolerance, the concentrations of M3G and M6G were all decreased, the later one fell even more. Besides that, 50mg/kg of LCA administration can prevent auto-phosphorylation of CaMKIIα at Thr286 in acute or chronic morphine tolerance mice prefrontal cortexes (mPFCs due to synthesis increase of cyclic adenosine monophosphate (cAMP. As a consequence, UGT2B7 depression mediated by LCA can affect its selective catalysis ability to morphine, that may be responsible to acute or chronic morphine tolerance alleviation. These findings might assist to modify antinociception of morphine in clinic.

  7. Effects of low-dose morphine on perceived sleep quality in patients with refractory breathlessness: A hypothesis generating study.

    Science.gov (United States)

    Martins, Rodrigo T; Currow, David C; Abernethy, Amy P; Johnson, Miriam J; Toson, Barbara; Eckert, Danny J

    2016-02-01

    The management of chronic refractory breathlessness is one of the indications for regular low-dose (≤30 mg/24 h) oral sustained release morphine. Morphine may disrupt sleep in some conditions and improve sleep quality in others. This study aimed to determine any signal of regular, low-dose morphine on perceived sleep disruption due to breathlessness and perceived sleep quality. This is a secondary analysis of data from 38 participants with refractory breathlessness (30 male; 33 with COPD) aged 76 ± 0.9 years who completed a double-blind, randomized, placebo-controlled, cross-over study in which they received 20 mg oral sustained release morphine daily and placebo for 4 days each. Participant ratings of sleep disruption due to breathlessness and perceived sleep quality were obtained daily throughout the 8-day trial. Perceived sleep disruption due to breathlessness over the 4-day period ranged between 13% and 32% of participants for placebo and 13% and 26% for morphine, decreasing by each day of the study during the morphine arm. Most participants reported 'very good' or 'quite good' sleep throughout the trial and were less likely to perceive poor sleep quality during the morphine arm (odds ratio = 0.55, 95% confidence interval: 0.34-0.88, P = 0.01). Participants who reported decreased breathlessness during the 4 days on morphine were also likely to report improved sleep quality with morphine (P = 0.039). Four days of low-dose morphine improved perceived sleep quality in elderly participants with refractory breathlessness. Regular low-dose morphine targeted to reduce refractory breathlessness may yield associated benefits by reducing sleep disruption and improving sleep quality. © 2015 Asian Pacific Society of Respirology.

  8. Delinquency in incarcerated male adolescents is associated with single parenthood, exposure to more violence at home and in the community, and poorer self-image.

    Science.gov (United States)

    Erdelja, Stanislava; Vokal, Petra; Bolfan, Marija; Erdelja, Sergej Augustin; Begovac, Branka; Begovac, Ivan

    2013-10-28

    To assess the relationships between delinquency and demographic and family variables, academic performance, war stressors, home/community, school, and media violence exposure, self-image, and psychopathology. This cross-sectional study included 100 delinquent, incarcerated male adolescents and 100 matched schoolchildren from Croatia. It lasted from January 2008 to June 2009, and used socio-demographic questionnaire, questionnaire on children's stressful and traumatic war experiences, exposure to violence scale, the Offer Self-Image Questionnaire, and Youth Self-Report Questionnaire. Logistic regression analysis showed that delinquency in incarcerated adolescents was more likely related to having parents who did not live together (odds ratio [OR] 2.40; confidence interval [CI] 1.18-4.90, P=0.015), being more exposed to violence at home/community (OR 3.84; CI 1.58-9.34, P=0.003), and having poorer self-image (OR 1.09; CI=1.03-1.16, P>0.002). Preventive and therapeutic interventions in incarcerated delinquents should be specifically targeted toward single parenthood, family factors, trauma oriented interventions, and focused on multiple dimensions of self-concept of adolescents.

  9. The addition of tramadol to the standard of i.v. acetaminophen and morphine infusion for postoperative analgesia in neonates offers no clinical benefit: a randomized placebo-controlled trial.

    Science.gov (United States)

    Olischar, Monika; Palmer, Greta M; Orsini, Francesca; Davidson, Andrew J; Perkins, Elizabeth J; Lee, Katherine J; Everest, Neil J; Cranswick, Noel E; Hunt, Rod W

    2014-11-01

    Tramadol is used following neonatal cardiac and general surgery. However, its ability to opioid-spare or facilitate earlier extubation in postoperative neonates is unquantified. This randomized placebo-controlled trial aimed to assess whether tramadol's addition to standard analgesia resulted in earlier extubation or reduced analgesic/sedative requirements in postsurgical neonates. Neonates born ≥32 weeks postmenstrual age received either tramadol [T] 2 mg·kg(-1) or placebo [P] 6-hourly for up to 5 days postthoracoabdominal surgery in addition to morphine (commenced at 20 mcg·kg(-1) ·h(-1)) and 6-hourly i.v. acetaminophen. Time to extubation, morphine and midazolam amounts, hourly pain scores, and seizure activity were compared using an intention-to-treat and per-protocol analysis. Seventy-one neonates participated. Median survival time to extubation was similar between the groups (T 67 h [95% CI 51, 84] vs P 52 h [95%CI 43, 65]; P = 0.4), and similar numbers were extubated by 96 h (T 69% vs P 77%; difference -8%, 95%CI -28, 13%). Morphine and midazolam exposure was similar, with low pain scores in both groups (mean percentage of time with a pain score >5/20 during the 5 days: T 13% vs P 11%, difference in means 2.8 [95% CI -1.8, 7.6], P = 0.20). Most participants had normal cranial ultrasounds (T 86% vs P 86%); no seizures occurred clinically or electroencephalographically. Tramadol's addition to standard analgesia in this small group of postsurgical neonates did not appear to have any positive effect on time to extubation, morphine or midazolam exposure, or pain scores. This questions the benefit of tramadol for postsurgical neonates. Importantly, no seizures occurred in these ill neonates who may potentially be at greater risk of tramadol toxicity compared with adults. © 2014 John Wiley & Sons Ltd.

  10. Attenuation of morphine-induced dependence and tolerance by ceftriaxone and amitriptyline in mice.

    Science.gov (United States)

    Habibi-Asl, Bohlul; Vaez, Haleh; Najafi, Moslem; Bidaghi, Ali; Ghanbarzadeh, Saeed

    2014-12-01

    Tolerance to and dependence on the analgesic effect of opioids is a pharmacological phenomenon that occurs after their prolonged administration. The aim of this study was to evaluate the protective effects of ceftriaxone and amitriptyline on the development of morphine-induced tolerance and dependence. In this study, 18 groups (9 groups each for tolerance and dependency tests) of mice (n = 8) received saline [10 mL/kg, intraperitoneally (i.p.)], morphine (50 mg/kg, i.p.), ceftriaxone (50 mg/kg, i.p., 100 mg/kg, i.p., and 200 mg/kg, i.p.), amitriptyline (5 mg/kg, i.p., 10 mg/kg, i.p., and 15 mg/kg, i.p.), or a combination of ceftriaxone (50 mg/kg, i.p.) and amitriptyline (5 mg/kg, i.p.) once per day for 4 days for investigation and comparison of the effects of ceftriaxone and amitriptyline on the prevention of dependency and tolerance to morphine. Tolerance was assessed with administration of morphine (9 mg/kg, i.p.) and using the hot plate test on the 5(th) day. In dependency tests, withdrawal symptoms were assessed on the 4(th) day for each animal 30 minutes after the administration of naloxone (4 mg/kg, i.p.; 2 hours after the last dose of morphine). It was found that treatment with ceftriaxone or amitriptyline attenuated the development of tolerance to the antinociceptive effect of morphine and also reduced naloxone-precipitated withdrawal jumping and standing on feet. Furthermore, coadministration of ceftriaxone and amitriptyline at low doses (50 mg/kg, i.p. and 5 mg/kg, i.p., respectively) prior to morphine injection also decreased both morphine-induced tolerance and dependence. Results indicate that the treatment with ceftriaxone and amitriptyline, alone or in combination, could attenuate the development of morphine-induced tolerance and dependence. Copyright © 2014. Published by Elsevier B.V.

  11. Single-sweep spectral analysis of contact heat evoked potentials

    DEFF Research Database (Denmark)

    Hansen, Tine M; Graversen, Carina; Frøkjaer, Jens B

    2015-01-01

    AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single-sweep ch...

  12. Roles of the Nucleus Accumbens (Shell in the Acquisition and Expression of Morphine-Induced Conditioned Behavior in Freely Moving Rats

    Directory of Open Access Journals (Sweden)

    Sara Karimi

    2014-01-01

    Conclusions: Since stimulation of dopaminergic neurons increases tendency to dependence to morphine, therefore in the present study, the stimulation of the NAc suppressed morphine-induced CPP that this shows impairment of learning and memory formation.

  13. Dexketoprofen-induced antinociception in animal models of acute pain: synergy with morphine and paracetamol.

    Science.gov (United States)

    Miranda, Hugo F; Puig, Margarita M; Dursteler, Christian; Prieto, Juan Carlos; Pinardi, Gianni

    2007-02-01

    The antinociceptive activity of dexketoprofen was studied in mice using the acetic acid writhing test (acute tonic pain), the tail flick test (acute phasic pain) and the formalin assay (inflammatory pain). Isobolographic analysis was used to study the antinociceptive interactions between morphine and paracetamol co-administered with dexketoprofen. In the writhing test, the intraperitoneal administration of dexketoprofen or ketoprofen resulted in parallel dose-response curves with equal efficacy, but higher relative potency for dexketoprofen. In the tail flick test, the curves were parallel with similar efficacy and potency. The administration of morphine or paracetamol in both tests resulted in dose-response curves not parallel with that of dexketoprofen, which showed a potency between morphine and paracetamol. In the formalin assay, the antinociceptive activity of morphine during phase I was 122, 295 and 1695 times higher than dexketoprofen, ketoprofen and paracetamol, respectively. Isobolographic analysis demonstrated that the combination of sub-analgesic doses of dexketoprofen with morphine or with paracetamol was strongly synergic in all three tests. Synergistic drug combinations should improve effective pharmacological treatment of pain, minimizing drug specific adverse effects. These findings are undoubtedly worthy of additional controlled clinical trials in severe pain syndromes.

  14. Low-dose intrathecal naloxone to enhance intrathecal morphine analgesia: a case report.

    Science.gov (United States)

    Hamann, Scott; Sloan, Paul Alexander; Witt, William

    2008-01-01

    Ultra low doses of opioid antagonists such as naloxone block excitatory opioid receptor pathways may paradoxically enhance morphine analgesia. This case study reports safety and efficacy of ultra low-dose intrathecal (IT) naloxone added to IT morphine for the treatment of severe refractory chronic low back pain. A 56-year-old man with a history of severe chronic low back pain (post-laminectomy syndrome) was evaluated. Extensive multidisciplinary therapies had all failed. Initial treatment at our clinic was a lumbar IT trial of morphine (unsuccessful) up to 50 mg/day. We administered an IT bolus of morphine 2 mg combined with IT naloxone of 20 ng with the patient's consent and approval. The onset of pain relief was within 20 minutes and peaked at 1 hour with a 50 percent reduction in VAS pain score. There were no signs of adverse drug toxicity or hemodynamic compromise. An IT infusion of daily morphine 5 mg and naloxone 50 ng was started. Throughout the 3-year follow-up period, the patient maintained pain reduction of 60 to 80 percent, with a return to daily activities and no further hospitalizations.

  15. Naloxone inhibits and morphine potentiates the adrenal steroidogenic response to ACTH

    Science.gov (United States)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The administration of morphine to hypophysectomized rats potentiated the steroidogenic response of the adrenal cortex to exogenous adrenocorticotrophic hormone (ACTH) in a dose-dependent fashion. Conversely, the opiate antagonist naloxone inhibited the adrenal response to ACTH. Naloxone pretreatment also antagonized the potentiating effect of morphine on ACTH-induced steroidogenesis in a dose-dependent manner. Neither morphine nor naloxone, administered to hypophysectomized rats, had any direct effect on adrenal steroidogenesis. These adrenal actions were stereospecific since neither the (+)-stereoisomer of morphine, nor that or naloxone, had any effect on the adrenal response to ACTH. The administration of human beta-endorphin to hypophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose-dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone-secreting cells of the adrenal cortex.

  16. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

  17. Efficacy and tolerability of intravenous morphine patient-controlled analgesia (PCA) in women undergoing cesarean delivery.

    Science.gov (United States)

    Andziak, Marta; Beta, Jarosław; Barwijuk, Michal; Issat, Tadeusz; Jakimiuk, Artur J

    2015-06-01

    The aim of the study was to evaluate analgesic efficacy and tolerability of patient-controlled analgesia (PCA) with intravenous morphine. Our observational study included 50 women who underwent a Misgav-Ladach or modified Misgav-Ladach cesarean section. Automated PCA infusion device (Medima S-PCA Syringe Pump, Medima, Krakow, Poland) was used for postoperative pain control. Time of morphine administration or initiation of intravenous patient-controlled analgesia (IV PCA) with morphine was recorded, as well as post-operative pain at rest assessed by a visual analogue scale (VAS). All patients were followed up for 24 hours after discharge from the operating room, taking into account patient records, worst pain score at rest, number of IV PCA attempts, and drug consumption. Median of total morphine doses used during the postoperative period was 42.9mg (IQR 35.6-48.5), with median infusion time of 687.0 min. (IQR 531.0-757.5). Pain severity and total drug consumption improved after the first 3 hours following cesarean delivery (p PCA attempts per patient was 33 (IQR: 24-37), with median of 11 placebo attempts (IQR: 3-27). Patient-controlled analgesia with morphine is an efficient and acceptable analgesic method in women undergoing cesarean section.

  18. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

    Directory of Open Access Journals (Sweden)

    Woojin Kim

    2016-01-01

    Full Text Available Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.. BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36 or morphine (0.5, 2, and 5 mg/kg, i.p. alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg or 5-HT3 (MDL-72222, 15 μg receptor antagonist, but not with α2-adrenergic (idazoxan, 10 μg receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.

  19. Effect of Aqueous Extract of Crocus sativus L. on Morphine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Sayede Maryam Naghibi

    2012-01-01

    Full Text Available In the present study, the effect of aqueous extracts of saffron on morphine-induced memory impairment was investigated. On the training trial, the mice received an electric shock when the animals were entered into the dark compartment. Twenty-four and forty-eight hours later, the time latency for entering the dark compartment was recorded and defined as the retention trial. The mice were divided into (1 control, (2 morphine which received morphine before the training in the passive avoidance test, (3–5 three groups treated by 50, 150 and 450 mg/kg of saffron extract before the training trial, and (6 and 7 the two other groups received 150 and 450 mg/kg of saffron extract before the retention trial. The time latency in morphine-treated group was lower than control (P < 0.01. Treatment of the animals by 150 and 450 mg/kg of saffron extract before the training trial increased the time latency at 24 and 48 hours after the training trial (P < 0.05 and P < 0.01. Administration of both 150 and 450 mg/kg doses of the extract before retention trials also increased the time latency (P < 0.01. The results revealed that the saffron extract attenuated morphine-induced memory impairment.

  20. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice.

    Science.gov (United States)

    Kim, Woojin; Kim, Min Joon; Go, Donghyun; Min, Byung-Il; Na, Heung Sik; Kim, Sun Kwang

    2016-01-22

    Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2 adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.

  1. Degradation of morphine and codeine by gamma radiation in methanol solution

    International Nuclear Information System (INIS)

    Kantoglu, Oemer; Ergun, Ece

    2015-01-01

    The high concentrations of opiate and solvent in wastewater are toxic to biological life and affect the aquatic environment. Therefore, it must be treated by an advanced treatment process such as ionizing radiation. Effect of organic media on morphine and codeine during gamma irradiation was determined for the first time in this paper. Samples were irradiated at ambient temperature and in air environment at various doses (0, 10, 20, 30, 40, 50 and 60 kGy). Gamma irradiation-induced changes in the molecular structure of morphine and codeine were monitored by direct infusion electrospray ionization mass spectrometry in positive ion mode. The mass of the by-products were appeared to be more than the mass of the original alkaloids. Molecular structures of the by-products and reaction pathways were proposed. Oxygenated morphine and oxygenated codeine were identified in the presence of oxygen. However, solvent radical addition reactions were observed as the main mechanism for the by-product formation in oxygen-free irradiation. The results indicated that 89% of morphine and 98% of codeine were degraded at dose of 50 kGy. In addition, alkaloids and their by-products were not detected above 50 kGy. Here, we demonstrated that ionizing radiation process is a promising method to remove morphine and codeine in solvent/opiate rich industrial wastewater.

  2. L-type calcium channel blockers, morphine and pain: Newer insights

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2010-01-01

    Full Text Available Earlier, we had reported that co-administration of opioids and L-type calcium channel blockers (L-CCBs like diltiazem could prove useful in the treatment of cancer pain. Much of this report was based upon earlier published work involving animal models of pain exposed to brief periods of noxious radiant heat without any tissue injury. However, pain in clinical situations usually result from tissue injury. Thus, the aim of the current investigation was to study the analgesic effect of this combination of drugs in the rat formalin test which is associated with actual tissue injury. Wistar rats (n=60 received either L-CCB (nifedipine/nimodipine/verapamil/diltiazem i.p. or morphine (s.c. or both drugs. The formalin test was done 30 min after morphine or placebo injection. The naloxone reversal test was also done. Administration of L-CCBs alone, particularly diltiazem, increased pain in the formalin test. In contrast, co-administration of these L-CCBs with morphine led to decreased pain response, though statistically significant decrease was noted only with nimodipine + morphine. Naloxone reversed this analgesic effect, indicating that it was primarily an opioid-mediated effect. The results show that administration of L-CCBs alone may prove counterproductive in the therapeutic management of pain (anti-analgesic effect. However, co-administration of both drugs (morphine and nimodipine in quick succession could lead to adequate pain relief.

  3. Deletion of the δ opioid receptor gene impairs place conditioning but preserves morphine reinforcement.

    Science.gov (United States)

    Le Merrer, Julie; Plaza-Zabala, Ainhoa; Del Boca, Carolina; Matifas, Audrey; Maldonado, Rafael; Kieffer, Brigitte L

    2011-04-01

    Converging experimental data indicate that δ opioid receptors contribute to mediate drug reinforcement processes. Whether their contribution reflects a role in the modulation of drug reward or an implication in conditioned learning, however, has not been explored. In the present study, we investigated the impact of δ receptor gene knockout on reinforced conditioned learning under several experimental paradigms. We assessed the ability of δ receptor knockout mice to form drug-context associations with either morphine (appetitive)- or lithium (aversive)-induced Pavlovian place conditioning. We also examined the efficiency of morphine to serve as a positive reinforcer in these mice and their motivation to gain drug injections, with operant intravenous self-administration under fixed and progressive ratio schedules and at two different doses. Mutant mice showed impaired place conditioning in both appetitive and aversive conditions, indicating disrupted context-drug association. In contrast, mutant animals displayed intact acquisition of morphine self-administration and reached breaking-points comparable to control subjects. Thus, reinforcing effects of morphine and motivation to obtain the drug were maintained. Collectively, the data suggest that δ receptor activity is not involved in morphine reinforcement but facilitates place conditioning. This study reveals a novel aspect of δ opioid receptor function in addiction-related behaviors. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Role of morphine preconditioning and nitric oxide following brain ischemia reperfusion injury in mice

    Directory of Open Access Journals (Sweden)

    Maedeh Arabian

    2015-01-01

    Full Text Available Objective(s: Morphine dependence (MD potently protects heart against ischemia reperfusion (IR injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg or L-NAME (20 mg/kg 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P

  5. Effects of combined perioperative epidural bupivacaine and morphine, ibuprofen, and incisional bupivacaine on postoperative pain, pulmonary, and endocrine-metabolic function after minilaparotomy cholecystectomy

    DEFF Research Database (Denmark)

    Dahl, J B; Hjortsø, N C; Stage, J G

    1994-01-01

    BACKGROUND AND OBJECTIVES. The study investigates the effects of combined perioperative continuous epidural bupivacaine and morphine, ibuprofen, and incisional bupivacaine, compared with intermittent systemic morphine, ibuprofen, and incisional bupivacaine, on postoperative pain, respiratory...... with bupivacaine and morphine during 38 hours after the operation, or general anesthesia with morphine intramuscular for pain relief every 6-8 hours after the operation. All patients received ibuprofen before the operation until 6 days after the operation, and preoperative infiltration of the surgical field...

  6. Efficacy of intravenous paracetamol and dexketoprofen on postoperative pain and morphine consumption after a lumbar disk surgery.

    Science.gov (United States)

    Tunali, Yusuf; Akçil, Eren F; Dilmen, Ozlem Korkmaz; Tutuncu, Ayse C; Koksal, Guniz Meyanci; Akbas, Sedat; Vehid, Hayriye; Yentur, Ercument

    2013-04-01

    We compared the analgesic effects of intravenous (IV) paracetamol with that of dexketoprofen on postoperative pain and morphine consumption during the first 24 hour after a lumbar disk surgery. This prospective, placebo-controlled, double blind study investigated the analgesic effects of IV paracetamol and dexketoprofen on postoperative pain, morphine consumption, and morphine-related side effects after a lumbar disk surgery. Sixty American Society of Anesthesiologists 1 or 2 status patients scheduled for elective lumbar disk surgery under general anesthesia were included in the study. Patients were treated using patient-controlled analgesia with morphine for 24 hours after a lumbar disk surgery and randomized to receive IV paracetamol 1 g, dexketoprofen 50 mg, or isotonic saline (placebo). The primary endpoint was pain intensity measured by the visual analogue scale, and secondary endpoints were morphine consumption and related side effects. Pain intensity was lower in the dexketoprofen group (P=0.01) but not in the paracetamol group (P=0.21) when compared with the control group. Cumulative morphine consumption and morphine-related side effects did not reveal significant differences between the groups. The study showed that pain intensity during 24 hours after the lumbar disk surgery was significantly lowered by dexketoprofen, but not with paracetamol, as a supplemental analgesic to morphine patient-controlled analgesia when compared with controls.

  7. Study Of Morphological Changes Of Uterine Horn Of Surri Mouse Depended To Morphine Before Puberty And DuringPuberty

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    Shadkhast M

    2003-11-01

    Full Text Available : Morphine is the most important alkaloid of opium family which is found as much as ten percent in opium, and is in two types the sulfate morphine and the hydrochloride morphine."nMaterials and Methods: In this study morphological changes of uterus of surri mice due to oral consumption of sulfate morphine were studied. It was shown that, female surri mice following gradually increasing of morphine to water (0.1 and 0.01 mg/ml were depended to morphine. Female surri mice were classified in two age groups before puberty and depended to morphine during puberty. Each age group took morphine for 21 days. After finishing the period, the mice anesthetizing were weighted, then were anesthetizing and uterus was studied the length, width and apparent features."nResults&ConcIusion: In this study it was distinguished that length and width of uterine horn, between experimental and control groups, were significant (P< 0.01. Morphological changes such as anemia, the thinness and fragitidily walls of uterus and filiformity of uterine horns were observed."n"n"n"n"n"n 

  8. Dexmedetomidine versus morphine infusion following laparoscopic bariatric surgery : effect on supplemental narcotic requirement during the first 24 h

    NARCIS (Netherlands)

    Abu-Halaweh, Sami; Obeidat, Firas; Absalom, Anthony R.; AlOweidi, Abdelkareem; Abu Abeeleh, Mahmood; Qudaisat, Ibrahim; Robinson, Fay; Mason, Keira P.

    The primary aim of this pilot study was to determine whether the dexmedetomidine infusion initiated immediately after laparoscopic bariatric surgery, offers an advantage over a morphine infusion with respect to rescue morphine and paracetamol requirements over the first 24 post-operative hours.

  9. SOLID-PHASE EXTRACTION OF MORPHINE FROM WHOLE-BLOOD BY MEANS OF BOND ELUT CERTIFY COLUMNS

    NARCIS (Netherlands)

    CHEN, XH; HOMMERSON, ALC; ZWEIPFENNING, PGM; FRANKE, JP; HARMENBOVERHOF, CW; ENSING, K; DEZEEUW, RA

    The use of Bond Elut Certify columns for the isolation of morphine from whole blood was evaluated. In order to monitor possible losses and the elution profile of morphine, a small amount of the tritiated analogue was added to the samples. Four sample pretreatment methods, three protein precipitation

  10. SIMULTANEOUS MEASUREMENT OF EXTRACELLULAR MORPHINE AND SEROTONIN IN BRAIN-TISSUE AND CSF BY MICRODIALYSIS IN AWAKE RATS

    NARCIS (Netherlands)

    MATOS, FF; ROLLEMA, H; BASBAUM, AI

    In this report, we describe an HPLC with electrochemical detection assay for the simultaneous measurement of levels of morphine, serotonin, 5-hydroxyindole-3-acetic acid, and homovanillic acid in dialysates of various brain areas and CSF in the awake rat. Morphine could be detected in the dialysates

  11. Review Paper: Role of Nitric Oxide on Dopamine Release and Morphine-Dependency

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    Amir Arash Motahari

    2016-10-01

    Full Text Available The catastrophic effects of opioids use on public health and the economy are documented clearly in numerous studies. Repeated morphine administration can lead to either a decrease (tolerance or an increase (sensitization in its behavioral and rewarding effects. Morphine-induced sensitization is a major problem and plays an important role in abuse of the opioid drugs. Studies reported that morphine may exert its effects by the release of nitric oxide (NO. NO is a potent neuromodulator, which is produced by nitric oxide synthase (NOS. However, the exact role of NO in the opioid-induced sensitization is unknown. In this study, we reviewed the role of NO on opioid-induced sensitization in 2 important, rewarding regions of the brain: nucleus accumbens and ventral tegmentum. In addition, we focused on the contribution of NO on opioid-induced sensitization in the limbic system.

  12. Age-related postoperative morphine requirements in children following major surgery--an assessment using patient-controlled analgesia (PCA)

    DEFF Research Database (Denmark)

    Hansen, T G; Henneberg, S W; Hole, P

    1996-01-01

    To investigate if small children require less morphine for postoperative analgesia than do older children and adolescents we analysed the morphine consumption pattern of 28 consecutive children on intravenous patient-controlled analgesia (PCA) following major surgery. The median age......-specific morphine requirements between 2 comparable groups of children aged 4-8 years and 9-15 years were compared. We used the Pharmacia-Deltec pump in all children and the same settings: a bolus dose of 25 microgram/kg, an 8 minutes lockout interval and no background infusion. In addition, all children received...... paracetamol as a supplemently to the morphine. In this study children aged 4-8 years had significantly higher total postoperative morphine requirements compared to children aged 9-15 years, i.e. 11.6 microgram/kg/hour and 7.5 microgram/kg/hour respectively (p = 0.037). Hence, we conclude that children...

  13. Does adding low doses of oral naltrexone to morphine alter the subsequent opioid requirements and side effects in trauma patients?

    Science.gov (United States)

    Farahmand, Shervin; Ahmadi, Omid; Dehpour, Ahmadreza; Khashayar, Patricia

    2012-01-01

    The present study aims to assess the influence of ultra-low doses of opioid antagonists on the analgesic properties of opioids and their side effects. In the present randomized, double-blind controlled trial, the influence of the combination of ultra-low-dose naltrexone and morphine on the total opioid requirement and the frequency of the subsequent side effects was compared with that of morphine alone (added with placebo) in patients with trauma in the upper or lower extremities. Although the morphine and naltrexone group required 0.04 mg more opioids during the study period, there was no significant difference between the opioid requirements of the 2 groups. Nausea was less frequently reported in patients receiving morphine and naltrexone. The combination of ultra-low-dose naltrexone and morphine in extremity trauma does not affect the opioid requirements; it, however, lowers the risk of nausea. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Comparison of efficacy of intra-articular morphine and steroid in patients with knee osteoarthritis

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    Serbülent Gökhan Beyaz

    2012-01-01

    Full Text Available Introduction: Primary therapeutic aim in treatment of osteoarthritis of the knee is to relieve the pain of osteoarthritis. The aim of this study was to compare the efficacy of intra-articular triamcinolone with intra-articular morphine in pain relief due to osteoarthritis of the knee in the elderly population. Materials and Methods: Patients between 50 and 80 years of age were randomized into three groups. Group M received morphine plus bupivacaine intra-articularly, Group T received triamcinolone plus bupivacaine intra-articularly, and Group C received saline plus bupivacaine intra-articularly. Patients were evaluated before injection and in 2nd, 4th, 6th, and 12th weeks after injection. First-line supplementary analgesic was oral paracetamol 1500 mg/day. If analgesia was insufficient with paracetamol, oral dexketoprofen trometamol 50 mg/day was recommended to patients. Results: After the intra-articular injection, there was statistically significant decrease in visual analog scale (VAS scores in Groups M and T, when compared to Group C. The decrease of VAS scores seen at the first 2 weeks continued steadily up to the end of 12th week. There was a significant decrease in Groups M and T in the WOMAC scores, when compared to Group C. There was no significant difference in the WOMAC scores between morphine and steroid groups. Significantly less supplementary analgesics was used in the morphine and steroid groups. Conclusion: Intra-articular morphine was as effective as intra-articular triamcinolone for analgesia in patients with osteoarthritis knee. Intra-articular morphine is possibly a better option than intra-articular steroid as it has lesser side effects.

  15. Where there is no morphine: The challenge and hope of palliative care delivery in Tanzania

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    Kristopher Hartwig

    2014-01-01

    Full Text Available Background: In Tanzania, a country of 42 million, access to oral morphine is rare.Aim: To demonstrate the effectiveness of palliative care teams in reducing patients’ pain and in increasing other positive life qualities in the absence of morphine; and to document the psychological burden experienced by their clinical providers, trained in morphine delivery, as they observed their patients suffering and in extreme pain.Setting: One hundred and forty-fie cancer patients were included from 13 rural hospitals spread across Tanzania.Method: A mixed method study beginning with a retrospective quantitative analysis of cancer patients who were administered the APCA African POS tool four times. Bivariate analyses of the scores at time one and four were compared across the domains. The qualitative arm included an analysis of interviews with six nurses, each with more than fie years’ palliative care experience and no access to strong opioids.Results: Patients and their family caregivers identifid statistically signifiant (p < 0.001 improvements in all of the domains. Thematic analysis of nurse interviews described the patient and family benefis from palliative care but also their great distress when ‘bad cases’ arose who would likely benefi only from oral morphine.Conclusion: People living with chronic cancer-related pain who receive palliative care experience profound physical, spiritual and emotional benefis even without oral morphine. These results demonstrate the need for continued advocacy to increase the availability of oral morphine in these settings in addition to palliative care services.

  16. Morphine Produces Immunosuppressive Effects in Non-human Primates at the Proteomic and Cellular Levels

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Joseph N.; Ortiz, Gabriel M.; Angel, Thomas E.; Jacobs, Jon M.; Gritsenko, Marina A.; Chan, Eric Y.; Purdy, David E.; Murnane, Robert D.; Larsen, Kay; Palermo, Robert E.; Shukla, Anil K.; Clauss, Therese RW; Katze, Michael G.; McCune, Joseph M.; Smith, Richard D.

    2012-05-11

    Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. As a prelude to understanding how these changes might interact with lentiviral infection in vivo, animals from two non-human primate (NHP) species [African green monkey (AGMs) and pigtailed macaque (PTs)] were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g., lymph node, colon, cerebrospinal fluid (CSF), and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an inter-organ, inter-individual, and inter-species basis. In both species, morphine was associated with decreased levels of (Ki-67+) T cell activation but with only minimal changes in overall T cell counts, neutrophil counts, and NK cells counts. While changes in T cell maturation were observed, these varied across the various tissue/fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in the lymph node, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the interplay between opioid abuse and the response to infection with agents such as the human immunodeficiency virus, type 1 (HIV).

  17. Src Kinase Inhibition Attenuates Morphine Tolerance without Affecting Reinforcement or Psychomotor Stimulation.

    Science.gov (United States)

    Bull, Fiona A; Baptista-Hon, Daniel T; Sneddon, Claire; Wright, Lisa; Walwyn, Wendy; Hales, Tim G

    2017-11-01

    Prolonged opioid administration leads to tolerance characterized by reduced analgesic potency. Pain management is additionally compromised by the hedonic effects of opioids, the cause of their misuse. The multifunctional protein β-arrestin2 regulates the hedonic effects of morphine and participates in tolerance. These actions might reflect µ opioid receptor up-regulation through reduced endocytosis. β-Arrestin2 also recruits kinases to µ receptors. We explored the role of Src kinase in morphine analgesic tolerance, locomotor stimulation, and reinforcement in C57BL/6 mice. Analgesic (tail withdrawal latency; percentage of maximum possible effect, n = 8 to 16), locomotor (distance traveled, n = 7 to 8), and reinforcing (conditioned place preference, n = 7 to 8) effects of morphine were compared in wild-type, µ, µ, and β-arrestin2 mice. The influence of c-Src inhibitors dasatinib (n = 8) and PP2 (n = 12) was examined. Analgesia in morphine-treated wild-type mice exhibited tolerance, declining by day 10 to a median of 62% maximum possible effect (interquartile range, 29 to 92%). Tolerance was absent from mice receiving dasatinib. Tolerance was enhanced in µ mice (34% maximum possible effect; interquartile range, 5 to 52% on day 5); dasatinib attenuated tolerance (100% maximum possible effect; interquartile range, 68 to 100%), as did PP2 (91% maximum possible effect; interquartile range, 78 to 100%). By contrast, c-Src inhibition affected neither morphine-evoked locomotor stimulation nor reinforcement. Remarkably, dasatinib not only attenuated tolerance but also reversed established tolerance in µ mice. The ability of c-Src inhibitors to inhibit tolerance, thereby restoring analgesia, without altering the hedonic effect of morphine, makes c-Src inhibitors promising candidates as adjuncts to opioid analgesics.

  18. Attitudes towards morphine use among nurses and physicians working in French-speaking Switzerland

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    Ferreira M

    2013-10-01

    Full Text Available Maria Ferreira,1 Henk Verloo,2 Margarida Maria S Vieira,3 Pedro Marques-Vidal4 1Sion Hospital, Sion, Switzerland; 2Haute École de Santé La Source, Lausanne, Switzerland; 3Instituto de Ciências da Saúde, Universidade Católica Portuguesa, Lisbon, Portugal; 4Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland Abstract: There is little information regarding risk perceptions and attitudes towards morphine use in Switzerland. Thus, we aimed at assessing such attitudes in a sample of health professionals drawn from five nonuniversity hospitals in the French-speaking canton of Valais, Switzerland. The sample included 431 nurses and 40 physicians (age range: 20–63 years, and risk perceptions and attitudes towards morphine use were assessed using a validated questionnaire. More than half of the participants showed a negative attitude regarding most adverse events related to morphine. In bivariate analyses, participants working in geriatrics showed a more negative attitude towards use of morphine than did participants working in medicine and surgery. Compared with Swiss participants, non-Swiss participants also showed a more negative attitude regarding use of morphine. Conversely, no differences were found between the sexes, professions (nurses versus physicians, years of experience (≤14 years versus >14 years, or religions (Catholic versus other/no religion. These findings were further confirmed by multivariate adjustment. Our results indicate that attitudes regarding morphine use are mainly driven by its potential adverse effects and vary according to specialty and nationality. Educational measures directed at health professionals working in geriatrics or coming from abroad might reduce the high morphinophobia levels observed in these groups. Keywords: morphinophobia, cross-sectional study, nurses, physicians, Switzerland

  19. The effects of low doses of pregabalin on morphine analgesia in advanced cancer patients.

    Science.gov (United States)

    Mercadante, Sebastiano; Porzio, Giampiero; Aielli, Federica; Ferrera, Patrizia; Codipietro, Luigi; Lo Presti, Claudio; Casuccio, Alessandra

    2013-01-01

    The aim of this study was to evaluate the opioid response in patients receiving morphine and pregabalin, independently from the presumed pain mechanisms, in comparison with patients receiving morphine treatment only. A multicenter prospective randomized controlled study was carried out in a sample of 70 advanced cancer patients with pain requiring strong opioids. Thirty-five patients (group MO) were randomized to receive sustained-release morphine using initial doses of 60 mg/day. Thirty-five patients (group MO-PR) were randomized to start the same morphine doses and pregabalin in increasing doses, starting with 25 mg/day up to 150 mg/day in one week. The following data were also recorded before starting the treatments (T0) and then at week intervals for four weeks (W1-4): age, gender, primary cancer and known metastases, pain causes and mechanisms, symptoms associated with opioid therapy, pain intensity, Brief Pain Inventory (BPI), morphine doses and escalation indexes (OEIs), and quality of life. Forty-eight patients completed the study, twenty-eight and sixteen patients in group MO and MO-PR, respectively. Twenty patients were females, the mean age was 65.5 (± 10.3), and the mean Karnofsky status was 66.0 (± 18.9). No differences between groups were found in age (P = 0.839), Karnofsky status (P = 0.741), opioid doses as well as escalation indexes (OEI mg, P = 0.260, and OEI%, P = 0.270). No differences between the two groups were found in quality of life and all BPI items. The use of low doses of pregabalin added to morphine therapy in advanced cancer patients does not seem to provide advantageous analgesic effects, despite limitations of the present study due to the number of drop-outs.

  20. Impact of morphine dependency and detoxification by methadone on male’s rat reproductive system

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    Mahnaz Ghowsi

    2015-05-01

    Full Text Available Background: One of the problems that addicts suffer from is decreased libido. Erectile dysfunction has been reported in men using opioids for treatment of heroin addiction. Objective: The study was performed to investigate the effects of morphine and detoxification with methadone as causes of sexual dysfunction in addiction. Methods and Methods: A total of 40 adult male rats (Wistar were used. Animals were divided in to 4 groups. Control groups received saline for 30 days. Other 2 groups received 10 mg/kg morphine on day 1 and the morphine doses increased daily by 2 mg/kg increments per day until in day 30 a maximum of 68 mg/kg twice daily was achieved. Withdrawal syndrome sings were evaluated. At the end of period, one group of 2 morphine dependent groups was treated with methadone during 14 days. Animals in group 4 (saline solution+ methadone received saline for 30 consecutive days and then detoxified with methadone during 14 days. Partial weights of seminal vesicles, testes, prostates, seminal vesicles content, concentrations of luteinizing hormone, follicle stimulating hormone, and testosterone in serum were determined. Results: In the dependent group serum levels of testosterone (p<0.001, folicle stimulating hormone (p=0.0097 and luteinizing hormone (p=0.0031 as well as the weights of testes (p=0.0051, partial weights of prostates, seminal vesicles and seminal vesicles contents (p<0.001 were reduced as compared with control group. In the morphine dependent animals detoxified with methadone, testosterone concentrations and seminal vesicles contents remained lower than levels in the control group (p<0.001. Conclusion: The results suggest that morphine dependence may impair the reproductive function in male rats.

  1. Morphine Promotes Colonization of Anastomotic Tissues with Collagenase - Producing Enterococcus faecalis and Causes Leak.

    Science.gov (United States)

    Shakhsheer, Baddr A; Versten, Luke A; Luo, James N; Defazio, Jennifer R; Klabbers, Robin; Christley, Scott; Zaborin, Alexander; Guyton, Kristina L; Krezalek, Monika; Smith, Daniel P; Ajami, Nadim J; Petrosino, Joseph F; Fleming, Irma D; Belogortseva, Natalia; Zaborina, Olga; Alverdy, John C

    2016-10-01

    Despite ever more powerful antibiotics, newer surgical techniques, and enhanced recovery programs, anastomotic leaks remain a clear and present danger to patients. Previous work from our laboratory suggests that anastomotic leakage may be caused by Enterococcus faecalis strains that express a high collagenase phenotype (i.e., collagenolytic). Yet the mechanisms by which the practice of surgery shifts or selects for collagenolytic phenotypes to colonize anastomotic tissues remain unknown. Here, we hypothesized that morphine, an analgesic agent universally used in gastrointestinal surgery, promotes tissue colonization with collagenolytic E. faecalis and causes anastomotic leak. To test this, rats were administered morphine in a chronic release form as would occur during routine surgery or vehicle. Rats were observed for 6 days and then underwent exploratory laparotomy for anastomotic inspection and tissue harvest for microbial analysis. These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in gastrointestinal surgery. Results demonstrated that compared to placebo-treated rats, morphine-treated rats demonstrated markedly impaired anastomotic healing and gross leaks that correlated with the presence of high collagenase-producing E. faecalis adherent to anastomotic tissues. To determine the direct role of morphine on this response, various isolates of E. faecalis from the rats were exposed to morphine and their collagenase activity and adherence capacity determined in vitro. Morphine increased both the adhesiveness and collagenase production of four strains of E. faecalis harvested from anastomotic tissues, two that were low collagenase producers at baseline, and two that were high collagenase producers at baseline. These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in

  2. The role of gaseous neurotransmitters in the antinociceptive effects of morphine during acute thermal pain.

    Science.gov (United States)

    Gou, Gemma; Leánez, Sergi; Pol, Olga

    2014-08-15

    Treatment with a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium(II) dimer, CORM-2) or a classical inducible heme oxygenase (HO-1) inducer (cobalt protoporphyrin IX, CoPP) enhanced the antinociceptive effects of morphine during chronic pain but the role played by these compounds in acute thermal nociception was not evaluated. The effects of CORM-2 and CoPP treatments on the local antinociceptive actions of morphine and their interactions with nitric oxide during acute pain were evaluated by using wild type (WT), neuronal (nNOS-KO) or inducible (iNOS-KO) nitric oxide synthase knockout mice and assessing their thermal nociception to a hot stimulus with the hot plate test. Our results showed that the absence of nNOS or iNOS genes did not alter licking and jumping responses nor the antinociceptive effects produced by morphine indicating that the local thermal inhibitory effects produced by this drug in the absence of inflammation or injury are not mediated by the nitric oxide pathway triggered by nNOS or iNOS enzymes. Moreover, while the systemic administration of CORM-2 or CoPP inhibited licking and jumping latencies in all genotypes, these treatments only enhanced the local inhibition of jumping latencies produced by morphine in WT and nNOS-KO mice which effects were reversed by the peripheral administration of an HO-1 inhibitor. These data indicate that the co-administration of morphine with CORM-2 or CoPP produced remarkable local antinociceptive effects in WT and nNOS-KO mice and reveal that a significant interaction between carbon monoxide and nitric oxide systems occurs on the local antinociceptive effects produced by morphine during acute thermal nociception. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine.

    Science.gov (United States)

    Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z; Campbell, Claudia M; Strain, Eric C

    2014-02-01

    Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of