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Sample records for analgesics opioid

  1. Non-analgesic effects of opioids

    DEFF Research Database (Denmark)

    Højsted, Jette; Kurita, Geana Paula; Kendall, Sally;

    2012-01-01

    Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including...... cognition resulting in complex interactions between pain, opioids and cognition. The literature on this complexity is sparse and information regarding the cognitive effects of opioids in chronic pain patients is substantially lacking. Two previous systematic reviews on cancer pain and non-cancer pain...... groups: no effects or worsening of cognitive function in cancer pain patients and no effect or improvements in the chronic non-cancer pain patients, however, due to methodological limitations and a huge variety of designs definite conclusions are difficult to draw from the studies. In studies of higher...

  2. Clinical pharmacology of non opioid analgesics in neonates.

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    Allegaert, K; de Hoon, J; Van Overmeire, B; Devlieger, H

    2005-01-01

    An integrated approach of neonatal analgesia starts with the systematic evaluation of pain and should be followed by effective interventions, mainly based on the appropriate (i.e. safe and effective) administration of analgesics. In contrast to the more potent opioids, data on the pharmacokinetics and -dynamics of non-opioid analgesics in this specific population are still rare or even lacking. We therefore evaluated various aspects of developmental pharmacology of non-opioid analgesics (paracetamol, ibuprofen, acetylsalicyl acid) in neonates. We first performed a single dose propacetamol study in preterm and term neonates. Based on these preliminary findings, a repeated dose administration scheme was developed and tested and maturational aspects from preterm till teenage were documented. Although non-selective COX-inhibitors might be effective in the treatment of postoperative or inflammatory pain syndromes in neonates, potential efficacy should be balanced against the drugs' safety profile. Neonatal renal clearance strongly depends on glomerular filtration rate (GFR) and GFR itself strongly depends on the vaso-dilatative of prostaglandins on the afferent arterioli. We therefore evaluated the impact of the administration of ibuprofen or acetylsalicylic acid on renal clearance in preterm infants and hereby used amikacin clearance as a surrogate marker. We hereby documented the negative effect of ibuprofen on glomerular filtration rate in preterm infants up to 34 weeks and we were able to show that ibuprofen and acetylsalicylic acid had an equal impact on the glomerular filtration rate. PMID:16408826

  3. Tolerance to non-opioid analgesics is opioid-sensitive in nucleus raphe magnus

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    MerabGTsagareli

    2011-07-01

    Full Text Available Repeated injection of opioid analgesics can lead to a progressive loss of its effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs in the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM in the following four days result in progressively less antinociception, i.e. produce the development of tolerance to these drugs in mail rats. Special control experiments showed that post-treatment with μ-opioid antagonist naloxone in NRM significantly decreased antinociceptive effects of NSAIDs at the first day in behavioral tail flick reflex (TF and hot plate (HP latencies. At the second day, naloxone generally had trend effects in both TF and HP tests impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion on endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

  4. The role of urine toxicology in chronic opioid analgesic therapy.

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    Compton, Peggy

    2007-12-01

    The current trend of treating chronic nonmalignant pain with opioid therapy means that pain management nurses are increasingly involved in the care of patients who are prescribed and using potent opioid analgesics on a daily basis. Although demonstrated to be quite effective in certain patients, sanctioned access to these medications brings with it risks for abuse, addiction, and diversion. Urine toxicology analysis is a valuable, yet underutilized, tool to monitor patterns of medication use and potential use of illicit drugs to evaluate the effect of these on health outcomes. This review provides a guide for the use of urine toxicology in the nursing management of chronic pain patients on opioid therapy, detailing the information provided by urine toxicology analysis, the benefits and limitations of urine drug testing, principles of sample collection, and correct interpretation of findings. It is emphasized that the results of urine toxicology analysis should never be used in isolation to identify abuse, addiction, or diversion, and that patterns of medication and other drug use should always be evaluated with respect to evidence of improved functionality. Nurses involved in the care of patients with chronic pain are encouraged to consider urine toxicology analysis as an integral component in care plan for those on chronic opioid therapy, and to knowledgeably implement and interpret this powerful tool in the practice of pain care. PMID:18036504

  5. The unsolved case of "bone-impairing analgesics": the endocrine effects of opioids on bone metabolism.

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    Coluzzi, Flaminia; Pergolizzi, Joseph; Raffa, Robert B; Mattia, Consalvo

    2015-01-01

    The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density. PMID:25848298

  6. National consumption of opioid and nonopioid analgesics in Croatia: 2007–2013

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    Krnic D

    2015-08-01

    Full Text Available Darko Krnic,1 Andrea Anic-Matic,2 Svjetlana Dosenovic,2 Pero Draganic,1 Sasa Zezelic,1 Livia Puljak2 1Agency for Medicinal Products and Medical Devices, Zagreb, 2Laboratory for Pain Research, School of Medicine, University of Split, Split, Croatia Background: The increased consumption of analgesics has been documented worldwide during the last 2 decades. The aim of the study was to examine the trends in opioid and nonopioid analgesic consumption in Croatia between 2007 and 2013. Methods: Data on opioid consumption were extracted from the database of the national authority. All opioid and nonopioid analgesics were included in the analysis. Data were presented as defined daily doses per 1,000 inhabitants per day. Adequacy of opioid consumption was calculated using adequacy of consumption measure. Results: During the examined 7-year period, the total consumption and total cost of all analgesics in Croatia showed continuous increase. In the M01A group (anti-inflammatory and antirheumatic products, nonsteroids, ibuprofen had an exponential increasing trend, and in 2011, it overtook diclofenac consumption. Ibuprofen and diclofenac had the highest consumption also in the M02A group of topical products for joint and muscular pain. Tramadol was by far the most consumed type of opioids (N02A group and paracetamol in the group of other analgesics and antipyretics (N02B. The adequacy of consumption measure value was 0.19, indicating that Croatia is a country with a low opioid consumption. Conclusion: Between 2007 and 2013, both consumption of analgesics and their cost in Croatia had an increasing trend. Comparisons with data from other countries, based on the published literature, indicate that analgesic consumption in Croatia is still relatively low. Calculation of the adequacy of opioid consumption indicated that Croatia is a country with low opioid consumption. Further studies are necessary for establishing whether current analgesic consumption in

  7. Impairment of aspirin antiplatelet effects by non-opioid analgesic medication

    Institute of Scientific and Technical Information of China (English)

    Amin; Polzin; Thomas; Hohlfeld; Malte; Kelm; Tobias; Zeus

    2015-01-01

    Aspirin is the mainstay in prophylaxis of cardiovascular diseases. Impaired aspirin antiplatelet effects are associated with enhanced incidence of cardiovascular events. Comedication with non-opioid analgesic drugs has been described to interfere with aspirin,resulting in impaired aspirin antiplatelet effects. Additionally,nonopioid analgesic medication has been shown to enhance the risk of cardiovascular events and death. Pain is very frequent and many patients rely on analgesic drugs to control pain. Therefore effective analgesic options without increased risk of cardiovascular events are desirable. This review focuses on commonly used nonopioid analgesics,interactions with aspirin medication and impact on cardiovascular risk.

  8. Analgesic effect of interferon-alpha via mu opioid receptor in the rat.

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    Jiang, C L; Son, L X; Lu, C L; You, Z D; Wang, Y X; Sun, L Y; Cui, R Y; Liu, X Y

    2000-03-01

    Using the tail-flick induced by electro-stimulation as a pain marker, it was found that pain threshold (PT) was significantly increased after injecting interferon-alpha (IFN alpha) into the lateral ventricle of rats. This effect was dosage-dependent and abolished by monoclonal antibody (McAb) to IFN alpha. Naloxone could inhibit the analgesic effect of IFN alpha, suggesting that the analgesic effect of IFN alpha be related to the opioid receptors. Beta-funaltrexamine (beta-FNA), the mu specific receptor antagonist could completely block the analgesic effect of IFN alpha. The selective delta-opioid receptor antagonist, ICI174,864 and the kappa-opioid receptor antagonist, nor-BNI both failed to prevent the analgesic effect of IFN alpha. IFN alpha could significantly inhibit the production of the cAMP stimulated by forskolin in SK-N-SH cells expressing the mu-opioid receptor, not in NG108-15 cells expressing the delta-opioid receptor uniformly. The results obtained provide further evidence for opioid activity of IFN alpha and suggest that this effect is mediated by central opioid receptors of the mu subtype. The evidence is consistent with the hypothesis that multiple actions of cytokines, such as immunoregulatory and neuroregulatory effects, might be mediated by distinct domains of cytokines interacting with different receptors. PMID:10676852

  9. Impulsivity but not sensation seeking is associated with opioid analgesic misuse risk in patients with chronic pain

    OpenAIRE

    Marino, Elise N.; Rosen, Kristen D.; Gutierrez, Antonio; Eckmann, Maxim; Ramamurthy, Somayaji; Potter, Jennifer Sharpe

    2013-01-01

    Impulsivity and sensation seeking have been associated with substance use disorders, including opioid use disorders. This pilot study sought to examine whether impulsivity and sensation seeking, as measured by the Barratt Impulsiveness Scale (BIS) and Sensation Seeking Scale (SSS), were associated with opioid analgesic misuse risk in chronic, low-back pain patients prescribed opioid analgesics. Participants were 42 chronic, low-back pain patients enrolled in a larger study examining problemat...

  10. Primary care providers' judgments of opioid analgesic misuse in a community-based cohort of HIV-infected indigent adults

    OpenAIRE

    Vijayaraghavan, M.; Penko, J; D. Guzman; Miaskowski, C; Kushel, MB

    2011-01-01

    BACKGROUND: Primary care providers (PCPs) must balance treatment of chronic non-cancer pain with opioid analgesics with concerns about opioid misuse. OBJECTIVE: We co-enrolled community-based indigent adults and their PCPs to determine PCPs' accuracy of estimating opioid analgesic misuse and illicit substance use. DESIGN: Patient-provider dyad study. PARTICIPANTS: HIV-infected, community-based indigent adults ('patients') and their PCPs. MAIN MEASURES: Using structured interviews, we queried ...

  11. Physician-related barriers to cancer pain management with opioid analgesics

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Sjøgren, Per; Møldrup, Claus;

    2007-01-01

    OBJECTIVE: The purpose of this review is to summarize the results of studies on physician-related barriers to cancer pain management with opioid analgesics. METHODS: A literature search was conducted in PUBMED, using a combined text word and MeSH heading search strategy. Those articles whose full...... texts were not available in PUBMED were retrieved from the electronic databases of specific journals. RESULTS: Sixty-five relevant articles, published in the period from 1986 to 2006, were identified. Physicians' barriers to cancer pain management were studied in questionnaire surveys and in the reviews...... review revealed mostly general and common physician-related barriers to cancer pain management: concerns about side effects to opioids, prescription of not efficient doses of opioids, and very poor prescription for the treatment of side effects from opioids. In the future, the evaluation of the influence...

  12. The Analgesic Efficacy of Fentanyl: Relationship to Tolerance and μ-Opioid Receptor Regulation

    OpenAIRE

    Sirohi, Sunil; Dighe, Shveta V.; Walker, Ellen A; Yoburn, Byron C.

    2008-01-01

    This study determined if fentanyl analgesic efficacy predicts the magnitude of tolerance and μ-opioid receptor regulation. To estimate efficacy, mice were injected i.p. with saline or clocinnamox (CCAM), an irreversible μ-opioid receptor antagonist, (0.32 – 25.6 mg/kg) and 24 hr later fentanyl cumulative dose response studies were conducted. CCAM dose dependently shifted the fentanyl dose-response function to the right. The apparent efficacy (τ) of fentanyl, based on the operational model of ...

  13. Opioid Analgesics and Depressive Symptoms in Burn Patients: What Is the Real Relationship?

    Science.gov (United States)

    Hong, Narei; Jung, Myung Hun; Kim, Jee Wook; Chun, Wook; Choi, Ihn-Geun; Kang, Tae-Cheon; Kee, Baik Seok; Lee, Boung-Chul

    2016-01-01

    Objective Major burn injuries are strongly associated with both psychological trauma and severe pain, and opioids are the mainstay analgesics for the treatment of severe burn pain. The objectives of this study are to find the complex relationship between opioid dose, depression, and post-traumatic stress disorder (PTSD) symptoms during the acute management of pain in burn patients. Methods The symptoms of depression and PTSD were assessed in 43 burn patients immediately following wound stabilization and 2 weeks after the initial evaluation. Results Total opioid doses and Hamilton Depression Scale (HAMD) scores obtained during the second evaluation were positively but weakly correlated after controlling for age and total burn surface area (R=0.33, p=0.03). Moreover, pain management with opioids was significantly more common in burn patients with low Clinician Administered PTSD Scale scores (evaluation 1) and high HAMD scores (evaluation 2) (F=6.66, p=0.001). Conclusion High opioid dose following acute burn trauma might have correlation with depressive symptoms. Monitoring of depressive symptoms may be important following acute burn trauma and consequent opioids pain management, particularly when PTSD symptoms appear minimal during the early stabilization of patients. PMID:27489384

  14. Quality Improvement Initiative to Decrease Variability of Emergency Physician Opioid Analgesic Prescribing

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    John H. Burton

    2016-05-01

    Full Text Available Introduction: Addressing pain is a crucial aspect of emergency medicine. Prescription opioids are commonly prescribed for moderate to severe pain in the emergency department (ED; unfortunately, prescribing practices are variable. High variability of opioid prescribing decisions suggests a lack of consensus and an opportunity to improve care. This quality improvement (QI initiative aimed to reduce variability in ED opioid analgesic prescribing. Methods: We evaluated the impact of a three-part QI initiative on ED opioid prescribing by physicians at seven sites. Stage 1: Retrospective baseline period (nine months. Stage 2: Physicians were informed that opioid prescribing information would be prospectively collected and feedback on their prescribing and that of the group would be shared at the end of the stage (three months. Stage 3: After physicians received their individual opioid prescribing data with blinded comparison to the group means (from Stage 2 they were informed that individual prescribing data would be unblinded and shared with the group after three months. The primary outcome was variability of the standard error of the mean and standard deviation of the opioid prescribing rate (defined as number of patients discharged with an opioid divided by total number of discharges for each provider. Secondary observations included mean quantity of pills per opioid prescription, and overall frequency of opioid prescribing. Results: The study group included 47 physicians with 149,884 ED patient encounters. The variability in prescribing decreased through each stage of the initiative as represented by the distributions for the opioid prescribing rate: Stage 1 mean 20%; Stage 2 mean 13% (46% reduction, p<0.01, and Stage 3 mean 8% (60% reduction, p<0.01. The mean quantity of pills prescribed per prescription was 16 pills in Stage 1, 14 pills in Stage 2 (18% reduction, p<0.01, and 13 pills in Stage 3 (18% reduction, p<0.01. The group mean

  15. Opioid analgesic misuse is associated with incomplete antiretroviral adherence in a cohort of HIV-infected indigent adults in San Francisco

    OpenAIRE

    Jeevanjee, S; Penko, J; D. Guzman; Miaskowski, C; Bangsberg, DR; Kushel, MB

    2014-01-01

    There is little or no data examining the association between either pain or the use or misuse of opioid analgesic with adherence to antiretroviral medications (ARVs) among HIV-infected adults. We interviewed a community-based cohort of HIV-infected indigent adults prescribed antiretroviral medications (ARVs) quarterly to examine the association between (1) pain, (2) receipt of opioid analgesics, and (3) opioid analgesic misuse with self-reported ARV adherence. Of 281 participants, most (82.5 ...

  16. Stress-induced changes in the analgesic and thermic effects of opioid peptides in the rat.

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    Appelbaum, B D; Holtzman, S G

    1986-07-01

    Stress (e.g. restraint) potentiates analgesia and alters changes in body temperature induced by morphine administered either systemically or intracerebroventricularly (i.c.v.) in rats. In order to extend the generality of this phenomenon to opioid peptides, we determined whether the analgesic and thermic effects of i.c.v. D-Ala2-D-Leu5-enkephalin (DADLE) or D-Ala2-N-MePhe4-Gly5(ol)-enkephalin (DAGO), agonists selective for delta- and mu-opioid receptors, respectively, were affected by restraint stress. Analgesia was measured in the tail-flick test and core body temperature by rectal probe. The unstressed rats exhibited a dose-dependent increase in tail-flick latencies after administration of either DAGO or DADLE. Restrained rats treated with DAGO or DADLE had a greater analgesic response to each dose of peptide than did unstressed rats; both the magnitude and duration of the drug effect were increased. The unstressed group of rats responded to all doses of DAGO and DADLE with an increase of core temperature. In contrast, restrained rats showed a decrease of core temperature following injection with either DAGO or DADLE. Thus, restraint stress can significantly modify the effects of DAGO and DADLE on analgesia and body temperature in a manner that is qualitatively and quantitatively similar to that observed previously for morphine administered by the i.c.v. route. PMID:3015351

  17. Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats

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    Angela Maria Sousa

    2015-06-01

    Full Text Available BACKGROUND AND OBJECTIVES: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. METHODS: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5 mg, naloxone 200 µg or 0.9% NaCl, rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. CONCLUSIONS: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors.

  18. In vitro and in vivo pharmacological profile of the 5-benzyl analogue of 14-methoxymetopon, a novel μ opioid analgesic with reduced propensity to alter motor function

    OpenAIRE

    Spetea, Mariana; Bohotin, Catalina R.; Asim, Muhammad F; Stübegger, Kurt; Schmidhammer, Helmut

    2010-01-01

    Opioids are the most effective analgesics for pain management, and efficient pain control is a therapeutic priority. Herein, we describe the synthesis and pharmacological activities of the 5-benzyl analogue of the μ opioid analgesic 14-methoxymetopon (14-MM). The result of the replacement of the 5-methyl in 14-MM with a benzyl group on in vitro opioid receptor binding and functional profiles, and in vivo behavioural properties, i.e. nociception and motor activity, was investigated. In rodent ...

  19. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects.

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    Prozialeck, Walter C; Jivan, Jateen K; Andurkar, Shridhar V

    2012-12-01

    Kratom (Mitragyna speciosa) is a plant indigenous to Thailand and Southeast Asia. Kratom leaves produce complex stimulant and opioid-like analgesic effects. In Asia, kratom has been used to stave off fatigue and to manage pain, diarrhea, cough, and opioid withdrawal. Recently, kratom has become widely available in the United States and Europe by means of smoke shops and the Internet. Analyses of the medical literature and select Internet sites indicate that individuals in the United States are increasingly using kratom for the self-management of pain and opioid withdrawal. Kratom contains pharmacologically active constituents, most notably mitragynine and 7-hydroxymitragynine. Kratom is illegal in many countries. Although it is still legal in the United States, the US Drug Enforcement Administration has placed kratom on its "Drugs and Chemicals of Concern" list. Physicians should be aware of the availability, user habits, and health effects of kratom. Further research on the therapeutic uses, toxic effects, and abuse potential of kratom and its constituent compounds are needed. PMID:23212430

  20. Synthesis and analysis of the opioid analgesic [14C]-fentanyl

    International Nuclear Information System (INIS)

    The synthesis of [14C]-fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [14C]-Labelling was achieved in the first of two steps, a room temperature reduction of the in situ generated Schiff base from 1-phenylethyl-4-piperidone and [UL-14C]-aniline hydrochloride with sodium triacetoxyborohydride. A nearly instantaneous production of fentanyl was accomplished at room temperature with the addition of propionyl chloride. The overall radiochemical yield was 18%. The method described is efficiently adaptable for submicromolar scale while yielding a product of sufficient specific activity for in vivo studies. Our solvent system for thin layer chromatography was superior to the USP system reported for chromatographic analysis of fentanyl. This is the first reported preparation of [14C]-fentanyl with the radiolabel in the aniline benzene ring. (author)

  1. Synthesis and analysis of the opioid analgesic [[sup 14]C]-fentanyl

    Energy Technology Data Exchange (ETDEWEB)

    Bagley, J.R.; Wilhelm, J.A. (Anaquest Inc., Murray Hill, NJ (United States))

    1992-11-01

    The synthesis of [[sup 14]C]-fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [[sup 14]C]-Labelling was achieved in the first of two steps, a room temperature reduction of the in situ generated Schiff base from 1-phenylethyl-4-piperidone and [UL-[sup 14]C]-aniline hydrochloride with sodium triacetoxyborohydride. A nearly instantaneous production of fentanyl was accomplished at room temperature with the addition of propionyl chloride. The overall radiochemical yield was 18%. The method described is efficiently adaptable for submicromolar scale while yielding a product of sufficient specific activity for in vivo studies. Our solvent system for thin layer chromatography was superior to the USP system reported for chromatographic analysis of fentanyl. This is the first reported preparation of [[sup 14]C]-fentanyl with the radiolabel in the aniline benzene ring. (author).

  2. Analgesic drugs

    OpenAIRE

    Kerec Kos, Mojca

    2015-01-01

    In the management of pain analgesic drugs are chosen regarding the intensity and type of pain. The selection of analgesic drug depends on pharmacokinetic properties of the drug and available pharmaceutical dosage forms. Beside non-opioid analgesics (non-steroidal antiinflammatory drugs, acetaminophen), opioid analgesic drugs have an important role in the treatment of pain. Pri zdravljenju bolečine izberemo analgetik glede na jakost in vrsto bolečine. Na izbiro ustreznega analgetika vplivaj...

  3. Analgesic tone conferred by constitutively active mu opioid receptors in mice lacking β-arrestin 2

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    Hales Tim G

    2011-04-01

    Full Text Available Abstract Hedonic reward, dependence and addiction are unwanted effects of opioid analgesics, linked to the phasic cycle of μ opioid receptor activation, tolerance and withdrawal. In vitro studies of recombinant G protein coupled receptors (GPCRs over expressed in cell lines reveal an alternative tonic signaling mechanism that is independent of agonist. Such studies demonstrate that constitutive GPCR signaling can be inhibited by inverse agonists but not by neutral antagonists. However, ligand-independent activity has been difficult to examine in vivo, at the systems level, due to relatively low levels of constitutive activity of most GPCRs including μ receptors, often necessitating mutagenesis or pharmacological manipulation to enhance basal signaling. We previously demonstrated that the absence of β-arrestin 2 (β-arr2 augments the constitutive coupling of μ receptors to voltage-activated Ca2+ channels in primary afferent dorsal root ganglion neurons from β-arr2-/- mice. We used this in vitro approach to characterize neutral competitive antagonists and inverse agonists of the constitutively active wild type μ receptors in neurons. We administered these agents to β-arr2-/- mice to explore the role of constitutive μ receptor activity in nociception and hedonic tone. This study demonstrates that the induction of constitutive μ receptor activity in vivo in β-arr2-/- mice prolongs tail withdrawal from noxious heat, a phenomenon that was reversed by inverse agonists, but not by antagonists that lack negative efficacy. By contrast, the aversive effects of inverse agonists were similar in β-arr2-/- and β-arr2+/+ mice, suggesting that hedonic tone was unaffected.

  4. Trends in Any and High-Dose Opioid Analgesic Receipt Among Aging Patients With and Without HIV

    Science.gov (United States)

    Gordon, Kirsha; Edelman, E. Jennifer; Kerns, Robert D.; Crystal, Stephen; Dziura, James D.; Fiellin, Lynn E.; Gordon, Adam J.; Goulet, Joseph L.; Justice, Amy C.; Fiellin, David A.

    2016-01-01

    Harms of opioid analgesics, especially high-dose therapy among individuals with comorbidities and older age, are increasingly recognized. However, trends in opioid receipt among HIV-infected patients are not well characterized. We examined trends, from 1999 to 2010, in any and high-dose (≥120 mg/day) opioid receipt among patients with and without HIV, by age strata, controlling for demographic and clinical correlates. Of 127,216 patients, 64 % received at least one opioid prescription. Opioid receipt increased substantially among HIV-infected and uninfected patients over the study; high-dose therapy was more prevalent among HIV-infected patients. Trends in high-dose receipt stratified by three age groups revealed an increasing trend in each age strata, higher among HIV-infected patients. Correlates of any opioid receipt included HIV, PTSD and major depression. Correlates of high-dose receipt included HIV, PTSD, major depression and drug use disorders. These findings suggest a need for appropriate balance of risks and benefits, especially as these populations age. PMID:26384973

  5. A pilot study into the problematic use of opioid analgesics in chronic non-cancer pain patients.

    Science.gov (United States)

    Cowan, David T; Allan, Laurie; Griffiths, Peter

    2002-01-01

    Controversy surrounds the use of strong opioid analgesic drugs for chronic non-cancer pain. Specialists have concluded that fears of problematic drug use are often unfounded. In contrast, others claim the existence of significant problems.'Problematic drug use' includes the following definitions; addiction, abuse, physiological dependence and tolerance.We present a case study and the results of a pilot, longitudinal, cohort study, via a pilot questionnaire, of 22 chronic pain clinic patients following a trial of opioid drugs. The results suggest that chronic non-cancer pain patients can be maintained on opioids with few problems, and likewise can withdraw with minimal adverse effects, other than a return of pain. PMID:11722834

  6. The relative efficacy of indoprofen compared with opioid-analgesic combinations.

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    Cooper, S A; Breen, J F; Giuliani, R L

    1981-01-01

    This double-blind, parallel-design study used postsurgical dental outpatients as subjects. The patients self-administered a single dose of one of the study medications when they estimated their pain to be of moderate or severe intensity. The study medications were 200 mg of indoprofen, 650 mg of acetaminophen, 650 of acetaminophen with 60 mg of codeine, 650 mg of acetaminophen with 100 mg of d-propoxyphene N, and a placebo. On a report form, data were recorded on baseline pain and then hourly for four hours, intensity of pain, relief of pain, and side effects were reported. Also, an overall evaluation was recorded. Data were analyzed with the use of analysis of variance and Duncan's Multiple Range test. All four active treatments were statistically superior to placebo for sum pain intensity difference, total relief of pain, and overall evaluation parameters. Both opioid-analgesic combinations showed small additive effects over acetaminophen alone, and indoprofen was superior to both combination treatments and acetaminophen alone. PMID:6935400

  7. Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects.

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    Majumdar, Susruta; Grinnell, Steven; Le Rouzic, Valerie; Burgman, Maxim; Polikar, Lisa; Ansonoff, Michael; Pintar, John; Pan, Ying-Xian; Pasternak, Gavril W

    2011-12-01

    Pain remains a pervasive problem throughout medicine, transcending all specialty boundaries. Despite the extraordinary insights into pain and its mechanisms over the past few decades, few advances have been made with analgesics. Most pain remains treated by opiates, which have significant side effects that limit their utility. We now describe a potent opiate analgesic lacking the traditional side effects associated with classical opiates, including respiratory depression, significant constipation, physical dependence, and, perhaps most important, reinforcing behavior, demonstrating that it is possible to dissociate side effects from analgesia. Evidence indicates that this agent acts through a truncated, six-transmembrane variant of the G protein-coupled mu opioid receptor MOR-1. Although truncated splice variants have been reported for a number of G protein-coupled receptors, their functional relevance has been unclear. Our evidence now suggests that truncated variants can be physiologically important through heterodimerization, even when inactive alone, and can comprise new therapeutic targets, as illustrated by our unique opioid analgesics with a vastly improved pharmacological profile. PMID:22106286

  8. Further Evaluation of Delta Opioid Agonists as Candidate Adjuncts to Mu Opioid Analgesics: A Comparison of Interactions between Fentanyl and either Ketamine or the Delta Agonist SNC162 in Rhesus Monkeys

    OpenAIRE

    Banks, Matthew L.; Folk, John E.; Rice, Kenner C.; Negus, S. Stevens

    2010-01-01

    Mu-opioid receptor agonists such as fentanyl are effective analgesics, but their clinical use is limited by untoward effects. Adjunct medications may improve the effectiveness and/or safety of opioid analgesics. This study compared interactions between fentanyl and either the noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine or the delta-opioid receptor agonist SNC162 [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-phenyl)methyl]-N...

  9. Knowledge Toward Cancer Pain and the Use of Opioid Analgesics Among Medical Students in their Integrated Clinical Clerkship

    Directory of Open Access Journals (Sweden)

    Maria Fidelis C. Manalo

    2008-01-01

    Full Text Available Introduction: Among the focal issues of barriers to pain management include the physicians’ lack of knowledge about cancer pain and negative attitudes towards opioids. Many physicians and educators attribute this, at least in part, to limited exposure to pain and palliative care education during medical school.Aim: The researcher investigated the medical students’ knowledge about cancer pain and the use of opioid analgesics.Methods: The subjects were a sample of 50 students of the University of the Philippines College of Medicine in their integrated clinical clerkship year. Descriptive statistics (frequencies, means, standard deviation, rating scales were used to determine mean knowledge score and level of confidence with opioid use. The study also identified specific areas where students exhibited good or poor knowledge of opioids.Results: Approximately sixty-nine (69% of the study respondents mentioned that pain management was given to them during their Anesthesiology lectures while a few recalled that they had these lectures during their Family Medicine rotation in Supportive, Palliative and Hospice Care. More than a third (35% of the respondents admitted to not being confident with morphine use at present. The top three reasons cited as limitations in choice of opioids for cancer pain include fear of addiction, lack of adequate knowledge and experience and fear of side effects and complications. Out of a maximum of 13 correct answers, the mean knowledge score of the medical students was 6.6 ± 2.9. Less than 16% of the respondents had adequate knowledge on cancer pain and opioid use.Conclusions: The results show that basic knowledge of the role of opioids in cancer pain management among medical students in their integrated clinical clerkship year at the University of the Philippines is poor. The findings imply a need to look into making revisions in the medical curriculum to include a training program that will enable all students to

  10. Anti-analgesic effect of the mu/delta opioid receptor heteromer revealed by ligand-biased antagonism.

    Directory of Open Access Journals (Sweden)

    Laura Milan-Lobo

    Full Text Available Delta (DOR and mu opioid receptors (MOR can complex as heteromers, conferring functional properties in agonist binding, signaling and trafficking that can differ markedly from their homomeric counterparts. Because of these differences, DOR/MOR heteromers may be a novel therapeutic target in the treatment of pain. However, there are currently no ligands selective for DOR/MOR heteromers, and, consequently, their role in nociception remains unknown. In this study, we used a pharmacological opioid cocktail that selectively activates and stabilizes the DOR/MOR heteromer at the cell surface by blocking its endocytosis to assess its role in antinociception. We found that mice treated chronically with this drug cocktail showed a significant right shift in the ED50 for opioid-mediated analgesia, while mice treated with a drug that promotes degradation of the heteromer did not. Furthermore, promoting degradation of the DOR/MOR heteromer after the right shift in the ED50 had occurred, or blocking signal transduction from the stabilized DOR/MOR heteromer, shifted the ED50 for analgesia back to the left. Taken together, these data suggest an anti-analgesic role for the DOR/MOR heteromer in pain. In conclusion, antagonists selective for DOR/MOR heteromer could provide an avenue for alleviating reduced analgesic response during chronic pain treatment.

  11. Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations

    OpenAIRE

    Dennis C. Turk; O’Connor, Alec B.; Dworkin, Robert H.; Chaudhry, Amina; Katz, Nathaniel P.; Adams, Edgar H.; John S Brownstein; Comer, Sandra D; Dart, Richard; Dasgupta, Nabarun; Denisco, Richard A.; Klein, Michael; Leiderman, Deborah B.; Lubran, Robert; Rappaport, Bob A.

    2012-01-01

    Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Due to the many ...

  12. Use and Nonmedical Use of Prescription Opioid Analgesics in the General Population of Canada and Correlations with Dispensing Levels in 2009

    Directory of Open Access Journals (Sweden)

    Kevin D Shield

    2013-01-01

    Full Text Available BACKGROUND: In Canada, harm from nonmedical prescription opioid analgesic (POA use (NMPOU has increased in recent years; however, there are limitations to the current estimates of NMPOU. The 2009 Canadian Alcohol and Drug Use Monitoring Survey presents an opportunity to produce more accurate estimates of NMPOU.

  13. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531 influences the analgesic response to the short acting opioid Remifentanil in humans

    Directory of Open Access Journals (Sweden)

    Schalling Martin

    2009-07-01

    Full Text Available Abstract Background There is evidence from animal studies that serotonin (5-HT can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531. The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS. All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. Results At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG as compared to those with high expression(LA/LA, p Conclusion This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of

  14. Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists

    DEFF Research Database (Denmark)

    Ebert, B; Thorkildsen, C; Andersen, S; Christrup, Lona Louring; Hjeds, H

    1998-01-01

    Much evidence points to the involvement of N-methyl-D-aspartate (NMDA) receptors in the development and maintainance of neuropathic pain. In neuropathic pain, there is generally involved a presumed opioid-insensitive component, which apparently can be blocked by NMDA receptor antagonists. However...

  15. Abuse-Deterrent Formulations, an Evolving Technology Against the Abuse and Misuse of Opioid Analgesics

    OpenAIRE

    Schaeffer, Tammi

    2012-01-01

    The increased use of opioid pain medication has been mirrored by the increased misuse and abuse of these drugs. As part of a multidisciplinary approach to this epidemic, pharmaceutical companies, with the encouragement of the Food and Drug Administration, have increased the development of abuse-deterrent formulations. While all have the goal of treating pain while mitigating misuse and abuse, there are different technologies utilized to impart the abuse-deterrent properties. The goal of this ...

  16. [Analgesic and opioid-sparing effects of intravenous paracetamol in the early period after aortocoronary bypass surgery].

    Science.gov (United States)

    Eremenko, A A; Kuslieva, E V

    2008-01-01

    The study was to evaluate the analgesic and opioid-sparing effect of intravenous paracetamol injections in cardiosurgical patients in the early postoperative period. Adequate analgesia within the first 12-18 hours of the early postoperative period is very important for a good prognosis of the further course of pain syndrome and for the reduction of a risk for its progression to its chronic form. In early studies, propacetamol lowered morphine use after orthopedic and gynecological operations. The efficacy of paracetamol used in cardiac surgery has been little studied and the results of the studies are conflicting. The randomized, blind, placebo-controlled study included patients after aortocoronary bypass surgery, of them 22 patients received paracetamol and 23 had placebo. The test drug (perfalgan 100 ml or placebo) was intravenously injected 30 min before extubation and then every 6 hours within succeeding 18 hours. The intensity of the pain syndrome was rated by a 5-score verbal scale every 2 hours. With pain score of 2 or more, promedol was intramuscularly administered in a dose of 10 mg. Inspiratory volume was recorded before extubation and the first administration of a drug just after extubation and then every 2 hours. The baseline indices did not differ in both groups. Throughout the observation, the inspiratory volume was lower in the paracetamol group than in the placebo group; however, there was a statistically significant difference (p = 0.012) in the reduction in the manifestations of the pain syndrome (by 81%) only just after tracheal extubation. During this period, inspiratory volume values were higher in the paracetamol group; however, a statistically significant (39%) difference between the groups in the mean values was obtained only during and 2 hours after extubation. In the perfalgan group, the mean total use of promedol was 36% less than in the placebo-group, which was statistically significant (p = 0.019). The early postoperative use of

  17. Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated mu opioid receptor (MOR-1) splice variants

    Science.gov (United States)

    Majumdar, Susruta; Subrath, Joan; Le Rouzic, Valerie; Polikar, Lisa; Burgman, Maxim; Nagakura, Kuni; Ocampo, Julie; Haselton, Nathan; Pasternak, Anna R.; Grinnell, Steven; Pan, Ying-Xian; Pasternak, Gavril W.

    2012-01-01

    3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogs were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3′ or 4′ position of the phenyl ring and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower delta opioid receptor affinity than its naltrexamine analog, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity. PMID:22734622

  18. Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants.

    Science.gov (United States)

    Majumdar, Susruta; Subrath, Joan; Le Rouzic, Valerie; Polikar, Lisa; Burgman, Maxim; Nagakura, Kuni; Ocampo, Julie; Haselton, Nathan; Pasternak, Anna R; Grinnell, Steven; Pan, Ying-Xian; Pasternak, Gavril W

    2012-07-26

    3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogues were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3'or 4' position of the phenyl ring, and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower δ opioid receptor affinity than its naltrexamine analogue, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence, and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity. PMID:22734622

  19. Interaction of U-69,593 with. mu. -, delta- and k-opioid binding sites and its analgesic and intestinal effects in rats

    Energy Technology Data Exchange (ETDEWEB)

    La Regina, A.; Petrillo, P.; Sbacchi, M.; Tavani, A.

    1988-01-01

    The k-opioid compound U-69,593 was studied in rats in vitro in binding assays to assess its selectivity at the single types of opioid sites and in vivo to assess its analgesic activity and effect on intestinal propulsion. In vitro the U-69,593 inhibition curve of (/sup 3/H)-(-)-bremazocine binding suppressed at ..mu..- and delta-sites was biphasic and the inhibition constant (K/sub l/) at the high-affinity site (10-18nM) was two orders of magnitude smaller the K/sub l/ at the low-affinity site. The K/sub l/ at ..mu..- and delta-sites were respectively 3.3 and 8.5 ..mu..M. Thus (/sup 3/H)-(-)-bremazocine, suppressed at ..mu..- and delta-sites, may still bind more than one site, which U-69,593 might distinguish. In vivo U-69,593 i.p. prolonged the reaction time of rats on a 55/sup 0/C hot-plate and the dose of naloxone required to antagonize this effect was 40 times the dose that antagonized morphine-induced antinociception, suggesting the involvement of the k-receptor. In the intestinal transit test U-69,593 at doses between 0.5 and 15 mg/kg i.p. only slightly slowed intestinal transit of a charcoal meal in rats with no dose-relation; it partly but significantly antagonized morphine-induced constipation. These results suggest that the k-type of opioid receptor, with which U-69,593 interacts may induce analgesia, but has no appreciable role in the mechanisms of opioid-induced inhibition of intestinal transit in rats.

  20. Interaction of U-69,593 with μ-, δ- and k-opioid binding sites and its analgesic and intestinal effects in rats

    International Nuclear Information System (INIS)

    The k-opioid compound U-69,593 was studied in rats in vitro in binding assays to assess its selectivity at the single types of opioid sites and in vivo to assess its analgesic activity and effect on intestinal propulsion. In vitro the U-69,593 inhibition curve of [3H]-(-)-bremazocine binding suppressed at μ- and δ-sites was biphasic and the inhibition constant (K/sub l/) at the high-affinity site (10-18nM) was two orders of magnitude smaller the K/sub l/ at the low-affinity site. The K/sub l/ at μ- and δ-sites were respectively 3.3 and 8.5 μM. Thus [3H]-(-)-bremazocine, suppressed at μ- and δ-sites, may still bind more than one site, which U-69,593 might distinguish. In vivo U-69,593 i.p. prolonged the reaction time of rats on a 550C hot-plate and the dose of naloxone required to antagonize this effect was 40 times the dose that antagonized morphine-induced antinociception, suggesting the involvement of the k-receptor. In the intestinal transit test U-69,593 at doses between 0.5 and 15 mg/kg i.p. only slightly slowed intestinal transit of a charcoal meal in rats with no dose-relation; it partly but significantly antagonized morphine-induced constipation. These results suggest that the k-type of opioid receptor, with which U-69,593 interacts may induce analgesia, but has no appreciable role in the mechanisms of opioid-induced inhibition of intestinal transit in rats

  1. Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Kotlinska-Lemieszek A

    2015-09-01

    Full Text Available Aleksandra Kotlinska-Lemieszek,1 Pål Klepstad,2,3,6 Dagny Faksvåg Haugen2,4,5 1Palliative Medicine Chair and Department, University Hospital of the Lord’s Transfiguration, Karol Marcinkowski University of Medical Sciences, Poznan, Poland; 2European Palliative Care Research Centre, Faculty of Medicine, Norwegian University of Science and Technology,Trondheim, Norway; 3Department of Anaesthesiology and Intensive Care Medicine, St Olavs Hospital, Trondheim, Norway; 4Regional Centre of Excellence for Palliative Care, Haukeland University Hospital, Bergen, Norway; 5Department of Clinical Medicine K1, University of Bergen, Bergen, Norway; 6Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway Background: Opioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug–drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines. Objective: To identify studies that report clinically significant drug–drug interactions involving opioids used for pain treatment in adult cancer patients. Design and data sources: Systematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980 through January 2014. In addition, reference lists of relevant full-text papers were hand-searched. Results: Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug–drug interactions involving opioids were grouped as follows: 1 sedation and respiratory depression, 2 other central nervous system symptoms, 3 impairment of pain

  2. Tapentadol hydrochloride: A novel analgesic

    Directory of Open Access Journals (Sweden)

    Dewan Roshan Singh

    2013-01-01

    Full Text Available Tapentadol is a novel, centrally acting analgesic with dual mechanism of action, combining mu-opioid receptor agonism with noradrenaline reuptake inhibition in the same molecule. It has an improved side effect profile when compared to opioids and nonsteroidal anti-inflammatory drugs. The dual mechanism of action makes Tapentadol a useful analgesic to treat acute, chronic, and neuropathic pain.

  3. Tapentadol hydrochloride: A novel analgesic

    OpenAIRE

    Dewan Roshan Singh; Kusha Nag; Shetti, Akshaya N.; Krishnaveni, N.

    2013-01-01

    Tapentadol is a novel, centrally acting analgesic with dual mechanism of action, combining mu-opioid receptor agonism with noradrenaline reuptake inhibition in the same molecule. It has an improved side effect profile when compared to opioids and nonsteroidal anti-inflammatory drugs. The dual mechanism of action makes Tapentadol a useful analgesic to treat acute, chronic, and neuropathic pain.

  4. The bifunctional μ opioid agonist/antioxidant [Dmt(1)]DALDA is a superior analgesic in an animal model of complex regional pain syndrome-type i.

    Science.gov (United States)

    Schiller, Peter W; Nguyen, Thi M-D; Saray, Amy; Poon, Annie Wing Hoi; Laferrière, André; Coderre, Terence J

    2015-11-18

    Reactive oxygen species (ROS) play an important role in the development of complex regional pain syndrome-Type I (CRPS-I), as also demonstrated with the chronic post ischemia pain (CPIP) animal model of CRPS-I. We show that morphine and the antioxidant N-acetylcysteine (NAC) act synergistically to reduce mechanical allodynia in CPIP rats. The tetrapeptide amide [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2) is a potent and selective μ opioid receptor (MOR) agonist with favorable pharmacokinetic properties and with antioxidant activity due to its N-terminal Dmt (2',6'-dimethyltyrosine) residue. In the CPIP model, [Dmt(1)]DALDA was 15-fold more potent than morphine in reversing mechanical allodynia and 4.5-fold more potent as analgesic in the heat algesia test. The results indicate that bifunctional compounds with MOR agonist/antioxidant activity have therapeutic potential for the treatment of CRPS-I. PMID:26352668

  5. Spinal Tolerance and Dependence: Some Observations on the Role of Spinal N-Methyl-D-Aspartate Receptors and Phosphorylation in the Loss of Opioid Analgesic Responses

    Directory of Open Access Journals (Sweden)

    Tony L Yaksh

    2000-01-01

    Full Text Available The continuous delivery of opiates can lead to a reduction in analgesic effects. In humans, as in other animals, some component of this change in sensitivity seems likely to have a strong pharmacodynamic component. Such loss of effect, deemed to be tolerance in the present article, can be readily demonstrated in animals with repeated bolus and continuous intrathecal infusion of mu and delta opioids and alpha-2 adrenergic agonists. Research has shown that this loss of effect can be diminished by concurrent treatment with N-methyl-D-aspartate (NMDA receptor antagonists and by the suppression of the activity of spinal protein kinase C (PKC. This suggests in part the probable role of PKC-mediated phosphorylation in the right shift in the dose-effect curves observed with continuous opiate or adrenergic exposure. Importantly, this right shift is seen to occur in parallel with an increase in the phosphorylating activity in the dorsal horn and in the expression of several PKC isozymes. The target of this phosphorylation is not certain. Phosphorylation of the NMDA receptor enhances its functionality, while phosphorylation of the opioid receptor or associated channels seems to diminish their activity or to enhance internalization. While the focus is on several specific components, the accumulating data emphasize the biological complexity of these changes in spinal drug reactivity.

  6. Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

    Energy Technology Data Exchange (ETDEWEB)

    Song, Suk Yun; Kang, Byung Chul; Rho, Kyung Min [Dept. of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

    2011-05-15

    To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 {+-} 0.7, which was significantly lower than that of group A, 8.2 {+-} 0.7 (p<0.05). The mean dose of intravenous pethidine was 114.3 {+-} 59.5 mg in group A and 90.5 {+-} 49.0 mg in group B, while the incidence of nausea was 67% in group A and 77% in group B. In both cases, the differences were not significantly different (p>0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

  7. Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

    International Nuclear Information System (INIS)

    To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 ± 0.7, which was significantly lower than that of group A, 8.2 ± 0.7 (p0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

  8. Superior analgesic effect of H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA), a multifunctional opioid peptide, compared to morphine in a rat model of neuropathic pain

    OpenAIRE

    Shimoyama, Megumi; Schiller, Peter W.; Shimoyama, Naohito; Toyama, Satoshi; Szeto, Hazel H.

    2012-01-01

    H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA), is a synthetic tetrapeptide with extraordinary selectivity for the mu-opioid receptor and is an extremely potent analgesic. [Dmt1]DALDA is unusual in the way that the greater part of its analgesic potency appears to be produced by its actions in the spinal cord. Furthermore, [Dmt1]DALDA inhibits norepinephrine re-uptake and is a mitochondria-targeted antioxidant. Such characteristics may make [Dmt1]DALDA particularly effective against neuropathic pain. T...

  9. Prescribing Opioid Analgesics for Acute Dental Pain: Time to Change Clinical Practices in Response to Evidence and Misperceptions.

    Science.gov (United States)

    Dionne, Raymond A; Gordon, Sharon M; Moore, Paul A

    2016-06-01

    As the nation comes to terms with a prescription opioid epidemic, dentistry is beginning to understand its own unintentional contribution and seek ways to address it. The article urges dental providers to reexamine entrenched prescribing habits and thought patterns regarding treatment of acute dental pain. It points to evidence suggesting that nonsteroidal anti-inflammatory drugs are nonaddictive and usually more effective for managing many cases of acute dental pain. The authors provide therapeutic recommendations to help dental providers change prescribing patterns. PMID:27517474

  10. A randomised controlled trial of opioid only versus combined opioid and non-steroidal anti inflammatory analgesics for pain relief in the first 48 hours after Caesarean section

    Directory of Open Access Journals (Sweden)

    Natalia Adamou

    2014-01-01

    Full Text Available Background: Post-Caesarean section pain is complex in nature, requiring a combination of pharmacological and non-pharmacological methods. Effective management of postoperative pain will reduce postoperative morbidity, hospital stay and cost. The objective of this study was to compare the clinical effectiveness and adverse effects of a combination of non-selective cyclooxygenase (COX inhibitor (Diclofenac sodium 50 mg and opioid (Pentazocine 60 mg to opiod only (Pentazocine 60 mg for pain management after Caesarean section (CS at Aminu Kano Teaching Hospital (AKTH. Materials and Methods: This was a randomised double-blind controlled study conducted at AKTH, Kano, Nigeria. A total of 166 patients scheduled to undergo either emergency or elective Caesarean section were studied. Group I received a combination of COX inhibitor and opiod while Group II received opiod only for pain management after CS. Results: The average age of the patients was 28.35 years (SD ± 6.426 in the group I and 26.9(SD ± 6.133 in group II. The mean parity was 3.27(SD ± 2.67 and 2.75(SD ± 2.14 while the mean gestational age at admission was 37.68(SD ± 2.69 and 38.18(SD ± 2.63 weeks in the first and second groups, respectively. Comparison of the level of pain experienced and patients satisfaction during the first 48 hours postoperatively revealed that the level of pain was statistically significantly less and patient′s satisfaction significantly better in group I compared to group II (P-value 0.00001. Conclusion: The use of combined compared to single agent analgesia is safe, significantly reduced pain and improved patient satisfaction after a caesarian section (CS.

  11. [Endogenous opioid system in the realization of the analgesic effect of alpha-tocopherol in reference to algomenorrhea].

    Science.gov (United States)

    Kryzhanovskiĭ, G N; Bakuleva, L P; Luzina, N L; Vinogradov, V A; Iarygin, K N

    1988-02-01

    Beta-endorphin-like immunoreactivity was studied in 7 patients with algomenorrhea during pain attack and 15 minutes after alpha-tocopherol administration with a therapeutic aim (till the analgetic effect was reached). There was an increase in beta-endorphin-like immunoreactivity after alpha-tocopherol administration. Naloxone administration to 9 patients with algomenorrhea of various etiology resumed the pain. The effect of alpha-tocopherol application for pain relief depended on the pathogenesis of algomenorrhea. At the same time naloxone administration failed to resume the pain in patients, in whom alpha-tocopherol had a strong analgetic effect. It is assumed that the endogenous opioid system participates in alpha-tocopherol effect on pain relief in patients with algomenorrhea. PMID:2964879

  12. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  13. Vital Statistics: Opioid-Related Deaths by County: Beginning 2003

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset contains opioid-related death crude rates and adjusted rates by county. The opioid-related deaths include heroin and opioid analgesics mortalities.

  14. Synthesis, modeling, and pharmacological evaluation of UMB 425, a mixed μ agonist/δ antagonist opioid analgesic with reduced tolerance liabilities.

    Science.gov (United States)

    Healy, Jason R; Bezawada, Padmavani; Shim, Jihyun; Jones, Jace W; Kane, Maureen A; MacKerell, Alexander D; Coop, Andrew; Matsumoto, Rae R

    2013-09-18

    Opioid narcotics are used for the treatment of moderate-to-severe pain and primarily exert their analgesic effects through μ receptors. Although traditional μ agonists can cause undesired side effects, including tolerance, addition of δ antagonists can attenuate said side effects. Herein, we report 4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (UMB 425) a 5,14-bridged morphinan-based orvinol precursor synthesized from thebaine. Although UMB 425 lacks δ-specific motifs, conformationally sampled pharmacophore models for μ and δ receptors predict it to have efficacy similar to morphine at μ receptors and similar to naltrexone at δ receptors, due to the compound sampling conformations in which the hydroxyl moiety interacts with the receptors similar to orvinols. As predicted, UMB 425 exhibits a mixed μ agonist/δ antagonist profile as determined in receptor binding and [(35)S]GTPγS functional assays in CHO cells. In vivo studies in mice show that UMB 425 displays potent antinociception in the hot plate and tail-flick assays. The antinociceptive effects of UMB 425 are blocked by naloxone, but not by the κ-selective antagonist norbinaltorphimine. During a 6-day tolerance paradigm, UMB 425 maintains significantly greater antinociception compared to morphine. These studies thus indicate that, even in the absence of δ-specific motifs fused to the C-ring, UMB 425 has mixed μ agonist/δ antagonist properties in vitro that translate to reduced tolerance liabilities in vivo. PMID:23713721

  15. Analysis of the Utilization of Opioids Analgesics for Cancer Pain in Inpatient Department of Our Hospital in 2014%我院2014年癌痛病房阿片类镇痛药使用分析

    Institute of Scientific and Technical Information of China (English)

    屠文莲; 黄辉; 赵刚

    2015-01-01

    OBJECTIVE:To provide reference for rational use of opioids analgesics. METHODS:1 882 prescriptions of opi-oids analgesics for cancer pain collected from our hospital in 2014 were analyzed by defined daily dose(DDD)and drug utilization index(DUI). RESULTS:The diseases of opioids analgesics prescriptions for cancer pain in our hospital in 2014 were mainly lung cancer,accounting for 42.19%. Commonly used opioids analgesics included Morphine sulfate sustained-release tablets,Oxycodone Hydrochloride sustained-release tablets and so on,and their DUI were all below 1.0. Top one drug in the list of amount and con-sumption sum was Morphine sulfate sustained-release tablets,and its main dosage form were tablets,injection and patches,in which tablets occupied the largest proportion,reaching 97.30%. CONCLUSIONS:The application of opioids analgesics for cancer pain in our hospital is basically rational in terms of drug types,dosage form and route of administration,but the dose of opioids an-algesics is small and their DUI is lower than 1;at the same time,there are a few irrational prescription.%目的:为阿片类镇痛药的合理使用提供参考.方法:抽取2014年我院癌痛病房患者阿片类镇痛药处方1 882张,以限定日剂量(DDD)作为药物利用情况的客观指标,以药物利用指数(DUI)作为药物评价的判断指标,分析其使用情况.结果:我院当年癌痛病房阿片类镇痛药处方中病种分布最多的为肺癌,占42.19%.常用药物有硫酸吗啡缓释片、盐酸羟考酮缓释片等,其DUI都<1.0.药物使用数量、销售金额排名第1位的均为硫酸吗啡缓释片;药物剂型主要为片剂、注射剂及贴剂,其中片剂所占构成比最大,达到97.30%.结论:我院在使用阿片类镇痛药治疗癌痛时,在用药种类、剂型、给药途径上基本合理规范,但阿片类镇痛药使用剂量偏小,各类药物的DUI均<1,同时还存在着一定数量的不合理处方.

  16. Estudio de utilización de analgésicos opiáceos en un hospital general universitario Study of opioid analgesic use in a general university hospital

    Directory of Open Access Journals (Sweden)

    P. Gómez Salcedo

    2009-10-01

    el metamizol los analgésicos más ampliamente utilizados. Conclusiones: Los datos de nuestro estudio reflejan una tendencia al incremento del consumo de opiáceos en el hospital, lo que consideramos una mejora en el tratamiento del dolor, tanto agudo como crónico, pues en este incremento se ven involucrados todos los principios activos opiáceos. En un hospital con elevada actividad y complejidad asistencial como el Hospital La Paz, este tipo de estudios constituyen una herramienta que nos permite conocer y comparar el uso de opiáceos en los distintos hospitales y servicios clínicos. Nos permiten conocer la evolución del consumo así como detectar posibles desviaciones e implementar acciones de mejora en los diferentes servicios clínicos implicados en el tratamiento del dolor.Objective: The aim of this study was to analyze opioid analgesic use in the La Paz University Hospital in 2008 in order to identify patterns of use and consumption. To that end, data from inpatients were analyzed overall, as well as by hospitals and departments. We analyzed data on consumption in the previous 5 years and quantified the use of the remaining active principles administered as analgesics in our hospital. Materials and methods: Following the Wold Health Organization's guidelines for studieson medication use in hospitals, data are shown as defined daily dose (DDD per 100 hospital stays. Data on drug use were obtained from the drug management program, Farma Tools (Dominion®, which is used by the Pharmacy Service at La Paz Hospital. Results: The overall value of opioid utilization in 2008 was 8.1 DDD per 100 hospital stays. The most widely used active principles were parenteral morphine and transdermal fentanyl. Together, these drugs represented 83% of total opioid consumption. Analysis by hospital revealed that the General and Traumatology Hospitals showed the highest opioid drug consumption and followed the same utilization pattern as overall use. The services most

  17. 阿片类镇痛药体外对精子运动的影响%Effects of opioid analgesics on sperm motility in vitro

    Institute of Scientific and Technical Information of China (English)

    许波; 王志萍; 王雁娟; 胡毅平; 王丽君; 汪小海

    2012-01-01

    阿芬太尼相比均有显著性的差异(P<0.05),芬太尼与阿芬太尼相比无显著性差别(P>0.05).结论:不同阿片受体镇痛药在相同作用时间内,低浓度布托啡诺、地佐辛对精子运动无影响,高浓度呈现完全抑制精子活力,而相同低浓度芬太尼、阿芬太尼、舒芬太尼均显著抑制精子活力,所测相同浓度范围内仅部分抑制精子活力.与此相反,高浓度喷他佐辛可促进精子运动.%Objective; To observe the effects of short-term exposure to opioid analgesics on human sperm motility. Methods:Twenty normal semen samples were collected, each divided into 19 groups, one as the control and the others treated in vitro with six opioid analgesics at three different concentrations, respectively, and sperm motility was assessed by computer-assisted sperm analysis at 15 min, 2 h and 4 h. Results-. Compared with the control group, fentanyl, alfentanil and sufentanil at 1×10-15, 2×10-3 and 0.05 mg/ml significantly decreased the percentage of grade a + b sperm at 15 min, 2 h and 4 h ( P 0. 05). Pentazocine effected no significant difference at 3×10 -3 and 0. 05 mg/ml (P > 0.05 ) but a gradual increase in the percentage of grade a + b sperm at 0.5 mg/ml at the three time points ( P 0.05). Conclusion; Given the same length of time of treatment, butorphanol and dezocine totally inhibit sperm motility at a high concentration, but make no significant change at a low concentration. While fentanyl, alfentanil and sufentanil can significantly decrease sperm motility at the same low concentration, and partially inhibit it at all concentrations. On the contrary, a high concentration of pentazocine can promote human sperm motility.

  18. Aerosol Stable Peptide-Coated Liposome Nanoparticles: A Proof-of-Concept Study with Opioid Fentanyl in Enhancing Analgesic Effects and Reducing Plasma Drug Exposure

    Science.gov (United States)

    HOEKMAN, JOHN D; SRIVASTAVA, PRAMOD; HO, RODNEY J Y

    2014-01-01

    Previous we reported a novel pressurized olfactory drug (POD) delivery device that deposit aerosolized drug preferentially to upper nasal cavity. This POD device provided sustained CNS levels of soluble morphine analgesic effects. However, analgesic onset of less soluble fentanyl was more rapid but brief, likely due to hydrophobic fentanyl redistribution readily back to blood. To determine whether fentanyl incorporated into an aerosol stable liposome that binds to nasal epithelial cells will enhance CNS drug exposure and analgesic effects and reduce plasma exposure, we constructed RGD liposomes anchored with acylated integrin binding peptides (palmitoyl-GRGDS). The RGD liposomes, which assume gel-phase membrane structure at 25°C were stable under the stress of aerosolization as only 2.2 ± 0.5 % calcein leakage detected. The RGD mediated integrin binding of liposome is also verified to be unaffected by aerosolization. Rats treated with fentanyl in RGD-liposome and POD device exhibited greater analgesic effect, compared to the free drug counterpart (AUCeffect = 1387.l vs. 760.1 %MPE*min); while ~20% reduced plasma drug exposure was noted (AUC0-120 = 208.2 vs 284.8 ng*min/ml). Collectively, fentanyl incorporated in RGD-liposomes are physically and biologically stable under aerosolization, enhanced the overall analgesic effects and reduced plasma drug exposure for the first 2 hours. PMID:24909764

  19. Postoperative opioid analgesia: time for a reconsideration?

    DEFF Research Database (Denmark)

    Kehlet, H; Rung, G W; Callesen, T

    1996-01-01

    ;72:375-8). Many initial improvements simply involved the administration of opioid analgesics in new ways, such as continuous or on demand intravenous (i.v.) or epidural infusion. These methods allow lower total opioid dosages, provide a more stable concentration of opioid at the receptor and correspondingly...

  20. A randomized, open, parallel group, multicenter trial to investigate analgesic efficacy and safety of a new transdermal fentanyl patch compared to standard opioid treatment in cancer pain

    DEFF Research Database (Denmark)

    Kress, Hans G; Von der Laage, Dorothea; Hoerauf, Klaus H;

    2008-01-01

    pharmacokinetically bioequivalent to the marketed fentanyl patch. To determine noninferiority in efficacy in cancer patients and to compare safety, a clinical trial comparing the new fentanyl patch with standard oral or transdermal opioid treatment was planned. The design was an open, parallel group, multicenter...... trial, in which 220 patients were randomized to receive either the fentanyl patch or standard opioid treatment for 30 days. The primary efficacy variable, pain intensity (PI) on a 0-10-point numerical rating scale, was recorded once daily. The primary endpoint was the relative area under the curve of PI...

  1. A randomized, open, parallel group, multicenter trial to investigate analgesic efficacy and safety of a new transdermal fentanyl patch compared to standard opioid treatment in cancer pain

    DEFF Research Database (Denmark)

    Kress, H.G.; Laage, D. Von der; Hoerauf, K.H.;

    2008-01-01

    pharmacokinetically bioequivalent to the marked fentanyl patch. To determine noninferiority in efficacy in cancer patients and to compare safety, a clinical trial comparing the new fentanyl patch with standard oral or transdermal opioid treatment was planned. The design was an open, parallel group, multicenter trial......, in which 220 patients were randomized to receive either the fentanyl patch or standard opioid treatment for 30 days. The primary efficacy variable, pain intensity (PI) on a 0-10-point numerical rating scale, was recorded once daily. The primary endpoint was the relative area under the curve of PI...

  2. Acute Metabolic Changes Associated With Analgesic Drugs

    DEFF Research Database (Denmark)

    Hansen, Tine Maria; Olesen, Anne Estrup; Simonsen, Carsten Wiberg;

    2016-01-01

    BACKGROUND AND PURPOSE: Magnetic resonance spectroscopy (MRS) is used to measure brain metabolites. Limited data exist on the analgesic-induced spectroscopy response. This was an explorative study with the aims to investigate the central effects of two analgesic drugs, an opioid and a selective...

  3. Differences between opioids

    DEFF Research Database (Denmark)

    Drewes, Asbjørn Mohr; Jensen, Rasmus D; Møller Nielsen, Lecia;

    2013-01-01

    Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids to...... morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients...... who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences...

  4. A comparative study of efficacy and safety of gabapentin versus amitriptyline as coanalgesics in patients receiving opioid analgesics for neuropathic pain in malignancy

    OpenAIRE

    Manasi Banerjee; Santanu Pal; Biswamit Bhattacharya; Balaram Ghosh; Shirsendu Mondal; Joydeep Basu

    2013-01-01

    Objective: To assess the efficacy and safety of gabapentin and amitriptyline along with opioids in patients suffering from neuropathic pain in malignancy. Materials and Methods: Eighty-eight adult patients between 18 and 70 years of age with neuropathic pain in stage III malignant disease, matched for baseline charactistics, were randomly assigned to two groups. Group A received oral tramadol and gabapentin and group B received oral tramadol and amitriptyline. The treatment duration of e...

  5. A comparative study of efficacy and safety of gabapentin versus amitriptyline as coanalgesics in patients receiving opioid analgesics for neuropathic pain in malignancy

    OpenAIRE

    Banerjee, Manasi; Pal, Santanu; Bhattacharya, Biswamit; Ghosh, Balaram; Mondal, Shirsendu; Basu, Joydeep

    2013-01-01

    Objective: To assess the efficacy and safety of gabapentin and amitriptyline along with opioids in patients suffering from neuropathic pain in malignancy. Materials and Methods: Eighty-eight adult patients between 18 and 70 years of age with neuropathic pain in stage III malignant disease, matched for baseline charactistics, were randomly assigned to two groups. Group A received oral tramadol and gabapentin and group B received oral tramadol and amitriptyline. The treatment duration of each p...

  6. Opioid Use in Fibromyalgia: A Cautionary Tale.

    Science.gov (United States)

    Goldenberg, Don L; Clauw, Daniel J; Palmer, Roy E; Clair, Andrew G

    2016-05-01

    Multiple pharmacotherapies are available for the treatment of fibromyalgia (FM), including opioid analgesics. We postulate that the mechanism of action of traditional opioids predicts their lack of efficacy in FM. Literature searches of the MEDLINE and Cochrane Library databases were conducted using the search term opioid AND fibromyalgia to identify relevant articles, with no date limitations set. Citation lists in returned articles and personal archives of references were also examined for additional relevant items, and articles were selected based on the expert opinions of the authors. We found no evidence from clinical trials that opioids are effective for the treatment of FM. Observational studies have found that patients with FM receiving opioids have poorer outcomes than patients receiving nonopioids, and FM guidelines recommend against the use of opioid analgesics. Despite this, and despite the availability of alternative Food and Drug Administration-approved pharmacotherapies and the efficacy of nonpharmacologic therapies, opioids are commonly used in the treatment of FM. Factors associated with opioid use include female sex; geographic variation; psychological factors; a history of opioid use, misuse, or abuse; and patient or physician preference. The long-term use of opioid analgesics is of particular concern in the United States given the ongoing public health emergency relating to excess prescription opioid consumption. The continued use of opioids to treat FM despite a proven lack of efficacy, lack of support from treatment guidelines, and the availability of approved pharmacotherapy options provides a cautionary tale for their use in other chronic pain conditions. PMID:26975749

  7. Peripherally applied opioids for postoperative pain

    DEFF Research Database (Denmark)

    Nielsen, B N; Henneberg, S W; Schmiegelow, K;

    2015-01-01

    2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity...... scores, consumption of supplemental analgesics and time to first analgesic were included. Trials with sample sizes of fewer than 10 patients per treatment group or trials with opioids administered intra-articularly or as peripheral nerve blocks were excluded. RESULTS: Data from 26 studies, including 1531...

  8. Redoubling the ring size of an endomorphin-2 analog transforms a centrally acting mu-opioid receptor agonist into a pure peripheral analgesic.

    Science.gov (United States)

    Piekielna, Justyna; De Marco, Rossella; Gentilucci, Luca; Cerlesi, Maria Camilla; Calo', Girolamo; Tömböly, Csaba; Artali, Roberto; Janecka, Anna

    2016-05-01

    The study reports the synthesis and biological evaluation of two opioid analogs, a monomer and a dimer, obtained as products of the solid-phase, side-chain to side-chain cyclization of the pentapeptide Tyr-d-Lys-Phe-Phe-AspNH2 . The binding affinities to the mu, delta, and kappa opioid receptors, as well as results obtained in a calcium mobilization functional assay are reported. Tyr-[d-Lys-Phe-Phe-Asp]2 -NH2 1 was a potent and selective full agonist of mu with sub-nanomolar affinity, while the dimer (Tyr-[d-Lys-Phe-Phe-Asp]2 -NH2 )2 2 showed a significant mixed mu/kappa affinity, acting as an agonist at the mu. Molecular docking computations were utilized to explain the ability of the dimeric cyclopeptide 2 to interact with the receptor. Interestingly, in spite of the increased ring size, the higher flexibility allowed 2 to fold and fit into the mu receptor binding pocket. Both cyclopeptides were shown to elicit strong antinociceptive activity after intraventricular injection but only cyclomonomer 1 was able to cross the blood-brain barrier. However, the cyclodimer 2 displayed a potent peripheral antinociceptive activity in a mouse model of visceral inflammatory pain. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 309-317, 2016. PMID:27038094

  9. Conocimiento básico de los riesgos del uso de analgésicos no opioides en pacientes ambulatorios Basic knowledge of risks for non-opioid analgesics (NOA) in ambulatory patients

    OpenAIRE

    Svetlana Vladislavovna Doubova; Dolores Mino-León; Laura del Pilar Torres-Arreola; Guillermina Romero-Quechol

    2007-01-01

    OBJETIVO: Evaluar el conocimiento básico de los pacientes acerca de los analgésicos no opioides (ANOP) e identificar los posibles factores relacionados con la falta de información sobre este tipo de analgésicos. MATERIAL Y MÉTODOS: Participaron 629 pacientes >50 años con síndrome doloroso de origen no oncológico y que recibieron ANOP. Se analizaron sus características generales, la información recibida y su conocimiento sobre ANOP. La variable dependiente fue la falta de conocimiento básico (...

  10. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J;

    2011-01-01

    Melatonin is an endogenous indoleamine, produced mainly by the pineal gland. Melatonin has been proven to have chronobiotic, antioxidant, antihypertensive, anxiolytic and sedative properties. There are also experimental and clinical data supporting an analgesic role of melatonin. In experimental...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid µ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...... may reduce anxiety, which leads to lower levels of pain. In this paper, we review the current evidence regarding the analgesic properties of melatonin in animals and humans with chronic pain....

  11. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J;

    2011-01-01

    Melatonin is an endogenous indoleamine, produced mainly by the pineal gland. Melatonin has been proven to have chronobiotic, antioxidant, antihypertensive, anxiolytic and sedative properties. There are also experimental and clinical data supporting an analgesic role of melatonin. In experimental...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid μ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...... may reduce anxiety, which leads to lower levels of pain. In this paper, we review the current evidence regarding the analgesic properties of melatonin in animals and humans with chronic pain....

  12. Current Evidence for Spinal Opioid Selection in Postoperative Pain

    OpenAIRE

    Bujedo, Borja Mugabure

    2014-01-01

    Background Spinal opioid administration is an excellent option to separate the desirable analgesic effects of opioids from their expected dose-limiting side effects to improve postoperative analgesia. Therefore, physicians must better identify either specific opioids or adequate doses and routes of administration that result in a mainly spinal site of action rather than a cerebral analgesic one. Methods The purpose of this topical review is to describe current available clinical evidence to d...

  13. A comparative study of efficacy and safety of gabapentin versus amitriptyline as coanalgesics in patients receiving opioid analgesics for neuropathic pain in malignancy

    Directory of Open Access Journals (Sweden)

    Manasi Banerjee

    2013-01-01

    Full Text Available Objective: To assess the efficacy and safety of gabapentin and amitriptyline along with opioids in patients suffering from neuropathic pain in malignancy. Materials and Methods: Eighty-eight adult patients between 18 and 70 years of age with neuropathic pain in stage III malignant disease, matched for baseline charactistics, were randomly assigned to two groups. Group A received oral tramadol and gabapentin and group B received oral tramadol and amitriptyline. The treatment duration of each patient was 6 months. Visual analog scale (VAS was the primary efficacy parameter. Verbal rating scale (VRS score, percentage of pain relief (PPR, and global pain score (GPS were the secondary efficacy parameters. Oral morphine tablets or fentanyl transdermal patch were used as rescue medication. Data analysis was carried out in Graph Pad instat. Results: There was decline in VAS pain score from baseline in both the groups in the early phase of the study though there was no statistically detectable difference between them at any study point. Similar changes were seen in the secondary efficacy parameters too. Thus both the drugs were effective in providing relief to cancer patients with neuropathic pain though there was no statistically detectable difference in efficacy between them. Six patients in group A and eight patients in group B required rescue medication. A total of 12 subjects in the gabapentin group and 15 subjects in the amitriptyline group experienced adverse events which were of mild to moderate grades. Conclusions: Amitriptyline may be a suitable alternative for management of neuropathic pain in cancer patients although gabapentin is widely used for this purpose. The lower cost of amitriptyline may favor patient compliance with lesser number of drop-outs.

  14. Opioids for low back pain.

    Science.gov (United States)

    Deyo, Richard A; Von Korff, Michael; Duhrkoop, David

    2015-01-01

    Back pain affects most adults, causes disability for some, and is a common reason for seeking healthcare. In the United States, opioid prescription for low back pain has increased, and opioids are now the most commonly prescribed drug class. More than half of regular opioid users report back pain. Rates of opioid prescribing in the US and Canada are two to three times higher than in most European countries. The analgesic efficacy of opioids for acute back pain is inferred from evidence in other acute pain conditions. Opioids do not seem to expedite return to work in injured workers or improve functional outcomes of acute back pain in primary care. For chronic back pain, systematic reviews find scant evidence of efficacy. Randomized controlled trials have high dropout rates, brief duration (four months or less), and highly selected patients. Opioids seem to have short term analgesic efficacy for chronic back pain, but benefits for function are less clear. The magnitude of pain relief across chronic non-cancer pain conditions is about 30%. Given the brevity of randomized controlled trials, the long term effectiveness and safety of opioids are unknown. Loss of long term efficacy could result from drug tolerance and emergence of hyperalgesia. Complications of opioid use include addiction and overdose related mortality, which have risen in parallel with prescription rates. Common short term side effects are constipation, nausea, sedation, and increased risk of falls and fractures. Longer term side effects may include depression and sexual dysfunction. Screening for high risk patients, treatment agreements, and urine testing have not reduced overall rates of opioid prescribing, misuse, or overdose. Newer strategies for reducing risks include more selective prescription of opioids and lower doses; use of prescription monitoring programs; avoidance of co-prescription with sedative hypnotics; and reformulations that make drugs more difficult to snort, smoke, or inject. PMID

  15. Opioid-induced respiratory depression: reversal by non-opioid drugs

    OpenAIRE

    van der Schier, Rutger; Roozekrans, Margot; van Velzen, Monique; Dahan, Albert; Niesters, Marieke

    2014-01-01

    The human body is critically dependent on the ventilatory control system for adequate uptake of oxygen and removal of carbon dioxide (CO2). Potent opioid analgesics, through their actions on μ-opioid receptor (MOR) expressed on respiratory neurons in the brainstem, depress ventilation. Opioid-induced respiratory depression (OIRD) is potentially life threatening and the cause of substantial morbidity and mortality. One possible way of prevention of OIRD is by adding a respiratory stimulant to ...

  16. Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans

    OpenAIRE

    Bershad, Anya K.; Jaffe, Jerome H.; Childs, Emma; de Wit, Harriet

    2014-01-01

    Preclinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their abuse potential. Despite this evidence in laboratory animals, the effects of opioids on responses to psychosocial stress have not been determined in humans. Here we examined the ...

  17. Opioid-induced hyperalgesia and burn pain.

    Science.gov (United States)

    Holtman, Joseph R; Jellish, W Scott

    2012-01-01

    The treatment of pain produced during the management of burn injury has been an ongoing problem for physicians caring for these patients. The main therapeutic option for analgesia has been the repeated and prolonged use of opioids. The adverse effects of opioids are well known but the long term use of opioids which produces tolerance with accompanying dose escalation and dependence is most problematic. Another potentially important consequence of opioid exposure that sometimes masks as tolerance is that of opioid induced hyperalgesia. This syndrome is manifest as enhanced pain, sensitivity and loss of analgesic efficacy in patients treated with opioids who actually become sensitized to painful stimuli. This article focuses on the treatment of burn pain and how current analgesic therapies with opioids may cause hyperalgesia and affect the adequacy of treatment for burn pain. This article also provides possible modalities to help therapeutically manage these patients and considers future analgesic strategies which may help to improve pain management in this complicated patient population. PMID:23143613

  18. The evidence of neuraxial administration of analgesics for cancer-related pain

    DEFF Research Database (Denmark)

    Kurita, G P; Benthien, K S; Nordly, M;

    2015-01-01

    retrieved was 2147, and 84 articles were selected for full reading. The final selection comprised nine articles regarding randomised controlled trials (RCTs) divided in four groups: neuraxial combinations of opioid and adjuvant analgesic compared with neuraxial administration of opioid alone (n = 4); single...... neuraxial drug in bolus compared with continuous administration (n = 2); single neuraxial drug compared with neuraxial placebo (n = 1); and neuraxial opioid combined with or without adjuvant analgesic compared with other comprehensive medical management than neuraxial analgesics (n = 2). The RCTs presented...

  19. Adjuncts to opioid therapy.

    Science.gov (United States)

    Goldstein, Frederick J

    2002-09-01

    Administration of opioids to alleviate moderate to severe acute pain and chronic cancer pain is an established management process. However, advancements in clinical pharmacologic research have shown that opioids are also effective in chronic noncancerous pain. Many patients properly treated for prolonged periods with opioids develop tolerance and subsequently, physical dependence. This process is not necessarily harmful to the patient and will not cause the patient to develop an addiction (properly defined as psychologic dependence). For many patients who have been on opioid therapy for months or years, analgesic effectiveness tragically becomes less. In addition, opioid-induced constipation can be severe and cause pain; patients do not develop tolerance to this adverse reaction. Therefore, such issues become a management problem and require additional intervention. Currently, many different classes of drugs can serve as effective adjuncts to opioids for treatment of pain. Adding adjunctive medication to opioid therapy improves pain management primarily by nonopioid mechanisms of action. Clinical outcomes of such combinations include greater analgesia and attenuation of opioid-induced adverse reactions such as nausea and vomiting, constipation, sedation, and respiratory depression. Adjuncts include acetaminophen, antiarrhythmics, anticonvulsants, antidepressants, antipsychotics, baclofen, benzodiazepines, capsaicin, calcium channel blockers, clonidine hydrochloride, central nervous system stimulants, corticosteroids, local anesthetics, N-methyl-D-aspartate receptor antagonists, nonsteroidal antiinflammatory drugs, pentoxifylline, and scopolamine. Some adjuncts (eg, acetaminophen) are routinely used today, whereas others (eg, nifedipine [calcium channel blocker]) are used on a limited basis but have great potential for more widespread application. All professionals (eg, nurses, pharmacists, physicians, physicians' assistants, social workers, members of the clergy

  20. To Make Opioid Painkiller without Tolerance

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Opioid analgesics such as morphine are the most powerful and widely-used drugs to relieve pain in clinical treatment. They largely work through the μ-opioid receptors in the central nervous system, alleviating the perception of pain. But repeated application of the drugs within a certain period of time could lead to side-effects, like addiction and tolerance. In order to develop new effective painkillers with less side-effects, researchers strive to have a deeper understanding of the mechanism responsible for the analgesic efficacy of the drugs and the formation of their adverse effects.

  1. μ-Opioid receptor desensitization: Is morphine different?

    OpenAIRE

    Connor, Mark; Osborne, Peregrine B.; Christie, MacDonald J.

    2004-01-01

    Opioid tolerance and dependence are important phenomena. The contribution of acute μ-opioid receptor regulatory mechanisms to the development of analgesic tolerance or physical dependence are unknown, and even the mechanisms underlying relatively rapid receptor desensitization in single cells are unresolved. To a large degree, the uncertainty surrounding the mechanisms and consequences of short-term regulation of μ-opioid receptors in single cells arises from the limitations in the experiment...

  2. Selective antagonism of opioid-induced ventilatory depression by an ampakine molecule in humans without loss of opioid analgesia

    OpenAIRE

    Felden, Lisa

    2010-01-01

    Despite sensible guidelines for the use of opioid analgesics, respiratory depression remains a significant risk with a possibility of fatal outcomes. Clinicians need to find a balance of analgesia with manageable respiratory effects. The ampakine CX717 (Cortex Pharmaceuticals, Irvine, CA, USA), an allosteric enhancer of glutamate-stimulated AMPA receptor activation, has been shown to counteract opioid-induced respiratory depression in rats while preserving opioid-induced analgesia. Adopting a...

  3. Postoperative urinary retention: evaluation of patients using opioids analgesic Retención urinaria post-operatoria: evaluación de pacientes en tratamiento analgésico con opioides Retenção urinária pós-operatória: avaliação de pacientes em uso de analgesia com opióides

    Directory of Open Access Journals (Sweden)

    Maria do Carmo Barretto de Carvalho Fernandes

    2007-04-01

    Full Text Available The study aimed to determine the occurrence of urinary retention in patients using opioid analgesic and to describe the method used for vesical relief. A prospective and consecutive series of 1,316 patients undergoing surgery from September 1999 to April 2003 and using opioids post surgery were studied. From the 1,136 patients, 594 did not use urinary catheters pre-surgery. From these 594 patients, 128 (22% suffered post operative urinary retention. Urinary retention was significantly related to the use of continuous epidural analgesia (p=0.009. About 69% of patients experiencing urinary retention post surgery returned to spontaneous micturition following a single catheterization. The incidence found of urinary retention was similar to the literature, more frequent in men who received continuous epidural analgesia. The findings suggest orientation and careful nursing team observation of post operative micturition, emphasizing the intermittent aseptically catheterization for urinary retention in order to prevent potential complications of the urinary tract.Los objetivos de este estudio fueron determinar la incidencia de retención urinaria post-operatoria en pacientes que se encontraban en uso de analgésicos opioides, así como describir el método utilizado en el vaciado vesical. Se trata de una serie prospectiva y consecutiva de 1.316 pacientes quirúrgicos, estudiados de septiembre de 1999 a abril de 2003. De ellos, 594 pacientes no usaron cateterismo de demora en el pre-operatorio. Así mismo, 128 pacientes de este grupo presentó retención urinaria, con una incidencia del 22% (128/594. Hubo una asociación estadísticamente significativa entre la ocurrencia de retención urinaria y el uso de analgesia epidural continua (p=0,009. El 69% de los pacientes presentó una micción espontánea luego de haber realizado apenas un cateterismo. La incidencia de retención urinaria encontrada es semejante a la descrita en la literatura, siendo m

  4. Analgesic stairway in the treatment of oncological pain

    Directory of Open Access Journals (Sweden)

    Sarah María Regueira Betancourt

    2015-10-01

    Full Text Available Pain represents the main symptom in an important group of patients who are in active treatment for cancer and in sick people in a very advanced stage. The objective of this article is to review the basic pharmacology of the nonsteroidal antiinflammatory drugs, weak opioids, bigger opioids, as well as the different special pharmacological and non- pharmacological techniques that constitute the analgesic stairway in the management of patients who are suffering from oncological pain.

  5. Three Newly Approved Analgesics: An Update

    OpenAIRE

    Saraghi, Mana; Hersh, Elliot V.

    2013-01-01

    Since 2008, three new analgesic entities, tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor), and bupivacaine liposome injectable suspension (EXPAREL) were granted US Food and Drug Administration (FDA) approval to treat acute pain. Tapentadol immediate-release is a both a mu-opioid agonist and a norepinephrine reuptake inhibitor, and is indicated for the treatment of moderate to severe pain. Diclofenac potassium soft gelatin capsules are a novel formula...

  6. Molecular physiology of enteric opioid receptors.

    Science.gov (United States)

    Galligan, James J; Akbarali, Hamid I

    2014-09-10

    Opioid drugs have powerful antidiarrheal effects and many patients taking these drugs for chronic pain relief experience chronic constipation that can progress to opioid-induced bowel dysfunction. Three classes of opioid receptors are expressed by enteric neurons: μ-, δ-, and κ-opioid receptors (MOR, DOR, and KOR). MOR and DOR couple to inhibition of adenylate cylase and nerve terminal Ca(2+) channels and activation of K(+) channels. These effects reduce neuronal activity and neurotransmitter release. KOR couples to inhibition of Ca(2+) channels and inhibition of neurotransmitter release. In the human gastrointestinal tract, MOR, DOR, and KOR link to inhibition of acetylcholine release from enteric interneurons and purine/nitric oxide release from inhibitory motorneurons. These actions inhibit propulsive motility. MOR and DOR also link to inhibition of submucosal secretomotor neurons, reducing active Cl(-) secretion and passive water movement into the colonic lumen. These effects account for the constipation caused by opioid receptor agonists. Tolerance develops to the analgesic effects of opioid receptor agonists but not to the constipating actions. This may be due to differential β-arrestin-2-dependent opioid receptor desensitization and internalization in enteric nerves in the colon compared with the small intestine and in neuronal pain pathways. Further studies of differential opioid receptor desensitization and tolerance in subsets of enteric neurons may identify new drugs or other treatment strategies of opioid-induced bowel dysfunction. PMID:25207608

  7. A Prospective Cohort Study Evaluating the Ability of Anticipated Pain, Perceived Analgesic Needs, and Psychological Traits to Predict Pain and Analgesic Usage following Cesarean Delivery

    Directory of Open Access Journals (Sweden)

    Brendan Carvalho

    2016-01-01

    Full Text Available Introduction. This study aimed to determine if preoperative psychological tests combined with simple pain prediction ratings could predict pain intensity and analgesic usage following cesarean delivery (CD. Methods. 50 healthy women undergoing scheduled CD with spinal anesthesia comprised the prospective study cohort. Preoperative predictors included 4 validated psychological questionnaires (Anxiety Sensitivity Index (ASI, Fear of Pain (FPQ, Pain Catastrophizing Scale, and Eysenck Personality Questionnaire and 3 simple ratings: expected postoperative pain (0–10, anticipated analgesic threshold (0–10, and perceived analgesic needs (0–10. Postoperative outcome measures included post-CD pain (combined rest and movement and opioid used for the 48-hour study period. Results. Bivariate correlations were significant with expected pain and opioid usage (r=0.349, anticipated analgesic threshold and post-CD pain (r=-0.349, and perceived analgesic needs and post-CD pain (r=0.313. Multiple linear regression analysis found that expected postoperative pain and anticipated analgesic needs contributed to post-CD pain prediction modeling (R2=0.443, p<0.0001; expected postoperative pain, ASI, and FPQ were associated with opioid usage (R2=0.421, p<0.0001. Conclusion. Preoperative psychological tests combined with simple pain prediction ratings accounted for 44% and 42% of pain and analgesic use variance, respectively. Preoperatively determined expected postoperative pain and perceived analgesic needs appear to be useful predictors for post-CD pain and analgesic requirements.

  8. Translation of Structure-Activity Relationships from Cyclic Mixed Efficacy Opioid Peptides to Linear Analogues

    OpenAIRE

    Anand, Jessica P.; Porter-Barrus, Vanessa R.; Waldschmidt, Helen V.; Yeomans, Larisa; Pogozheva, Irina D.; Traynor, John R.; Mosberg, Henry I.

    2014-01-01

    Most opioid analgesics used in the treatment of pain are mu opioid receptor (MOR) agonists. While effective, there are significant drawbacks to opioid use, including the development of tolerance and dependence. However, the co-administration of a MOR agonist with a delta opioid receptor (DOR) antagonist slows the development of MOR-related side effects, while maintaining analgesia. We have previously reported a series of cyclic mixed efficacy MOR agonist/DOR antagonist ligands. Here we descri...

  9. Genome-wide association study identifies a potent locus associated with human opioid sensitivity

    OpenAIRE

    Nishizawa, D; Fukuda, K.; Kasai, S; Hasegawa, J.; Aoki, Y; Nishi, A; Saita, N; Koukita, Y; Nagashima, M.; Katoh, R; Satoh, Y.; Tagami, M; Higuchi, S; Ujike, H; Ozaki, N.

    2012-01-01

    Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid s...

  10. Repeated Time-to-event Analysis of Consecutive Analgesic Events in Postoperative Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Rasmussen, Sten; Kreilgaard, Mads;

    2015-01-01

    the probability. RESULTS: A Gompertz distribution RTTE model described the data well. The probability of having one or more analgesic events within 24 h was 80% for the first event, 55% for the second event, 31% for the third event, and 18% for fourth or more events for a typical woman of age 80 yr...... analgesic events. Thus, RTTE modeling of analgesic events is proposed as a valuable tool when investigating new approaches to pain management such as opioid-sparing analgesia....

  11. Postoperative use of analgesics in dogs and cats by Canadian veterinarians.

    OpenAIRE

    Dohoo, S E; Dohoo, I.R.

    1996-01-01

    Four hundred and seventeen Canadian veterinarians were surveyed to determine their postoperative use of analgesics in dogs and cats following 6 surgical procedures, and to determine their opinions toward pain perception and perceived complications associated with the postoperative use of potent opioid analgesics. Three hundred and seventeen (76%) returned the questionnaire. The percentage of animals receiving analgesics postoperatively ranged from 84% of dogs and 70% of cats following orthope...

  12. Drug Interaction and Serotonin Toxicity with Opioid Use: Another Reason to Avoid Opioids in Headache and Migraine Treatment.

    Science.gov (United States)

    Ansari, Hossein; Kouti, Leila

    2016-08-01

    Treatment of headache, specifically migraine attacks, has always been a challenging subject, especially for neurologist and pain specialists. Triptans are generally underutilized, despite being the gold standard abortive medication for migraine attacks. On the other hand, opioid analgesics are overused as a treatment for headache. One reason for this could be physician unfamiliarity with drug interactions between opioids and other medications, especially the possibility of serotonin toxicity. The general awareness of potential serotonin toxicity with using opioid analgesics is low. In this review, we will conduct a theoretic and evidence-based review of the potential for developing serotonin syndrome in patients who are using opioids analgesics, especially in combination with antidepressants, a common co-prescribed combination. We also review the current diagnostic criteria for serotonin syndrome and identify possible shortcomings of those criteria. Our aim is to increase the awareness of health care providers about potential drug interaction of opioid analgesics with other classes of medication. We place particular emphasis on tramadol since this drug is one of the most commonly used opioid analgesics for headache. The potential for developing serotonin syndrome is relatively high in the patients who are using opioid for pain control. The use of opioids in migraine headache is already discouraged due to the high risk of medication overuse headache and also an increase in headache-related disability (Katsarava et al. Neurology 62:788-790, 2004; Bigal and Lipton. Neurology 71:1821-8, 2008; Casucci and Cevoli. Neurol Sci. 34 Suppl 1:S125-8, 2013). This is another reason that physicians and health care providers should avoid using this class of medication for pain, specifically headache and migraine treatment. PMID:27457368

  13. Spinal opioids in adult patients with cancer pain: a systematic review: a European Palliative Care Research Collaborative (EPCRC) opioid guidelines project

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Kaasa, Stein; Sjøgren, Per

    2011-01-01

    A systematic review, undertaken according to an initiative to revise European Association for Palliative Care guidelines on the use of opioids for cancer pain, which aimed to analyse analgesic efficacy and side effects of spinal opioids in adult cancer patients previously treated with systemic...

  14. C7β-Methyl Analogues of the Orvinols: The Discovery of Kappa Opioid Antagonists with Nociceptin/Orphanin FQ Peptide (NOP) Receptor Partial Agonism and Low, or Zero, Efficacy at Mu Opioid Receptors

    OpenAIRE

    Cueva, Juan Pablo; Roche, Christopher; Ostovar, Mehrnoosh; Kumar, Vinod; Clark, Mary J.; Hillhouse, Todd M.; Lewis, John W.; Traynor, John R.; Husbands, Stephen. M.

    2015-01-01

    Buprenorphine is a successful analgesic and treatment for opioid abuse, with both activities relying on its partial agonist activity at mu opioid receptors. However, there is substantial interest in its activities at the kappa opioid and nociceptin/orphanin FQ peptide receptors. This has led to an interest in developing compounds with a buprenorphine-like pharmacological profile but with lower efficacy at mu opioid receptors. The present article describes aryl ring analogues of buprenorphine ...

  15. A Prospective Cohort Study Evaluating the Ability of Anticipated Pain, Perceived Analgesic Needs, and Psychological Traits to Predict Pain and Analgesic Usage following Cesarean Delivery.

    Science.gov (United States)

    Carvalho, Brendan; Zheng, Ming; Harter, Scott; Sultan, Pervez

    2016-01-01

    Introduction. This study aimed to determine if preoperative psychological tests combined with simple pain prediction ratings could predict pain intensity and analgesic usage following cesarean delivery (CD). Methods. 50 healthy women undergoing scheduled CD with spinal anesthesia comprised the prospective study cohort. Preoperative predictors included 4 validated psychological questionnaires (Anxiety Sensitivity Index (ASI), Fear of Pain (FPQ), Pain Catastrophizing Scale, and Eysenck Personality Questionnaire) and 3 simple ratings: expected postoperative pain (0-10), anticipated analgesic threshold (0-10), and perceived analgesic needs (0-10). Postoperative outcome measures included post-CD pain (combined rest and movement) and opioid used for the 48-hour study period. Results. Bivariate correlations were significant with expected pain and opioid usage (r = 0.349), anticipated analgesic threshold and post-CD pain (r = -0.349), and perceived analgesic needs and post-CD pain (r = 0.313). Multiple linear regression analysis found that expected postoperative pain and anticipated analgesic needs contributed to post-CD pain prediction modeling (R (2) = 0.443, p Preoperative psychological tests combined with simple pain prediction ratings accounted for 44% and 42% of pain and analgesic use variance, respectively. Preoperatively determined expected postoperative pain and perceived analgesic needs appear to be useful predictors for post-CD pain and analgesic requirements. PMID:27143966

  16. [Chronic use of analgesics].

    Science.gov (United States)

    Bronder, E; Klimpel, A; Pommer, W; Molzahn, M

    1990-01-01

    Quantitative aspects of longterm analgesic intake are presented, based on a case-control-study on the relation between regular analgesic intake and endstage renal failure in the area of West Berlin (1984-86). Lifetime analgesic consumption of more than 1000 persons were investigated. A total of 285 longterm analgesic users (185 cases = 35.8%; 100 controls = 19.3%) were detected. An odd ratio of 2.44 (95% CI: 1.77-3.39) was computed. Regular analgesic intake was defined as an intake of at least 15 analgesic doses per month continuously over a period of at least 12 months. 90% of the regular users preferred mixed analgesics compounds, in most cases with the psychotropic additive caffeine. PMID:2238838

  17. Obstructive sleep apnea, pain, and opioids: is the riddle solved?

    Science.gov (United States)

    Lam, Karen K.; Kunder, Samuel; Wong, Jean; Doufas, Anthony G.; Chung, Frances

    2016-01-01

    Purpose of review Perioperative opioid-based pain management of patients suffering from obstructive sleep apnea (OSA) may present challenges because of concerns over severe ventilatory compromise. The interaction between intermittent hypoxia, sleep fragmentation, pain, and opioid responses in OSA, is complex and warrants a special focus of perioperative outcomes research. Recent findings Life-threatening opioid-related respiratory events are rare. Epidemiologic evidence suggests that OSA together with other serious renal and heart disease, is among those conditions predisposing patients for opioid-induced ventilatory impairment (OIVI) in the postoperative period. Both intermittent hypoxia and sleep fragmentation, two distinct components of OSA, enhance pain. Intermittent hypoxia may also potentiate opioid analgesic effects. Activation of major inflammatory pathways may be responsible for the effects of sleep disruption and intermittent hypoxia on pain and opioid analgesia. Recent experimental evidence supports that these, seemingly contrasting, phenotypes of pain-increasing and opioid-enhancing effects of intermittent hypoxia, are not mutually exclusive. Although the effect of intermittent hypoxia on OIVI has not been elucidated, opioids worsen postoperative sleep-disordered breathing in OSA patients. A subset of these patients, characterized by decreased chemoreflex responsiveness and high arousal thresholds, might be at higher risk for OIVI. Summary OSA may complicate opioid-based perioperative management of pain by altering both pain processing and sensitivity to opioid effect. PMID:26545144

  18. Association Between Human Pain-Related Genotypes and Variability in Opioid Analgesia

    DEFF Research Database (Denmark)

    Nielsen, Lecia M; Olesen, Anne E; Branford, Ruth;

    2015-01-01

    On an individual level, there is a difference in the analgesic response to a given opioid. Various factors such as gender, age, and genetic variation can affect the analgesic response. The genetic variation can influence pharmacokinetics (eg drug transporters and drug-metabolizing enzymes) and...

  19. 不同阿片类镇痛药对体外人精子活力的影响%Effect of opioid analgesics on human sperm motility in vitro

    Institute of Scientific and Technical Information of China (English)

    许波; 王志萍; 王雁娟; 胡毅平; 王丽君; 汪小海

    2011-01-01

    的作用与浓度有关.%Objective To assess the effects of fentanyl (F),alfentanil (A),sufentaril (S),butorphanol (B),dezocine (D) and pentazocine (P) on human sperm motility in vitro.Methods Twenty samples of semen with normal sperm motility were collected.The semen was mixed with HTF liquid culture medium and sperm concentration was adjusted to (40-80) × 106/ml.Then semen suspension 50 μl was added into the culture dishes.The semen suspensions were randomly divided into 3 groups:group Ⅰ control-semen suspension 50 μl + 0.9% NaCl 50 μl.GroupⅡ single opioid-semen suspension 50 μl + 50 μl of 4 concentrations of F,A,S,B,D and P (10-3,10-4,10-5,10-7 mol/L).Group Ⅲ combined opioid-naloxone-semen suspension 50 μl + 25 μl of 3concentrations of naloxone (2 × 10-8,1 × 10-7,2 × 10-7 mol/L) + 25 μl of 4 concentrations of F,A,S,B and D.After being incubated for 1 h the sperm motility was assessed by sperm analyzer and the amplitude of change in sperm motility was calculated.Median inhibition concentration (IC50) and complete inhibition concentration ( IC100 ) of the 6 opioids were calculated from concentration-response curve.Results ( 1 ) The shape of concentration-response curve for F,A and S was straight line.The maximal decrease in sperm motility was (56 ± 5)%(F),(58±7)% (A) and(79±:6)% (S).(2) The shape of concentration-response curve for B,D and P was sigmoid.Low concentrations of B,D and P did not affect sperm motility.Median and high concentrations of B and D could inhibit sperm motility.The maximal inhibition was 100%.High concentration of P increased sperm motility.The maximal increase was (19 ± 6)%.(3) Naloxone shifted the concentration-response curve for F,A,S,B and D to the right,and decreased the maximal inhibitory effect of F,A and S dose-dependently but did not affect the maximal inhibitory effect of B and D.(4) IC50 was in the order of A≈ F > D > S≈- B.IC100 was D > B.Conclusion F,A and S inhibit sperm motility by acting on opioid receptor on human

  20. Pharmacopsychosocial Treatment of Opioid Dependence Harm Reduction Palliation or Simply Good Medical Practice

    OpenAIRE

    Reid Finlayson, A. J.; Martin, Peter R.

    2011-01-01

    Opioid alkaloids have been used medicinally for centuries as analgesics, for their antidiarrheal and antitussive properties, and as hypnotics. Opioids were initially derived from the poppy plant (Papaver somniferum) by the ancients of the Mediterranean Basin. Written records of the medicinal uses of opioids date to before the time of Hippocrates (460–377 BC). Paracelsus prescribed opium in a medicinal drink of wine and spices in the 16th century. Sir William Osler, the renowned Canadian physi...

  1. Epigenetics of μ-Opioid receptors: Intersection with HIV-1 infection of the Central Nervous System

    OpenAIRE

    Regan, Patrick M.; Dave, Rajnish S.; Datta, Prasun K.; Khalili, Kamel

    2012-01-01

    The abuse of intravenous drugs, such as heroin, has become a major public health concern due to the increased risk of HIV-1 infection. Opioids such as heroin were originally identified and subsequently abused for their analgesic effects. However, many investigations have found additional effects of opioids, including regulation of the immune system. As such, chronic opioid abuse has been shown to promote HIV-1 pathogenesis and facilitate HIV-1-associated neurocognitive dysfunction. Clinical o...

  2. Safe management of chronic pain in pregnancy in an era of opioid misuse and abuse.

    Science.gov (United States)

    Pritham, Ursula A; McKay, Laura

    2014-01-01

    Safe and effective management of chronic pain in pregnancy is challenging. Use of over-the-counter analgesics, opioids, opioid substitution therapies, complementary and alternative therapies, antidepressants, and anxiolytics each have benefits and risks for the mother and neonate that must be considered. Because of their potency, opioids are often used despite associated risks for adverse effects, abuse, diversion, and addiction. Development of a pain management protocol for the counsel and care of pregnant women with pain is necessary. PMID:25123962

  3. Assessment and Treatment of Abuse Risk in Opioid Prescribing for Chronic Pain

    OpenAIRE

    Juliana Serraillier; Jamison, Robert N.; Edward Michna

    2011-01-01

    Opioid analgesics provide effective treatment for noncancer pain, but many physicians have concerns about adverse effects, tolerance, and addiction. Misuse of opioids is prominent in patients with chronic back pain and early recognition of misuse risk could help physicians offer adequate patient care while implementing appropriate levels of monitoring to reduce aberrant drug-related behaviors. In this review, we discuss opioid abuse and misuse issues that often arise in the treatment of patie...

  4. Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial

    OpenAIRE

    Vanita Ahuja; Sukanya Mitra; Sunita Kazal; Anju Huria

    2015-01-01

    Background and Aims: Flupirtine maleate is a centrally acting, non-opioid analgesic with unique muscle relaxant properties as compared to common analgesics. The aim of this study was to compare post-operative analgesic efficacy of flupirtine maleate and ibuprofen in patients undergoing gynaecological ambulatory surgeries. Methods: This prospective, randomised controlled study was conducted in 60 women of American Society of Anesthesiologists physical status I/II, 18–70 years of age and schedu...

  5. The role of opioids in cancer pain

    OpenAIRE

    Quigley, Columba

    2005-01-01

    Columba Quigley, as a specialist in palliative medicine, works in a hospital based support team. She also works with a community based palliative care team and in a hospice, where patients are admitted for terminal care, respite, and control of symptoms. Pain occurs often in patients with cancer, particularly those with advanced disease. In addition, pain is one of the most feared symptoms in people with a diagnosis of cancer. Using analgesics (particularly opioids) appropriately effectively ...

  6. Managing Opioid-Tolerant Patients in the Perioperative Surgical Home.

    Science.gov (United States)

    Wenzel, John T; Schwenk, Eric S; Baratta, Jaime L; Viscusi, Eugene R

    2016-06-01

    Management of acute postoperative pain is important to decrease perioperative morbidity and improve patient satisfaction. Opioids are associated with potential adverse events that may lead to significant risk. Uncontrolled pain is a risk factor in the transformation of acute pain to chronic pain. Balancing these issues can be especially challenging in opioid-tolerant patients undergoing surgery, for whom rapidly escalating opioid doses in an effort to control pain can be associated with increased complications. In the perioperative surgical home model, anesthesiologists are positioned to coordinate a comprehensive perioperative analgesic plan that begins with the preoperative assessment and continues through discharge. PMID:27208711

  7. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

    DEFF Research Database (Denmark)

    Dahl, Jørgen Berg; Nielsen, Rasmus; Wetterslev, Jørn;

    2014-01-01

    well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists......, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin....... Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all...

  8. ORAL OPIOIDS IN THE TREATMENT OF CANCER PAIN

    NARCIS (Netherlands)

    ZYLICZ, Z; TWYCROSS, RG

    1991-01-01

    Persistent severe cancer pain should be treated with opioid drugs, principally morphine. It can be administered orally, rectally and parenterally. Morphine is metabolised in the liver mainly to glucuronides, of which morphine-6-glucuronide is a powerful analgesic. Oral morphine should be administere

  9. Opioid-induced respiratory depression: reversal by non-opioid drugs.

    Science.gov (United States)

    van der Schier, Rutger; Roozekrans, Margot; van Velzen, Monique; Dahan, Albert; Niesters, Marieke

    2014-01-01

    The human body is critically dependent on the ventilatory control system for adequate uptake of oxygen and removal of carbon dioxide (CO2). Potent opioid analgesics, through their actions on μ-opioid receptor (MOR) expressed on respiratory neurons in the brainstem, depress ventilation. Opioid-induced respiratory depression (OIRD) is potentially life threatening and the cause of substantial morbidity and mortality. One possible way of prevention of OIRD is by adding a respiratory stimulant to the opioid treatment, which through activation of non-opioidergic pathways will excite breathing and consequently will offset OIRD and should not affect analgesia. Various new respiratory stimulants are currently under investigation including (a) potassium channel blockers acting at the carotid bodies, and (b) ampakines and (c) serotonin receptor agonists acting within the brainstem. (a) GAL-021 targets BKCa-channels. Initial animal and human experimental evidence indicates that this potassium channel blocker is a potent respiratory stimulant that reverses OIRD without affecting antinociception. GAL021 is safe and better tolerated than the older K(+)-channel blocker doxapram and more efficacious in its effect on respiration. (b) Ampakines modulate glutamatergic respiratory neurons in brainstem respiratory centers. Various ampakines have been studied showing their ability to increase respiratory drive during OIRD by increasing respiratory rate. Currently, CX717 is the most promising ampakine for use in humans as it is safe and does not affect opioid analgesia. (c) While animal studies show that serotonin receptor agonists increase respiratory drive via activation of serotonin receptors in brainstem respiratory centers, human studies are without success. Further clinical studies are required to improve our care of patients that are treated with potent opioid analgesics. The use of non-opioid adjuvants may reduce the probability of OIRD but does never relieve us of our duty to

  10. Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia

    OpenAIRE

    Lunzer, Mary M.; Yekkirala, Ajay; Hebbel, Robert P.; Portoghese, Philip S.

    2007-01-01

    Sickle cell anemia is a common genetic disorder in African Americans. Opioid analgesics are traditionally the treatment for the severe pain associated with this disease. Here we reveal that the opioid antagonist naloxone possesses potent analgesic activity in two transgenic mouse models of sickle cell anemia (NY1DD and hBERK1) and not in their respective controls (ICR-CD1 and C57BL/6J) when administered by three parenteral routes [intracerebroventricular (i.c.v.), intrathecal, and subcutaneou...

  11. Radioreceptor assay of narcotic analgesics in serum.

    Science.gov (United States)

    Grevel, J; Thomas, J; Richards, M L; Sadée, W

    1984-09-01

    A sensitive radioreceptor assay (RRA) to determine the serum concentrations of fentanyl, pentazocine and morphine was developed on the basis of the drug's competition with a labeled tracer ((3)H-naloxone) for the membrane bound opioid receptor in rat brain homogenates. The binding data were computer-fitted to a standard curve by means of nonlinear least square regression. Sensitivity of the assay applied directly to serum samples without extraction was limited to approximately 3, 5 and 25 ng/ml for fentanyl, morphine and pentazocine, respectively, because of endogenous plasma constituents that interfere with the opioid receptor binding. With the use of petrol-ether extraction the sensitivity was improved to 0.3 ng/ml fentanyl and 3 ng/ml pentazocine (0.3 ml serum samples). No RRA-active metabolites were detectable after HPLC separation of serum from a patient treated with fentanyl. The plasma concentration time course of fentanyl in a patient, measured by RRA, was similar to that obtained by a radioimmunoassay (RIA). The RRA represents a general procedure for the detection of clinically used opioid analgesics and their active metabolites. PMID:24277330

  12. Glia: novel counter-regulators of opioid analgesia.

    Science.gov (United States)

    Watkins, Linda R; Hutchinson, Mark R; Johnston, Ian N; Maier, Steven F

    2005-12-01

    Development of analgesic tolerance and withdrawal-induced pain enhancement present serious difficulties for the use of opioids for pain control. Although neuronal mechanisms to account for these phenomena have been sought for many decades, their bases remain unresolved. Within the past four years, a novel non-neuronal candidate has been uncovered that opposes acute opioid analgesia and contributes to development of opioid tolerance and tolerance-associated pain enhancement. This novel candidate is spinal cord glia. Glia are important contributors to the creation of enhanced pain states via the release of neuroexcitatory substances. New data suggest that glia also release neuroexcitatory substances in response to morphine, thereby opposing its effects. Controlling glial activation could therefore increase the clinical utility of analgesic drugs. PMID:16246435

  13. Recent pharmacological advances in paediatric analgesics.

    Science.gov (United States)

    Anderson, B J; Palmer, G M

    2006-08-01

    Growth and development are two linked processes that distinguish children from adults. The use of size as the primary covariate during pharmacokinetic (PK) analyses allows exploration of the effects of age. Allometric scaling models have assisted understanding of the developmental clearance changes in common analgesic drugs such as paracetamol, morphine, tramadol and local anaesthetics agents. Single nucleotide polymorphisms (pharmacogenomics [PG]) and their impact on hepatic drug metabolism for opioids, tramadol, non-steroidal anti-inflammatory drugs (NSAIDs) and drug receptor responses are increasingly reported. Altered chemical structure or formulations of common analgesics alter pharmacodynamic (PD) effects enhancing safety and efficacy for NSAIDs by stereoselectivity and the addition of nitric oxide, for intravenous paracetamol by formulation and structural difference from propacetamol and for local anaesthetics through stereoselectivity. This article focuses upon recent data for analgesics used in paediatric pain management including paracetamol, NSAIDs, morphine, tramadol, amide local anaesthetics and ketamine. It centres on PK and clinical studies in neonates, infants and children. PG studies are acknowledged as potentially allowing individual drug therapy tailoring through a decrease in between-patient population variability, although the impact of PG in the very young is less certain. There are few data describing age-related PD changes in children despite recognition that the number, affinity and type of receptors or the availability of natural ligands changes with age. PMID:16854558

  14. [Dextromethorphan enhances analgesic activity of propacetamol--experimental study].

    Science.gov (United States)

    Dobrogowski, Jan; Wordliczek, Jerzy; Przewłocka, Barbara

    2005-01-01

    While many pre-clinical and clinical studies have suggested that the addition of N-methyl-d--aspartate (NMDA) receptor antagonists, such as dextromethorphan, to opioid analgesics, such as morphine may enhance the analgesic effects. The aim of the study was to assess the effect of non-competitive NMDA antagonists and paracetamol (propacetamol) on pain threshold and analgesic potency of this drugs and their combinations in formalin model for pain in rats. Intraperitoneal administration of paracetamol only in doses of 100 g/kg or higher resulted in increase of pain threshold in tail flick and paw pressure tests. The results of our study suggest that there was no significant difference in pain threshold between separate administration of dextromethorphan and in combination with paracetamol. In a formalin model for pain we have shown that paracetamol in non-analgesic doses (10 mg/kg) administered in combination with dextrometorphan, ketamine and mamantine was more effective than those drugs given separately but the best analgesic effect was obtained when combination of paracetamol and dextromethorphan was applied. The addition of higher doses of these combined drugs, that is paracetamol and all three NMDA antagonists did not result in enhancement of dose-dependant analgesia. In conclusion it should be stated that NMDA antagonists improve analgesic effect of paracetamol in the formalin model for pain. although only to a limited extend. PMID:17037292

  15. The role of κ-opioid receptor activation in mediating antinociception and addiction

    OpenAIRE

    Wang, Yu-hua; Sun, Jian-feng; Tao, Yi-min; Chi, Zhi-Qiang; Liu, Jing-gen

    2010-01-01

    The κ-opioid receptor (KOR), a member of the opioid receptor family, is widely expressed in the central nervous system and peripheral tissues. Substantial evidence has shown that activation of KOR by agonists and endogenous opioid peptides in vivo may produce a strong analgesic effect that is free from the abuse potential and the adverse side effects of μ-opioid receptor (MOR) agonists, such as morphine. In addition, activation of the KOR has also been shown to exert an inverse effect on morp...

  16. Analgesic effect of the aqueous and ethanolic extracts of clove

    Directory of Open Access Journals (Sweden)

    Mina Kamkar Asl

    2013-04-01

    Full Text Available Objective: The beneficial effects of clove on toothache have been well documented. We have also previously shown the analgesic effects of clove essential oil. The present work was done to investigate the analgesic effects of the aqueous extract of clove using hot plate test. The possible role of opioid receptors in the analgesic effects of clove was also investigated using naloxone. Materials and Methods: Ninety male mice were divided into nine groups: (1 Saline, (2-4 Aaqueous (Aq 50, Aq 100, and Aq 200 groups which were treated with 50, 100, and 200 mg/kg of aqueous extract of clove, respectively, (5-7 Ethanolic (Eth 50, Eth 100, and Eth 200 groups which were treated with 50, 100, and 200 mg/kg of ethanolic extract of clove, respectively, and (8-9 Aq 100- Naloxone and Aq 200- Naloxone which were pretreated with 4 mg/kg of naloxone before injection of 100 or 200 mg/kg of the aqueous extract. The hot plate test was performed as a base record 10 min before injection of drugs and consequently repeated every 10 minutes after the injection. Results: The maximal percent effect (MPE in the animal groups treated with 50, 100, and 200 mg/kg of aqueous extract was significantly higher than the control group. Pretreatment with naloxone reduced the analgesic effects of both 100 and 200 mg/kg of the aqueous extract. Administration of all three doses of the ethanloic extract also non-significantly increased the MPE. Conclusion: The results of the present study showed that aqueous extract of clove has analgesic effect in mice demonstrated by hot plate test which is reversible by naloxone. The role of opioid system in the analgesic effect of clove might be suggested. However, more investigations are needed to elucidate the exact mechanism(s.

  17. Bidirectional effects of fentanyl on dendritic spines and AMPA receptors depend upon the internalization of mu opioid receptors

    OpenAIRE

    Lin, Hang; Higgins, Paul; Loh, Horace H.; Law, Ping-Yee; Liao, Dezhi

    2009-01-01

    Fentanyl is a frequently used and abused opioid analgesic and can cause internalization of mu opioid receptors (MORs). Receptor internalization modulates the signaling pathways of opioid receptors. Because changes in dendritic spines and synaptic AMPA receptors play important roles in addiction and memory loss, we investigated how fentanyl affects dendritic spines and synaptic AMPA receptors in cultured hippocampal neurons. Fentanyl at low concentrations (0.01 and 0.1 µM) caused collapse of d...

  18. Effects of repeated tramadol and morphine administration on psychomotor and cognitive performance in opioid-dependent volunteers

    OpenAIRE

    Mintzer, Miriam Z.; Ryan K. Lanier; Lofwall, Michelle R.; Bigelow, George E.; Strain, Eric C.

    2010-01-01

    Tramadol is an atypical, mixed mechanism analgesic used to treat moderate to severe pain. Based on evidence that tramadol has relatively low abuse potential and can relieve opioid withdrawal, tramadol may be useful for treating opioid dependence. The purpose of this study was to assess the performance side-effect profile of tramadol. Nine opioid-dependent volunteers completed a performance battery following 5–7 days of subcutaneous morphine (15 mg, 4 times/day) and two doses of oral tramadol ...

  19. The use of analgesic drugs by South African veterinarians : continuing education

    OpenAIRE

    K.E. Joubert

    2001-01-01

    According to a survey, non-steroidal anti-inflammatory agents were the most popular analgesic used in South Africa for management of peri-operative pain, acute post-operative pain and chronic pain. The most popular non-steroidal anti-inflammatory agents are flunixin meglumine and phenylbutazone. The most popular opioid type drug is buprenorphine, followed by morphine. In the peri-operative setting, analgesic agents were not actively administered to 86.3 % of cats and 80.7 % of dogs. Analgesic...

  20. Pharmacotherapy of Pain in the Older Population: The Place of Opioids.

    Science.gov (United States)

    Prostran, Milica; Vujović, Katarina Savić; Vučković, Sonja; Medić, Branislava; Srebro, Dragana; Divac, Nevena; Stojanović, Radan; Vujović, Aleksandar; Jovanović, Lepa; Jotić, Ana; Cerovac, Nataša

    2016-01-01

    Pain is a common symptom in older people. It is possible that pain is underreported in older persons due to an incorrect belief that it is an inevitable part of aging. Opioid analgesics are potent medications, with confirmed efficacy for the treatment of moderate to severe pain. These drugs are commonly used in older persons. However, there is insufficient evidence regarding safety of opioids in older patients. One of the reasons for this is the lack of randomized, controlled clinical trials. People of advanced age often have comorbidites and use other prescription drugs, as well as over-the-counter (OTC) compounds, thus making them more suceptible to the risk of interactions with opioids. Significant pharmacokinetic and pharmacodynamic changes that occur with advancing age increase the risk of adverse effects of opioids. There are also some discrepancies between guidelines, which recommend the use of lower doses of opioids in older patients, and the findings in the literature which suggest that pain is often undertreated in this age group. It seems that there are significant variations in the tolerability of different opioid analgesics in older people. Morphine, fentanyl, oxycodone, and buprenorphine are still the preferred evidence-based choices for add-on opioid therapy for these patients. However, the safety and efficacy of other opioids in older patients, especially if comorbidities and polypharmacy are present, is still questionable. This review addresses the most important aspects of the use of opioids in older persons, focusing on pharmacokinetics, pharmacodynamics, adverse effects, and interactions. PMID:27378916

  1. Study of analgesic activity of ethanol extract of Phlogacanthus thyrsiflorus on experimental animal models

    Directory of Open Access Journals (Sweden)

    Apurba Mukherjee, Meghali Chaliha and Swarnamoni Das

    2009-12-01

    Full Text Available The aim of the study was to evaluate the central and peripheral analgesic action of Phlogacanthus thyrsiflorus in experimental animal models. The extract was prepared by percolation method and acute oral toxicity testing was performed as per OECD guidelines. Analgesic activity was assessed by tail flick method (for central action and glacial acetic acid-induced writhing test (for peripheral action. Leaves extract (500 mg/kg, p.o. and aspirin (100 mg/kg showed significant peripheral analgesic activity (p<0.05. Leaves extract (500 mg/kg, p.o. and pethidine (50 mg/kg, i.p. also showed significant central analgesic activity (p<0.05. Naloxone (1 mg/kg, s.c. was used to find the mechanism of central analgesic action. Some partial agonistic activity for the opioid receptors seems to be probable mechanism of action.

  2. [Sustained-release Opioids: Morphine, Oxycodone and Tapentadol].

    Science.gov (United States)

    Takahashi, Yoshika; Iseki, Masako

    2015-11-01

    Opioid analgesics are widely used for managing moderate to severe pain. In cancer pain management sustained-release opioids are used for continuous pain as well as immediate-release opioids for breakthrough pain. Sustained-release drugs have the advantage of stabilizing the blood concentration, although it takes some time to exert their effects. In Japan, the currently available oral sustained-release opioids include six types of sustained-release morphine (three are once-a-day formulations, while the rest are twice-a-day), one type of oxycodone and tapentadol. In this article, we will discuss the pharmacokinetic properties of MS Contin, Morphes, Kadian, P guard and Pacif as sustained-release morphine, Oxycontin as sustained-release oxycodone and Tapenta as sustained-release tapentadol. PMID:26689063

  3. Is mechanism and symptom-based analgesia an answer to opioid-Induced hyperalgesia?

    Directory of Open Access Journals (Sweden)

    Mayank Gupta

    2015-01-01

    Full Text Available "Cancer Pain" and "Pain in cancer patient" are not synonymous. Opioid-induced Hyperalgesia (OIH is a paradoxical state of nociceptive sensitization caused by exposure to opioids. Neuropathic pain is only partially responsive to opioids; injudicious increase in dose of opioids in neuropathic pain may not only result in inadequate pain relief but also OIH. Majority of literature on OIH is in non-cancer pain with systemic use of opioids. We describe the development and successful treatment of OIH in a 55-year-old male patient with Small cell Carcinoma Lung. Opioid tapering, rotation, systemic desensitization helps in combatting OIH. The use of anti-neuropathic adjuvant analgesics helps not only in preventing and treating OIH but also in understanding putative mechanisms underlying neuropathic pain and OIH.

  4. Use of analgesic drugs for pain management in sheep.

    Science.gov (United States)

    Lizarraga, I; Chambers, J P

    2012-03-01

    Awareness of pain and its effects is increasing within the veterinary profession, but pain management in food animals has been neglected. Sheep seldom receive analgesics despite various conditions, husbandry practice and experimental procedures being known to be painful, e.g. footrot, mastitis, vaginal prolapse, castration, vasectomy, penis deviation, and laparoscopy. The evidence supporting use of analgesic drugs in this species is reviewed here. Opioid agonists are of dubious efficacy and are short acting. α₂-agonists such as xylazine are good, short-lived analgesics, but induce hypoxaemia. Non-steroidal anti-inflammatory drugs (NSAID) such as ketoprofen provide long-lasting analgesia, but not as marked as that from α₂-agonists; they should be more widely used for inflammatory pain. Local anaesthetics reliably block pain signals, but may also induce motor blockade. Balanced analgesia using more than one class of drug, such as an α₂ agonist (e.g. medetomidine) and N-methyl-D-aspartate antagonist (e.g. ketamine), with the combination selected for the circumstances, probably provides the best analgesia for severe pain. It should be noted that there are no approved analgesic drugs for use in sheep and therefore the use of such drugs in this species has to be off-label. This information may be useful to veterinary practitioners, biomedical researchers, and regulators in animal welfare to develop rational analgesic regimens which ultimately may improve the health and welfare of sheep in both farming and experimental conditions. PMID:22352925

  5. Methylnaltrexone in the treatment of opioid-induced constipation

    Directory of Open Access Journals (Sweden)

    Beverley Greenwood-Van Meerveld

    2008-12-01

    Full Text Available Beverley Greenwood-Van Meerveld1, Kelly M Standifer21Veterans Affairs Medical Center, Oklahoma Center for Neuroscience, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Department of Pharmaceutical Sciences, Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: Constipation is a significant problem related to opioid medications used to manage pain. This review attempts to outline the latest findings related to the therapeutic usefulness of a μ opioid receptor antagonist, methylnaltrexone in the treatment of opioid-induced constipation. The review highlights methylnaltrexone bromide (RelistorTM; Progenics/Wyeth a quaternary derivative of naltrexone, which was recently approved in the United States, Europe and Canada. The Food and Drug Administration in the United States approved a subcutaneous injection for the treatment of opioid bowel dysfunction in patients with advanced illness who are receiving palliative care and when laxative therapy has been insufficient. Methylnaltrexone is a peripherally restricted, μ opioid receptor antagonist that accelerates oral–cecal transit in patients with opioidinduced constipation without reversing the analgesic effects of morphine or inducing symptoms of opioid withdrawal. An analysis of the mechanism of action and the potential benefits of using methylnaltrexone is based on data from published basic research and recent clinical studies.Keywords: methylnaltrexone, constipation, opioid

  6. Use of opioid analgesics in the treatment of cancer pain

    DEFF Research Database (Denmark)

    Caraceni, Augusto; Hanks, Geoffrey; Kaasa, Stein;

    2012-01-01

    methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence...

  7. Urinretention ved postoperativ smertebehandling med epidurale opioider

    DEFF Research Database (Denmark)

    Hansen, B J; Rosenberg, J; Andersen, J T

    1990-01-01

    The incidence of retention of urine in cases of postoperative epidural opioid analgesia varies from 15% to 90%. The extent to which this phenomenon depends upon the dosage employed has not been elucidated. The cause of postoperative retention of urine (PU) is probably a combination of the central...... no clinical trials on man have hitherto been undertaken. When postoperative retention of urine occurs after epidural opioid treatment, clean intermittent catheterization or introduction of a thin suprapubic catheter are recommended....... catheterization. Inhibition of per- and postoperatively increased sympathetic activity may possibly prevent PU. Carbacholine is not effective in the treatment of postoperative retention of urine. In animal experimental studies, kappa-receptor agonists have an analgesic effect without urodynamic side-effects but...

  8. Neuropathic pain - the case for opioid therapy.

    Science.gov (United States)

    Allen, Stephen C

    2008-01-01

    For many patients, neuropathic pain (NeP) is arguably more difficult to control than nociceptive or 'normal' pain. We also now recognise the great burden that NeP has on the lives of patients - it is not only a matter of treating pain in isolation, but managing all of the issues that affect the patient's quality of life. Until relatively recently we have had little understanding of the pathophysiology causing NeP and have relied on the secondary effects of non-analgesic drugs as the mainstays of treatment. Greater understanding of the pathophysiology of NeP has led to more appropriate therapy and an increased use of multiple drug therapy - 'rational polypharmacy'. Traditional opinions concerning the treatment of NeP have been challenged and it is because of this that the use of opioids in NeP has been re-evaluated. Opioids will never replace tricyclic antidepressants and anti-epileptic drugs as first-line therapy for NeP. However, they are now fully established as effective and useful second- or third-line drugs. Many patients in the past have been potentially undertreated as a result of our inertia to use opioids. The case for opioid therapy in NeP has been firmly established. PMID:18758203

  9. PK20, a new opioid-neurotensin hybrid peptide that exhibits central and peripheral antinociceptive effects

    Directory of Open Access Journals (Sweden)

    Tsuda Yuko

    2010-12-01

    Full Text Available Abstract Background The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor. Results Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia. Conclusions The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.

  10. Structural basis for bifunctional peptide recognition at human δ-opioid receptor.

    Science.gov (United States)

    Fenalti, Gustavo; Zatsepin, Nadia A; Betti, Cecilia; Giguere, Patrick; Han, Gye Won; Ishchenko, Andrii; Liu, Wei; Guillemyn, Karel; Zhang, Haitao; James, Daniel; Wang, Dingjie; Weierstall, Uwe; Spence, John C H; Boutet, Sébastien; Messerschmidt, Marc; Williams, Garth J; Gati, Cornelius; Yefanov, Oleksandr M; White, Thomas A; Oberthuer, Dominik; Metz, Markus; Yoon, Chun Hong; Barty, Anton; Chapman, Henry N; Basu, Shibom; Coe, Jesse; Conrad, Chelsie E; Fromme, Raimund; Fromme, Petra; Tourwé, Dirk; Schiller, Peter W; Roth, Bryan L; Ballet, Steven; Katritch, Vsevolod; Stevens, Raymond C; Cherezov, Vadim

    2015-03-01

    Bifunctional μ- and δ-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human δ-OR bound to the bifunctional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics. PMID:25686086

  11. The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review

    OpenAIRE

    Khansari, MahmoudReza; Sohrabi, MasourReza; Zamani, Farhad

    2013-01-01

    Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the μ-, κ- and δ-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and block...

  12. Investigation of in vitro Opioid Receptor Binding Activities of Some Turkish Salvia species

    OpenAIRE

    Özge Gündüz Çınar; Hasan Kırmızıbekmez; Galip Akaydın; Erdem Yesilada

    2011-01-01

    Kappa Opioid Peptide Receptor (KOPr) activation produces analgesic, psychotomimetic, diuretic and antipruritic effects. KOPr ligands are investigated for their potential roles in the treatment of addiction, depression, feeding behavior, psychosis and schizophrenia. In this study the methanolic extracts of a number of Salvia species which are native to Turkey (S. tomentosa, S. tchihatcheffii , S. rosifolia, S. dichroantha and S. sclarea) were tested for their potential binding to opioid recept...

  13. Pharmacotherapy of Pain in the Older Population: The Place of Opioids

    OpenAIRE

    Prostran, Milica; Vujović, Katarina Savić; Vučković, Sonja; Medić, Branislava; Srebro, Dragana; Divac, Nevena; Stojanović, Radan; Vujović, Aleksandar; Jovanović, Lepa; Jotić, Ana; Cerovac, Nataša

    2016-01-01

    Pain is a common symptom in older people. It is possible that pain is underreported in older persons due to an incorrect belief that it is an inevitable part of aging. Opioid analgesics are potent medications, with confirmed efficacy for the treatment of moderate to severe pain. These drugs are commonly used in older persons. However, there is insufficient evidence regarding safety of opioids in older patients. One of the reasons for this is the lack of randomized, controlled clinical trials....

  14. Radioreceptor opioid assay

    International Nuclear Information System (INIS)

    A radioreceptor assay is described for assaying opioid drugs in biological fluids. The method enables the assay of total opioid activity, being specific for opioids as a class but lacking specificity within the class. A radio-iodinated opioid and the liquid test sample are incubated with an opiate receptor material. The percentage inhibition of the binding of the radio-iodinated compound to the opiate receptor is calculated and the opioid activity of the test liquid determined from a standard curve. Examples of preparing radio-iodinated opioids and assaying opioid activity are given. A test kit for the assay is described. Compared to other methods, this assay is cheap, easy and rapid. (U.K.)

  15. Dexmedetomidine infusion to facilitate opioid detoxification and withdrawal in a patient with chronic opioid abuse

    Directory of Open Access Journals (Sweden)

    Surjya Prasad Upadhyay

    2011-01-01

    Full Text Available Many patients are admitted to the intensive care unit (ICU for acute intoxication, serious complication of overdose, or withdrawal symptoms of illicit drugs. An acute withdrawal of drugs with addiction potential is associated with a sympathetic overactivity leading to marked psychomimetic disturbances. Acute intoxication or withdrawal of such drugs is often associated with life-threatening complications which require ICU admission and necessitate prolonged sedative analgesic medications, weaning from which is often complicated by withdrawal and other psychomimetic symptoms. Dexmedetomidine, an alpha-2 (α2 agonist, has been used successfully to facilitate withdrawal and detoxification of various drugs and also to control delirium in ICU patients. Herein, we report a case of a chronic opioid abuse (heroin patient admitted with acute overdose complications leading to a prolonged ICU course requiring sedative-analgesic medication; the drug withdrawal-related symptoms further complicated the weaning process. Dexmedetomidine infusion was successfully used as a sedative-analgesic to control the withdrawal-related psychomimetic symptoms and to facilitate smooth detoxification and weaning from opioid and other sedatives.

  16. Opioid Drugs in Patients With Liver Disease: A Systematic Review

    Science.gov (United States)

    Soleimanpour, Hassan; Safari, Saeid; Shahsavari Nia, Kavous; Sanaie, Sarvin; Alavian, Seyed Moayed

    2016-01-01

    Context The liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients. Evidence Acquisition This review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles. Results In patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered. Conclusions Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased

  17. Satisfaction, adherence and health-related quality of life with transdermal buprenorphine compared with oral opioid medications in the usual care of osteoarthritis pain

    OpenAIRE

    Conaghan, Philip G; Serpell, Michael; McSkimming, Paula; Junor, Rod; Dickerson, Sara

    2016-01-01

    Background: Osteoarthritis (OA) causes substantial pain and reduced health-related quality of life (HRQL). Although opioid analgesics are commonly used, the relative benefits of different opioids are poorly studied. Transdermal buprenorphine (TDB) offers an alternative to oral opioids for the treatment of moderate-to-severe chronic pain. This observational study of people with OA pain assessed satisfaction, HRQL and medication adherence. Methods: Patients in the UK with self-repor...

  18. Non-medical use of non-opioid psychotherapeutic medications in a community-based cohort of HIV-infected indigent adults

    OpenAIRE

    Vijayaraghavan, M.; Freitas, D.; Bangsberg, DR; Miaskowski, C; Kushel, MB

    2014-01-01

    Background: Non-opioid psychotherapeutic medications significantly increase the risk of opioid overdose-related deaths. We prospectively followed HIV-infected indigent adults sampled from the community to examine rates of and factors associated with non-medical use of benzodiazepines, muscle relaxants, and prescription stimulants. Methods: We interviewed participants quarterly for 2 years about alcohol and illicit substance use; depression; use of prescribed opioid analgesics, benzodiazepines...

  19. Satisfaction, adherence and health-related quality of life with transdermal buprenorphine compared with oral opioid medications in the usual care of osteoarthritis pain

    OpenAIRE

    Conaghan, Philip G.; Serpell, Michael; McSkimming, Paula; Junor, Rod; Dickerson, Sara

    2016-01-01

    Background Osteoarthritis (OA) causes substantial pain and reduced health-related quality of life (HRQL). Although opioid analgesics are commonly used, the relative benefits of different opioids are poorly studied. Transdermal buprenorphine (TDB) offers an alternative to oral opioids for the treatment of moderate-to-severe chronic pain. This observational study of people with OA pain assessed satisfaction, HRQL and medication adherence. Methods Patients in the UK with self-reported knee and/o...

  20. Use of Nonopioid Analgesics and the Impact on Patient Outcomes.

    Science.gov (United States)

    Sanzone, Anthony G

    2016-05-01

    Although opioids are widely used for the management of pain in patients with hip fracture, these medications are known to have a wide range of adverse effects that can result in suboptimal outcomes or serious life-threatening complications. Common opioid-related adverse events include gastrointestinal effects, central nervous system effects, and respiratory depression. Hip fractures occur most frequently among the elderly-the very population that is most susceptible to the adverse effects of opioids and the risks of serious physiological complications. There has been much interest during recent years in identifying alternative analgesic approaches that are less opioid-dependent. There is good evidence to show that nerve blocks can be effective in managing the acute pain associated with hip fracture. However, sciatic and femoral nerve blocks seem to increase the risk of several clinically significant adverse events. A retrospective cohort study that examined the effectiveness of scheduled intravenous acetaminophen as part of the pain management protocol for hip fracture patients revealed significant improvement in pain scores, narcotic use, length of stay, and missed physical therapy sessions. Limited data exist in patients with hip fracture on the effects of infiltration of the surgical site with the local anesthetic agent, bupivacaine. However, extensive use of bupivacaine in hip arthroplasty surgery suggests that it may be highly beneficial in the patient with hip fracture. PMID:27101320

  1. The use of analgesic drugs by South African veterinarians : continuing education

    Directory of Open Access Journals (Sweden)

    K.E. Joubert

    2001-07-01

    Full Text Available According to a survey, non-steroidal anti-inflammatory agents were the most popular analgesic used in South Africa for management of peri-operative pain, acute post-operative pain and chronic pain. The most popular non-steroidal anti-inflammatory agents are flunixin meglumine and phenylbutazone. The most popular opioid type drug is buprenorphine, followed by morphine. In the peri-operative setting, analgesic agents were not actively administered to 86.3 % of cats and 80.7 % of dogs. Analgesic premedications were frequently administered, e.g. xylazine or ketamine, but no specific drug was administered for post-operative pain. Veterinarians need to critically review their anaesthetic and analgesic practices in order to achieve balanced anaesthesia.

  2. Use of strong opioids for non-cancer pain in the community: a case study.

    Science.gov (United States)

    Cowan, David T; While, Alison; Griffiths, Peter

    2004-02-01

    The continued extension of prescribing rights among nurses may necessitate that effective pain management will require more involvement of nurses in the prescription of controlled drugs. The prescription of strong opioid analgesic drugs for chronic non-cancer pain (CNCP) is viewed as controversial. Misconceptions about opioid drugs fuel this controversy. This case study highlights the knowledge gap that exists between pain and addiction medicine and highlights the problems that CNCP patients treated in the community with opioid therapy may encounter. Community nurses are in an ideal position to be instrumental in identifying such vulnerable patients and ensuring that appropriate interventions are available. PMID:15007281

  3. Does mutual compensation of the cognitive effects induced by pain and opioids exist?

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Malver, Lasse Paludan; Andresen, Trine;

    2015-01-01

    hypotheses: (1) the analgesic effect of opioids improves cognitive function by decreasing pain, and (2) pain antagonizes cognitive effects of opioids. METHODS: Randomized, placebo-controlled, crossover study. Three experiments were conducted with 22 healthy males. Sustained attention, memory and motor....... CONCLUSION: Pain and remifentanil seemed to have additive deleterious cognitive effects. This study represents an initial step to enhance our basic understanding of some of the cognitive effects following a painful stimulus and an opioid infusion separately and combined in a sequence comparable to clinical...

  4. A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism

    Directory of Open Access Journals (Sweden)

    Wentworth Sean

    2010-06-01

    Full Text Available Abstract Background Opioids are the most widely used analgesics for the treatment of clinical pain. They produce their therapeutic effects by binding to μ-opioid receptors (MORs, which are 7 transmembrane domain (7TM G-protein-coupled receptors (GPCRs, and inhibiting cellular activity. However, the analgesic efficacy of opioids is compromised by side-effects such as analgesic tolerance, dependence and opioid-induced hyperalgesia (OIH. In contrast to opioid analgesia these side effects are associated with cellular excitation. Several hypotheses have been advanced to explain these phenomena, yet the molecular mechanisms underlying tolerance and OIH remain poorly understood. Results We recently discovered a new human alternatively spliced isoform of MOR (MOR1K that is missing the N-terminal extracellular and first transmembrane domains, resulting in a 6TM GPCR variant. To characterize the pattern of cellular transduction pathways activated by this human MOR1K isoform, we conducted a series of pharmacological and molecular experiments. Results show that stimulation of MOR1K with morphine leads to excitatory cellular effects. In contrast to stimulation of MOR1, stimulation of MOR1K leads to increased Ca2+ levels as well as increased nitric oxide (NO release. Immunoprecipitation experiments further reveal that unlike MOR1, which couples to the inhibitory Gαi/o complex, MOR1K couples to the stimulatory Gαs complex. Conclusion The major MOR1 and the alternative MOR1K isoforms mediate opposite cellular effects in response to morphine, with MOR1K driving excitatory processes. These findings warrant further investigations that examine animal and human MORK1 expression and function following chronic exposure to opioids, which may identify MOR1K as a novel target for the development of new clinically effective classes of opioids that have high analgesic efficacy with diminished ability to produce tolerance, OIH, and other unwanted side-effects.

  5. Biphalin preferentially recruits peripheral opioid receptors to facilitate analgesia in a mouse model of cancer pain - A comparison with morphine.

    Science.gov (United States)

    Lesniak, Anna; Bochynska-Czyz, Marta; Sacharczuk, Mariusz; Benhye, Sandor; Misicka, Aleksandra; Bujalska-Zadrozny, Magdalena; Lipkowski, Andrzej W

    2016-06-30

    The search for new drugs for cancer pain management has been a long-standing goal in basic and clinical research. Classical opioid drugs exert their primary antinociceptive effect upon activating opioid receptors located in the central nervous system. A substantial body of evidence points to the relevance of peripheral opioid receptors as potential targets for cancer pain treatment. Peptides showing limited blood-brain-barrier permeability promote peripheral analgesia in many pain models. In the present study we examined the peripheral and central analgesic effect of intravenously administered biphalin - a dimeric opioid peptide in a mouse skin cancer pain model, developed by an intraplantar inoculation of B16F0 melanoma cells. The effect of biphalin was compared with morphine - a golden standard in cancer pain management. Biphalin produced profound, dose-dependent and naloxone sensitive spinal analgesia. Additionally, the effect in the tumor-bearing paw was largely mediated by peripheral opioid receptors, as it was readily attenuated by the blood-brain-barrier-restricted opioid receptor antagonist - naloxone methiodide. On the contrary, morphine facilitated its analgesic effect primarily by activating spinal opioid receptors. Both drugs induced tolerance in B16F0 - implanted paws after chronic treatment, however biphalin as opposed to morphine, showed little decrease in its activity at the spinal level. Our results indicate that biphalin may be considered a future alternative drug in cancer pain treatment due to an enhanced local analgesic activity as well as lower tolerance liability compared with morphine. PMID:27094782

  6. IRAS Modulates Opioid Tolerance and Dependence by Regulating μ Opioid Receptor Trafficking.

    Science.gov (United States)

    Li, Fei; Ma, Hao; Wu, Ning; Li, Jin

    2016-09-01

    Imidazoline receptor antisera-selected (IRAS) protein, the mouse homologue named Nischarin, was found to target to early endosomes with properties of sorting nexins in vitro. Recently, we generated IRAS knockout mice and found IRAS deficiency exacerbated the analgesic tolerance and physical dependence caused by opioids, suggesting that IRAS plays a role in regulating μ opioid receptor (MOR) functions. In the present study, we found that IRAS interacts with MOR and regulates MOR trafficking in vitro. In the CHO or HEK293 cells co-expressing MOR and IRAS, IRAS, through its PX domain, interacted with MOR. The interaction facilitated the recycling of internalized MOR and prevented MOR downregulation induced by DAMGO, the MOR agonist. Functionally, IRAS accelerated MOR resensitization and attenuated DAMGO-induced MOR desensitization, which is believed as one of mechanisms mediating opioid tolerance and dependence. Taken together, we propose that IRAS is a new MOR interacting protein and regulates agonist-induced trafficking of MOR via sorting internalized MOR to the recycling pathway, which may be a molecular mechanism underlying IRAS modulating opioid tolerance and dependence. PMID:26363797

  7. [Pharmacotherapy of cancer pain : 2. Use of opioids.].

    Science.gov (United States)

    Cherny, N I; Portenoy, R K; Raber, M; Zenz, M

    1995-01-01

    The adequate use of opioids in the treatment of chronic cancer pain requires sound knowledge of selection criteria for the various opioids, the routes of administration, dosages, dosing schemes and possible side effects. Drug selection depends on the intensity of pain rather than on the specific pathophysiology. Mild to moderate pain can often be treated effectively by so-called "weak" opioids. These include codeine, dihydrocodeine and dextropropoxyphene. Non-opioid analgesics, like acetylsalicylic acid or paracetamol can be added according to the "analgesic ladder" proposed by the World Health Organization (WHO). If adequate pain relief is not achieved "strong" opioids are required. The route of administration that is the safest and the least invasive for the patient should be chosen. Non-invasive (oral, rectal, sublingual, transdermal and intranasal) and invasive routes (intravenous, subcutaneous, spinal and epidural) are available (Table 8). Noninvasive routes are preferred, and most patients can be maintained on oral opioids. Alternatively, in some patients pain can be managed by the sublingual (buprenorphine) route. A transdermal preparation exists for fentanyl, but has not yet been approved for the German market. If the oral route cannot be used or if large doses are required, it will be necessary to change to an invasive route. Intravenous bolus injections provide the fastest onset of analgesic action. They are mostly used in very severe pain. Repeated injections can be avoided by using intravenous or subcutaneous infusions. Various types of pumps delivering analgesics at constant basal infusion rates with the option of rescue doses in case of breakthrough pain are available (patient-controlled analgesia=PCA). Opioids frequently used for s. c. infusion are morphine and hydromorphone. Adjuvant drugs (antiemetics, anxiolytics) can be added. Epidural or intrathecal administration of opioids should only be used in intractable pain or if severe side effects, such

  8. Orally active opioid compounds from a non-poppy source.

    Science.gov (United States)

    Raffa, Robert B; Beckett, Jaclyn R; Brahmbhatt, Vivek N; Ebinger, Theresa M; Fabian, Chrisjon A; Nixon, Justin R; Orlando, Steven T; Rana, Chintan A; Tejani, Ali H; Tomazic, Robert J

    2013-06-27

    The basic science and clinical use of morphine and other "opioid" drugs are based almost exclusively on the extracts or analogues of compounds isolated from a single source, the opium poppy (Papaver somniferum). However, it now appears that biological diversity has evolved an alternative source. Specifically, at least two alkaloids isolated from the plant Mitragyna speciosa, mitragynine ((E)-2-[(2S,3S)-3-ethyl-8-methoxy-1,2,3,4,6,7,12,12b-octahydroindolo[3,2-h]quinolizin-2-yl]-3-methoxyprop-2-enoic acid methyl ester; 9-methoxy coryantheidine; MG) and 7-hydroxymitragynine (7-OH-MG), and several synthetic analogues of these natural products display centrally mediated (supraspinal and spinal) antinociceptive (analgesic) activity in various pain models. Several characteristics of these compounds suggest a classic "opioid" mechanism of action: nanomolar affinity for opioid receptors, competitive interaction with the opioid receptor antagonist naloxone, and two-way analgesic cross-tolerance with morphine. However, other characteristics of the compounds suggest novelty, particularly chemical structure and possible greater separation from side effects. We review the chemical and pharmacological properties of these compounds. PMID:23517479

  9. In vivo and in vitro evaluation of novel μ-opioid receptor agonist compounds.

    Science.gov (United States)

    Nikaido, Yoshiaki; Kurosawa, Aya; Saikawa, Hitomi; Kuroiwa, Satoshi; Suzuki, Chiharu; Kuwabara, Nobuo; Hoshino, Hazime; Obata, Hideaki; Saito, Shigeru; Saito, Tamio; Osada, Hiroyuki; Kobayashi, Isao; Sezutsu, Hideki; Takeda, Shigeki

    2015-11-15

    Opioids are the most effective and widely used drugs for pain treatment. Morphine is an archetypal opioid and is an opioid receptor agonist. Unfortunately, the clinical usefulness of morphine is limited by adverse effects such as analgesic tolerance and addiction. Therefore, it is important to study the development of novel opioid agonists as part of pain control. The analgesic effects of opioids are mediated by three opioid receptors, namely opioid μ-, δ-, and κ-receptors. They belong to the G protein-coupled receptor superfamily and are coupled to Gi proteins. In the present study, we developed a ligand screening system to identify novel opioid μ-receptor agonists that measures [(35)S]GTPγS binding to cell membrane fractions prepared from the fat body of transgenic silkworms expressing μ-receptor-Gi1α fusion protein. We screened the RIKEN Natural Products Depository (NPDepo) chemical library, which contains 5848 compounds, and analogs of hit compounds. We successfully identified a novel, structurally unique compound, that we named GUM1, with agonist activity for the opioid μ-receptor (EC50 of 1.2 µM). The Plantar Test (Hargreaves' Method) demonstrated that subcutaneous injection of 3mg/kg of GUM1 into wild-type rats significantly extended latency time. This extension was also observed in a rat model of morphine tolerance and was inhibited by pre-treatment of naloxone. The unique molecular skeleton of GUM1 makes it an attractive molecule for further ligand-opioid receptor binding studies. PMID:26476280

  10. Step 7: Educates Staff in Nondrug Methods of Pain Relief and Does Not Promote Use of Analgesic, Anesthetic Drugs

    Science.gov (United States)

    Leslie, Mayri Sagady; Romano, Amy; Woolley, Deborah

    2007-01-01

    Step 7 of the Ten Steps of Mother-Friendly Care insures that staff are knowledgeable about nondrug methods of pain relief and that analgesic or anesthetic drugs are not promoted unless required to correct a complication. The rationales for compliance and systematic reviews are presented on massage, hypnosis, hydrotherapy, and the use of opioids, regional analgesia, and anesthesia. PMID:18523667

  11. Treatment of Chronic Pain in Older People Evidence-Based Choice of Strong-Acting Opioids

    NARCIS (Netherlands)

    van Ojik, Annette L.; Jansen, Paul A. F.; Brouwers, Jacobus R. B. J.; van Roon, Eric N.

    2012-01-01

    In the treatment of chronic malignant and non-malignant pain, opioids are used as strong analgesics. Frail elderly patients often have multiple comorbidities and use multiple medicines, leading to an increased risk of clinically relevant drug-drug and drug-disease interactions. Age-related changes a

  12. Prescription Opioids during Pregnancy

    Science.gov (United States)

    ... Sometimes opioids are mixed with street drugs like heroin and cocaine. When your health care provider gives you a prescription for a ... Sometimes opioids are mixed with street drugs like heroin and cocaine. When your health care provider gives you a prescription for a ...

  13. Update on prescription extended-release opioids and appropriate patient selection

    Directory of Open Access Journals (Sweden)

    Brennan MJ

    2013-07-01

    Full Text Available Michael J Brennan The Pain Center of Fairfield, Fairfield, CT, USA Abstract: Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice. Keywords: chronic pain, opioid analgesics, extended release, abuse prevention

  14. American Society for Pain Management Nursing Position Statement: Prescribing and Administering Opioid Doses Based Solely on Pain Intensity.

    Science.gov (United States)

    Pasero, Chris; Quinlan-Colwell, Ann; Rae, Diana; Broglio, Kathleen; Drew, Debra

    2016-06-01

    The foundation of safe and effective pain management is an individualized, comprehensive pain assessment, which includes, but is not limited to, determining the intensity of pain if the patient is able to report it. An unforeseen consequence of the widespread use of pain intensity rating scales is the practice of prescribing specific doses of opioid analgesics based solely on specific pain intensity. Many factors in addition to pain intensity influence opioid requirements, and there is no research showing that a specific opioid dose will relieve pain of a specific intensity in all patients. The American Society for Pain Management Nursing (ASPMN) holds the position that the practice of prescribing doses of opioid analgesics based solely on a patient's pain intensity should be prohibited because it disregards the relevance of other essential elements of assessment and may contribute to untoward patient outcomes. PMID:27108082

  15. Nitrous oxide as an opioid agonist: some experimental and clinical applications

    International Nuclear Information System (INIS)

    The interactions of nitrous oxide at analgesic concentrations with the endogenous opioid system is investigated, both in vitro and in vivo, with particular emphasis on the possibility that nitrous oxide is a possible tool both experimentally, diagnostically and therapeutically. In vitro findings show that nitrous oxide displaces (3H) - naloxone from its binding sites in a definite and measurable manner, indicating a direct action of nitrous oxide at opioid receptors, in this case the mu site. An additional finding is that nitrous oxide unmasks a heretofore undiscovered super high affinity sites which may be an opioid auto-receptor. Naloxone was demonstrated to reverse acute alcoholic intoxication in some cases. The investigative as well as therapeutic role of nitrous oxide was investigated. It is concluded that nitrous oxide at analgesic concentrations (ie. low concentrations of nitrous oxide diluted with high concentrations of oxygen) is a safe and effective therapeutic agent

  16. The Roles of Opioid Receptors and agonists in health and disease Conditions

    Directory of Open Access Journals (Sweden)

    A.O. Ibegbu

    Full Text Available Opioid receptors are found in the central nervous system (CNS and are classified as mu (µ, kappa (κ, delta (δ and sigma (σ opioid receptors. Opioid receptors belong to the large family of G protein coupled receptors (GPCRs, and have diverse and important physiological roles. Opioid receptors are not uniformly distributed in the CNS and are found in areas concerned with pain, with the highest concentration in the cerebral cortex, followed by the amygdala, septum, thalamus, hypothalamus, midbrain and spinal cord. Activated delta opioid receptors are coupled to Gi1 while activated mu opioid receptors are coupled to Gi3 in neuroblastoma cells. Mu opioid receptors are activated by mu receptor agonists and are coupled through the Gαi1 and GαoA. Both mu and kappa opioid receptors are coupled via both Gi and Gz and opioid receptors are important targets for thousands of pharmacological agents. GPCRs typically require activation by agonists for their signalling activity to be initiated but some of the GPCRs may display basal or spontaneous signalling activity in the absence of an agonist. The stimulation of these receptors triggers analgesic effects and affects the function of the nervous system, gastrointestinal tract and other body systems. Hundreds of analogs of opioid peptides have been synthesized in an effort to make the compounds more active, selective, and resistant to biodegradation than the endogenous ligands. All these modifications resulted in obtaining very selective agonists and antagonists with high affinity at mu-, delta-, and kappa-opioid receptors, which are useful in further studies on the pharmacology of opioid receptors in a mammalian organism.

  17. Interaction and regulatory functions of μ- and δ-opioid receptors in nociceptive afferent neurons

    Institute of Scientific and Technical Information of China (English)

    Xu Zhang; Lan Bao

    2012-01-01

    μ-opioid receptor (MOR) agonists such as morphine are powerful analgesics used for pain therapy.However,the use of these drugs is limited by their side-effects,which include antinociceptive tolerance and dependence.Earlier studies reported that MOR analgesic tolerance is reduced by blockade of δ-opioid receptors (DORs) that interact with MORs.Recent studies show that the MOR/DOR interaction in nociceptive afferent neurons in the dorsal root ganglion may contribute to morphine analgesic tolerance.Further analysis of the mechanisms for regulating the trafficking of receptors,ion channels and signaling molecules in nociceptive afferent neurons would help to understand the nociceptive mechanisms and improve pain therapy.

  18. Metabolism and Disposition of Prescription Opioids: A Review.

    Science.gov (United States)

    DePriest, A Z; Puet, B L; Holt, A C; Roberts, A; Cone, E J

    2015-07-01

    Opioid analgesics are commonly prescribed for acute and chronic pain, but are subject to abuse. Consequently, toxicology testing programs are frequently implemented for both forensic and clinical applications. Understanding opioid metabolism and disposition is essential for assessing risk of toxicity and, in some cases, providing additional information regarding risk of therapeutic failure. Opioids significantly metabolized by the cytochromeP450 (CYP450) enzyme system maybe subjectto drug-drug interactions, including codeine, hydrocodone, oxycodone, fentanyl, meperidine, methadone, buprenorphine, and tramadol. CYP2D6 metabolism is polymorphic, and pharmacogenetic testing has been investigated for codeine, tramadol, oxycodone, and hydrocodone. CYP2B6 pharmacogenetic testing of methadone may reduce the risk of cardiac toxicity associated with the S-enantiomer. Opioids metabolized primarily by uridine 5'-diphospho-glucuronsyltransferase (UGT) enzymes include morphine, hydromorphone, dihydrocodeine, oxymorphone, levorphanol, and tapentadol. Parent and metabolite disposition is described for blood, oral fluid, and urine. Parent drug is most commonly detected in blood and oral fluid, whereas metabolites typically predominate in urine. Oral fluid/blood ratios exceed 1 for most opioids, making this an excellent alternative matrix for testing of this drug class. Metabolites of codeine, hydrocodone, and oxycodone are commercially available, and knowledge of metabolism is necessary for correct interpretation. PMID:26227254

  19. Using opioids in general practice for chronic non-cancer pain: an overview of current evidence.

    Science.gov (United States)

    Currow, David C; Phillips, Jane; Clark, Katherine

    2016-05-01

    Chronic non-cancer pain (lasting more than 3 months) is highly prevalent in Australia (17% of males and 20% of females) and its optimal management is crucial to the health and wellbeing of the community. For 5% of the population, such pain interferes markedly with daily function. Part of the treatment for acute non-cancer pain for many people will include opioid analgesics at least for days to weeks. However, as pain becomes chronic, evidence to support ongoing prescription of opioids is lacking. There is increasing pressure to ensure that prescribing opioid analgesics is minimised to reduce not only the risk of dependence and illicit diversion but also the potential harms associated with tolerance, side effects and complications. Frameworks for considering opioid prescribing include assessing suitability of the patient for opioids; initiating a trial of therapy; and monitoring long term use. There is limited evidence of the long term efficacy of opioids for chronic non-cancer pain, and documented clinical consequences beyond addiction include acceleration of loss of bone mineral density, hypogonadism and an association with increased risk of acute myocardial infarction. Careful clinical selection of patients can help optimise the evidence-based use of opioids for chronic non-cancer pain: only treat pain that has been as well defined as possible when non-opioid therapies have not been effective; consider referral to specialist services for assessment if doses are above 100 mg oral morphine equivalent per 24 hours or the duration of therapy is longer than 4 weeks; limit prescribing to only one practitioner; seek an agreement with the patient for the initiation and potential withdrawal of opioids if the therapeutic trial is not effective. PMID:27125804

  20. Correlation versus Causation? Pharmacovigilance of the Analgesic Flupirtine Exemplifies the Need for Refined Spontaneous ADR Reporting

    OpenAIRE

    Anderson, Nora; Borlak, Juergen

    2011-01-01

    Annually, adverse drug reactions result in more than 2,000,000 hospitalizations and rank among the top 10 causes of death in the United States. Consequently, there is a need to continuously monitor and to improve the safety assessment of marketed drugs. Nonetheless, pharmacovigilance practice frequently lacks causality assessment. Here, we report the case of flupirtine, a centrally acting non-opioid analgesic. We re-evaluated the plausibility and causality of 226 unselected, spontaneously rep...

  1. Effects of stress and. beta. -funal trexamine pretreatment on morphine analgesia and opioid binding in rats

    Energy Technology Data Exchange (ETDEWEB)

    Adams, J.U.; Andrews, J.S.; Hiller, J.M.; Simon, E.J.; Holtzman, S.G.

    1987-12-28

    This study was essentially an in vivo protection experiment designed to test further the hypothesis that stress induces release of endogenous opiods which then act at opioid receptors. Rats that were either subjected to restraint stress for 1 yr or unstressed were injected ICV with either saline or 2.5 ..mu..g of ..beta..-funaltrexamine (..beta..-FNA), an irreversible opioid antagonist that alkylates the mu-opioid receptor. Twenty-four hours later, subjects were tested unstressed for morphine analgesia or were sacrificed and opioid binding in brain was determined. (/sup 3/H)D-Ala/sup 2/NMePhe/sup 4/-Gly/sup 5/(ol)enkephalin (DAGO) served as a specific ligand for mu-opioid receptors, and (/sup 3/H)-bremazocine as a general ligand for all opioid receptors. Rats injected with saline while stressed were significantly less sensitive to the analgesic action of morphine 24 hr later than were their unstressed counterparts. ..beta..-FNA pretreatment attenuated morphine analgesia in an insurmountable manner. Animals pretreated with ..beta..-FNA while stressed were significantly more sensitive to the analgesic effect of morphine than were animals that received ..beta..-FNA while unstressed. ..beta..-FNA caused small and similar decreases in (/sup 3/H)-DAGO binding in brain of both stressed and unstressed animals. 35 references, 2 figures, 2 tables.

  2. Strong opioids for noncancer pain due to musculoskeletal diseases: Not more effective than acetaminophen or NSAIDs.

    Science.gov (United States)

    Berthelot, Jean-Marie; Darrieutort-Lafitte, Christelle; Le Goff, Benoit; Maugars, Yves

    2015-12-01

    The classification of morphine as a step III analgesic, based on pharmacological data, creates a strong bias toward a belief in the efficacy of this drug. However, double-blind emergency-room trials showed similar levels of pain relief with intravenous acetaminophen as with intravenous morphine in patients with renal colic, low back pain or acute limb pain. In patients with chronic noncancer low back pain, morphine and other strong opioids in dosages of up to 100mg/day were only slightly more effective than their placebos, no more effective than acetaminophen, and somewhat less effective than nonsteroidal anti-inflammatory drugs (NSAIDs). In patients with osteoarthritis, strong opioids were not more effective than NSAIDs and, in some studies, than placebos. The only randomized controlled trial in patients with sciatica found no difference with the placebo. Chronic use of strong opioids can induce hyperalgesia in some patients. Hyperpathia with increased sensitivity to cold leading the patient to request higher dosages should suggest opioid-induced hyperalgesia. Pain specialists in the US have issued a petition asking that strong opioids be used in dosages no higher than 100mg/day of morphine-equivalent, in an effort to decrease the high rate of mortality due to the misuse and abuse of strong opioids (10,000 deaths/year in the US). Healthcare providers often overestimate the efficacy of step III analgesics, despite pain score decreases of only 0.8 to 1.2 points. PMID:26453108

  3. The future of topical analgesics.

    Science.gov (United States)

    Arnstein, Paul M

    2013-07-01

    Topically applied analgesic therapies have been used throughout history to treat a variety of patient conditions that present with pain. Before modem pharmaceuticals became readily available, mud-based emollients, salves, cold therapies, and other natural remedies were often used. Now we have effective therapies and are developing advanced topical analgesics as we learn more about the physiology and pathophysiology of pain. The use of topical analgesics may be associated with fewer patient systemic side effects than are seen with oral, parenteral, or transdermally administered agents, making the topical route of administration attractive to prescribers and patients. With further refinement of existing drugs and the development of novel agents, topical analgesics may offer relief for treating patient pain conditions that are currently challenging to treat, such as pain resulting from burns, wound debridement, and pressure ulcers. Recognizing the value of a multimodal approach, topical analgesics may offer a therapeutic option that can become part of a comprehensive treatment plan for the patient. With continued advancements in targeted drug-delivery systems, topical analgesics may be able to provide a method to prevent or reverse the phenomena of peripheral and central sensitization, or the neuroplastic changes believed to be responsible for the transition from acute to chronic pain states in patients. For those patients at risk for developing chronic pain states, such as complex regional pain syndrome, the combination of cutaneous stimulation (achieved through rubbing during application) and analgesic effects produced by the drug itself may prevent the disabling pain that often emerges during the subacute phase of disease. In summary, better utilization of currently available topical analgesics and continued research promise to ensure that topical analgesics are, and will continue to be, important tools in the treatment of patients with resistant pain. PMID

  4. Combined parecoxib and I.V. paracetamol provides additional analgesic effect with better postoperative satisfaction in patients undergoing anterior cruciate ligament reconstruction

    OpenAIRE

    Zeinab Ahmed Elseify; Salwa Omar El-Khattab; Ahmed Metwally Khattab; Eman Mohammed Atta; Layal Fares Ajjoub

    2011-01-01

    Background : Adequacy of postoperative analgesia is one of the most important factors that determine early hospital discharge and patients′ ability to resume their normal activities postoperatively. The optimal non-opioid analgesic technique for postoperative pain management would reduce pain and enhance patient satisfaction, and it also facilitates earlier mobilization and rehabilitation by reducing pain-related complications after surgery. The aim of this study was to evaluate the analgesic...

  5. Rehabilitation of total knee arthroplasty: clinical and rehabilitation differences between two analgesic treatments (Riabilitazione di artroprotesi totale di ginocchio: differenze cliniche e riabilitative tra due trattamenti analgesici)

    OpenAIRE

    Germana Mojica; Luisa Patrevita; Annalisa Coppo; Federica Taddei; Giuseppe Massazza

    2014-01-01

    Pain is a significant problem in a patient who has undergone total knee arthroplasty (PTG), since it influences the quality of life and the rehabilitation and functional recovery of the patient. In our study, we compared due different treatments with opioid analgesics in patients operated of PTG, with the aim of determining any clinical and rehabilitation differences. 56 post-PTG rehabilitative inpatients were chosen and randomised into two groups of analgesic treatment with a fixed administr...

  6. Analgesic use among nursing homes residents, with and without dementia, in Poland.

    Science.gov (United States)

    Neumann-Podczaska, Agnieszka; Nowak, Tomasz; Suwalska, Aleksandra; Łojko, Dorota; Krzymińska-Siemaszko, Roma; Kozak-Szkopek, Elżbieta; Wieczorowska-Tobis, Katarzyna

    2016-01-01

    Many age-associated diseases are accompanied by pain. There is no doubt that pain is underrecognized among elderly nursing home residents and the diagnosing of pain is a real challenge in subjects with dementia. The aim of the study was to characterize analgesic use among nursing home residents and to delineate the putative associations between pain management and cognitive functions of elderly persons. The study involved 392 subjects (males:females - 81:311) with a mean age of 83.6±5.9 years. The residents' medical files in relation to diagnoses and drug consumption were analyzed, and the screening of cognitive functions was performed using the Mini-Mental State Examination (MMSE). One hundred and thirteen residents (28.8%) received some analgesics. Among them 84 (21.4%) used them routinely, 25 (6.4%) - pro re nata (PRN) and four (1.0%) - both routinely and PRN. Non-opioid analgesics were taken routinely by 53 residents, weak opioids by nine subjects, and one person was receiving strong opioids. Additionally, three individuals were taking a combination preparation of tramadol and acetaminophen. The rate of subjects who were not receiving any pain treatment was higher in residents with MMSE between 0 and 9 points than in those with MMSE between 24 and 30 points (P=0.0151). Furthermore, ten residents (9.1%) with severe dementia were treated with analgesics PRN. The results of our study point to a remarkably low use of analgesics in nursing home residents in Poland and indicate a need to introduce pain evaluation and monitoring of drug treatment appropriateness as a standard procedure in the geriatric assessment in nursing homes. PMID:27051281

  7. Synthesis and analgesic properties of N-substituted trans-4a-aryldecahydroisoquinolines.

    Science.gov (United States)

    Zimmerman, D M; Cantrell, B E; Swartzendruber, J K; Jones, N D; Mendelsohn, L G; Leander, J D; Nickander, R C

    1988-03-01

    A representative series of N-substituted derivatives of the morphine-based trans-4a-aryldecahydroisoquinoline were synthesized and evaluated for opioid analgesic activities. Compounds with potent analgesic activity and high affinities for the mu and kappa opioid receptors were discovered. The effect of varying the N-substituent in the trans-4a-aryldecahydroisoquinoline paralleled, to a certain extent, previous findings with other morphine part structures. Replacement of the N-methyl with a phenethyl group significantly increased analgesic potency. The N-cyclopropylmethyl analogue was found in rodents to have mixed agonist-antagonist properties; however, its antagonist activity was far weaker than those reported for the N-(cyclopropylmethyl)morphinan and -benzomorphan derivatives. Resolution of the stereoisomers and determination of their absolute configuration by X-ray crystallography showed that the opioid receptor effects were predominantly found with the 4aR,8aR isomer, the same relative absolute configuration of morphine. Unexpectedly, the 4aR,8aR N-cyclopropylmethyl analogue (compound 30), which in rodents had mixed agonist-antagonist properties similar to those of pentazocine, was found in rhesus monkeys to behave as a full morphine-like agonist. PMID:2831363

  8. LABORATORY MODELS FOR SCREENING ANALGESICS

    Directory of Open Access Journals (Sweden)

    Parle Milind

    2013-01-01

    Full Text Available Pain is a complex unpleasant phenomenon composed of sensory experiences that include time, space, intensity, emotion, cognition and motivation. Analgesics are the agents, which selectively relieve pain by acting in the CNS or by peripheral pain mechanisms without significantly altering consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical and technical problems. Philosophically, there is a problem that pain cannot be monitored directly in animals but can only be measured by examining their responses to nociceptive stimuli. The observed reactions are almost always motor responses ranging from spinal reflexes to complex behavior. The animal models employed for screening of analgesic agents, include Pain-state models based on the use of thermal stimuli, mechanical stimuli, electrical stimuli and chemical stimuli. The neuronal basis of most of the above laboratory models is poorly understood, however their application is profitable in predicting analgesic activity of newly discovered substances.

  9. ANALGESIC AND ANTIINFLAMMATORY EFFECTS OF TOTAL EXTRACT, FLAVONOID FRACTION AND VOLATILE OIL OF SALVIA HYDRANGEA

    Directory of Open Access Journals (Sweden)

    V.A HAJ HASHEMI

    2000-12-01

    Full Text Available Background. Gol-e-arvaneh with the scientific name of salvia hydrangea (Labiatea belongs to Salvia genus. In traditional medicine it has been used as analgesic, relieving headache, cold remedy, antipyretic and diuretic. Since until now this plant has not been investigated pharacologically. This study was aimed to find any anti-inflammatory or analgesic activity of the plant. Methods. At first, total extract, flavonoid fraction and volatile oil was prepared. Analgesic effect was assessed using light tail flick and acetic acid writhing test. Male wistar rats (180-220g and mice (25±2g were used in these tests. Carrageen in test was used for assessing anti-inflammatory activity. Results. Total extract and flavonoid fraction could not produce analgesic effect in light tail flick test, while morphine as a standard drug 15 and 30 min. after administration produced 35% and 90% of MPE respectively. In writhing test, total extract and flavonoid fraction had considerable analgesic effect which was comparable to that of indomethacin. Results of Carageenin test showed that both total extract and flavonoid fraction had marked anti-inflammatory activity and volatile oil had only a slight effect. Discussion. Since potent drugs (such as opioids show positive response to light tail flick test, it seems that the plant lacks such compounds. Considerable analgesic activity of total extract and flavonoid fraction in writhing test and also their anti-inflammatory activity indicate that this plant is probably useful for relieving pains, particularly with inflammatory origin.

  10. Methylnaltrexone: the evidence for its use in the management of opioid-induced constipation

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    Peter Deibert

    2009-12-01

    Full Text Available Peter Deibert1, Carola Xander2, Hubert E Blum3, Gerhild Becker41Department of Rehabilitative and Preventive Sports Medicine, 2German Cochrane Center, Department for Medical Statistics, 3Department of Hepatology, Gastroenterology, Endocrinology and infectious Diseases, 4Department of Palliative Care, University Hospital, Medical Clinic, Freiburg, GermanyIntroduction: Constipation is a distressing side effect of opioid treatment, being so irksome in some cases that patients would rather suffer the pain than the side effect of opioid analgesics. Stool softeners or stimulating laxatives are often ineffective or even aggravate the situation. A new efficacious and safe drug is needed to limit the frequently observed side effects induced by effective opioid-based analgesic therapy and to improve the quality of life for patients, most of whom are impaired by a severe disease.Aims: The purpose of this article is to assess current evidence supporting the use of the peripherally acting µ-opioid receptor antagonist, methylnaltrexone, to restrict passage across the blood–brain barrier in patients with opioid-induced bowel dysfunction.Evidence review: There are now convincing data from phase II and multicenter phase III randomized, double-blind, placebo-controlled trials that methylnaltrexone induces laxation in patients with long-term opioid use without affecting central analgesia or precipitation of opioid withdrawal. Onset of the effect is rapid and improvement is maintained for at least 3 months during the drug treatment. The action of methylnaltrexone is dose dependent. Weight-related dosing appeared to be effective. There were no severe side effects or signs of opioid withdrawal. Adverse events, most frequently abdominal cramping or nausea, were usually mild to moderate. Methylnaltrexone is contraindicated in patients with known or suspected mechanical intestinal stenosis. Patients receiving methylnaltrexone must be monitored.Place in therapy

  11. Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty

    DEFF Research Database (Denmark)

    Andersen, Lasse Østergaard; Kehlet, H

    2014-01-01

    In recent years, there has been an increasing interest in local infiltration analgesia (LIA) as a technique to control postoperative pain. We conducted a systematic review of randomized clinical trials investigating LIA for total knee arthroplasty (TKA) and total hip arthroplasty (THA) to evaluate...... the analgesic efficacy of LIA for early postoperative pain treatment. In addition, the analgesic efficacy of wound catheters and implications for length of hospital stay (LOS) were evaluated. Twenty-seven randomized controlled trials in 756 patients operated on with THA and 888 patients operated on...... reported to have similar or improved analgesic efficacy. In TKA, most trials reported reduced pain and reduced opioid requirements with LIA compared with a control group treated with placebo/no injection. Compared with femoral nerve block, epidural or intrathecal morphine LIA provided similar or improved...

  12. Analgesic effects of lappaconitine in leukemia bone pain in a mouse model

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    Xiao-Cui Zhu

    2015-05-01

    Full Text Available Bone pain is a common and severe symptom in cancer patients. The present study employed a mouse model of leukemia bone pain by injection K562 cells into tibia of mouse to evaluate the analgesic effects of lappacontine. Our results showed that the lappaconitine treatment at day 15, 17 and 19 could effectively reduce the spontaneous pain scoring values, restore reduced degree in the inclined-plate test induced by injection of K562 cells, as well as restore paw mechanical withdrawal threshold and paw withdrawal thermal latency induced by injection of K562 cells to the normal levels. Additionally, the molecular mechanisms of lappaconitine’s analgesic effects may be related to affect the expression levels of endogenous opioid system genes (POMC, PENK and MOR, as well as apoptosis-related genes (Xiap, Smac, Bim, NF-κB and p53. Our present results indicated that lappaconitine may become a new analgesic agent for leukemia bone pain management.

  13. Dual Alleviation of Acute and Neuropathic Pain by Fused Opioid Agonist-Neurokinin 1 Antagonist Peptidomimetics.

    Science.gov (United States)

    Betti, Cecilia; Starnowska, Joanna; Mika, Joanna; Dyniewicz, Jolanta; Frankiewicz, Lukasz; Novoa, Alexandre; Bochynska, Marta; Keresztes, Attila; Kosson, Piotr; Makuch, Wioletta; Van Duppen, Joost; Chung, Nga N; Vanden Broeck, Jozef; Lipkowski, Andrzej W; Schiller, Peter W; Janssens, Frans; Ceusters, Marc; Sommen, François; Meert, Theo; Przewlocka, Barbara; Tourwé, Dirk; Ballet, Steven

    2015-12-10

    Herein, the synthesis and biological evaluation of dual opioid agonists-neurokinin 1 receptor (NK1R) antagonists is described. In these multitarget ligands, the two pharmacophores do not overlap, and this allowed maintaining high NK1R affinity and antagonist potency in compounds 12 and 13. Although the fusion of the two ligands resulted in slightly diminished opioid agonism at the μ- and δ-opioid receptors (MOR and DOR, respectively), as compared to the opioid parent peptide, balanced MOR/DOR activities were obtained. Compared to morphine, compounds 12 and 13 produced more potent antinociceptive effects in both acute (tail-flick) and neuropathic pain models (von Frey and cold plate). Similarly to morphine, analgesic tolerance developed after repetitive administration of these compounds. To our delight, compound 12 did not produce cross-tolerance with morphine and high antihyperalgesic and antiallodynic effects could be reinstated after chronic administration of each of the two compounds. PMID:26713106

  14. Sucrose ingestion causes opioid analgesia

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    Segato F.N.

    1997-01-01

    Full Text Available The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean ± SEM, N = 12 for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 ± 0.04, 0.10 ± 0.05, 0.15 ± 0.08 and 0.49 ± 0.07, respectively. One-way ANOVA indicated a significant difference (F(3,47 = 9.521, P<0.001 and the Tukey multiple comparison test (P<0.05 showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7 receiving sucrose exhibited an analgesia index of 0.20 ± 0.10 while rats receiving only sucrose (N = 7 had an index of 0.68 ± 0.11 (t = 0.254, 10 degrees of freedom, P<0.03. This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.

  15. Perioperative analgesic requirements in severely obese adolescents and young adults undergoing laparoscopic versus robotic-assisted gastric sleeve resection

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    Anita Joselyn

    2015-01-01

    Full Text Available Purpose: One of the major advantages for patients undergoing minimally invasive surgery as compared to an open surgical procedure is the improved recovery profile and decreased opioid requirements in the perioperative period. There are no definitive studies comparing the analgesic requirements in patients undergoing two different types of minimally invasive procedure. This study retrospectively compares the perioperative analgesic requirements in severely obese adolescents and young adults undergoing laparoscopic versus robotic-assisted, laparoscopic gastric sleeve resection. Materials and Methods: With Institutional Review Board approval, the medication administration records of all severely obese patients who underwent gastric sleeve resection were retrospectively reviewed. Intra-operative analgesic and adjuvant medications administered, postoperative analgesic requirements, and visual analog pain scores were compared between those undergoing a laparoscopic procedure versus a robotic-assisted procedure. Results: This study cohort included a total of 28 patients who underwent gastric sleeve resection surgery with 14 patients in the laparoscopic group and 14 patients in the robotic-assisted group. Intra-operative adjuvant administration of both intravenous acetaminophen and ketorolac was similar in both groups. Patients in the robotic-assisted group required significantly less opioid during the intra-operative period as compared to patients in the laparoscopic group (0.15 ± 0.08 mg/kg vs. 0.19 ± 0.06 mg/kg morphine, P = 0.024. Cumulative opioid requirements for the first 72 postoperative h were similar in both the groups (0.64 ± 0.25 vs. 0.68 ± 0.27 mg/kg morphine, P = NS. No difference was noted in the postoperative pain scores. Conclusion: Although intraoperative opioid administration was lower in the robotic-assisted group, the postoperative opioid requirements, and the postoperative pain scores were similar in both groups.

  16. Analgesic prescription pattern in the management of dental pain among dentists in İstanbul

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    Sinan Şermet

    2012-01-01

    Full Text Available OBJECTIVES: To determine the pattern of analgesic prescriptions and the information given to their patients about use of these drugs by the dentists working in Istanbul.METHODS: A questionnaire was distributed to 250 dentists working in Istanbul. The questionnaires consisted of open-ended questions about analgesic use in dentistry and were handed out directly to dentists. They were analyzed and responses to each question expressed as absolute frequencies. The cases and the analgesics prescribed by dentists for each case were determined by the descriptive statistics method; “frequency”.RESULTS: Responses to questionnaires were received from 130 (52% dentists. The most commonly prescribed analgesic was naproxen, a nonsteroidal anti-inflammatory drug (NSAID. It is also estimated that dentists did not prescribe selective COX-2 inhibitors or opioid analgesics. Some dentists reported prescribing more than one NSAIDs for the same patient (n = 11 cases. Although more than 75% of the dentists reported that they gave information to their patients about the use of analgesics, the content of the information was limited.DISCUSSION: The results of the questionnaires applied to the dentists showed that dentists most commonly prescribe naproxen for the management of dental pain and they rarely prescribe incompatible analgesic combinations. The results also showed that dentists informed their patients inadequately about analgesic use. Incomplete information given by dentists about drug interactions, storage conditions and price of the prescribed drugs is an important point of the study that may also affect the success ratio of the therapy and the compliance of the patients.

  17. PET and SPECT imaging of the opioid system: receptors, radioligands and avenues for drug discovery and development.

    Science.gov (United States)

    Lever, John R

    2007-01-01

    As we celebrate the bicentennial of the isolation of morphine by Sertürner, opioids continue to dominate major sectors of the analgesic market worldwide. The pharmaceutical industry stands to benefit greatly from molecular imaging in preclinical and early clinical trials of new or improved opioid drugs. At this juncture, it seems fitting to summarize the past twenty or so years of research on molecular imaging of the opioid system from the viewpoint of drug discovery and development. Opioid receptors were first imaged in human volunteers by positron emission tomography (PET) in 1984. Now, quantitative PET imaging of the major opioid receptor types (micro, delta , kappa) is possible in the brain and peripheral organs of healthy persons and patient populations. Radioligands are under development for single photon emission computed tomography (SPECT) of opioid receptors as well. These functional, nuclear imaging techniques can trace the fate of radiolabeled molecules directly, but non-invasively, and allow precise pharmacokinetic and pharmacodynamic measurements. Molecular imaging provides unique data that can aid in selecting the best drug candidates, determining optimal dosing regimens, clearing regulatory hurdles and lowering risks of failure. Using a historical perspective, this review touches on opioid receptors as drug targets, and focuses on the status and use of radiotracers for opioid receptor PET and SPECT. Selected studies are discussed to illustrate the power of molecular imaging for facilitating opioid drug discovery and development. PMID:17266587

  18. Asociación de Fentanilo TTS matricial + Citrato de Fentanilo Oral Transmucosa (CFOT, en pacientes que no han recibido tratamiento previo con opioides y padecen dolor crónico intenso de etiología osteoarticular: Haciendo realidad el Ascensor Analgésico Combination of TTS-Fentanyl and Oral Transmucosal Fentanyl citrate (OTFC in opioid-naive patients suffering severe osteoarticular pain: Towards a fast-track analgesic ladder

    Directory of Open Access Journals (Sweden)

    F. Collado

    2007-05-01

    Full Text Available Objetivos: Exponer los resultados obtenidos en 250 pacientes que sin haber tenido contacto previo con opioides, acceden a nuestra Unidad de Tratamiento del Dolor, padeciendo un dolor intenso (EVA ≥ 8 de más de 6 meses de evolución y afectos de un dolor de origen osteoarticular. Métodos: Estudio abierto, prospectivo y controlado. Los pacientes fueron tratados, inicialmente, con fentanilo TTS matricial de 12 µg/h + citrato de fentanilo oral transmucosa (CFOT de 200-400 pg., para el dolor irruptivo. A los 12 días de tratamiento, se aumento la dosificación del parche matricial de fentanilo TTS, a 25 ug/h. Se valoró la situación de los pacientes mensualmente y si el dolor no estaba controlado, se aumento la dosificación de fentanilo TTS matricial. Si por el contrario, el dolor permanecía controlado durante más de un mes y no se precisaba ningún comprimido de CFOT, se redujo la dosificación del fentanilo TTS matricial. Se analizaron los registros de intensidad del dolor, calidad del descanso nocturno, efectos secundarios y consumo medio de fetanilo TTS y CFOT, obtenidos al inicio, 1º, 3º y 6º mes de tratamiento. Resultados: La EVA medio pasó del 8,86 + 0,25, inicial hasta un 2,1 + 0,74, al 6º mes. El descanso nocturno, mejoró en una proporción idéntica a la del alivio del dolor. Solo 17 pacientes (6,80% abandonaron el tratamiento por efectos secundarios 11 por náuseas-vómitos, 5 por sedación excesiva y 1 por dermatitis. Al final del estudio, solo 1 paciente precisaba dosis superiores a los 100 µg/h. de fentanilo TTS. La mayoría de ellos (58,64% estaban tratados con un parche de 50 µg/h, el 33,47% seguía con el parche de 25 µg/h, el 4,72% necesitaba un parche de 75 µg/h y un 1,71% alcanzó el parche de 100 µg/h. Un solo paciente (0,42%, precisó 125 µg/h de fentanilo TTS. Al final del primer mes, el consumo medio de CFOT fue de 5,08 comprimidos/día. El tercer mes, su consumo descendió a una media de 2,88/día. Al

  19. Opioid-prescribing practices in chronic cancer pain in a tertiary care pain clinic

    Directory of Open Access Journals (Sweden)

    Raghu S Thota

    2011-01-01

    Full Text Available Introduction: Under treatment of pain is a recognized global issue. Opioid analgesic medication is the mainstay of treatment in cancer patients as per the World Health Organization (WHO pain relief ladder, yet 50% of cancer patients worldwide do not receive adequate pain relief or are undertreated. Aim: The aim of this study was to audit the ongoing opioid-prescribing practices in our tertiary cancer pain clinic during January-June 2010. Materials& Methods: The prescribed type of opioid, dose, dosing interval, and laxatives details were analyzed. Results: Five hundred pain files were reviewed and 435 were found complete for audit. Three hundred forty-eight (80% patients were prescribed opioids. Two hundred fifty-nine (74.4% received weak opioids while 118 (33.9% received strong opioids. A total of 195 (45% patients had moderate and 184 (42% had severe pain. Ninety-three (26.7% patients received morphine; however, only 31.5% (58 of 184 in severe pain received morphine as per the WHO pain ladder. Only 73 of 93 (78.4% patients received an adequate dose of morphine with an adequate dosing interval and only 27 (29% were prescribed laxatives with morphine. Conclusion: This study shows that the under treatment of pain and under dosing of opioids coupled with improper side effect management are major issues.

  20. Neuroimmune Interaction in the Regulation of Peripheral Opioid-Mediated Analgesia in Inflammation.

    Science.gov (United States)

    Hua, Susan

    2016-01-01

    Peripheral immune cell-mediated analgesia in inflammation is an important endogenous mechanism of pain control. Opioid receptors localized on peripheral sensory nerve terminals are activated by endogenous opioid peptides released from immune cells to produce significant analgesia. Following transendothelial migration of opioid-containing leukocytes into peripheral sites of inflammation, opioid peptides are released into a harsh milieu associated with an increase in temperature, low pH, and high proteolytic activity. Together, this microenvironment has been suggested to increase the activity of opioid peptide metabolism. Therefore, the proximity of immune cells and nerve fibers may be essential to produce adequate analgesic effects. Close associations between opioid-containing immune cells and peripheral nerve terminals have been observed. However, it is not yet determined whether these immune cells actually form synaptic-like contacts with peripheral sensory terminals and/or whether they secrete opioids in a paracrine manner. This review will provide novel insight into the peripheral mechanisms of immune-derived analgesia in inflammation, in particular, the importance of direct interactions between immune cells and the peripheral nervous system. PMID:27532001

  1. Assessment and Treatment of Abuse Risk in Opioid Prescribing for Chronic Pain

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    Robert N. Jamison

    2011-01-01

    Full Text Available Opioid analgesics provide effective treatment for noncancer pain, but many physicians have concerns about adverse effects, tolerance, and addiction. Misuse of opioids is prominent in patients with chronic back pain and early recognition of misuse risk could help physicians offer adequate patient care while implementing appropriate levels of monitoring to reduce aberrant drug-related behaviors. In this review, we discuss opioid abuse and misuse issues that often arise in the treatment of patients with chronic back pain and present an overview of assessment and treatment strategies that can be effective in improving compliance with the use of prescription opioids for pain. Many persons with chronic back pain have significant medical, psychiatric and substance use comorbidities that affect treatment decisions and a comprehensive evaluation that includes a detailed history, physical, and mental health evaluation is essential. Although there is no “gold standard” for opioid misuse risk assessment, several validated measures have been shown to be useful. Controlled substance agreements, regular urine drug screens, and interventions such as motivational counseling have been shown to help improve patient compliance with opioids and to minimize aberrant drug-related behavior. Finally, we discuss the future of abuse-deterrent opioids and other potential strategies for back pain management.

  2. Sucrose-induced analgesia in mice: Role of nitric oxide and opioid receptor-mediated system

    Directory of Open Access Journals (Sweden)

    Abtin Shahlaee

    2013-01-01

    Full Text Available Background: The mechanism of action of sweet substance-induced analgesia is thought to involve activation of the endogenous opioid system. The nitric oxide (NO pathway has a pivotal role in pain modulation of analgesic compounds such as opioids. Objectives: We investigated the role of NO and the opioid receptor-mediated system in the analgesic effect of sucrose ingestion in mice. Materials and Methods: We evaluated the effect of intraperitoneal administration of 10 mg/kg of NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME and 20 mg/kg of opioid receptor antagonist, naltrexone on the tail flick response in sucrose ingesting mice. Results: Sucrose ingestion for 12 days induced a statistically significant increase in the latency of tail flick response which was unmodified by L-NAME, but partially inhibited by naltrexone administration. Conclusions: Sucrose-induced nociception may be explained by facilitating the release of endogenous opioid peptides. Contrary to some previously studied pain models, the NO/cyclic guanosine monophosphate (cGMP pathway had no role in thermal hyperalgesia in our study. We recommend further studies on the involvement of NO in other animals and pain models.

  3. Analgesic properties of a dexmedetomidine infusion after uvulopalatopharyngoplasty in patients with obstructive sleep apnea

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    Waleed M Abdelmageed

    2011-01-01

    Full Text Available Background: Dexmedetomidine is an alpha 2 -adrenergic agonist with sedative and analgesic properties. This study aimed to investigate if the use of a continuous dexmedetomidine infusion with i.v. morphine patient-controlled analgesia (PCA could improve postoperative analgesia while reducing opioid consumption and opioid-related side effects. Methods: In this prospective randomized, double-blinded, controlled study, 39 patients with obstructive sleep apnea syndrome undergoing uvulopalatopharyngoplasty were assigned to two groups. Group D (dexmedetomidine group received a loading dose of dexmedetomidine 1 μg.kg-1 i.v., 30 minutes before the anticipated end of surgery, followed by infusion at 0.6 μg.kg-1 h-1 for 24 hours. Group P (placebo group received a bolus and infusion of placebo. In both groups, postoperative pain was initially controlled by i.v. morphine titration and then PCA with morphine. Cumulative PCA morphine consumption, pain intensities, sedation scores, cardiovascular and respiratory variables and opioid-related adverse effects were recorded for 48 hours after operation. Results: Compared with placebo group, patients in the dexmedetomidine group required 52.7% less PCA morphine during the first 24 hours postoperatively, with significantly better visual analogue scale scores, less incidence of respiratory obstruction (5 vs. 12 patients, respectively; P = .037 and longer time to first analgesic request (21 (11 vs. 9 (4 minutes; P = .002. Fewer patients in group D experienced nausea and vomiting than those in group P (7 vs. 24 patients, respectively; P < .05. Conclusion: Continuous dexmedetomidine infusion may be a useful analgesic adjuvant for patients susceptible to opioid-induced respiratory depression.

  4. Step 7: Educates Staff in Nondrug Methods of Pain Relief and Does Not Promote Use of Analgesic, Anesthetic Drugs: The Coalition for Improving Maternity Services:

    OpenAIRE

    Leslie, Mayri Sagady; Romano, Amy; Woolley, Deborah

    2007-01-01

    Step 7 of the Ten Steps of Mother-Friendly Care insures that staff are knowledgeable about nondrug methods of pain relief and that analgesic or anesthetic drugs are not promoted unless required to correct a complication. The rationales for compliance and systematic reviews are presented on massage, hypnosis, hydrotherapy, and the use of opioids, regional analgesia, and anesthesia.

  5. Nerve Injury Diminishes Opioid Analgesia through Lysine Methyltransferase-mediated Transcriptional Repression of μ-Opioid Receptors in Primary Sensory Neurons.

    Science.gov (United States)

    Zhang, Yuhao; Chen, Shao-Rui; Laumet, Geoffroy; Chen, Hong; Pan, Hui-Lin

    2016-04-15

    The μ-opioid receptor (MOR, encoded by Oprm1) agonists are the mainstay analgesics for treating moderate to severe pain. Nerve injury causes down-regulation of MORs in the dorsal root ganglion (DRG) and diminishes the opioid effect on neuropathic pain. However, the epigenetic mechanisms underlying the diminished MOR expression caused by nerve injury are not clear. G9a (encoded by Ehmt2), a histone 3 at lysine 9 methyltransferase, is a key chromatin regulator responsible for gene silencing. In this study, we determined the role of G9a in diminished MOR expression and opioid analgesic effects in animal models of neuropathic pain. We found that nerve injury in rats induced a long-lasting reduction in the expression level of MORs in the DRG but not in the spinal cord. Nerve injury consistently increased the enrichment of the G9a product histone 3 at lysine 9 dimethylation in the promoter of Oprm1 in the DRG. G9a inhibition or siRNA knockdown fully reversed MOR expression in the injured DRG and potentiated the morphine effect on pain hypersensitivity induced by nerve injury. In mice lacking Ehmt2 in DRG neurons, nerve injury failed to reduce the expression level of MORs and the morphine effect. In addition, G9a inhibition or Ehmt2 knockout in DRG neurons normalized nerve injury-induced reduction in the inhibitory effect of the opioid on synaptic glutamate release from primary afferent nerves. Our findings indicate that G9a contributes critically to transcriptional repression of MORs in primary sensory neurons in neuropathic pain. G9a inhibitors may be used to enhance the opioid analgesic effect in the treatment of chronic neuropathic pain. PMID:26917724

  6. Differential effects of LY235959, a competitive antagonist of the NMDA receptor on kappa-opioid receptor agonist induced responses in mice and rats.

    Science.gov (United States)

    Bhargava, H N; Thorat, S N

    1997-02-01

    The effects of the competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, LY235959, were determined on the analgesic and hypothermic effects as well as on the development of tolerance to these effects of U-50,488H, a kappa-opioid receptor agonist in mice and rats. In the mouse, a single injection of LY235959 given 10 min prior to U-50,488H did not modify the analgesic action of the latter. Similarly, chronic administration of LY235959 twice a day for 4 days did not modify U-50,488H-induced analgesia in mice. Repeated pretreatment of mice with LY235959 dose-dependently attenuated the development of tolerance to the analgesic actions of U-50,488H. In the rat, LY235959 by itself produced a significant analgesia and prior treatment of rats with LY235959 enhanced the analgesic action of U-50,488H. Similar effects were seen with the hypothermic action. Pretreatment of rats with LY235959 attenuated the development of tolerance to the analgesic but not to the hypothermic action of U-50,488H. These results provide evidence that LY235959 produces differential actions on nociception and thermic responses by itself and when given acutely with U-50,488H in mice and rats. However, when the animals are pretreated with LY235959, similar inhibitory effects are observed on the development of tolerance to the analgesic action of U-50,488H in both the species. These studies demonstrate an involvement of the NMDA receptor in the development of kappa-opioid tolerance and suggest that the biochemical consequences of an opioid's interaction with the opioid receptor are not the only factors that contribute to the acute and chronic actions of opioid analgesic drugs. PMID:9045999

  7. Tapentadol in the management of opioid-naïve patients with cancer pain

    OpenAIRE

    E. López Ramírez; D. M. Muñoz Carmona; J. Contreras Martínez; A. de la Torre-Luque

    2016-01-01

    Introduction: Tapentadol is a centrally acting analgesic with two mechanisms of action (μ opioid agonism and norepinephrine reuptake inhibition). Patients and methods: Tapentadol in 53 cancer opioid-naïve patients with chronic and/or acute pain treated with tapentadol in 3 Radiotherapy Departments from October 2011 to February 2013. Results: Patients included 18 women (33.96 %) and 35 men (66.04 %) aged 28-85 years (mean: 62.7). Treatment was suspended due to death in 16.98 %, improvement in ...

  8. Effect of fentanyl on 5-HT efflux involves both opioid and 5-HT1A receptors

    OpenAIRE

    Tao, Rui; Karnik, Meghana; Ma, Zhiyuan; Auerbach, Sidney B

    2003-01-01

    Fentanyl is a μ-opioid analgesic that might disinhibit 5-HT neurons and thus increase 5-HT efflux. However, fentanyl also binds to 5-HT1A receptors, and if it activates 5-HT1A somatodendritic autoreceptors, the resultant inhibition might offset opioid-mediated increases in 5-HT efflux. To test this hypothesis, we used microdialysis to study effects of fentanyl on extracellular 5-HT in the dorsal raphe nucleus (DRN) of unanesthetized rats.Systemic administration of fentanyl (0.01–0.2 mg kg−1, ...

  9. Opioid tolerance in periaqueductal gray neurons isolated from mice chronically treated with morphine

    OpenAIRE

    Bagley, Elena E.; Chieng, Billy C H; Christie, MacDonald J.; Connor, Mark

    2005-01-01

    The midbrain periaqueductal gray (PAG) is a major site of opioid analgesic action, and a significant site of cellular adaptations to chronic morphine treatment (CMT). We examined μ-opioid receptor (MOP) regulation of voltage-gated calcium channel currents (ICa) and G-protein-activated K channel currents (GIRK) in PAG neurons from CMT mice.Mice were injected s.c. with 300 mg kg−1 of morphine base in a slow release emulsion three times over 5 days, or with emulsion alone (vehicles). This protoc...

  10. The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

    OpenAIRE

    L. Gonçalves; Friend, L. V.; Dickenson, A. H.

    2015-01-01

    Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerabl...

  11. Ready Conversion of Patients with Well-Controlled, Moderate to Severe, Chronic Malignant Tumor–related Pain on Other Opioids to Tapentadol Extended Release

    OpenAIRE

    Imanaka, Keiichiro; Tominaga, Yushin; Etropolski, Mila; Ohashi, Hiroki; Hirose, Keiichiro; Matsumura, Taka

    2014-01-01

    Background and Objectives The effectiveness and tolerability of tapentadol extended release (ER), a centrally acting analgesic with μ-opioid receptor agonist and norepinephrine (noradrenaline) reuptake inhibitor activities, have been demonstrated in patients with chronic pain, including those switching directly from prior opioid therapy. The objective of the current study was to evaluate the effectiveness and safety of conversion to oral tapentadol ER (50–250 mg twice daily) from previous aro...

  12. Treating Pain with Opioids

    Science.gov (United States)

    ... it costs. Ask if they have a drug discount program that can help you pay less for your medicine. Buy your medicine from the pharmacy that gives you the cheapest price.  Sign up for patient assistance programs: Most companies that make medicines have programs that Opioids: Howhaerleptpheeoypulesetdh? ...

  13. The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism

    Directory of Open Access Journals (Sweden)

    Coluzzi F

    2015-03-01

    Full Text Available Flaminia Coluzzi,1,2 Joseph Pergolizzi,3,4 Robert B Raffa,5 Consalvo Mattia1,2 1Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anesthesiology, Intensive Care Medicine and Pain Therapy, Faculty of Pharmacy and Medicine – Polo Pontino, Sapienza University of Rome, Latina, Italy; 2SIAARTI Study Group on Acute and Chronic Pain, Rome, Italy; 3Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 4Naples Anesthesia and Pain Associates, Naples, FL, 5Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1 the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2 reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3 chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine. Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily should be monitored for the early detection of hormonal impairment and low bone mass density. Keywords: opioids side effects, bone metabolism, fractures, OPIAD, endocrine system, chronic pain

  14. Effects of stress and β-funal trexamine pretreatment on morphine analgesia and opioid binding in rats

    International Nuclear Information System (INIS)

    This study was essentially an in vivo protection experiment designed to test further the hypothesis that stress induces release of endogenous opiods which then act at opioid receptors. Rats that were either subjected to restraint stress for 1 yr or unstressed were injected ICV with either saline or 2.5 μg of β-funaltrexamine (β-FNA), an irreversible opioid antagonist that alkylates the mu-opioid receptor. Twenty-four hours later, subjects were tested unstressed for morphine analgesia or were sacrificed and opioid binding in brain was determined. [3H]D-Ala2NMePhe4-Gly5(ol)enkephalin (DAGO) served as a specific ligand for mu-opioid receptors, and [3H]-bremazocine as a general ligand for all opioid receptors. Rats injected with saline while stressed were significantly less sensitive to the analgesic action of morphine 24 hr later than were their unstressed counterparts. β-FNA pretreatment attenuated morphine analgesia in an insurmountable manner. Animals pretreated with β-FNA while stressed were significantly more sensitive to the analgesic effect of morphine than were animals that received β-FNA while unstressed. β-FNA caused small and similar decreases in [3H]-DAGO binding in brain of both stressed and unstressed animals. 35 references, 2 figures, 2 tables

  15. [Study of analgesic efficacy of propacetamol in the postoperative period using a double blind placebo controlled method].

    Science.gov (United States)

    Nikoda, V V; Maiachkin, R B

    2002-01-01

    The efficiency and safety of postoperative use of propacetamol was estimated in 30 patients by means of double blind placebo controlled method. The first group consisted of 15 patients to whom propacetamol was introduced intravenously in single dose of 2 g along with patient controlled anesthesia with promedol. Placebo in combination with patient control anesthesia were used in 15 patients from the 2nd group. Intravenous introducing of propacetamol in dose of 2 g in 15 minutes provides relief of pain intensity in postoperative period. So it permits to consider propacetamol as basic non-opioid analgesic. In early postoperative period combination of propacetamol and opioid analgesic (promedol) reduces demands in the latter by 44%. PMID:12462772

  16. Impulsivity and risk for prescription opioid misuse in a chronic pain patient sample.

    Science.gov (United States)

    Vest, Noel; Reynolds, Caleb J; Tragesser, Sarah L

    2016-09-01

    Misuse of, and addiction to, prescription opioid pain relievers is a growing concern, in both non-clinical samples and chronic pain patients receiving opioid analgesic therapy. Research is needed to identify which patients may be more prone to misuse or dependence on opioids in a chronic pain treatment setting. Based on literature showing the role of impulsivity in substance use disorders generally, we predicted that impulsivity may also be important to understanding which individuals may be at risk for opioid misuse when opioids are prescribed for pain. The present study examined associations between impulsivity facets and measures of prescription opioid misuse and symptoms. Four facets of impulsivity were examined: urgency, sensation seeking, lack of premeditation, and lack of perseverance. 143 patients receiving treatment for chronic pain at a regional pain clinic completed a series of questionnaires including the UPPS and measures of opioid risk and misuse. Consistent with predictions, urgency was associated with risk for future misuse (β=0.246, pSensation seeking was also associated with current misuse (β=0.279, p<0.01). These results suggest that identifying facets of impulsivity is important to understanding and assessing for risk of prescription opioid misuse in the context of chronic pain treatment. These data indicate that patients who react impulsively to negative mood states and cravings may be especially prone to developing aberrant use patterns when taking prescription opioids. This is the first known study to identify the role of urgency in predicting risk for OUDs in chronic pain patients. PMID:27156219

  17. Weighing the balance: how analgesics used in chronic pain influence sleep?

    Science.gov (United States)

    Bohra, Miqdad H; Kaushik, Chhavi; Temple, Daniel; Chung, Sharon A; Shapiro, Colin M

    2014-08-01

    Pain and sleep share a bidirectional relationship, with each influencing the other. Several excellent reviews have explored this relationship. In this article, we revisit the evidence and explore existing research on this complex inter-relationship. The primary focus of the article is on the pharmacological treatment of chronic non-malignant pain and the main purpose is to review the effect of various pharmacological agents used in the management of chronic pain on sleep. This has not been comprehensively done before. We explore the clinical use of these agents, their impact on sleep architecture and sleep physiology, the mechanism of action on sleep parameters and sleep disorders associated with these agents. Pharmacological classes reviewed include antidepressants, opioid analgesics, anti-epileptics, cannabinoids and non-steroidal anti-inflammatory agents, drugs most commonly used to manage chronic pain. The objective is to help health professionals gain better insight into the complex effect that commonly used analgesics have on an individual's sleep and how this could impact on the effectiveness of the drug as an analgesic. We conclude that antidepressants have both positive and negative effects on sleep, so do opioids, but in the latter case the evidence shifts towards the counterproductive side. Some anticonvulsants are sleep sparing and non-steroidal anti-inflammatory drugs (NSAIDs) are sleep neutral. Cannabinoids remain an underexplored and researched group. PMID:26516542

  18. Correlation of Pain Scores, Analgesic Use, and Beck Anxiety Inventory Scores During Hospitalization in Lower Extremity Amputees

    OpenAIRE

    Trame, Cathy D; Greene, Erin; Moddeman, Gail; Booth, Branyan A; Konstantakos, Emmanuel K; Parada, Stephen; Siebuhr, Karl; Laughlin, Richard T.

    2008-01-01

    Post amputation pain can be debilitating for patients and families. Chronic pain is a common phenomenon after lower extremity amputation, occurring in up to 80% of this population. The purpose of this pilot study was to correlate post amputation pain scores to opioid analgesic consumption and Beck Anxiety Inventory (BAI) scores. Twenty-three patients with lower extremity amputation at an 827-bed acute care inner-city hospital were surveyed pre-operatively and post-operatively to determine if ...

  19. Analgesic use among nursing homes residents, with and without dementia, in Poland

    Directory of Open Access Journals (Sweden)

    Neumann-Podczaska A

    2016-03-01

    Full Text Available Agnieszka Neumann-Podczaska,1 Tomasz Nowak,2 Aleksandra Suwalska,3 Dorota Łojko,4 Roma Krzymińska-Siemaszko,2 Elżbieta Kozak-Szkopek,5 Katarzyna Wieczorowska-Tobis2 1Department of Geriatrics and Gerontology, 2Department of Palliative Medicine, Laboratory of Geriatrics, 3Department of Psychiatry, Laboratory of Neuropsychobiology, 4Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, 5Department of Geriatrics, Medical University of Warsaw, Warsaw, Poland Abstract: Many age-associated diseases are accompanied by pain. There is no doubt that pain is underrecognized among elderly nursing home residents and the diagnosing of pain is a real challenge in subjects with dementia. The aim of the study was to characterize analgesic use among nursing home residents and to delineate the putative associations between pain management and cognitive functions of elderly persons. The study involved 392 subjects (males:females – 81:311 with a mean age of 83.6±5.9 years. The residents’ medical files in relation to diagnoses and drug consumption were analyzed, and the screening of cognitive functions was performed using the Mini-Mental State Examination (MMSE. One hundred and thirteen residents (28.8% received some analgesics. Among them 84 (21.4% used them routinely, 25 (6.4% – pro re nata (PRN and four (1.0% – both routinely and PRN. Non-opioid analgesics were taken routinely by 53 residents, weak opioids by nine subjects, and one person was receiving strong opioids. Additionally, three individuals were taking a combination preparation of tramadol and acetaminophen. The rate of subjects who were not receiving any pain treatment was higher in residents with MMSE between 0 and 9 points than in those with MMSE between 24 and 30 points (P=0.0151. Furthermore, ten residents (9.1% with severe dementia were treated with analgesics PRN. The results of our study point to a remarkably low use of analgesics in nursing home residents in

  20. Oral or transdermal opioids for osteoarthritis of the knee or hip.

    OpenAIRE

    Da Costa, Bruno; Nüesch, Eveline; Kasteler, Rahel; Husni, Elaine; Welch, Vivian; Rutjes, Anne W.S.; Jüni, Peter

    2014-01-01

    BACKGROUND Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people. Opioids may be a viable treatment option if people have severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory. This is an update of a Cochrane review first published in 2009. OBJECTIVES To determine the effects on pain, function, safety, and addiction of oral or transd...

  1. Responsible opioid use.

    Science.gov (United States)

    Compton, Peggy; Weaver, Michael F

    2015-06-01

    Editor's Note The journal is delighted to introduce a new feature in this issue that focuses on the complex and multifaceted issue of managing pain and related symptoms while responsibly attending to minimizing substance abuse. How should the seemingly disparate disciplines of drug abuse and symptom control interact? Should these be two separate fields or should practitioners/investigators in one also be qualified in the other? Is that even feasible? We are honored to have two leading, academically based clinician scientists coordinating this new feature. Peggy Compton is Professor and Associate Dean for Academic Affairs at the School of Nursing & Health Studies, Georgetown University in Washington, DC. Many readers know of Peggy's work from her years on the faculty of the University of California at Los Angeles (UCLA). Peggy brings both clinical and scientific addictionology expertise as well as the invaluable perspective of nursing to this arena. Her collaborator is Michael F. Weaver. Mike is Professor of Psychiatry and Behavioral Sciences, and Medical Director of the Center for Neurobehavioral Research on Addictions, at the University of Texas Health Sciences Center at Houston. Prior to moving to Texas, Dr. Weaver became internationally known for his work in addiction medicine at the Medical College of Virginia. We look forward to detailed explorations of many interacting issues in symptom control and substance abuse in the articles featured in this new journal feature in coming issues. The commentary below, the article by Kanouse and Compton, the Issue Brief issued by the U.S. Department of Health and Human Services, and my editorial, all of which appear in this journal issue, introduce the new feature, which I am confident will make valuable contributions to the pain management and substance abuse literature. Arthur G. Lipman, Editor ABSTRACT Abusers of prescription opioids represent two distinct populations: those who develop addiction via opioids prescribed

  2. Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators.

    Science.gov (United States)

    Kruegel, Andrew C; Gassaway, Madalee M; Kapoor, Abhijeet; Váradi, András; Majumdar, Susruta; Filizola, Marta; Javitch, Jonathan A; Sames, Dalibor

    2016-06-01

    Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta-opioid receptors. These results show that mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu-opioid receptor, which do not recruit β-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+)-mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids. PMID

  3. Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine.

    Science.gov (United States)

    Zadina, James E; Nilges, Mark R; Morgenweck, Jenny; Zhang, Xing; Hackler, Laszlo; Fasold, Melita B

    2016-06-01

    Opioids acting at the mu opioid receptor (MOR) are the most effective analgesics, however adverse side effects severely limit their use. Of particular importance, abuse liability results in major medical, societal, and economic problems, respiratory depression is the cause of fatal overdoses, and tolerance complicates treatment and increases the risk of side effects. Motor and cognitive impairment are especially problematic for older adults. Despite the host of negative side effects, opioids such as morphine are commonly used for acute and chronic pain conditions. Separation of analgesia from unwanted effects has long been an unmet goal of opioid research. Novel MOR agonist structures may prove critical for greater success. Here we tested metabolically stable analogs of the endomorphins, endogenous opioids highly selective for the MOR. Compared to morphine, the analogs showed dramatically improved analgesia-to-side-effect ratios. At doses providing equal or greater antinociception than morphine in the rat, the analogs showed reduced a) respiratory depression, b) impairment of motor coordination, c) tolerance and hyperalgesia, d) glial p38/CGRP/P2X7 receptor signaling, and e) reward/abuse potential in both conditioned place preference and self-administration tests. Differential effects on glial activation indicate a mechanism for the relative lack of side effects by the analogs compared to morphine. The results suggest that endomorphin analogs described here could provide gold standard pain relief mediated by selective MOR activation, but with remarkably safer side effect profiles compared to opioids like morphine. PMID:26748051

  4. Practice guidelines for transdermal opioids in malignant pain.

    Science.gov (United States)

    Skaer, Tracy L

    2004-01-01

    Patients with moderate-to-severe malignancy-related pain require opioid pharmacotherapy. Many cancer patients continue to be prescribed subtherapeutic doses of pain medications resulting in undue suffering and diminished quality of life. Pain associated with malignancy and its treatment may exacerbate other symptoms associated with cancer, including nausea, fatigue, weakness, dyspnoea, constipation and impaired cognition. The choice of analgesic pharmacotherapy should be individualised and based on the intensity of pain reported by the patient, rather than its specific aetiology. When selecting pain management pharmacotherapy, the healthcare provider should consider the patient's pain level, activity level and any comorbid illness. Intolerable adverse effects, ineffective pain relief or a change in the patient's clinical status can dictate the need for a new pain management regimen. Healthcare providers must be able to readily quantify the relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal formulations of fentanyl and buprenorphine are effective pharmacotherapy that can be safely used for cancer patients with pain. However, clinicians need to be cognisant that the US/UK manufacturer's recommendations for equianalgesic dose administration of transdermal fentanyl may result in initial doses that produce subtherapeutic concentrations and unrelieved pain in some patients. A less conservative dose administration algorithm for transdermal fentanyl using a 2:1 (mg/day of oral morphine : microg/h of transdermal fentanyl) conversion ratio that considers both a review of the literature and clinical experience should help clinicians individualise cancer pain pharmacotherapy. PMID:15537367

  5. Treating Chronic Pain with Opioids: Comparing Effectiveness and Cost

    Science.gov (United States)

    Treating Chronic Pain with Opioids: Comparing Effectiveness and Cost What are opioids? Opioids are very strong prescription ... using opioids. We compared the effectiveness, safety, and cost of different opioids. We chose these as Consumer ...

  6. US Food and Drug Administration's Risk Evaluation and Mitigation Strategy for extended-release and long-acting opioids: pros and cons, and a European perspective.

    Science.gov (United States)

    Mercadante, Sebastiano; Craig, David; Giarratano, Antonello

    2012-12-24

    Prescriptions for opioid analgesics to manage moderate-to-severe chronic non-cancer pain have increased markedly over the last decade. An unintentional consequence of greater prescription opioid utilization has been the parallel increase in misuse, abuse and overdose, which are serious risks associated with all opioid analgesics. In response to disturbing rises in prescription opioid abuse, the US Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could dramatically change the development, release, marketing and prescription of extended-release opioids, questions remain on how these programmes may influence prescribing practices, patient safety and ultimately patient access to these agents. The extent of the availability and misuse of prescription opioids in Europe is difficult to assess from the data currently available, due in large part to the considerable differences in prescribing patterns and regulations between countries. Balancing the availability of prescription opioids for those patients who have pain, while discouraging illicit use, is a complex challenge and requires effective efforts on many levels, particularly in Europe where policies are quite different between countries. PMID:23116252

  7. Fisiología y farmacología clínica de los opioides epidurales e intratecales Physiology and clinical pharmacology of epidural and intrathecal opioids

    Directory of Open Access Journals (Sweden)

    B. Mugabure

    2005-02-01

    intradural. La metadona es otro fármaco al que se le ha observado una selectividad medular moderada tras su administración epidural. Sin embargo, su prolongada vida media puede resultar en su acumulación plasmática y presencia de efectos supraespinales a lo largo del tiempo. La administración epidural de fentanilo ofrece muy pocas ventajas sobre su utilización intravenosa, salvo en obstetricia donde parece producir una analgesia selectiva medular de grado moderado. Finalmente, la administración epidural de sufentanilo o alfentanilo parece producir analgesia por recaptación sistémica y redistribución hacia los receptores opioides cerebrales.The history of intrathecal and epidural anaesthesia is in parallel with the development of general anaesthesia. The first published report on opioids for intrathecal anaesthesia belongs to a Romanian surgeon, who presented his experience at Paris in 1901. It was almost a century before the opioids were used for epidural analgesia. Epidural and intrathecal opioids are today part of a routine regimen for intra and postoperative analgesia. Over the last 30 years, the use of epidural opioids has became a standard for analgesia in labor and delivery, and for the management of acute and chronic pain. It has been widely asumed that any opioid placed in the epidural or intrathecal spaces will produce highly selective spinally mediated analgesia that is superior to that produced by other analgesic techniques. Unfortunately, this is simply not true. In fact, multiples opioids are currently employed for spinal use despite the fact that clinical evidence has shown that spinal administration does not produce analgesia with a selective spinal mechanism or the analgesia produced is not superior to that produced by intravenous administration. Appropriate use of spinal opioids necessitates under-standing the physiology and clinical pharmacology of these drugs and which opioids produce selective spinal analgesia and which do not. In short, spinal

  8. Nitrous oxide as an opioid agonist: some experimental and clinical applications

    International Nuclear Information System (INIS)

    The purpose of the present investigation is primarily to determine whether N2O at analgesic concentrations acts vid the opioid system. Interaction at an opioid receptor level will be studied by means of a ligand binding study. An in vitro study is presented in which the effect of 50% N2O mixed with 50% O2 and 100% N2O on (3H) naloxone binding is presented. Secondly, possible therapeutic and diagnostic applications of the use of N2O in conditions possibly related to abnormalities of the opioid system viz alcoholism, depression, schizophrenia and anxiety will be investigated. Thirdly, possible hematological abnormalities induced by the use of N2O will be studied

  9. Opioids: The Prescription Drug & Heroin Overdose Epidemic

    Science.gov (United States)

    ... Pain Medication Facts Prevention Treatment & Recovery Overdose Response Health Professionals Resources Law Enforcement Resources Opioids: The Prescription Drug & Heroin Overdose Epidemic Opioids are natural or synthetic chemicals ...

  10. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Karine Thibault

    Full Text Available Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  11. Enhanced analgesic effect of morphine-nimodipine combination after intraspinal administration as compared to systemic administration in mice

    Indian Academy of Sciences (India)

    Dilip Verma; Subrata Basu Ray; Ishan Patro; Shashi Wadhwa

    2005-09-01

    Calcium plays an important role in the pathophysiology of pain. A number of studies have investigated the effect of L-type calcium channel blockers on the analgesic response of morphine. However, the results are conflicting. In the present study, the antinociceptive effect of morphine (2.5 g) and nimodipine (1 g) co-administered intraspinally in mice was observed using the tail flick test. It was compared to the analgesic effect of these drugs (morphine – 250 g subcutaneously; nimodipine – 100 g intraperitoneally) after systemic administration. Nimodipine is highly lipophilic and readily crosses the blood brain barrier. Addition of nimodipine to morphine potentiated the analgesic response of the latter when administered through the intraspinal route but not when administered through systemic route. It may be due to direct inhibitory effect of morphine and nimodipine on neurons of superficial laminae of the spinal cord after binding to -opioid receptors and L-type calcium channels respectively.

  12. The analgesic effect of wound infiltration with local anaesthetics after breast surgery

    DEFF Research Database (Denmark)

    Byager, N; Hansen, Mads; Mathiesen, Ole; Dahl, J B

    2014-01-01

    -operative pain after breast surgery. METHODS: A systematic review was performed by searching PubMed, Google Scholar, the Cochrane database and Embase for randomised, blinded, controlled trials of wound infiltration with local anaesthetics for post-operative pain relief in female adults undergoing breast surgery......BACKGROUND: Wound infiltration with local anaesthetics is commonly used during breast surgery in an attempt to reduce post-operative pain and opioid consumption. The aim of this review was to evaluate the effect of wound infiltration with local anaesthetics compared with a control group on post...... statistically significant reduction in post-operative, supplemental opioid consumption that was, however, of limited clinical relevance. CONCLUSION: Wound infiltration with local anaesthetics may have a modest analgesic effect in the first few hours after surgery. Pain after breast surgery is, however...

  13. Morphine protects against methylmercury intoxication: a role for opioid receptors in oxidative stress?

    Directory of Open Access Journals (Sweden)

    Allan Costa-Malaquias

    Full Text Available Mercury is an extremely dangerous environmental contaminant responsible for episodes of human intoxication throughout the world. Methylmercury, the most toxic compound of this metal, mainly targets the central nervous system, accumulating preferentially in cells of glial origin and causing oxidative stress. Despite studies demonstrating the current exposure of human populations, the consequences of mercury intoxication and concomitant use of drugs targeting the central nervous system (especially drugs used in long-term treatments, such as analgesics are completely unknown. Morphine is a major option for pain management; its global consumption more than quadrupled in the last decade. Controversially, morphine has been proposed to function in oxidative stress independent of the activation of the opioid receptors. In this work, a therapeutic concentration of morphine partially protected the cellular viability of cells from a C6 glioma cell line exposed to methylmercury. Morphine treatment also reduced lipid peroxidation and totally prevented increases in nitrite levels in those cells. A mechanistic study revealed no alteration in sulfhydryl groups or direct scavenging at this opioid concentration. Interestingly, the opioid antagonist naloxone completely eliminated the protective effect of morphine against methylmercury intoxication, pointing to opioid receptors as the major contributor to this action. Taken together, the experiments in the current study provide the first demonstration that a therapeutic concentration of morphine is able to reduce methylmercury-induced oxidative damage and cell death by activating the opioid receptors. Thus, these receptors may be a promising pharmacological target for modulating the deleterious effects of mercury intoxication. Although additional studies are necessary, our results support the clinical safety of using this opioid in methylmercury-intoxicated patients, suggesting that normal analgesic doses could

  14. Analgesic efficacy of lidocaine and multimodal analgesia for chest tube removal: A randomized trial study1

    Science.gov (United States)

    Pinheiro, Valdecy Ferreira de Oliveira; da Costa, José Madson Vidal; Cascudo, Marcelo Matos; Pinheiro, Ênio de Oliveira; Fernandes, Maria Angela Ferreira; de Araujo, Ivonete Batista

    2015-01-01

    Objective: to assess the analgesic efficacy of subcutaneous lidocaine and multimodal analgesia for chest tube removal following heart surgery. Methods: sixty volunteers were randomly allocated in two groups; 30 participants in the experimental group were given 1% subcutaneous lidocaine, and 30 controls were given a multimodal analgesia regime comprising systemic anti-inflammatory agents and opioids. The intensity and quality of pain and trait and state anxiety were assessed. The association between independent variables and final outcome was assessed by means of the Chi-squared test with Yates' correction and Fisher's exact test. Results: the groups did not exhibit significant difference with respect to the intensity of pain upon chest tube removal (p= 0.47). The most frequent descriptors of pain reported by the participants were pressing, sharp, pricking, burning and unbearable. Conclusion: the present study suggests that the analgesic effect of the subcutaneous administration of 1% lidocaine combined with multimodal analgesia is most efficacious. PMID:26625989

  15. Dissociation of μ- and δ-opioid inhibition of glutamatergic synaptic transmission in superficial dorsal horn

    Directory of Open Access Journals (Sweden)

    Vaughan Christopher W

    2010-10-01

    Full Text Available Abstract Background There is anatomical and behavioural evidence that μ- and δ-opioid receptors modulate distinct nociceptive modalities within the superficial dorsal horn. The aim of the present study was to examine whether μ- and δ-opioid receptor activation differentially modulates TRP sensitive inputs to neurons within the superficial dorsal horn. To do this, whole cell patch clamp recordings were made from lamina I - II neurons in rat spinal cord slices in vitro to examine the effect of opioids on TRP agonist-enhanced glutamatergic spontaneous miniature excitatory postsynaptic currents (EPSCs. Results Under basal conditions the μ-opioid agonist DAMGO (3 μM reduced the rate of miniature EPSCs in 68% of neurons, while the δ- and κ-opioid agonists deltorphin-II (300 nM and U69593 (300 nM did so in 13 - 17% of neurons tested. The TRP agonists menthol (400 μM and icilin (100 μM both produced a Ca2+-dependent increase in miniature EPSC rate which was unaffected by the voltage dependent calcium channel (VDCC blocker Cd2+. The proportion of neurons in which deltorphin-II reduced the miniature EPSC rate was enhanced in the presence of icilin (83%, but not menthol (0%. By contrast, the proportion of DAMGO and U69593 responders was unaltered in the presence of menthol (57%, 0%, or icilin (57%, 17%. Conclusions These findings demonstrate that δ-opioid receptor activation selectively inhibits inputs activated by icilin, whereas μ-opioid receptor activation has a more widespread effect on synaptic inputs to neurons in the superficial dorsal horn. These findings suggest that δ-opioids may provide a novel analgesic approach for specific, TRPA1-like mediated pain modalities.

  16. The Influence of Genotype Polymorphism on Morphine Analgesic Effect for Postoperative Pain in Children

    Science.gov (United States)

    Lee, Mi Geum; Kim, Hyun Jung; Lee, Keun Hwa

    2016-01-01

    Background Although opioids are the most commonly used medications to control postoperative pain in children, the analgesic effects could have a large inter-individual variability according to genotypes. The aim of this study was to investigate the association between single nucleotide polymorphisms and the analgesic effect of morphine for postoperative pain in children. Methods A prospective study was conducted in 88 healthy children undergoing tonsillectomy, who received morphine during the operation. The postoperative pain score, frequency of rescue analgesics, and side effects of morphine were assessed in the post-anesthesia care unit. The children were genotyped for OPRM1 A118G, ABCB1 C3435T, and COMT Val158Met. Results Children with at least one G allele for OPRM1 (AG/GG) had higher postoperative pain scores compared with those with the AA genotype at the time of discharge from the post-anesthesia care unit (P = 0.025). Other recovery profiles were not significantly different between the two groups. There was no significant relationship between genotypes and postoperative pain scores in analysis of ABCB1 and COMT polymorphisms. Conclusions Genetic polymorphism at OPRM1 A118G, but not at ABCB1 C3435T and COMT Val158Met, influences the analgesic effect of morphine for immediate acute postoperative pain in children. PMID:26839669

  17. Evaluation of analgesic activity of the leaves of Passiflora incarnata Linn

    Directory of Open Access Journals (Sweden)

    Suvarna Ingale

    2012-01-01

    Full Text Available Passiflora incarnata also known as ′Passion flower′ is used as an anxiolytic and sedative throughout the world from ancient time. The plant is used as an analgesic, antispasmodic, sedative- hypnotic and narcotic. It is also used in neuralgia, epilepsy, insomnia, ulcers, haemorrhoids and neurosis in many parts of the world. There was no report on analgesic activity of P. incarnata. Hence, the present study is designed to assess analgesic activity of leaves of P. incarnata using sodium chloride-induced eye wiping test and formalin test. In formalin test, n-butanol extract of leaves of P. incarnata (BEPI in the doses of 150 and 300 mg/kg as well as BEPI-F1 showed significant reduction in duration of paw licking in neurogenic and inflammatory phase(P<0.001. Pretreatment with naloxone reversed the analgesia induced by BEPI, while atropine did not reverse the analgesia induced by BEPI significantly (P≤0.001. In eye wiping test, BEPI in the doses of 150 and 300 mg/kg, i.p. exerted significant reduction ( P≤0.001 in number of eye wipes compared to control group. Thus, the result concludes that BEPI and the fraction separated, BEPI-F1 has significant analgesic activity, which may be mediated through central mechanism by modulation of opioid receptors and nicotinic receptors.

  18. Simultaneous determination of 18 abused opioids and metabolites in human hair using LC-MS/MS and illegal opioids abuse proven by hair analysis.

    Science.gov (United States)

    Kim, Jihyun; Ji, Dajeong; Kang, Soyoung; Park, Meejung; Yang, Wonkyung; Kim, Eunmi; Choi, Hwakyung; Lee, Sooyeun

    2014-02-01

    Natural and synthetic opioids have efficient analgesic activity but can also be addictive. Thus, the determination of opioids and their metabolites in biological specimens is of interest in clinical and forensic toxicology laboratories. The analysis of drugs in hair provides valuable information on previous chronic drug use and has been successfully applied to the diagnosis of drug abuse, tolerance, compliance and gestational drug exposure. Despite the abuse of prescription opioids along with heroin and other illegal opiates, few studies have been conducted on the simultaneous determination of the broad range of opioids covering those drugs in hair. In the present study, an analytical method for the simultaneous detection in hair of 18 opioids and metabolites considered to have a high abuse risk based on the results of urine drug screening was established and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the purpose of clinical and forensic applications. The drugs and metabolites were extracted from hair using methanol and analyzed using LC-MS/MS. The validation results proved that the method was selective, accurate and precise with acceptable linearity within calibration ranges. No significant variation was observed by different sources of matrices. The limits of detection and the limits of quantification ranged from 0.05 to 0.25ng/10mg hair and from 0.05 to 0.5ng/10mg hair, respectively. The developed method was successfully applied to 15 hair samples from opioids users. This method will be very useful for monitoring the inappropriate use of opioid drugs. PMID:24270290

  19. Interaction of co-expressed mu- and delta-opioid receptors in transfected rat pituitary GH(3) cells.

    Science.gov (United States)

    Martin, N A; Prather, P L

    2001-04-01

    opioid receptor subtypes in receptor binding studies and the synergistic interaction of mu- and delta-opioids in analgesic assays. PMID:11259622

  20. Anti-nociceptive Activity of Ethnomedicinally Important Analgesic Plant Isodon rugosus Wall. ex Benth: Mechanistic Study and Identifications of Bioactive Compounds.

    Science.gov (United States)

    Zeb, Anwar; Ahmad, Sajjad; Ullah, Farhat; Ayaz, Muhammad; Sadiq, Abdul

    2016-01-01

    Isodon rugosus Wall. ex Benth. is extensively used as traditional medicine for the management of various types of pain including tooth ache, gastric pain, abdominal pain, ear ache, and generalized body pain. The current study is designed to scientifically verify the purported uses of I. rugosus as analgesic agent and to figure out its possible mechanism of action. Bioactive compounds responsible for analgesic activity were identified using GC and GC-MS analysis. Analgesic potentials were evaluated using acetic acid induced writhing, hot plate test, and formalin induced paw licking test. In acetic acid induced writhing chloroform fraction (Ir.Chf) exhibited 53% analgesia while formalin test displayed 61% inhibition at phase-I and 45% at phase-II respectively at a dose of 100 mg/kg. Similarly, in hot plate test Ir.Chf displayed average reaction time of 7 min at 15, 30, 45, and 60 min intervals. The possible mechanism of action was found to be the central pathway via opioidergic receptors as the mice showed morphine like analgesic activity at pre-administration of naloxone (opioid antagonist) in hot plate and formalin tests. In GC-MS analysis, 83 compounds were identified among which eight compounds including benzyl alcohol, sebacic acid, myristic acid, phytol, sugiol, Tocopherol, α-Amyrin, and stigmasterol were sorted out as previously reported analgesic compounds. Current study revealed that analgesic potential of I. rugosus can attributed to the presence of analgesic compounds. It may also be concluded that opioids receptors are involved in the analgesic mechanism of I. rugosus due to effective antagonism of nalaxone. PMID:27458379

  1. Pure analgesics in a rheumatological outpatient clinic

    Directory of Open Access Journals (Sweden)

    M.A. Cimmino

    2011-09-01

    Full Text Available Objective: Pure analgesics are only rarely used by Italian clinicians and this holds true also for rheumatologists. This work is concerned with an evaluation of the use of analgesics in a rheumatological outpatient clinic during the period 1989-1999. Methods: The records of 1705 patients consecutively seen at the clinic were downloaded on a specifically built website. Results: 4469 visits were considered. In 260 of them (5.8%, analgesics were prescribed to 234 (13.7% patients. The number of patients with a prescription of analgesics steadily increased during the years 1989-1999. The diagnoses in patients assuming analgesics were: osteoarthritis (47.1%, inflammatory arthritis (24.2%, soft tissue rheumatisms (13.7%, nonspecific arthralgia/myalgia (7.5%, and connective tissue diseases (2.6%. Peripheral analgesics were used in 188 (82.5% patients and central analgesics were used in the remaining 40 patients (17.5%. Analgesic drugs were used mainly in degenerative joint conditions. The indications for analgesics in the 55 patients with inflammatory arthrits were: (a partial or total remission of arthritis; for this reason non-steroidal anti-inflammatory drugs were no longer required in 18 patients; (b to increase the analgesic effect of NSAIDs in 23 patients; (c contraindications to NSAIDs in 14 patients (renal failure in 2 patients, gastritis in 10, allergy and bleeding in the remaining two. Conclusions: About 14% of our outpatients were treated with analgesics with an increasing trend in the examined period. The main indications for analgesics are degenerative conditions but they can be used also in selected patients with arthritis.

  2. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P;

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  3. Analgesic Activity of Sphaeranthus indicus Linn

    Directory of Open Access Journals (Sweden)

    P. Malairajan

    2012-12-01

    Full Text Available The ethanol extracts of the whole plant Sphaeranthus indicus Linn. (ALSI (Compositae was tested for analgesic activity by tail immersion method in rat models. The test extracts were tested at 250 mg and 500 mg/kg body weight. The analgesic activity was assessed by keeping pentazocine 10 mg/kg as standard drug. The parameters studied were tail withdrawal reflex and percentage protection. In tail immersion method ALSI pretreatment caused significant increase in analgesic activity and percentage protection found was 66.6 and 67.4 respectively. The result suggested that ALSI possess significant and dose dependent analgesic activity.

  4. Analgesic principle from Abutilon indicum.

    Science.gov (United States)

    Ahmed, M; Amin, S; Islam, M; Takahashi, M; Okuyama, E; Hossain, C F

    2000-04-01

    Bioactivity guided isolation of Abutilon indicum yielded eugenol [4-allyl-2-methoxyphenol], which was found to possess significant analgesic activity. At doses of 10, 30, and 50 mg/kg body weight, eugenol exhibited 21.30 (p < 0.05), 42.25 (p < 0.01) and 92.96% (p < 0.001) inhibition of acetic acid induced writhing in mice. At a dose of 50 mg/kg body weight, eugenol showed 33.40% (p < 0.05) prolongation of tail flicking time determined by the radiant heat method. PMID:10798248

  5. Analgesic Potential of Essential Oils

    Directory of Open Access Journals (Sweden)

    José Ferreira Sarmento-Neto

    2015-12-01

    Full Text Available Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes.

  6. Opioids and Efflux Transporters. 1. P-Glycoprotein Substrate Activity of N-Substituted Analogs of Meperidine.

    OpenAIRE

    Mercer, Susan L.; Cunningham, Christopher W.; Hassan, Hazem; Eddington, Natalie D.; Coop, Andrew

    2006-01-01

    P-Glycoprotein (P-gp) is an efflux transporter which is up-regulated at the blood brain barrier in both morphine and oxycodone tolerant rats. Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-gp, suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of compounds, and show that a meperidine anal...

  7. Medication-assisted therapy for opioid addiction

    OpenAIRE

    Tai, Betty; Saxon, Andrew J.; Ling, Walter

    2013-01-01

    The “Medication-Assisted Therapy for Opioid Addiction” session was chaired by Dr. Betty Tai and had three presenters. The presenters (and their topics) were: Dr. Andrew J. Saxon (Methadone and Buprenorphine for Treatment of Opioid Addiction and HIV Risk Reduction), Dr. Walter Ling (Opioid Antagonist Treatment for Opioid Addiction), and Dr. Betty Tai (Chronic Care Model for Substance Use Disorder).

  8. Analgesic and sedative effects of perioperative gabapentin in total knee arthroplasty A randomized, double-blind, placebo-controlled, dose-finding study

    DEFF Research Database (Denmark)

    Lunn, Troels Haxholdt; Husted, Henrik; Laursen, Mogens Berg;

    2015-01-01

    Gabapentin has shown acute postoperative analgesic effects, but the optimal dose and procedure-specific benefits vs harm have not been clarified. In this randomized, double-blind, placebo-controlled dose-finding study, 300 opioid-naive patients scheduled for total knee arthroplasty were randomized...... (1:1:1) to either gabapentin 1300 mg/d (group A), gabapentin 900 mg/d (group B), or placebo (group C) daily from 2 hours preoperatively to postoperative day 6 in addition to a standardized multimodal analgesic regime. The primary outcome was pain upon ambulation 24 hours after surgery, and the...

  9. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

    Directory of Open Access Journals (Sweden)

    Khanna IK

    2015-12-01

    Full Text Available Ish K Khanna, Sivaram PillarisettiNeuroPn Therapeutics, Alpharetta, GA, USAAbstract: Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed µ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other µ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain.Keywords: buprenorphine, opioids, opioid dependence, partial agonist, hyperalgesia, neuropathic pain

  10. American Society for Pain Management Nursing guidelines on monitoring for opioid-induced sedation and respiratory depression.

    Science.gov (United States)

    Jarzyna, Donna; Jungquist, Carla R; Pasero, Chris; Willens, Joyce S; Nisbet, Allison; Oakes, Linda; Dempsey, Susan J; Santangelo, Diane; Polomano, Rosemary C

    2011-09-01

    As the complexity of analgesic therapies increases, priorities of care must be established to balance aggressive pain management with measures to prevent or minimize adverse events and to ensure high quality and safe care. Opioid analgesia remains the primary pharmacologic intervention for managing pain in hospitalized patients. Unintended advancing sedation and respiratory depression are two of the most serious opioid-related adverse events. Multiple factors, including opioid dosage, route of administration, duration of therapy, patient-specific factors, and desired goals of therapy, can influence the occurrence of these adverse events. Furthermore, there is an urgent need to educate all members of the health care team about the dangers and potential attributes of administration of sedating medications concomitant with opioid analgesia and the importance of initiating rational multimodal analgesic plans to help avoid adverse events. Nurses play an important role in: 1) identifying patients at risk for unintended advancing sedation and respiratory depression from opioid therapy; 2) implementing plans of care to assess and monitor patients; and 3) intervening to prevent the worsening of adverse events. Despite the frequency of opioid-induced sedation, there are no universally accepted guidelines to direct effective and safe assessment and monitoring practices for patients receiving opioid analgesia. Moreover, there is a paucity of information and no consensus about the benefits of technology-supported monitoring, such as pulse oximetry (measuring oxygen saturation) and capnography (measuring end-tidal carbon dioxide), in hospitalized patients receiving opioids for pain therapy. To date, there have not been any randomized clinical trials to establish the value of technologic monitoring in preventing adverse respiratory events. Additionally, the use of technology-supported monitoring is costly, with far-reaching implications for hospital and nursing practices. As a

  11. The analgesic and sedative properties of dexmedetomidine infusion after uvulopalatopharyngoplasty

    Directory of Open Access Journals (Sweden)

    W.Abd El Megid ¹* and Ahmed M. Nassar

    2009-09-01

    Full Text Available Background: Dexmedetomidine is an alpha2 - adrenergic agonist with sedative and analgesic properties. This study aimed to investigate if the use of continuous dexmedetomidine infusion with i.v. morphine patient-controlled analgesia (PCA could improve postoperative analgesia while reducing opioid consumption and opioid-related side effects. Materials & methods: In this prospective randomized, double-blinded, controlled study, 24 patients with obstructive sleep apnea syndrome undergoing uvulopalatopharyngoplasty were assigned to two groups. Group D received a loading dose of dexmedetomidine 1µg kg¯¹ i.v., 30 min before the anticipated end of surgery, followed by a continuous infusion at a rate of 0.6 µg kg¯¹ hr¯¹ for 24 hr. Group P received a volume-matched bolus and infusion of placebo. In both groups, postoperative pain was initially controlled by i.v. morphine titration and then PCA with morphine. Cumulative PCA morphine consumption, pain intensities, sedation scores, cardiovascular and respiratory variables and narcotic-related adverse effects were recorded for 48 h after operation. Results: Extubation time was significantly prolonged in dexmedetomidine group (16±7 vs. 11±6 min p=0.074 in the placebo group. Visual analogue scale scores were significantly greater during the first 2h after tracheal extubation in the placebo group than in the dexmedetomidine group. The time to first analgesic request was significantly longer in the dexmedetomidine group than in the placebo group (21±11 vs. 9±4min; p=0.002. Compared with group P, patients in group D required 52.7% less morphine by PCA during the first 24h postoperative period, whereas levels of sedation were similar between the 2 groups at each observational time point. Fewer patients in group D experienced nausea and vomiting than those in group P (P< 0.05. There was no bradycardia, hypotension, or respiratory depression. Continuous dexmedetomidine infusion may be a useful anesthetic

  12. The analgesic activity of Bestatin as a potent APN inhibitor

    Directory of Open Access Journals (Sweden)

    Mei-RongJia

    2010-06-01

    Full Text Available Bestatin, a small molecular weight dipeptide, is a potent inhibitor of various aminopeptidases as well as LTA4 hydrolase. Various physiological functions of Bestatin have been identified, viz.: (1 an immunomodifier for enhancing the proliferation of normal human bone marrow granulocyte–macrophage progenitor cells to form CFU-GM colonies; Bestatin exerts a direct stimulating effect on lymphocytes via its fixation on the cell surface and an indirect effect on monocytes via aminopeptidase B inhibition of tuftsin catabolism; (2 an immunorestorator and curative or preventive agent for spontaneous tumor; Bestatin alone or its combination with chemicals can prolongate the disease-free interval and survival period in adult acute or chronic leukemia, therefore, it was primarily marketed in 1987 in Japan as an anticancer drug and servers as the only marketed inhibitor of Aminopeptidase N (APN/CD13 to cure leukemia to date; (3 a pan-hematopoietic stimulator and restorator; Bestatin promotes granulocytopoiesis and thrombocytopoiesis in vitro and restores them in myelo-hypoplastic men; (4 an inhibitor of several natural opioid peptides. Based on the knowledge that APN can cleave several bioactive neuropeptides such as Met-enkaphalins, Leu-enkaphalins, β-Endorphin, and so on, the antiaminopeptidase action of Bestatin also allows it to protect endopeptides against their catabolism, exhibiting analgesic activity. Although many scientific studies and great accomplishments have been achieved in this field, a large amount of problems are unsolved. This article reviews the promising results obtained for future development of the analgesic activity of Bestatin that can be of vital interest in a number of severe and chronic pain syndromes.

  13. Development and Validation of a Novel LC-MS/MS Opioid Confirmation Assay: Evaluation of β-glucuronidase Enzymes and Sample Cleanup Methods.

    Science.gov (United States)

    Yang, He S; Wu, Alan H B; Lynch, Kara L

    2016-06-01

    With the rise in the use and misuse of prescription opioids, there is an increasing need for the confirmed identification of opioid analgesics in toxicology laboratories. The goals of this study were to (i) systematically evaluate the hydrolysis efficiency of four β-glucuronidase enzymes under optimized condition; (ii) evaluate compound recovery, matrix effects and precision of three protein precipitation plates and (iii) develop and validate a qualitative liquid-chromatography mass spectrometry (LC-MS/MS) assay to identify 13 opioids in urine. A recombinant β-glucuronidase exhibited the best overall hydrolysis efficiency for seven opioid glucuronide conjugates compared with β-glucuronidase from red abalone, Escherichia coli and Patella vulgata One of the protein precipitation plates tested exhibited overall better recovery of the opioids and lower ion suppression compared with the other two plates. An ESI positive mode LC-MS/MS assay for qualitative opioid analysis was developed and validated. Linearity, LOD, precision, matrix effect, recovery, carryover and interference of the method were evaluated. Sixty-two patient samples were analyzed by both a legacy GC-MS opioid method and the LC-MS/MS method, and 22 samples were analyzed by the LC-MS/MS and an LC-MS/MS reference method. The results of the comparisons showed good concordance. Overall, we described an efficient sample preparation procedure for a sensitive qualitative opioid confirmation assay in urine. PMID:27121711

  14. Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

    Science.gov (United States)

    Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

    2015-12-01

    The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. PMID:26302337

  15. Effectiveness and Tolerability of Tapentadol Prolonged Release Compared With Prior Opioid Therapy for the Management of Severe, Chronic Osteoarthritis Pain

    OpenAIRE

    Steigerwald, Ilona; Schenk, Michael; Lahne, Uwe; Gebuhr, Peter; Falke, Dietmar; Hoggart, Barbara

    2013-01-01

    Background Tapentadol prolonged release (PR; 100–250 mg twice daily) has been efficacious and well tolerated for managing moderate-to-severe, chronic osteoarthritis hip or knee pain in phase 3 studies with washout of previous analgesic treatment. Objective The objective of this study was to evaluate the effectiveness and tolerability of tapentadol PR (50–250 mg twice daily) after direct rotation from World Health Organization (WHO) step III opioids in patients with severe osteoarthritis knee ...

  16. Towards safer use of opioids.

    LENUS (Irish Health Repository)

    Carson, R W R

    2009-09-01

    The main aim of our work was to improve the safety of opioid use in our institution, an acute generalhospital with 620 beds. Initially, all reported opioid errors from 2001 - 2006 were audited. The findings directed a range of multidisciplinary staff educational inputs to improve opioid prescribing and administration practice, and encourage drug error reporting. 448 drug errors were reported, of which 54 (12%) involved opioids; of these, 43 (79%) involved codeine, morphine or oxycodone. 31 of the errors (57%) were associated with administration, followed by 12 (22%) with dispensing and 11 (20%) with prescribing. There were 2 reports of definite patient harm. A subsequent audit examined a 17-month period following the introduction of the above teaching: 17 errors were noted, of which 14 (83%) involved codeine, morphine or oxycodone. Again, drug administration was most error-prone, comprising 11 (65%) of reports. However, just 2 (12%) of the reported errors now involved prescribing, which was a reduction.

  17. Newer approaches to opioid detoxification

    Directory of Open Access Journals (Sweden)

    Siddharth Sarkar

    2012-01-01

    Full Text Available Opioid use disorders present with distressing withdrawal symptoms at the time of detoxification. The pharmacological agents and methods currently in use for detoxification mainly include buprenorphine, methadone, and clonidine. Many other pharmacological agents have been tried for opioid detoxification. This review takes a look at the newer pharmacological options, both opioid agonists and non-agonist medications that have been utilized for detoxification. Peer reviewed articles were identified using PubMed and PsychInfo databases. The keywords included for the search were a combination of ′opioid′ and ′detoxification′ and their synonyms. All the articles published in the last 10 years were screened for. Relevant data was extracted from identified studies. Many newer pharmacological agents have been tried in detoxification of opioids. However, the quest for a safe, efficacious, cost-effective pharmacological option which requires minimal monitoring still continues. The role of non-pharmacological measures and alternative medicine needs further evaluation.

  18. Analgesic effects of adding lidocaine to morphine pumps after orthopedic surgeries

    Directory of Open Access Journals (Sweden)

    Mahmoud Reza Alebouyeh

    2014-01-01

    Full Text Available Background: Opiate is used in patient-controlled intravenous analgesia pumps (PCIA for controlling pain in post-surgical patients. Other drugs are remarkably added to opioid pumps to enhance quality, lengthen analgesia, and reduce side effects. Lidocaine, a local anesthetic which inhibits sodium channels, has anesthetic and analgesic effects when injected locally or intravenously. The objective of this study is to evaluate the analgesic effects of adding lidocaine 1% to different doses of morphine via IV pump to patient-controlled analgesia (PCA after orthopedic surgeries. Materials and Methods: In a randomized clinical trial, 60 patients who had undergone orthopedic surgery of lower extremities were divided into three equal groups to control postoperative pain. Intravenous pump with 5 ml/h flow rate was used as the analgesic method. The solution consisted of lidocaine 1% plus 20 mg morphine for the first group, lidocaine 1% plus 10 mg morphine for the second group, and only 20 mg morphine for the third group (control group. Patients were checked every 12 h, and Visual Analog Scale (VAS, extra opioid doses, nausea/vomiting, and sedation scale were examined. Results: Pain score was lower in the first group compared to the other two groups. Mean VAS was 2.15 ± 0.2, 2.75 ± 0.2, and 2 ± 0.25 on the first day and 1.88 ± 0.1, 2.74 ± 0.3, and 2.40 ± 0.3 on the second day, respectively, in the three groups and the difference was statistically significant (P < 0.01 and <0.05, respectively. Also, 10% of patients in the first group needed extra opioid doses, while this figure was 30% in the second group and 25% in the third group (P < 0.01. Nausea/vomiting and sedation scores were not statistically different among the three groups. Conclusion: Compared to lidocaine 1% plus 10 mg morphine or 20 mg morphine alone in PCIA, adding lidocaine 1% to 20 mg morphine decreases the pain score and opioid dose after orthopedic surgeries without having side

  19. [3H]naloxone as an opioid receptor label: Analysis of binding site heterogeneity and use for determination of opioid affinities of casomorphin analogues

    International Nuclear Information System (INIS)

    The nonselective antagonist [3H]naloxone was used to identify opioid receptors in rat brain membranes. The multiple naloxone binding sites were related to different opioid receptors by means of selective opiod ligands as well as various β-casomorphin analogues. Analysis of binding site heterogeneity was performed using several computer curve fitting methods. The results indicate that structurally modified casomorphin peptides are able to discriminate between μ1 and μ2 binding sites. The affinities to the μ sites obtained with [3H]naloxone as label are in a good agreement with those from experiments with the μ selective radioligand [3H]DAGO. The μ1 site affinities of these casomorphin derivatives are well correlated with their antinociceptive potencies. This finding suggests the mediation of the analgesic activity via the high-affinity μ1 subtype. (author)

  20. In vivo antinociception of potent mu opioid agonist tetrapeptide analogues and comparison with a compact opioid agonist - neurokinin 1 receptor antagonist chimera

    Directory of Open Access Journals (Sweden)

    Guillemyn Karel

    2012-01-01

    Full Text Available Abstract Background An important limiting factor in the development of centrally acting pharmaceuticals is the blood-brain barrier (BBB. Transport of therapeutic peptides through this highly protective physiological barrier remains a challenge for peptide drug delivery into the central nervous system (CNS. Because the most common strategy to treat moderate to severe pain consists of the activation of opioid receptors in the brain, the development of active opioid peptide analogues as potential analgesics requires compounds with a high resistance to enzymatic degradation and an ability to cross the BBB. Results Herein we report that tetrapeptide analogues of the type H-Dmt1-Xxx2-Yyy3-Gly4-NH2 are transported into the brain after intravenous and subcutaneous administration and are able to activate the μ- and δ opioid receptors more efficiently and over longer periods of time than morphine. Using the hot water tail flick test as the animal model for antinociception, a comparison in potency is presented between a side chain conformationally constrained analogue containing the benzazepine ring (BVD03, Yyy3: Aba, and a "ring opened" analogue (BVD02, Yyy3: Phe. The results show that in addition to the increased lipophilicity through amide bond N-methylation, the conformational constraint introduced at the level of the Phe3 side chain causes a prolonged antinociception. Further replacement of NMe-D-Ala2 by D-Arg2 in the tetrapeptide sequence led to an improved potency as demonstrated by a higher and maintained antinociception for AN81 (Xxx2: D-Arg vs. BVD03 (Xxx2: NMe-D-Ala. A daily injection of the studied opioid ligands over a time period of 5 days did however result in a substantial decrease in antinociception on the fifth day of the experiment. The compact opioid agonist - NK1 antagonist hybrid SBCHM01 could not circumvent opioid induced tolerance. Conclusions We demonstrated that the introduction of a conformational constraint has an important

  1. Evaluation of analgesic effect of tapentadol, a central novel analgesic versus tramadol, a widely used opioid analgesic in treatment of low back pain: a randomized controlled trial

    OpenAIRE

    Zaki Anwar Zaman; Deepak Kumar

    2013-01-01

    Background: The objective of the study was to compare efficacy and tolerability (safety) of tapentadol with tramadol in the treatment of low back pain. Methods: The study was a prospective, randomized, single blinded, total 102 patients are recruited for study in which 44 patients are prescribed (50mgtwice daily) tapentadol and 58 patients prescribed (50mg twice daily) tramadol for 4 weeks. Follow-up was done on days 7, 14, 28 and 4 week after stoppage of treatment. Assessment of improvement ...

  2. Evaluation of analgesic effect of tapentadol, a central novel analgesic versus tramadol, a widely used opioid analgesic in treatment of low back pain: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Zaki Anwar Zaman

    2013-08-01

    Full Text Available Background: The objective of the study was to compare efficacy and tolerability (safety of tapentadol with tramadol in the treatment of low back pain. Methods: The study was a prospective, randomized, single blinded, total 102 patients are recruited for study in which 44 patients are prescribed (50mgtwice daily tapentadol and 58 patients prescribed (50mg twice daily tramadol for 4 weeks. Follow-up was done on days 7, 14, 28 and 4 week after stoppage of treatment. Assessment of improvement were performed by Indian Health Assessment Questionnaire Disability Index (Indian HAQDI, Visual Analogue Scale (VAS, Numerical Rating Scale (NRS and measurement of Pain Relief Rate (PRR. Adverse events were recorded. Results: Scores in Indian HAQDI, VAS and NRS improved significantly in both groups in the last visit but more so with tapentadol. PRR was reasonably higher with tapentadol [27(n=4461.36%] patients experiencing significant to complete pain relief at the end of the study, compared to tramadol [25(n=58 43.10%]. Adverse effects was less in tapentadol group [15(n=4434.09%] versus 33(n=5856.89%], p<0.05]. Conclusion: Tapentadol has better sustained efficacy and tolerability than tramadol in low back pain. [Int J Basic Clin Pharmacol 2013; 2(4.000: 392-396

  3. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid recepto

  4. Opioids in Chronic Musculoskeletal Conditions

    OpenAIRE

    Calvo-Alén, Jaime

    2010-01-01

    The use of opioids for benign disorders has been limited by concerns about these compounds' potential adverse events and their possible misuse. However, during the last few years an increased use in nonmalignant disorders, including rheumatologic diseases, has been observed. Herein, we review the scientific evidence for opioid therapy in three common scenarios in clinical rheumatology. Low back pain is a very frequent reason for consultation. Overall, the large majority of studies show a posi...

  5. Analgesic effect of simultaneous exposure to infrared laser radiation and μT magnetic field in rats

    Science.gov (United States)

    Cieslar, Grzegorz; Mrowiec, Janina; Kasperczyk, Slawomir; Sieron-Stoltny, Karolina; Sieron, Aleksander

    2008-03-01

    The aim of the experiment was to estimate the effect of repeated simultaneous exposures to infrared laser radiation and μT variable magnetic field used in magnetostimulation on pain perception in rats, as well as the involvement of endogenous opioid system in the mechanism of this effect. In experimental group clean-shaven scull of male Wistar rats placed individually in a specially designed plastic chamber were simultaneously exposed to infrared laser radiation (wavelength - 855 nm, mean power - 4,1 mW, energy density - 30 J/cm2) and variable magnetic field of saw-like shape of impulse, at a frequency of basic impulse 180-195 Hz and mean induction value of 120 μT generated by magneto-laser applicator of device for magnetostimulation Viofor JPS (Med & Life, Poland) 12 minutes daily for 2 periods of 5 consecutive days, with 2 days-lasting break between them, while control animals were sham-exposed. The pain perception was determined by means of "hot plate" test on the basis of calculated analgesic index. As a result of repeated exposures a significant increase in analgesic index persisting also till 14 th day after the end of a cycle of exposures was observed. This analgesic effect was inhibited by prior i.p. injection of opioid antagonist - Naloxone.

  6. [Mechanism of action of the analgesic flupirtine].

    Science.gov (United States)

    Nickel, B; Herz, A; Jakovlev, V; Tibes, U

    1985-01-01

    To answer the questions of mode and site of action partly supplementary, partly new investigations with flupirtine (Katadolon) were carried out which are described below. The investigation for opiate receptor affinity of flupirtine in rat brain homogenate did not show any reduction in 3He-etorphine binding up to the highest concentration of flupirtine of 10(-5) mol/1. This result suggests that flupirtine either has a very low opiate receptor affinity or lacks it fully. Therefore the analgesic activity of flupirtine is not based on opiate mechanism. The intracerebroventricular and intrathecal administration of flupirtine and the other analgesics tested showed dose dependent analgesic activity in doses which, when applied systemically, did not cause any analgesia in rats. Thus these substances show cerebral or spinal analgesic activity. In relation to the effective doses (ED50 in micrograms/rat) flupirtine was of the same efficacy in both kinds of administration. Pethidine tested comparatively was found to be less potent by intrathecal than by intracerebroventricular application. On the other hand, morphine was weaker by intracerebroventricular than by intrathecal application. As in the experiments by oral administration, naloxone did not show any effect on the analgesic activity of flupirtine, neither by intracerebroventricular nor by intrathecal application. On the other hand, the analgesic effects of pethidine and morphine were completely suppressed by naloxone. These results demonstrate that the analgesic activity of flupirtine is not caused by the opiate mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3002399

  7. Effect of intraoperative esmolol infusion on anesthetic, analgesic requirements and postoperative nausea-vomitting in a group of laparoscopic cholecystectomy patients

    OpenAIRE

    Necla Dereli; Zehra Baykal Tutal; Munire Babayigit; Aysun Kurtay; Mehmet Sahap; Eyup Horasanli

    2015-01-01

    PURPOSE: Postoperative pain and nausea/vomitting (PNV) are common in laparoscopic cholecystectomy patients. Sympatholytic agents might decrease requirements for intravenous or inhalation anesthetics and opioids. In this study we aimed to analyze effects of esmolol on intraoperative anesthetic-postoperative analgesic requirements, postoperative pain and PNV. METHODS: Sixty patients have been included. Propofol, remifentanil and vecuronium were used for induction. Study groups were as follows;...

  8. [Non-opioid pain medication in the elderly].

    Science.gov (United States)

    Burkhardt, H; Wehling, M

    2015-08-01

    Non-opioid analgesics are frequently used to control chronic pain in elderly patients; however some of these drugs show high rates of adverse drug reactions. Among these are significant clinical problems which impede an effective and safe pain control. This review provides recent data concerning non-steroidal anti-inflammatory drugs (NSAID), acetaminophen, metamizol and flupirtin. Due to their risk profile NSAIDs are less appropriate due to high incidence rates and drug-related risk patterns. Acetaminophen, metamizol and flupirtin may be recommended instead; however a shortcoming of acetaminophen in comparison to NSAIDs is its weaker action to control pain. Metamizol is still banned in some countries due to rare but potentially severe hematological side effects and flupirtin frequently causes unfavorable sedation. PMID:26242359

  9. MECHANISM OF ANALGESIC EFFECTS OF PROPOFOL ON INCISIONAL PAIN: A RAT MODEL STUDY

    Institute of Scientific and Technical Information of China (English)

    HUANG Zhi-hua; SONG Xiao-xing; HU Jiong; YU Bu-wei

    2009-01-01

    Objective To clarify the role of propofol in controlling incisional pain and its potential effects on the spinal opioid receptor expression.Methods A postoperative model of nociception was established in male Sprague-Dawley rats weighing 200-250 g. A total of 96 rats were randomly divided into 8 groups. All drugs were administered intravenously either 5min pre-operation or 5min post-operation. The analgesic effects of systemic propofol were demonstrated by the measurement of a cumulative pain score (CPS). After that, the lumbar enlargement of the spinal cord was removed to evaluate the mRNA level of the μ-opioid receptor (MOR) and δ-opioid receptor (DOR) by RT-PCR.Results CPS and DOR mRNA expressions significantly increased after the operation. Both propofol post-treatment and propofol pre-treatment groups showed significant suppression of the increased CPS and the expression of DOR mRNA evoked by pain stimulation. Interestingly, propofol pre-treatment had a more pronounced effect in decreasing CPS and the expression of DOR mRNA. Furthermore, these observations were dose-dependent. MOR mRNA expression significantly increased after operation in all animals and propofol treatment had no impact on it.Conclusion Based on these findings, we suggest that propofol can serve as a valuable adjunct in acute postoperative pain management. Systemic propofol induces an analgesic effect on acute incisional pain in a dose-dependant manner, and this effect is mediated in the spinal cord and may be associated with the spinal DOR.

  10. Spider peptide Phα1β induces analgesic effect in a model of cancer pain.

    Science.gov (United States)

    Rigo, Flavia Karine; Trevisan, Gabriela; Rosa, Fernanda; Dalmolin, Gerusa D; Otuki, Michel Fleith; Cueto, Ana Paula; de Castro Junior, Célio José; Romano-Silva, Marco Aurelio; Cordeiro, Marta do N; Richardson, Michael; Ferreira, Juliano; Gomez, Marcus V

    2013-09-01

    The marine snail peptide ziconotide (ω-conotoxin MVIIA) is used as an analgesic in cancer patients refractory to opioids, but may induce severe adverse effects. Animal venoms represent a rich source of novel drugs, so we investigated the analgesic effects and the side-effects of spider peptide Phα1β in a model of cancer pain in mice with or without tolerance to morphine analgesia. Cancer pain was induced by the inoculation of melanoma B16-F10 cells into the hind paw of C57BL/6 mice. After 14 days, painful hypersensitivity was detected and Phα1β or ω-conotoxin MVIIA (10-100 pmol/site) was intrathecally injected to evaluate the development of antinociception and side-effects in control and morphine-tolerant mice. The treatment with Phα1β or ω-conotoxin MVIIA fully reversed cancer-related painful hypersensitivity, with long-lasting results, at effective doses 50% of 48 (32-72) or 33 (21-53) pmol/site, respectively. Phα1β produced only mild adverse effects, whereas ω-conotoxin MVIIA induced dose-related side-effects in mice at analgesic doses (estimated toxic dose 50% of 30 pmol/site). In addition, we observed that Phα1β was capable of controlling cancer-related pain even in mice tolerant to morphine antinociception (100% of inhibition) and was able to partially restore morphine analgesia in such animals (56 ± 5% of inhibition). In this study, Phα1β was as efficacious as ω-conotoxin MVIIA in inducing analgesia in a model of cancer pain without producing severe adverse effects or losing efficacy in opioid-tolerant mice, indicating that Phα1β has a good profile for the treatment of cancer pain in patients. PMID:23718272

  11. Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis?

    LENUS (Irish Health Repository)

    Heaney, A

    2012-12-01

    Summary Cancer is a leading cause of morbidity and mortality worldwide and the ratio of incidence is increasing. Mortality usually results from recurrence or metastases. Surgical removal of the primary tumour is the mainstay of treatment, but this is associated with inadvertent dispersal of neoplastic cells into the blood and lymphatic systems. The fate of the dispersed cells depends on the balance of perioperative factors promoting tumour survival and growth (including surgery per se, many anaesthetics per se, acute postoperative pain, and opioid analgesics) together with the perioperative immune status of the patient. Available evidence from experimental cell culture and live animal data on these factors are summarized, together with clinical evidence from retrospective studies. Taken together, current data are sufficient only to generate a hypothesis that an anaesthetic technique during primary cancer surgery could affect recurrence or metastases, but a causal link can only be proved by prospective, randomized, clinical trials. Many are ongoing, but definitive results might not emerge for a further 5 yr or longer. Meanwhile, there is no hard evidence to support altering anaesthetic technique in cancer patients, pending the outcome of the ongoing clinical trials.

  12. Pharmacogenomic study of the role of the nociceptin/orphanin FQ receptor and opioid receptors in diabetic hyperalgesia.

    Science.gov (United States)

    Rutten, Kris; Tzschentke, Thomas M; Koch, Thomas; Schiene, Klaus; Christoph, Thomas

    2014-10-15

    Targeting functionally independent receptors may provide synergistic analgesic effects in neuropathic pain. To examine the interdependency between different opioid receptors (µ-opioid peptide [MOP], δ-opioid peptide [DOP] and κ-opioid peptide [KOP]) and the nociceptin/orphanin FQ peptide (NOP) receptor in streptozotocin (STZ)-induced diabetic polyneuropathy, nocifensive activity was measured using a hot plate test in wild-type and NOP, MOP, DOP and KOP receptor knockout mice in response to the selective receptor agonists Ro65-6570, morphine, SNC-80 and U50488H, or vehicle. Nocifensive activity was similar in non-diabetic wild-type and knockout mice at baseline, before agonist or vehicle administration. STZ-induced diabetes significantly increased heat sensitivity in all mouse strains, but MOP, DOP and KOP receptor knockouts showed a smaller degree of hyperalgesia than wild-type mice and NOP receptor knockouts. For each agonist, a significant antihyperalgesic effect was observed in wild-type diabetic mice (all Pfunctional independence, may yield an effective and favorable therapeutic analgesic profile. PMID:25169429

  13. Analgesic activity of Ugni molinae (murtilla) in mice models of acute pain.

    Science.gov (United States)

    Delporte, C; Backhouse, N; Inostroza, V; Aguirre, M C; Peredo, N; Silva, X; Negrete, R; Miranda, H F

    2007-05-30

    Leaf extracts of Ugni molinae Turcz. (Myrtaceae) are used in Chilean folk medicine as analgesic and anti-inflammatory. The antinociceptive effect of dichloromethane (DCM), ethyl acetate (EA) and methanol (ME) leaf extracts was assessed by intraperitoneal, oral and topical administration in writhing, tail flick, and tail formalin tests in mice. The extracts showed a dose-dependent antinociceptive activity in all the assays under different administration routes. The ED(50) values for the different tests for the DCM, EA, ME extract and reference drug (ibuprofen) were as follows. Writhing test in acetic acid (i.p. administration): 0.21, 0.37, 1.37 and 0.85mg/kg, respectively; tail flick test (oral administration): 199, 189, 120 and 45.9mg/kg. The EC(50) values for tail flick test were (topical administration): 2.0, 0.35, 1.4 and 8.2% (w/v), respectively; and the topical analgesic effects were (formalin assay) 75.5, 77.5, 31.6 and 76.5%, respectively. Ugni molinae extracts produce antinociception in chemical and thermal pain models through a mechanism partially linked to either lipooxygenase and/or cyclooxygenase via the arachidonic acid cascade and/or opioid receptors. Flavonoid glycosides and triterpenoids have been isolated from the plant and can be associated with the observed effect. Our results corroborate the analgesic effects of Ugni molinae, and justify its traditional use for treating pain. PMID:17403589

  14. Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol.

    Science.gov (United States)

    Gaynes, B I; Barkin, R L

    1999-07-01

    This report reviews the causes of ocular pain and discusses the pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage of tramadol, a novel non-narcotic oral analgesic. Tramadol is a synthetic analog of codeine with a dual mechanism of action that involves agonist activity at the mu opioid receptor, as well as inhibition of monoaminergic (norepinephrine and serotonin) re-uptake. Unlike opiate analgesics, tramadol has very low propensity toward physical dependence. Common dose-related adverse effects of tramadol include dizziness, nausea, vomiting, dry mouth, and/or drowsiness. Clinically, tramadol has been shown to be equivalent to acetaminophen (325 mg)-codeine (30 mg) combinations for the treatment of moderate or severe nonocular pain. Tramadol appears to be an effective analgesic agent for pain control due to postoperative surgical trauma, as well as in various chronic malignant and nonmalignant disease states. Tramadol has shown variable effectiveness in the control of pain related to dental procedures. The usefulness of tramadol in pain states from ophthalmic origin has yet to be clinically established. PMID:10445636

  15. Analgesic effects of intra-articular fentanyl, pethidine and dexamethasone after knee arthroscopic surgery

    Directory of Open Access Journals (Sweden)

    H Saryazd

    2006-07-01

    Full Text Available BACKGROUND: Many different methods have been used in an effort to provide adequate analgesia after knee arthroscopic surgery. In this study analgesic effect of intra-articular fentanyl, pethidine and dexamethasone was compared. METHODS: In a double blind randomized study 48 male patients undergoing knee arthroscopic meniscectomy were allocated to groups receiving intra-articular fentanyl 50 µg or pethidine 20 mg or dexamethasone 8 mg at the end of arthroscopy during general aesthesia. Postoperative pain scores using visual analogue scale were measured and also analgesic requirements and the time of ability to walk were recorded. RESULTS: Pain scores at one, two, six and 24 h after intra-articular injection were not significantly different for fentanyl and pethidine but were higher significantly for dexamethasone at all four mentioned times. The mean average time of ability to walk was significantly longer for dexamethasone. The analgesic requirements during the first 24 h after intraarticular injection were significantly greater only for dexamethasone too. CONCLUSION: Better postoperative analgesia, less pain score and shorter time to walk were achieved by fentanyl and pethidine in comparison to dexamethasone but the results were not significantly different between fentanyl group and pethidine. KEYWORDS: Arthroscopy, opioid, pain.

  16. Dose-related analgesic effects of flupirtine.

    OpenAIRE

    Hummel, T; Friedmann, T; Pauli, E.; Niebch, G.; Borbe, H. O.; Kobal, G

    1991-01-01

    1. Flupirtine is a novel and, in all probability, centrally acting, analgesic. The present investigation was conducted in order to investigate dose-related effects of perorally administered flupirtine in man, with special regard to specifically analgesic actions, employing a model based on pain-related chemosomatosensory evoked potentials and subjective intensity estimates of painful stimuli. 2. Plasma concentrations of flupirtine measured 2 h after dosing linearly increased as a function of ...

  17. Pain Raises Risk of Opioid Addiction

    Science.gov (United States)

    ... fullstory_160033.html Pain Raises Risk of Opioid Addiction Men and younger people had higher odds of ... had a 41 percent higher risk of opioid addiction than those with no pain. That increased risk ...

  18. Molecular Physiology of Enteric Opioid Receptors

    OpenAIRE

    Galligan, James J.; Akbarali, Hamid I.

    2014-01-01

    Opioid drugs have powerful antidiarrheal effects and many patients taking these drugs for chronic pain relief experience chronic constipation that can progress to opioid-induced bowel dysfunction. Three classes of opioid receptors are expressed by enteric neurons: μ-, δ-, and κ-opioid receptors (MOR, DOR, and KOR). MOR and DOR couple to inhibition of adenylate cylase and nerve terminal Ca2+ channels and activation of K+ channels. These effects reduce neuronal activity and neurotransmitter rel...

  19. Low-dose spinal neostigmine further enhances the analgesic effect of spinal bupivacaine combined with epidural dexamethasone, following orthopedic surgery

    Directory of Open Access Journals (Sweden)

    Gabriela Rocha Lauretti

    2014-01-01

    Full Text Available Background: Opioids are considered mainstream for combined spinal-epidural anesthesia, but frequently limited by adverse effects. The aim of this study was to examine whether low-dose spinal neostigmine, epidural dexamethasone or their combination enhances analgesia from spinal bupivacaine without adverse effects. Materials and Methods : A total of 60 patients undergoing orthopedic surgery were randomized to one of four groups and evaluated for 24-h after surgery for analgesia (time to first rescue analgesic and rescue analgesic consumption. Patients received 15 mg bupivacaine plus the test drug intrathecally (saline or 1 microgram (μg neostigmine. The epidural test drug was either saline or 10 mg dexamethasone. The Control group (CG received spinal and epidural saline. The Neostigmine group (NG, spinal neostigmine and epidural saline; the Dexamethasone group (DG, spinal saline and epidural dexamethasone; and the Neostigmine-dexamethasone group (NDG, spinal neostigmine and epidural dexamethasone. Results: The CG (282 ± 163 min and NG (524 ± 142 min were similar in their times to first rescue analgesic and analgesic consumption. The time to first rescue analgesic was longer for the DG (966 ± 397 min compared with CG and NG (P < 0.0002, and the DG had less ketoprofen consumption and lower overall visual analogue scale-pain sores compared with CG and NG (P < 0.0005. Addition of 1 mg-neostigmine (NDG resulted in longer time to rescue analgesic (1205 ± 303 min; P < 0.02 and lower ketoprofen consumption (P < 0.05 compared to DG. Sporadic cases of vesical catheterization and emesis were observed, however adverse effects were similar among groups. Conclusion: Spinal 1 microgram (μg neostigmine further enhanced analgesia from spinal bupivacaine combined with epidural dexamethasone, without increasing the incidence of adverse effects.

  20. The analgesic efficacy of ultrasound-guided transversus abdominis plane block for retroperitoneoscopic donor nephrectomy: A randomized controlled study

    Directory of Open Access Journals (Sweden)

    Beena K Parikh

    2013-01-01

    Full Text Available Background: Transversus abdominis plane (TAP block is suitable for lower abdominal surgeries. Blind TAP block has many complications and uncertainty of its effects. Use of ultrasonography increases the safety and efficacy. This study was conducted to evaluate the analgesic efficacy of ultrasound (USG-guided TAP block for retroperitoneoscopic donor nephrectomy (RDN. Methods: In a prospective randomized double-blind study, 60 patients undergoing laparoscopic donor nephrectomy were randomly divided into two groups by closed envelope method. At the end of surgery, USG-guided TAP block was given to the patients of both the groups. Study group (group S received inj. Bupivacaine (0.375%, whereas control group (group C received normal saline. Inj. Tramadol (1 mg/kg was given as rescue analgesic at visual analog scale (VAS more than 3 in any group at rest or on movement. The analgesic efficacy was judged by VAS both at rest and on movement, time to first dose of rescue analgesic, cumulative dose of tramadol, sedation score, and nausea score, which were also noted at 30 min, 2, 4, 6, 12, 18, and 24 h postoperatively. Total tramadol consumption at 24 h was also assessed. Results: Patients in group S had significantly lower VAS score, longer time to first dose of rescue analgesic (547.13±266.96 min vs. 49.17±24.95 min and lower tramadol consumption (103.8±32.18 mg vs. 235.8±47.5 mg in 24 h. Conclusion: The USG-guided TAP block is easy to perform and effective as a postoperative analgesic regimen in RDN, with opioids-sparing effect and without any complications.

  1. Effect of Tramadol (μ-opioid receptor agonist on orthodontic tooth movements in a rat model

    Directory of Open Access Journals (Sweden)

    E. Javadi

    2012-01-01

    Full Text Available Objective: Tramadol is a synthetic analgesic of opioids which has more flexible mechanisms of action than typical opioids. Since it has been reported in previous study that typical opioids like morphine can affect the bone homeostasis, it is worthwhile to examine the effects of tramadol on tooth movement. In this study we investigated effects of tramadol on orthodontic tooth movement in rats.Materials and Methods: 30 male wistar rats were selected and received orthodontic appliance. 3 groups were designed based on the substance that they received daily injections of during a 2-week orthodontic treatment. 1. Control group with no injection.2.Control group with normal saline injection.3. the tramadol group. After the two-week treatment period the amount of tooth movement were measured in all the groups. Also the histological analysis was performed assessing the root resorption, osteoclasts numbers and bone resorption.Results: The amount of tooth movement was not significantl in the tramadol group comparing to the other groups (P>0.05.The results of 3 histological parameters (amount of root resorption, osteoclastic numbers and bone resorption were statistically insignificant (P>0.05.Conclusion: Tramadol as an atypical opioid does not interfere with the process of bone remodeling and tooth movement in rat. Tramadol does not affect osteoclastic activity and bone resorption and it does not cause to change the resulted root resorption either.

  2. The Analgesic Effect of Obturator Nerve Block Added to a Femoral Triangle Block After Total Knee Arthroplasty

    DEFF Research Database (Denmark)

    Runge, Charlotte; Børglum, Jens; Jensen, Jan Mick;

    2016-01-01

    BACKGROUND AND OBJECTIVES: Total knee arthroplasty (TKA) is associated with severe pain, and effective analgesia is essential for the quality of postoperative care and ambulation. The analgesic effects of adding an obturator nerve block (ONB) to a femoral triangle block (FTB) after TKA have not...... been tested previously. We hypothesized that combined ONB and FTB will reduce opioid consumption and pain compared with those of a single FTB or local infiltration analgesia (LIA). METHODS: Seventy-eight patients were randomized to combined ONB and FTB, single FTB, or LIA after primary unilateral TKA...

  3. Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl

    OpenAIRE

    Ide, Soichiro; Nishizawa, Daisuke; Fukuda, Ken-ichi; Kasai, Shinya; Hasegawa, Junko; Hayashida, Masakazu; Minami, Masabumi; Ikeda, Kazutaka

    2014-01-01

    Background The P2X7 receptor is a member of the P2X family of adenosine 5′-triphosphate-gated cation channels. Several recent studies have demonstrated that this receptor is involved in mechanisms related to pain and inflammation. However, unknown is whether polymorphisms of the P2RX7 gene that encodes the human P2X7 receptor influence pain sensitivity and analgesic effects of opioids. The P2RX7 gene is known to be highly polymorphic. Thus, the present study examined associations between fent...

  4. Antinociceptive Interactions between the Imidazoline I2 Receptor Agonist 2-BFI and Opioids in Rats: Role of Efficacy at the μ-Opioid Receptor.

    Science.gov (United States)

    Siemian, Justin N; Obeng, Samuel; Zhang, Yan; Zhang, Yanan; Li, Jun-Xu

    2016-06-01

    Although μ-opioids have been reported to interact favorably with imidazoline I2 receptor (I2R) ligands in animal models of chronic pain, the dependence on the μ-opioid receptor ligand efficacy on these interactions had not been previously investigated. This study systematically examined the interactions between the selective I2 receptor ligand 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI) and three μ-opioid receptor ligands of varying efficacies: fentanyl (high efficacy), buprenorphine (medium-low efficacy), and 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[(3'-isoquinolyl) acetamido] morphine (NAQ; very low efficacy). The von Frey test of mechanical nociception and Hargreaves test of thermal nociception were used to examine the antihyperalgesic effects of drug combinations in complete Freund's adjuvant-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to examine the rate-suppressing effects of each drug combination. Dose-addition and isobolographical analyses were used to characterize the nature of drug-drug interactions in each assay. 2-BFI and fentanyl fully reversed both mechanical and thermal nociception, whereas buprenorphine significantly reversed thermal but only slightly reversed mechanical nociception. NAQ was ineffective in both nociception assays. When studied in combination with fentanyl, NAQ acted as a competitive antagonist (apparent pA2 value: 6.19). 2-BFI/fentanyl mixtures produced additive to infra-additive analgesic interactions, 2-BFI/buprenorphine mixtures produced supra-additive to infra-additive interactions, and 2-BFI/NAQ mixtures produced supra-additive to additive interactions in the nociception assays. The effects of all combinations on schedule-controlled responding were generally additive. Results consistent with these were found in experiments using female rats. These findings indicate that lower-efficacy μ-opioid receptor agonists may interact more favorably with I2R

  5. Pharmacopsychosocial Treatment of Opioid Dependence Harm Reduction Palliation or Simply Good Medical Practice

    Directory of Open Access Journals (Sweden)

    A.J. Reid Finlayson

    2011-01-01

    Full Text Available Opioid alkaloids have been used medicinally for centuries as analgesics, for their antidiarrheal and antitussive properties, and as hypnotics. Opioids were initially derived from the poppy plant (Papaver somniferum by the ancients of the Mediterranean Basin. Written records of the medicinal uses of opioids date to before the time of Hippocrates (460–377 BC. Paracelsus prescribed opium in a medicinal drink of wine and spices in the 16th century. Sir William Osler, the renowned Canadian physician of the late 1800’s remarked that opium was “God’s own Medicine”. Opioids are considered superb medications by modern physicians, who widely prescribed them still and for the most part without significant adverse consequences. Yet there is a “dark side” to opioids for those who develop dependence on these drugs (1. Opioids have significant dependence liability because of compelling biphasic central effects, behavioral activation at low doses and sedation at higher doses, accompanied by allostatic neuroadaptation of the CNS, leading to use of rapidly escalating doses. These dynamics may be amplified in persons having altered dopamine receptors in the limbic system, suggesting a possible genetic association (2. Dependent individuals may be unable to stop compulsive self-administration of opioids, in part because of these plastic changes in the brain akin to learning and memory that are highly resistant to modification. Synaptic alterations in neurons of the reward and limbic circuits may irreversibly modify emotions and responses to the environment, thereby permeating the behavioral repertoire of the addict. Accordingly, it may be impossible for most actively dependent individuals to live a fulfilling life simply because so much of their effort becomes devoted to activities necessary to obtain illicit opioids, use them, and recover from their use. Indeed, some individuals who have been dependent on opioids may never be able to return to a

  6. Alcohol, tobacco and analgesics--Busselton, 1972.

    Science.gov (United States)

    Woodings, T

    1975-08-01

    Mass health examinations carried out in Busselton in November and December, 1972, revealed that drinking and smoking were more prevalent amongst men, whereas more women took analgesic drugs. Compared with older age groups more young people consumed alcohol, tobacco and analgesics. Younger people are also taking up smoking and drinking at earlier ages than the older age groups. These findings stress the need for better health education to alter the attitudes of younger people. The people of Busselton would support legislation to allow spot breathalyser tests for drivers, women (70%) providing stronger support than men (57%). This suggests that public opinion could support continuing legislation to combat road accidents. Comparisons between the North Shore, Sydney, and Busselton populations indicated somewhat higher proportions of the urban people were consuming alcohol, tobacco and analgesics, particularly urban women. However, both Australian samples revealed disturbingly high proportions of subjects taking excessive monthly quantities of analgesics (3% to 5%) compared with the United Kingdom (2-8%). Previous reports of the high proportion of Traralgon people taking drugs or medication is supported by the Busselton data, which suggest the Australia requires stricter statutory control of analgesics, compulsory warnings on labels and restriction of sales to pharmacists. PMID:1160770

  7. The role of surfactants in the formulation of elastic liposomal gels containing a synthetic opioid analgesic

    Science.gov (United States)

    Singh, Sima; Vardhan, Harsh; Kotla, Niranjan G; Maddiboyina, Balaji; Sharma, Dinesh; Webster, Thomas J

    2016-01-01

    Transdermal drug delivery systems have made significant contributions to the medical community, but have yet to completely substitute oral or parenteral delivery. Recently, various strategies have been used to augment the transdermal delivery of therapeutics. Primarily, they include iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, microneedles, and vesicular systems. Among these strategies, elastic liposomes appear promising. Elastic vesicle scaffolds have been developed and evaluated as novel topical and transdermal delivery systems, with an infrastructure consisting of hydrophobic and hydrophilic moieties together, and as a result, such scaffolds can accommodate drug molecules with a wide range of solubility. High deformability of these vesicles provides for better penetration of intact vesicles. This system is much more efficient at delivering low- and high-molecular-weight drugs to the skin in terms of quantity and depth. In this work, elastic liposomes of Tramadol HCl were prepared using a solvent evaporation method with different surfactants and were characterized using microscopy, and particle size, shape, drug content, ex vivo release, and zeta potential were also calculated. The prepared elastic liposomes were found to be in the range of 152.4 nm with a zeta potential of −22.4 mV; the entrapment efficiencies of the selected formulation was found to be 79.71%±0.27%. All formulations in the form of a gel were evaluated for physicochemical properties and were found to be homogeneous with no grittiness, and the pH of all formulations was found to be neutral. The optimized selected elastic liposomal formulation followed the Higuchi equation and Fickian diffusion and released the drug for a period of 24 hours. The overall results provide much promise for the continued investigation of deformable vesicles as transdermal drug carriers. PMID:27114707

  8. Drug-Poisoning Deaths Involving Opioid Analgesics: United States, 1999-2011

    Science.gov (United States)

    ... also involved benzodiazepines (sedatives used to treat anxiety, insomnia, and seizures), up from 527 such deaths in ... YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act ...

  9. Opioid use in the elderly.

    NARCIS (Netherlands)

    Wilder-Smith, O.H.G.

    2005-01-01

    Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication. We provide an overview of the factors liable to influence opioid action in th

  10. Randomized trial of opioids versus tricyclic antidepressants for radiation-induced mucositis pain in head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ehrnrooth, E.; Grau, C.; Zachariae, R.; Andersen, Joern [Aarhus Univ. Hospital (Denmark). Dept. of Oncology

    2001-11-01

    Patients who receive radiotherapy for head and neck cancer are likely to develop painful mucositis. The pain is characterized by a burning or stinging sensation similar to neuropathic pain sensations. The purpose of the present study was to compare the analgesic effect of a tricyclic antidepressant (TC), commonly used in the treatment of neuropathic pain, with the effect of opioids on radiation-induced mucositis pain. Forty-three patients receiving 66-68 Gy external radiation according to the DAHANCA guidelines (the Danish Head and Neck Cancer Study Group) were randomized to either morphine or TC when mucositis pain was insufficiently managed with weak analgesics. Patients with insufficient pain control in either treatment arm received supplementary medication from the opposite treatment arm. Pain was evaluated weekly using a VAS scale and the McGill Pain Questionnaire. The degree of mucositis and the degree of depression were measured at the same time intervals. Twenty-two patients entered the opioid arm and 21 the TC arm. Two patients in each arm were non-evaluable. VAS pain scores were significantly reduced in the opioid treatment arm one week after randomization (p=0.01). Eight patients in the TC arm were managed with TC alone, but for 11 patients it was necessary to add morphine. The 20 evaluable patients in the morphine arm required no additional treatment. There were no significant differences in side effects between the two groups. Higher pain scores in the TC arm, but not in the opioid arm, were significantly correlated with higher BDI scores. Some head and neck cancer patients with radiation-induced nucositis pain may have sufficient pain control on TC alone. This might be useful in patients with relative counter-indications to opioid treatment.

  11. Randomized trial of opioids versus tricyclic antidepressants for radiation-induced mucositis pain in head and neck cancer

    International Nuclear Information System (INIS)

    Patients who receive radiotherapy for head and neck cancer are likely to develop painful mucositis. The pain is characterized by a burning or stinging sensation similar to neuropathic pain sensations. The purpose of the present study was to compare the analgesic effect of a tricyclic antidepressant (TC), commonly used in the treatment of neuropathic pain, with the effect of opioids on radiation-induced mucositis pain. Forty-three patients receiving 66-68 Gy external radiation according to the DAHANCA guidelines (the Danish Head and Neck Cancer Study Group) were randomized to either morphine or TC when mucositis pain was insufficiently managed with weak analgesics. Patients with insufficient pain control in either treatment arm received supplementary medication from the opposite treatment arm. Pain was evaluated weekly using a VAS scale and the McGill Pain Questionnaire. The degree of mucositis and the degree of depression were measured at the same time intervals. Twenty-two patients entered the opioid arm and 21 the TC arm. Two patients in each arm were non-evaluable. VAS pain scores were significantly reduced in the opioid treatment arm one week after randomization (p=0.01). Eight patients in the TC arm were managed with TC alone, but for 11 patients it was necessary to add morphine. The 20 evaluable patients in the morphine arm required no additional treatment. There were no significant differences in side effects between the two groups. Higher pain scores in the TC arm, but not in the opioid arm, were significantly correlated with higher BDI scores. Some head and neck cancer patients with radiation-induced nucositis pain may have sufficient pain control on TC alone. This might be useful in patients with relative counter-indications to opioid treatment

  12. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available BACKGROUND: Postherpetic neuralgia (PHN is a complication of acute herpes zoster, which is emerging as a preferred clinical trial model for chronic neuropathic pain. Although there are published meta-analyses of analgesic therapy in PHN, and neuropathic pain in general, the evidence base has been substantially enhanced by the recent publication of several major trials. Therefore, we have conducted a systematic review and meta-analysis for both efficacy and adverse events of analgesic therapy for PHN. METHODS AND FINDINGS: We systematically searched databases (MEDLINE 1966-2004, EMBASE 1988-2004, CINAHL 1982-2002, and PubMed [29 October 2004] for trials of PHN. We also searched references of retrieved studies and review articles for further trials. We included trials that examined adult patients with PHN of greater duration than 3 mo, that were blinded, randomised, and had at least one measure of pain outcome. Dichotomous pain outcome data were extracted for 50% decrease in baseline pain using a hierarchy of pain/pain-relief measurement tools. Where available, dichotomous data were also collected for adverse events. Calculated estimates of efficacy included relative benefit and number needed to treat. Of 62 studies identified, 35 were randomised controlled trials. Of these, 31 were placebo controlled and suitable for meta-analysis, from which it was possible to extract dichotomous efficacy outcome data from 25. This meta-analysis revealed that there is evidence to support the use of the following orally administered therapies: tricyclic antidepressants, "strong" opioids, gabapentin, tramadol, and pregabalin. Topical therapies associated with efficacy were lidocaine 5% patch and capsaicin. Finally, a single study of spinal intrathecal administration of lidocaine and methyl prednisolone demonstrated efficacy, although this has yet to be replicated. Data suggest that the following therapies are not associated with efficacy in PHN: certain NMDA

  13. Pharmacokinetic profiles of the analgesic drug flupirtine in cats.

    Science.gov (United States)

    De Vito, V; Lebkowska-Wieruszewska, B; Owen, H; Kowalski, C J; Giorgi, M

    2014-11-01

    Flupirtine (FLU) is a non-opioid analgesic drug with no antipyretic or antiphlogistic effects, used in the treatment of a wide range of pain states in human beings. There is a substantial body of evidence on the efficacy of FLU in humans but this is inadequate to recommend its off-label use in veterinary clinical practice. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy cats. Six mixed breed adult cats were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, paired, cross-over design (2 × 2 Latin-square). Group 1 (n  =  3) received a single dose of 5 mg/kg of FLU injected IV into the jugular vein. Group 2 (n  =  3) received the same dose via PO route. The wash out period was 1 week. Blood samples (1 mL) were collected at assigned times and plasma was then analysed by a validated HPLC method. No adverse effects at the point of injection and no behavioural changes or alterations in health parameters were observed in the animals during or after the study (up to 7 days after the full study). After IV administration, FLU was detectable in plasma up to 36 h. After PO administration, FLU plasma concentrations were lower than those following IV administration, but they were detectable over the same time range. The terminal part of both mean pharmacokinetic curves showed a similar trend of elimination. The oral bioavailability was approximately 40%. This is the first study of FLU in an animal species of veterinary interest and it could pave the way for the use of this active ingredient in the veterinary field. PMID:25011711

  14. The molecular mechanisms of the analgesic action of melatonin

    Institute of Scientific and Technical Information of China (English)

    LI Shu-hui; LI Xiao-hui

    2008-01-01

    Objective To analyse the potential involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin. Methods A trauma-pain model was established in Wistar rats by combining right-hind limb amputation with 50 ℃ tail-flick test. Antinoeiception was determined by tail-flick latency to hot waster at 50 ℃. RT-PCR was used to observe the the expression of the M1OR and KOR gene. Results Melatonin produced the antinociceptive effect in dose-dependent manner after i. p or i. c. v. administration. Injected i. c. v. to rats, naloxone (10 μg) obviously antagonized the antinoeiceptive effect induced by i. p. melatonin. The expression of the M1OR gene in the rat hypothalamus and the KOR gene in the hippocampus was both significantly reduced at day 3 after injury, which was parallel to the reduction of the rat pain thresholds. However, the expression of the M1OR gene in the hippocampus and the KOR gene in the hypothalamus was not changed. Treatment of trauma-pain rats with melatonin (30-120 mg·kg-1) i. p. administrated induced the up-regulation of M1OR mRNA in the hypothalamus and the KOR mRNA in the hippocampus in a concentration-dependent manner. Conclusions The present observations suggest that Melatonin-induced antinociceptive effect may partially contribute to the up-regulation of M1OR mRNA level in the hypothalamus and the KOR mRNA level in the hippocampus.

  15. δ-阿片受体抑制阿片诱发痛觉过敏的研究进展%The role of δ- opioid receptor in the inhibition of opioid induced hyperalgesia

    Institute of Scientific and Technical Information of China (English)

    李依泽; 王海云; 王国林

    2012-01-01

    Background Opioids are the most powerful analgesics for the treatment of moderate to severe pain.Although opioids have analgesic effect,they have many side effects at the same time.Long term opioids exposure can induce hyperalgesia and tolerance.Moreover,increasing the dose of opioids,paradoxically,aggravates the hyperalgesia and tolerance,causing a vicious cycle.The use of opioids,therefore,is largely limited in the clinical setting. Objective The relevant literatures involved in the role of δ-opioid receptors in the attenuation of opioid induced hyperalgesia (OIH) in recent years were summarized,which helps readership to update the latest information about this topic. Content The structure,distribution,physiological function and the progress of antihyperalgesic effect of δ-opioid receptors were reviewed in this article.Those researches suggest that OIH and tolerance can be attenuated by the inhibition of δ-opioid receptor phosphorylation,knocking out δ-opioid receptor coding genes and the application of δ-opioid receptor antagonists. Trend Since the antihyperalgesia effect of δ-opioid receptor is widely acknowledged,δ- opioid receptor may become a new target to relieve pain in the clinical setting.%背景 阿片类药物是治疗中、重度疼痛的主要药物,长时间应用可出现阿片诱发的痛觉过敏和耐受,而增加药物剂量可造成更严重的痛觉过敏和耐受,从而形成恶性循环,很大程度上限制了阿片类药物在临床工作中的应用.目的 通过对近年δ-阿片受体在痛觉过敏中所起作用的研究进行总结,帮助读者了解国外相关研究的最新趋势和进展.内容 就δ-阿片受体的结构、分布、生理功能和δ-阿片受体的抗痛觉过敏作用的研究进展进行综述.得出如下结论,通过抑制δ-阿片受体磷酸化、敲除δ-阿片受体编码基因和应用δ-阿片受体拮抗剂等方法,可抑制痛觉过敏和耐受的形成.趋向 随着越来越多的学者对

  16. Use of analgesic drugs and risk of ovarian cancer

    DEFF Research Database (Denmark)

    Ammundsen, Henriette B; Faber, Mette T; Jensen, Allan;

    2012-01-01

    The role of analgesic drug use in development of ovarian cancer is not fully understood. We examined the association between analgesic use and risk of ovarian cancer. In addition, we examined whether the association differed according to histological types.......The role of analgesic drug use in development of ovarian cancer is not fully understood. We examined the association between analgesic use and risk of ovarian cancer. In addition, we examined whether the association differed according to histological types....

  17. Analgesic effects of dexamethasone in burn injury

    DEFF Research Database (Denmark)

    Werner, Mads U; Lassen, Birgit Vibeke; Kehlet, Henrik

    2002-01-01

    BACKGROUND AND OBJECTIVES: Glucocorticoids are well-known adjuvant analgesics in certain chronic pain states. There is, however, a paucity of data on their analgesic efficacy in acute pain. Therefore, the aim of the study was to examine the analgesic effects of dexamethasone in a validated burn m...... administration of dexamethasone 2 hours before a burn injury does not reduce the inflammatory-mediated changes in quantitative sensory thresholds, pain perception, or skin erythema in humans....... differences between treatments in regard to skin erythema (P >.8), thermal or mechanical thresholds (P >.2), thermal or mechanical pain response (P >.2), or mechanical secondary hyperalgesia (P >.2). Dexamethasone had no analgesic effects in normal skin. CONCLUSIONS: The study indicates that systemic...... model of acute inflammatory pain in humans. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Intravenous dexamethasone 8 mg or placebo was administered on 2 separate study days. Two hours after drug administration, a first-degree burn...

  18. Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Vanita Ahuja

    2015-01-01

    Full Text Available Background and Aims: Flupirtine maleate is a centrally acting, non-opioid analgesic with unique muscle relaxant properties as compared to common analgesics. The aim of this study was to compare post-operative analgesic efficacy of flupirtine maleate and ibuprofen in patients undergoing gynaecological ambulatory surgeries. Methods: This prospective, randomised controlled study was conducted in 60 women of American Society of Anesthesiologists physical status I/II, 18-70 years of age and scheduled to undergo gynaecological ambulatory surgeries. The participants were randomised to receive either 100 mg oral flupirtine maleate (group flupirtine, n = 30 or 800 mg oral ibuprofen (group ibuprofen, n = 30, 1 h prior to surgery and then every 8 h for 48 h. Verbal Numerical Rating Scale (VNRS on movement was assessed at 0, 2, 4, 6 and 8 h following surgery. Following discharge from hospital, the patients were interviewed telephonically at 12, 24 and 48 h post-operatively. VNRS was statistically analysed using Mann-Whitney test. Results: VNRS on movement was statistically reduced at 2 h after surgery (P = 0.04 in group flupirtine as compared to group ibuprofen. The analgesic efficacy was similar in both the groups at 4, 6, 8, 12, 24 and 48 h after surgery. The satisfaction scores at 24 and 48 h post-operatively were superior in group flupirtine as compared to group ibuprofen (P < 0.001. Conclusion: Analgesic efficacy of flupirtine maleate was comparable with ibuprofen in patients in ambulatory gynaecological patients up to 48 h postoperatively with superior satisfaction scores.

  19. Antagonism of kappa opioid mediated effects in the rat by cyclo(Leu-Gly)

    International Nuclear Information System (INIS)

    The effect of cyclo(Leu-Gly) on U-50,488H- induced pharmacological actions was determined in male Sprague-Dawley rats. Intraperitoneal (i.p.) administration of U-50,488H to rats produced analgesia (tail-flick) and increased urinary output. Cyclo (Leu-Gly) antagonized the analgesic response to U-50,488H. A dose of 10 mg/kg (i.p.) of U-50,488H increased the spontaneous urinary output which was anatagonized by cyclo (Leu-Gly). To determine whether cyclo (Leu-Gly) was acting as a kappa-opioid receptor antagonist, the effect of cyclo (Leu-Gly) on the binding of [3H] ethylketocyclazoncine (EKC) to membranes of rat cerebral cortex and spinal cord was determined. The IC50 values of cyclo(Leu-Gly) in displacing [3H]EKC from its binding sites in cortex and spinal cord were 1.44 and 0.40 mM, respectively. Chronic administration of U-50,488H for 4 days induced tolerance to its analgesic effect. The latter was not affected by cyclo(Leu-Gly) given once a day for 4 days. It is concluded that cyclo(Leu-Gly) antagonizes acute actions of U-50,488H and that such effects of cyclo(Leu-Gly) are not mediated via a direct action on kappa-opioid receptors

  20. Antimicrobial and analgesic activities of Wendlandia thyrsoidea leaf extracts

    Directory of Open Access Journals (Sweden)

    Basavaraja Basavanakote

    2009-01-01

    Full Text Available The leaves of Wendlandia thyrsoidea were extracted with different solvents and screened for their antimicrobial and analgesic activities. The antimicrobial activity was evaluated using the minimum inhibitory concentration method and the analgesic activity was carried out by the acetic acid-induced writhing method. The ethyl acetate extract exhibited potent antimicrobial activity, whereas, the methanol extract showed a significant analgesic activity.

  1. Opioid Therapy for Chronic Nonmalignant Pain

    Directory of Open Access Journals (Sweden)

    Russell K Portenoy

    1996-01-01

    Full Text Available Long term administration of an opioid drug for chronic nonmalignant pain continues to be controversial, but is no longer uniformly rejected by pain specialists. This is true despite concerns that the regulatory agencies that oversee physician prescribing of opioid drugs continue to stigmatize the practice. The changing clinical perspective has been driven, in part, by widespread acknowledgement of the remarkably favourable outcomes achieved during opioid treatment of cancer pain. These outcomes contrast starkly with popular teaching about chronic opioid therapy and affirm the potential for prolonged efficacy, tolerable side effects, enhanced function associated with improved comfort and minimal risk of aberrant drug-related behaviours consistent with addiction. A large anecdotal experience in populations with nonmalignant pain suggests that these patients are more heterogeneous and that opioid therapy will greatly benefit some and will contribute to negative outcomes for others. The few controlled clinical trials that have been performed support the safety and efficacy of opioid therapy, but have been too limited to ensure generalization to the clinical setting. A critical review of the medical literature pertaining to chronic pain, opioid pharmacology and addiction medicine can clarify misconceptions about opioid therapy and provide a foundation for patient selection and drug administration. The available data support the view that opioids are no panacea for chronic pain, but should be considered in carefully selected patients using clinically derived guidelines that stress a structured approach and ongoing monitoring of efficacy, adverse effects, functional outcomes and the occurrence of aberrant drug-related behaviours.

  2. The analgesic efficacy of etoricoxib compared with oxycodone/acetaminophen in an acute postoperative pain model: a randomized, double-blind clinical trial.

    Science.gov (United States)

    Chang, David J; Desjardins, Paul J; King, Thomas R; Erb, Tara; Geba, Gregory P

    2004-09-01

    Our objective in this study was to compare the analgesic effects of etoricoxib and oxycodone/acetaminophen in a postoperative dental pain model. Patients experiencing moderate to severe pain after extraction of two or more third molars were randomized to single doses of etoricoxib 120 mg (n = 100), oxycodone/acetaminophen 10/650 mg (n = 100), or placebo (n = 25). The primary end-point was total pain relief over 6 h. Other end-points included patient global assessment of response to therapy; onset, peak, and duration of effect; and rescue opioid analgesic use. Active treatments were statistically significantly superior to placebo for all efficacy measures. Total pain relief over 6 h for etoricoxib was significantly more than for oxycodone/acetaminophen (P acetaminophen by 5 min. The peak effect was similar for both drugs. Compared with oxycodone/acetaminophen patients, etoricoxib patients experienced a longer analgesic duration, had a smaller percentage requiring rescue opioids during 6 and 24 h, and required less rescue analgesia during 6 and 24 h. Oxycodone/acetaminophen treatment resulted in more frequent adverse events (AEs), drug-related AEs, nausea, and vomiting compared with etoricoxib treatment. In conclusion, etoricoxib 120 mg provided superior overall efficacy compared with oxycodone/acetaminophen 10/650 mg and was associated with significantly fewer AEs. PMID:15333415

  3. Prescription trajectories and effect of total hip arthroplasty on the use of analgesics, hypnotics, antidepressants, and anxiolytics: results from a population of total hip arthroplasty patients.

    Science.gov (United States)

    Blågestad, Tone; Nordhus, Inger H; Grønli, Janne; Engesæter, Lars B; Ruths, Sabine; Ranhoff, Anette H; Bjorvatn, Bjørn; Pallesen, Ståle

    2016-03-01

    Total hip arthroplasty (THA) has been shown to reduce pain and improve function. In addition, it is suggested that THA improves sleep and alleviates symptoms of anxiety and depression. Patients with chronic pain are frequent users of analgesic and psychotropic drugs and thereby risk adverse drug events. The impact of THA on such drug use has not been thoroughly investigated. Based on merged data from the Norwegian Prescription Database and the Norwegian Arthroplasty Register, this study sought to investigate redeemed medications in a complete population (N = 39,688) undergoing THA in 2005 to 2011. User rates and redeemed drug volume of analgesics (nonsteroid anti-inflammatory drugs (NSAIDs), opioids, and nonopioids) and psychotropics (hypnotics, anxiolytics, and antidepressants) were calculated for 4 quarters before and 4 quarters after surgery. We analysed preoperative prescription trends (Q1 vs Q4), postoperative prescription (Q4 vs Q5), and long-term effect of surgery (Q4 vs Q8). Before surgery, use of all drug groups increased from Q1 to Q4. Use of opioids, nonopioids, and hypnotics dramatically increased from Q4 to Q5. Long-term (Q4 vs Q8) surgery reduced prescriptions of analgesics, hypnotics, and anxiolytics, but not antidepressants. Overall, the present results extend the positive effects of THA to include reduced reliance on medication to alleviate symptoms. PMID:26588693

  4. Mitigating the risk of opioid abuse through a balanced undergraduate pain medicine curriculum

    Directory of Open Access Journals (Sweden)

    Morley-Forster PK

    2013-12-01

    Full Text Available Patricia K Morley-Forster,1,2 Joseph V Pergolizzi,3–5 Robert Taylor Jr,5 Robert A Axford-Gatley,6 Edward M Sellers71Department of Anesthesia and Perioperative Medicine, University of Western Ontario, London, ON, Canada; 2Outpatient Pain Clinic, St Joseph’s Hospital, London, ON, Canada; 3Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 4Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA; 5NEMA Research Inc, Naples, FL, USA; 6Clinical Content and Editorial Services, Complete Healthcare Communications, Inc, Chadds Ford, PA, USA; 7DL Global Partners Inc, Toronto, ON, CanadaAbstract: Chronic pain is highly prevalent in the United States and Canada, occurring in an estimated 30% of the adult population. Despite its high prevalence, US and Canadian medical schools provide very little training in pain management, including training in the safe and effective use of potent analgesics, most notably opioids. In 2005, the International Association for the Study of Pain published recommendations for a core undergraduate pain management curriculum, and several universities have implemented pilot programs based on this curriculum. However, when outcomes have been formally assessed, these initiatives have resulted in only modest improvements in physician knowledge about chronic pain and its treatment. This article discusses strategies to improve undergraduate pain management curricula and proposes areas in which those efforts can be augmented. Emphasis is placed on opioids, which have great potency as analgesics but also substantial risks in terms of adverse events and the risk of abuse and addiction. The authors conclude that the most important element of an undergraduate pain curriculum is clinical experience under mentors who are capable of reinforcing didactic learning by modeling best practices.Keywords: chronic pain, curricular content, medical education, opioids, pain

  5. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study

    Directory of Open Access Journals (Sweden)

    Mefkur Bakan

    2015-06-01

    Full Text Available BACKGROUND AND OBJECTIVES: Intraoperative use of opioids may be associated with postoperative hyperalgesia and increased analgesic consumption. Side effects due to perioperative use of opioids, such as postoperative nausea and vomiting may delay discharge. We hypothesized that total intravenous anesthesia consisting of lidocaine and dexmedetomidine as an opioid substitute may be an alternative technique for laparoscopic cholecystectomy and would be associated with lower fentanyl requirements in the postoperative period and less incidence of postoperative nausea and vomiting. METHODS: 80 Anesthesiologists I-II adults were scheduled for elective laparoscopic cholecystectomy. Patients were randomly allocated into two groups to have either opioid-free anesthesia with dexmedetomidine, lidocaine, and propofol infusions (Group DL or opioid-based anesthesia with remifentanil, and propofol infusions (Group RF. All patients received a standard multimodal analgesia regimen. A patient controlled analgesia device was set to deliver IV fentanyl for 6 h after surgery. The primary outcome variable was postoperative fentanyl consumption. RESULTS: Fentanyl consumption at postoperative 2nd hour was statistically significantly less in Group DL, compared with Group RF, which were 75 ± 59 µg and 120 ± 94 µg respectively, while it was comparable at postoperative 6th hour. During anesthesia, there were more hypotensive events in Group RF, while there were more hypertensive events in Group DL, which were both statistically significant. Despite higher recovery times, Group DL had significantly lower pain scores, rescue analgesic and ondansetron need. CONCLUSION: Opioid-free anesthesia with dexmedetomidine, lidocaine and propofol infusions may be an alternative technique for laparoscopic cholecystectomy especially in patients with high risk for postoperative nausea and vomiting.

  6. Validity testing of patient objections to acceptance of tamper-resistant opioid formulations

    Directory of Open Access Journals (Sweden)

    Argoff CE

    2013-05-01

    Full Text Available Charles E Argoff,1 Steven P Stanos,2 Matthew S Wieman31Department of Neurology, Albany Medical College Neurology Group, Albany, NY, USA; 2Rehabilitation Institute of Chicago, Center for Pain Management, Northwestern University Medical School, Feinberg School of Medicine, Chicago, IL, USA; 3Department of Medical Sciences, Endo Pharmaceuticals Inc, Chadds Ford, PA, USABackground: Tamper-resistant formulations (TRFs of oral opioid drugs are intended to prevent certain types of abuse (eg, intranasal, intravenous. Patients raising objections to receiving a TRF may have valid concerns or may be seeking a formulation that can be more easily misused.Methods: US clinicians experienced in pain management met in October 2011 to discuss common patient objections to being switched from a non-TRF opioid to a TRF of the same opioid. Retail pharmacy, health insurance, and scientific data were used to assess the potential validity of these patient objections.Results: Clinical experience switching patients from a non-TRF to a TRF opioid was limited to oxycodone controlled release (CR, as it was the only TRF available at that time; knowledge of other TRFs was limited to the scientific literature. Common objections from patients included “costs more,” “not covered by insurance,” “can't feel it working,” and “causes adverse events.” Objective retail pharmacy and insurance coverage information for oxycodone CR was accessible and indicated that patient objections were based on cost and coverage varied by insurer. Unpublished trial results (ClinicalTrials.gov revealed that TRF oxycodone CR has a slower initial release than the non-TRF formulation, which may reduce positive subjective effects. The complaint “I can't feel it working” may reflect lessened positive subjective effects rather than reduced analgesic efficacy. Most tolerability complaints lacked objective support.Conclusion: The general process used to assess the validity of patient

  7. Effects of opioids on local anesthesia in the rat: a codeine and tramadol study

    Directory of Open Access Journals (Sweden)

    Talita Girio Carnaval

    2013-12-01

    Full Text Available Opioids are central analgesics that act on the CNS (central nervous system and PNS (peripheral nervous system. We investigated the effects of codeine (COD and tramadol (TRAM on local anesthesia of the sciatic nerve. Eighty Wistar male rats received the following SC injections in the popliteal fossa: local anesthetic with epinephrine (LA; local anesthetic without vasoconstrictor (LA WV; COD; TRAM; LA + COD; LA + TRAM; COD 20 minutes prior to LA (COD 20' + LA or TRAM 20 minutes prior to LA (TRAM 20' + LA. As a nociceptive function, the blockade was considered the absence of a paw withdraw reflex. As a motor function, it was the absence of claudication. As a proprioceptive function, it was the absence of hopping and tactile responses. All data were compared using repeated-measures analysis of variance (ANOVA. Opioids showed a significant increase in the level of anesthesia, and the blockade duration of LA + COD was greater than that of the remaining groups (p < 0.05. The associated use of opioids improved anesthesia efficacy. This could lead to a new perspective in controlling dental pain.

  8. Analgesic and thermic effects, and cerebrospinal fluid and plasma pharmacokinetics, of intracerebroventricularly administered morphine in normal and sensitized rats.

    Science.gov (United States)

    Bhargava, H N; Villar, V M; Cortijo, J; Morcillo, E J

    1998-02-01

    The relationship between asthma and opioids has barely been investigated. This study examines whether active sensitization of rats changes the analgesic and thermic effects of intracerebroventricular morphine or the pharmacokinetics of the drug. Morphine (5, 10 and 20 microg) was given intracerebroventricularly to sensitized (active immunization to ovalbumin and Al(OH)3 then airway challenge with ovalbumin after 12 days) and normal (i.e. non-sensitized) male Sprague-Dawley rats. The tail-flick latencies and changes in colon temperature were determined before morphine injection and at 30 min intervals for a period of 300 min afterwards. Results were expressed as the area under the time-response curve. The analgesic and hyperthermic response to morphine for sensitized rats was less than that obtained for normal rats. Cerebrospinal fluid and blood samples were collected periodically for a period of 240 min and morphine levels were determined by a highly sensitive radioimmunoassay. The pharmacokinetic parameters half-life, terminal elimination rate constant and the mean residence time were determined in both cerebrospinal fluid and plasma by non-compartmental analysis. The area under the cerebrospinal fluid concentration-time curve from time zero to infinity was higher for sensitized rats than for normal rats for all three doses of morphine but these differences did not correspond with similar changes in pharmacological responses. In conclusion, the attenuated analgesic and thermic responses to intracerebroventricular morphine in the sensitized rats might be a result of pharmacodynamic alterations rather than to pharmacokinetic changes. PMID:9530988

  9. Analgesic therapy of skeletal metastases with radionuclides

    International Nuclear Information System (INIS)

    The radionculide therapy of bone metastases is an unspecific palliative treatment of metastatic skeletal pain especially useful in patients suffering in multiple sites. In these cases the long-term administration of increasing doses of analgesics such as opiate which have important side effects can be reduced. The aim of this therapy is pain relief and improvement of quality of life in patients with advanced cancer. This report is focusing on options, indications and contraindications of the radionuclide therapy of metastases and on used radionuclides such as Strontium-89, Yttrium-90, Rhenium-186 (188) and Samarium-153. In oncology, the analgesic therapy using boneseeking radiopharmaceuticals in combination to drug administration should gain more importance because this therapy can be administered on an outpatient basis. (orig.)

  10. Low-dose intravenous ketamine and clonidine for poor postoperative opioid responsiveness: a double blind randomized study.

    Science.gov (United States)

    Salengros, J C; Hecquet, F; Touihri, K; Sekkat, J; Barvais, L; Engelman, E

    2011-01-01

    In the immediate postoperative period, some patients present with pain that responds poorly to intravenous opioids. In a double-blind randomized study, we tested the hypothesis that administering small doses of intravenous ketamine (0.125 mg/kg) combined with clonidine (0.5 microg/kg) would enhance the speed of onset and the quality of an opioid analgesic regimen in patients who initially responded poorly to opioids. We enrolled 68 patients in the study, all physical status I to III according to the American Society of Anesthesiologists classification. If the patient's numerical rating scale (NRS) score remained > or = 5 after an initial intravenous injection of 10 mg piritramide (2-mg boluses every 5 minutes) in the post-anesthesia care unit, patients were randomized to either intravenous placebo (sodium chloride 0.9%) or active substances (ketamine 0.125 mg/kg plus clonidine 0.5 microg/kg). Fifteen minutes after administration of either placebo or active agents, patients with severe pain (NRS > 4) again received intravenous opioids until NRS < 4. The primary endpoint of the study was to reduce by 20 minutes the time necessary to achieve an NRS < 4. There was no statistically significant difference between the two groups regarding the time required for patients to achieve an NRS < 4. It was concluded that in the immediate postoperative period, the acute administration of small combined doses of intravenous ketamine (0.125 mg/kg) and clonidine (0.5 mirog/kg) does not reduce the onset of an opioid-based analgesia in patients with an initial poor response to intravenous opioids. PMID:21919372

  11. Toward safe accessibility of opioid pain medicines in Vietnam and other developing countries: a balanced policy method.

    Science.gov (United States)

    Krakauer, Eric L; Nguyen, Thi Phuong Cham; Husain, Syeda Asra; Nguyen, Thi Hai Yen; Joranson, David E; Luong, Ngoc Khue; Maurer, Martha A

    2015-05-01

    Moderate or severe pain is common among people with advanced cancer and other life-threatening illnesses. Yet despite agreement that pain relief is a human right, the poorest 80% of the world's population rarely have access to strong opioid analgesics. Excessively restrictive opioid policies, especially in developing countries, both stem from and propagate misguided fears about opioids, so-called opiophobia. Because opiophobia, like any norm, is historically, socially, and culturally situated, efforts to change opiophobic policies will be most effective if guided by awareness of their historical, social, and cultural determinants. We describe some of these determinants in Vietnam and report on results of an ongoing project there to allay opiophobia and improve safe access to opioids for medical uses. We used a method that entails working with committed local partners, including a high-level official from the Ministry of Health, to review all Vietnamese policies governing opioid accessibility to identify the barriers; devising an action plan to safely reduce or circumnavigate the barriers; obtaining buy-in for the plan from all stakeholders, including drug regulators and the police; and assisting the Ministry of Health to implement the plan. Since the start of the project, morphine consumption has increased each year and as of 2010 was ninefold greater than in 2003, and the number of hospitals offering palliative care has increased from three to 15. We conclude that this balanced policy method appears to be helping to reduce barriers to opioid access in Vietnam and should be used in other developing countries. PMID:25523889

  12. Analgesic Treatment in Laparoscopic Gastric Bypass Surgery

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenberg, Jacob;

    2014-01-01

    This review aimed to present an overview of the randomized controlled trials investigating analgesic regimens used in laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Literature search was performed in PubMed and EMBASE databases in August 2013 in accordance to PRISMA guidelines. The...... literature search identified nine studies eligible for inclusion. The administration of nonsteroidal anti-inflammatory drugs, local anesthetics (intraperitoneally or subfascially/subcutaneously), transversus abdominis plane block, dexmedetomidine, and ketamine may improve analgesia compared to placebo...

  13. The analgesic activity of morphine-6-glucuronide.

    OpenAIRE

    Osborne, R; Van P. Thompson; Joel, S; Trew, D; Patel, N; Slevin, M.

    1992-01-01

    1. The pharmacokinetics, cardio-respiratory effects and analgesic effects of intravenous morphine-6-glucuronide were studied in 20 cancer patients with pain. Four different dose levels (0.5, 1, 2, and 4 mg 70 kg-1) were studied. Plasma concentrations of morphine-6-glucuronide were measured for 12 h after dosing. Pulse rate, respiratory rate and blood pressure were monitored, and pain relief was measured using two rating scales and a visual analogue scale. 2. The mean elimination half-life (+/...

  14. Analgesics and sedatives in vascular interventionist radiologic

    International Nuclear Information System (INIS)

    Interventionist radiology routinely requires the use of different drugs (analgesics and sedatives) in the course of a procedure. Aside from their therapeutic action, these drugs can produce secondary or undesirable effects, making necessary an in-depth knowledge of them to assure their safe and efficient management. The aim of this work is to provide the vascular interventionist radiologist with additional information on the management of those drugs that contribute to minimizing patient discomfort and pain in interventionist procedures. Author

  15. Physicians Experience with and Expectations of the Safety and Tolerability of WHO-Step III Opioids for Chronic (Low Back Pain: Post Hoc Analysis of Data from a German Cross-Sectional Physician Survey

    Directory of Open Access Journals (Sweden)

    Michael A. Ueberall

    2015-01-01

    Full Text Available Objective. To describe physicians’ daily life experience with WHO-step III opioids in the treatment of chronic (low back pain (CLBP. Methods. Post hoc analysis of data from a cross-sectional online survey with 4.283 Germany physicians. Results. With a reported median use in 17% of affected patients, WHO-step III opioids play a minor role in treatment of CLBP in daily practice associated with a broad spectrum of positive and negative effects. If prescribed, potent opioids were reported to show clinically relevant effects (such as ≥50% pain relief in approximately 3 of 4 patients (median 72%. Analgesic effects reported are frequently related with adverse events (AEs. Only 20% of patients were reported to remain free of any AE. Most frequently reported AE was constipation (50%, also graded highest for AE-related daily life restrictions (median 46%. Specific AE countermeasures were reported to be necessary in approximately half of patients (median 45%; nevertheless AE-related premature discontinuation rates reported were high (median 22%. Fentanyl/morphine were the most/least prevalently prescribed potent opioids mentioned (median 20 versus 8%. Conclusion. Overall, use of WHO-step III opioids for CLBP is low. AEs, especially constipation, are commonly reported and interfere significantly with analgesic effects in daily practice. Nevertheless, beneficial effects outweigh related AEs in most patients with CLBP.

  16. 42 CFR 8.11 - Opioid treatment program certification.

    Science.gov (United States)

    2010-10-01

    ... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP... opioid addiction. (2) To obtain certification from SAMHSA, an OTP must meet the Federal opioid treatment... before May 18, 2001 were the subject of a current, valid approval by FDA under 21 CFR, part...

  17. Transcriptomic and behavioural characterisation of a mouse model of burn pain identify the cholecystokinin 2 receptor as an analgesic target

    Science.gov (United States)

    Yin, Kathleen; Deuis, Jennifer R; Lewis, Richard J

    2016-01-01

    Burn injury is a cause of significant mortality and morbidity worldwide and is frequently associated with severe and long-lasting pain that remains difficult to manage throughout recovery. We characterised a mouse model of burn-induced pain using pharmacological and transcriptomic approaches. Mechanical allodynia elicited by burn injury was partially reversed by meloxicam (5 mg/kg), gabapentin (100 mg/kg) and oxycodone (3 and 10 mg/kg), while thermal allodynia and gait abnormalities were only significantly improved by amitriptyline (3 mg/kg) and oxycodone (10 mg/kg). The need for relatively high opioid doses to elicit analgesia suggested a degree of opioid resistance, similar to that shown clinically in burn patients. We thus assessed the gene expression changes in dorsal root ganglion neurons and pathophysiological mechanisms underpinning burn injury-induced pain using a transcriptomic approach. Burn injury was associated with significantly increased expression of genes associated with axon guidance, neuropeptide signalling, behavioural defence response and extracellular signalling, confirming a mixed neuropathic and inflammatory aetiology. Notably, among the pain-related genes that were upregulated post-injury was the cholecystokinin 2 receptor (Cckbr), a G protein-coupled receptor known as a pain target involved in reducing opioid effectiveness. Indeed, the clinically used cholecystokinin receptor antagonist proglumide (30 mg/kg) was effective at reversing mechanical allodynia, with additional analgesia evident in combination with low-dose oxycodone (1 mg/kg), including significant reversal of thermal allodynia. These findings highlight the complex pathophysiological mechanisms underpinning burn injury-induced pain and suggest that cholecystokinin-2 receptor antagonists may be useful clinically as adjuvants to decrease opioid requirements and improve analgesic management. PMID:27573516

  18. Opioid-induced respiratory depression: ABCB1 transporter pharmacogenetics.

    Science.gov (United States)

    Sadhasivam, S; Chidambaran, V; Zhang, X; Meller, J; Esslinger, H; Zhang, K; Martin, L J; McAuliffe, J

    2015-04-01

    Opioid-related respiratory depression (RD) is a serious clinical problem as it causes multiple deaths and anoxic brain injuries. Morphine is subject to efflux via P-glycoprotein transporter encoded by ABCB1, also known as MDR1. ABCB1 polymorphisms may affect blood-brain barrier transport of morphine and therefore individual response to its central analgesic and adverse effects. This study aimed to determine specific associations between common ABCB1 genetic variants and clinically important outcomes including RD and RD resulting in prolonged stay in hospital with intravenous morphine in a homogenous pediatric surgical pain population of 263 children undergoing tonsillectomy. Children with GG and GA genotypes of ABCB1 polymorphism rs9282564 had higher risks of RD resulting in prolonged hospital stays; adding one copy of the minor allele (G) increased the odds of prolonged hospital stay due to postoperative RD by 4.7-fold (95% confidence interval: 2.1-10.8, P=0.0002). PMID:25311385

  19. Reversal of morphine analgesic tolerance by ethanol in the mouse.

    Science.gov (United States)

    Hull, L C; Gabra, B H; Bailey, C P; Henderson, G; Dewey, W L

    2013-06-01

    The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the γ-aminobutyric acid (GABA)(B) receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABA(A) antagonist bicuculline but not by the GABA(B) antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment. PMID:23528610

  20. Post-operative intravenous patient-controlled analgesic efficacy of morphine with ketorolac versus nefopam after laparoscopic gynecologic surgery: a randomized non-inferiority trial

    Science.gov (United States)

    Yoon, Ji-Uk; Cheon, Ji-Hyun; Choi, Yoon-Mi; Ri, Hyun-Su; Baik, Seong-Wan

    2016-01-01

    Background Nefopam is a non-opioid non-steroidal centrally acting analgesic. This study was conducted to assess the analgesic efficacy of intravenous patient-controlled analgesia (IV-PCA) using nefopam alone, compared with a combination of morphine and ketorolac, after laparoscopic gynecologic surgery. Methods Sixty patients undergoing laparoscopic gynecologic surgery received IV-PCA. Group A (n = 30) received IV-PCA with a combination of morphine 60 mg and ketorolac 180 mg, while group B (n = 30) received nefopam 200 mg (basal rate 1 ml/h, bolus 1 ml, and lockout time 15 min for both). The primary outcome evaluated was analgesic efficacy using the visual analogue scale (VAS). Other evaluated outcomes included the incidence rate of postoperative nausea and vomiting (PONV), patient satisfaction of pain control, percentage of patients requiring additional opioids, and incidence rate of postoperative adverse effects. Results Group B was not inferior to group A in relation to the VAS in the post-anesthesia care unit, and at 12, 24, and 48 h after surgery (mean difference [95% confidence interval], 0.50 [–0.43 to 1.43], -0.30 [-1.25 to 0.65], -0.05 [-0.65 to 0.55], and 0.10 [-0.55 to 0.75], respectively). The incidence rate of nausea was lower in group B than in group A at 12 and 24 h after surgery (P = 0.004 and P = 0.017, respectively). There were no significant differences in the other outcomes between groups. Conclusions IV-PCA using nefopam alone has a non-inferior analgesic efficacy and produces a lower incidence of PONV in comparison with IV-PCA using a combination of morphine and ketorolac after laparoscopic gynecologic surgery. PMID:27066208

  1. Effect of intraoperative esmolol infusion on anesthetic, analgesic requirements and postoperative nausea-vomitting in a group of laparoscopic cholecystectomy patients

    Directory of Open Access Journals (Sweden)

    Necla Dereli

    2015-04-01

    Full Text Available PURPOSE: Postoperative pain and nausea/vomitting (PNV are common in laparoscopic cholecystectomy patients. Sympatholytic agents might decrease requirements for intravenous or inhalation anesthetics and opioids. In this study we aimed to analyze effects of esmolol on intraoperative anesthetic-postoperative analgesic requirements, postoperative pain and PNV. METHODS: Sixty patients have been included. Propofol, remifentanil and vecuronium were used for induction. Study groups were as follows; I - Esmolol infusion was added to maintenance anesthetics (propofol and remifentanil, II - Only propofol and remifentanil was used during maintenance, III - Esmolol infusion was added to maintenance anesthetics (desflurane and remifentanil, IV - Only desflurane and remifentanil was used during maintenance. They have been followed up for 24 h for PNV and analgesic requirements. Visual analog scale (VAS scores for pain was also been evaluated. RESULTS: VAS scores were significantly lowest in group I (p = 0.001-0.028. PNV incidence was significantly lowest in group I (p = 0.026. PNV incidence was also lower in group III compared to group IV (p = 0.032. Analgesic requirements were significantly lower in group I and was lower in group III compared to group IV (p = 0.005. Heart rates were significantly lower in esmolol groups (group I and III compared to their controls (p = 0.001 however blood pressures were similar in all groups (p = 0.594. Comparison of esmolol groups with controls revealed that there is a significant decrease in anesthetic and opioid requirements (p = 0.024-0.03. CONCLUSION: Using esmolol during anesthetic maintenance significantly decreases anesthetic-analgesic requirements, postoperative pain and PNV.

  2. Intrathecal ziconotide: a review of its use in patients with chronic pain refractory to other systemic or intrathecal analgesics.

    Science.gov (United States)

    Sanford, Mark

    2013-11-01

    Ziconotide (Prialt(®)) is a synthetic conopeptide analgesic that acts by selectively antagonizing N-type voltage-gated calcium channels. Intrathecal ziconotide is the only non-opioid intrathecal analgesic that is FDA-approved for use in patients with treatment-refractory, chronic pain. The efficacy of intrathecal ziconotide was demonstrated in randomized, double-blind, placebo-controlled trials in patients with treatment-refractory noncancer-related pain or cancer- or AIDS-related pain. Across trials, ziconotide recipients had significantly greater reductions in pain intensity during ziconotide treatment than those receiving placebo (primary endpoint). At the end of the titration period, approximately one-sixth to one-third of patients with noncancer chronic pain and one-half with cancer- or AIDS-related pain who received ziconotide reached a pain response threshold (≥30 % reduction in the pain intensity score). In ziconotide responders, analgesic effects were enduring, with some patients continuing treatment over extended periods. Across trials, the chief tolerability concerns in ziconotide recipients during the titration phase and during extended treatment were related to CNS adverse events. These were mostly of mild to moderate intensity, although serious adverse events were commonly attributed to ziconotide treatment, especially in trials with rapid ziconotide titration and that permitted higher dosages. In general, clinically important non-CNS adverse events were infrequent, and during the ziconotide titration phase, relatively few patients discontinued treatment because of adverse events. Ongoing research will assess various strategies for selecting patients for ziconotide treatment and for enhancing its efficacy and tolerability. At the present time, intrathecal ziconotide provides a treatment option for patients with severe, unremitting pain who have failed to respond to other intensive analgesic regimens. PMID:23999971

  3. Opiodes como coadyuvantes de la analgesia epidural en pediatría Opioids as adjuvants of epidural analgesia in the paediatric age

    Directory of Open Access Journals (Sweden)

    M. A. Vidal

    2006-03-01

    acute and chronic pain, being regarded as the standard drug to which new analgesics are compared. Fentanyl is a phenyl-piperidine derived opioid agonist with a high affinity for mu receptors that results in an analgesic potency 50-100 times higher than morphine. Tramadol is the most recent synthetic opioid used in Spain; it has a low affinity for mu, kappa and delta receptors, and an analgesic potency 1/10 of parenteral and 1/30 of spinal morphine. Epidural opioids have been widely used in adults, much less so in children. In this article, the existing studies evaluating its effects in the paediatric age are reviewed, with a reference to pharmacokinetics, clinical considerations and possible side effects after the administration of epidural morphine, fentanyl or tramadol.

  4. Long-term course of opioid addiction.

    Science.gov (United States)

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed. PMID:25747921

  5. Pattern of use of analgesics in a surgical unit

    OpenAIRE

    Mohammad Abdullah Al Masud; Syed Ashrafuzzaman; Md. Jalaluddin Iqbal

    2009-01-01

    The present study was designed to evaluate the prescribing pattern of analgesics in post-operative patients in a surgical unit. Total number of 180 prescriptions containing analgesics was collected randomly. The only drug in the operation day that was used was pethidine (90.6%). Patients (9.4%) did not receive any analgesics in the operation day. Associated analgesics in the operation day were either tramadol (42.2 %) or ketorolac (54.4%). Only 3.3% did not receive any such drugs. In first po...

  6. Paracetamol and analgesic nephropathy: Are you kidneying me?

    Directory of Open Access Journals (Sweden)

    Waddington F

    2014-12-01

    Full Text Available Freya Waddington, Mark Naunton, Jackson Thomas Faculty of Health, University of Canberra, Canberra, ACT, Australia Introduction: Analgesic nephropathy is a disease resulting from the frequent use of combinations of analgesic medications over many years, leading to significant impairment of renal function. The observation of a large number of cases of renal failure in patients abusing analgesic mixtures containing phenacetin led to the initial recognition of the nephrotoxicity from the use of analgesics. Phenacetin was subsequently exclusively blamed for this disease. However, the role of a single analgesic as a sole cause of analgesic nephropathy was challenged, and a number of researchers have since attempted to determine the extent of involvement of other analgesics including nonsteroidal anti-inflammatory drugs (NSAIDs, aspirin, and paracetamol. Case presentation: We present the case of an 83-year-old woman with a history of NSAID-induced nephropathy with poor pain control and reluctance to use paracetamol. We attempt to briefly review the evidence of paracetamol being implicated in the development of analgesic-induced nephropathy. Conclusion: There is a lack of concrete data regarding causative analgesics, including paracetamol. Patients should therefore not be withheld paracetamol, an effective and commonly recommended agent, for fear of worsening renal function. Keywords: kidney, paracetamol, nephropathy, phenacetin

  7. Neuraxial opioid-induced pruritus: a review.

    LENUS (Irish Health Repository)

    Szarvas, Szilvia

    2012-02-03

    When intrathecal and epidural opioids are administered, pruritus occurs as an unwanted and troublesome side effect. The reported incidence varies between 30% and 100%. The exact mechanisms of neuraxial opioid-induced pruritus remain unclear. Postulated mechanisms include the presence of an "itch center" in the central nervous system, medullary dorsal horn activation, and antagonism of inhibitory transmitters. The treatment of intrathecal opioid-induced pruritus remains a challenge. Many pharmacological therapies, including antihistamines, 5-HT(3)-receptor antagonists, opiate-antagonists, propofol, nonsteroid antiinflammatory drugs, and droperidol, have been studied. In this review, we will summarize pathophysiological and pharmacological advances that will improve understanding and ultimately the management of this troublesome problem.

  8. Zinc involvement in opioid addiction and analgesia – should zinc supplementation be recommended for opioid-treated persons?

    OpenAIRE

    Ciubotariu, Diana; Ghiciuc, Cristina Mihaela; Lupușoru, Cătălina Elena

    2015-01-01

    Introduction Zinc chelators were shown to facilitate some opioid-withdrawal signs in animals. Zinc deficiency, which affects more than 15 % the world’s population, is also common among opioid consumers and opioid-treated animals exhibit misbalances of zinc distribution. Aim The present study focuses on how zinc ions interfere with opioid dependence/addiction and analgesia, trying to preliminary discuss if zinc supplementation in opioid-users should be recommended in order to reduce the risk o...

  9. Pyrrolo- and Pyridomorphinans: Non-selective opioid antagonists and delta opioid agonists/mu opioid partial agonists

    OpenAIRE

    V. Kumar; Clark, M J; Traynor, J. R.; Lewis, J W; Husbands, S M

    2014-01-01

    Opioid ligands have found use in a number of therapeutic areas, including for the treatment of pain and opiate addiction (using agonists) and alcohol addiction (using antagonists such as naltrexone and nalmefene). The reaction of imines, derived from the opioid ligands oxymorphone and naltrexone, with Michael acceptors leads to pyridomorphinans with structures similar to known pyrrolo- and indolomorphinans. One of the synthesized compounds, 5e, derived from oxymorphone had substantial agonist...

  10. Teens Mix Prescription Opioids with Other Substances

    Science.gov (United States)

    Skip to main content En español Researchers Medical & Health Professionals Patients & Families Parents & ... Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ...

  11. College Students Using More Pot, Fewer Opioids

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160861.html College Students Using More Pot, Fewer Opioids Nearly 5 percent ... 2016 THURSDAY, Sept. 8, 2016 (HealthDay News) -- American college students' use of marijuana continues to increase, but the ...

  12. FDA Approves Implant to Battle Opioid Addiction

    Science.gov (United States)

    ... gov/medlineplus/news/fullstory_159050.html FDA Approves Implant to Battle Opioid Addiction Experts say steady dosing ... 26, 2016 (HealthDay News) -- A new long-acting implant that can help treat people addicted to heroin ...

  13. MicroRNAs Are Involved in the Development of Morphine-Induced Analgesic Tolerance and Regulate Functionally Relevant Changes in Serpini1

    Science.gov (United States)

    Tapocik, Jenica D.; Ceniccola, Kristin; Mayo, Cheryl L.; Schwandt, Melanie L.; Solomon, Matthew; Wang, Bi-Dar; Luu, Truong V.; Olender, Jacqueline; Harrigan, Thomas; Maynard, Thomas M.; Elmer, Greg I.; Lee, Norman H.

    2016-01-01

    Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The purpose of the present study was to test the hypothesis that miRNAs play a significant role in the development of analgesic tolerance as measured by thermal nociception. Dicer1 knockdown, miRNA profiling, bioinformatics, and confirmation of high value targets were used to test the proposition. Regionally targeted Dicer1 knockdown (via shRNA) had the anticipated consequence of eliminating the development of tolerance in C57BL/6J (B6) mice, thus supporting the involvement of miRNAs in the development of tolerance. MiRNA expression profiling identified a core set of chronic morphine-regulated miRNAs (miR's 27a, 9, 483, 505, 146b, 202). Bioinformatics approaches were implemented to identify and prioritize their predicted target mRNAs. We focused our attention on miR27a and its predicted target serpin peptidase inhibitor clade I (Serpini1) mRNA, a transcript known to be intricately involved in dendritic spine density regulation in a manner consistent with chronic morphine's consequences and previously found to be correlated with the development of analgesic tolerance. In vitro reporter assay confirmed the targeting of the Serpini1 3′-untranslated region by miR27a. Interestingly miR27a was found to positively regulate Serpini1 mRNA and protein levels in multiple neuronal cell lines

  14. MicroRNAs Are Involved in the Development of Morphine-Induced Analgesic Tolerance and Regulate Functionally Relevant Changes in Serpini1.

    Science.gov (United States)

    Tapocik, Jenica D; Ceniccola, Kristin; Mayo, Cheryl L; Schwandt, Melanie L; Solomon, Matthew; Wang, Bi-Dar; Luu, Truong V; Olender, Jacqueline; Harrigan, Thomas; Maynard, Thomas M; Elmer, Greg I; Lee, Norman H

    2016-01-01

    Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The purpose of the present study was to test the hypothesis that miRNAs play a significant role in the development of analgesic tolerance as measured by thermal nociception. Dicer1 knockdown, miRNA profiling, bioinformatics, and confirmation of high value targets were used to test the proposition. Regionally targeted Dicer1 knockdown (via shRNA) had the anticipated consequence of eliminating the development of tolerance in C57BL/6J (B6) mice, thus supporting the involvement of miRNAs in the development of tolerance. MiRNA expression profiling identified a core set of chronic morphine-regulated miRNAs (miR's 27a, 9, 483, 505, 146b, 202). Bioinformatics approaches were implemented to identify and prioritize their predicted target mRNAs. We focused our attention on miR27a and its predicted target serpin peptidase inhibitor clade I (Serpini1) mRNA, a transcript known to be intricately involved in dendritic spine density regulation in a manner consistent with chronic morphine's consequences and previously found to be correlated with the development of analgesic tolerance. In vitro reporter assay confirmed the targeting of the Serpini1 3'-untranslated region by miR27a. Interestingly miR27a was found to positively regulate Serpini1 mRNA and protein levels in multiple neuronal cell lines

  15. Exercise induced asthma and endogenous opioids.

    OpenAIRE

    Gaillard, R C; Bachman, M.; Rochat, T.; Egger, D; Haller, R.; Junod, A F

    1986-01-01

    Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers b...

  16. Is there a clinical interaction between low molecular weight heparin and non-steroidal analgesics after total hip replacement?

    Science.gov (United States)

    Weale, A E; Warwick, D J; Durant, N; Prothero, D

    1995-01-01

    The benefits of parenteral non-steroidal analgesic drugs and low molecular weight heparin anticoagulants have been shown before, but there is concern that the use of these agents in combination may potentiate haemorrhagic side-effects because of simultaneous inhibition of the clotting cascade and platelet mechanisms of haemostasis. In a prospective controlled trial, 60 patients undergoing total hip replacement were randomised into two groups. Those in one group received intramuscular ketorolac and those in the other group opioid analgesia. All patients received enoxaparin subcutaneously, once daily. There were 34 patients in the NSAID group and 26 in the opiate group. There were no significant differences between the two groups for intraoperative blood loss, postoperative drainage, transfusion requirements, bruising, wound oozing and leg swelling. From this study it would appear that there is a low risk of significant haemostatic potentiation associated with concurrent use of low molecular weight heparin and a modest dose of ketorolac tromethamine. PMID:7717643

  17. Bifunctional Peptide-Based Opioid Agonist-Nociceptin Antagonist Ligands for Dual Treatment of Acute and Neuropathic Pain.

    Science.gov (United States)

    Guillemyn, Karel; Starnowska, Joanna; Lagard, Camille; Dyniewicz, Jolanta; Rojewska, Ewelina; Mika, Joanna; Chung, Nga N; Utard, Valérie; Kosson, Piotr; Lipkowski, Andrzej W; Chevillard, Lucie; Arranz-Gibert, Pol; Teixidó, Meritxell; Megarbane, Bruno; Tourwé, Dirk; Simonin, Frédéric; Przewlocka, Barbara; Schiller, Peter W; Ballet, Steven

    2016-04-28

    Herein, the opioid pharmacophore H-Dmt-d-Arg-Aba-β-Ala-NH2 (7) was linked to peptide ligands for the nociceptin receptor. Combination of 7 and NOP ligands (e.g., H-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) led to binding affinities in the low nanomolar domain. In vitro, the hybrids behaved as agonists at the opioid receptors and antagonists at the nociceptin receptor. Intravenous administration of hybrid 13a (H-Dmt-d-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) to mice resulted in potent and long lasting antinociception in the tail-flick test, indicating that 13a was able to permeate the BBB. This was further supported by a cell-based BBB model. All hybrids alleviated allodynia and hyperalgesia in neuropathic pain models. Especially with respect to hyperalgesia, they showed to be more effective than the parent compounds. Hybrid 13a did not result in significant respiratory depression, in contrast to an equipotent analgesic dose of morphine. These hybrids hence represent a promising avenue toward analgesics for the dual treatment of acute and neuropathic pain. PMID:27035422

  18. Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7.

    Science.gov (United States)

    Minett, Michael S; Pereira, Vanessa; Sikandar, Shafaq; Matsuyama, Ayako; Lolignier, Stéphane; Kanellopoulos, Alexandros H; Mancini, Flavia; Iannetti, Gian D; Bogdanov, Yury D; Santana-Varela, Sonia; Millet, Queensta; Baskozos, Giorgios; MacAllister, Raymond; Cox, James J; Zhao, Jing; Wood, John N

    2015-01-01

    Loss-of-function mutations in the SCN9A gene encoding voltage-gated sodium channel Nav1.7 cause congenital insensitivity to pain in humans and mice. Surprisingly, many potent selective antagonists of Nav1.7 are weak analgesics. We investigated whether Nav1.7, as well as contributing to electrical signalling, may have additional functions. Here we report that Nav1.7 deletion has profound effects on gene expression, leading to an upregulation of enkephalin precursor Penk mRNA and met-enkephalin protein in sensory neurons. In contrast, Nav1.8-null mutant sensory neurons show no upregulated Penk mRNA expression. Application of the opioid antagonist naloxone potentiates noxious peripheral input into the spinal cord and dramatically reduces analgesia in both female and male Nav1.7-null mutant mice, as well as in a human Nav1.7-null mutant. These data suggest that Nav1.7 channel blockers alone may not replicate the analgesic phenotype of null mutant humans and mice, but may be potentiated with exogenous opioids. PMID:26634308

  19. Analgesic effect of Persian Gulf Conus textile venom

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    Nasim Tabaraki

    2014-10-01

    Results: SDS-PAGE indicated 12 bands ranged between 6 and 180 KDa. Finally, ten ng of Conus crude venom showed the best analgesic activity in formalin test. No death observed up to 100 mg/kg. Analgesic activity of crude venom was more significant (P

  20. Safety of nimesulide, meloxicam and rofecoxib as alternative analgesics.

    Science.gov (United States)

    Karakaya, G; Kalyoncu, A F

    2000-01-01

    Paracetamole and codeine are safe alternative analgesics for analgesic intolerant patients. Recently marketed selective and specific COX2 inhibitors are also considered to be safe for this group of patients. In this survey we wanted to disclose the safety of nimesulide and meloxicam and rofecoxib where they have been marketed recently in Turkey. PMID:11269899

  1. Motivational effects of cannabinoids are mediated by ??-opioid and k-opioid receptor

    OpenAIRE

    Ghozland, Sandy; Matthes, Hans W.D.; Simonin, Frederic; Filliol, Dominique; Kieffer, Brigitte L.; Maldonado, Rafael

    2002-01-01

    Repeated THC administration produces motivational and somatic adaptive changes leading to dependence in rodents. To investigate the molecular basis for cannabinoid dependence and its possible relationship with the endogenous opioid system, we explored ??9-tetrahydrocannabinol (THC) activity in mice lacking ??-, ??- or ??-opioid receptor genes. Acute THCinduced hypothermia, antinociception, and ypolocomotion remained unaffected in these mice, whereas THC tolerance and withdrawal...

  2. Development of opioid-induced constipation: post hoc analysis of data from a 12-week prospective, open-label, blinded-endpoint streamlined study in low-back pain patients treated with prolonged-release WHO step III opioids

    Directory of Open Access Journals (Sweden)

    Ueberall MA

    2015-08-01

    Full Text Available Michael A Ueberall,1 Gerhard HH Mueller-Schwefe2 1Institute for Neurological Sciences, Nuremberg, Germany; 2Interdisciplinary Center for Pain and Palliative Care Medicine, Göppingen, Germany Background: Opioid-induced constipation is the most prevalent patient complaint associated with longer-term opioid use and interferes with analgesic efficacy, functionality, quality of life, and patient compliance.Objectives: We aimed to compare the effects of prolonged-release (PR oxycodone plus PR naloxone (OXN vs PR oxycodone (OXY vs PR morphine (MOR on bowel function under real-life conditions in chronic low-back pain patients refractory to World Health Organization (WHO step I and/or II analgesics.Research design and methods: This was a post hoc analysis of the complete data set from a prospective, randomized, open-label, blinded endpoint (PROBE streamlined study (German pain study registry: 2012-0012-05; European Union Drug Regulating Authorities Clinical Trials [EudraCT]: 2012-001317-16, carried out in 88 centers in Germany, where a total of 901 patients requiring WHO step III opioids to treat low-back pain were enrolled and prospectively observed for 3 months. Opioid allocation was based on either optional randomization (n=453 or physician decision (n=448. In both groups, treatment doses could be adjusted as per the German prescribing information, and physicians were free to address all side effects and tolerability issues as usual. The primary endpoint was the proportion of patients maintaining normal bowel function throughout the complete treatment period, assessed with the Bowel Function Index (BFI. Secondary analyses addressed absolute and relative BFI changes, complete spontaneous bowel movements, use of laxatives, treatment emergent adverse events, analgesic effects, and differences between randomized vs nonrandomized patient groups.Results: BFI changed significantly with all three WHO step III treatments, however significantly less with OXN

  3. Effects of the extracts from Mitragyna speciosa Korth. leaves on analgesic and behavioral activities in experimental animals

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    Kitja Sawangjaroen

    2007-03-01

    Full Text Available The leaves of Mitragyna speciosa Korth. (M. speciosa were extracted with methanol to give methanol extract. The methanol extract was made in acid and then in alkaline and extracted with chloroform to give alkaloid extract. The effects of the methanol and alkaloid extracts on analgesic activities in hot plate test in mice and tail flick test in rats and behavioral activities in locomotor activity and pentobarbital-induced sleep in mice, were examined. In acute toxicity test, the LD50 values of oral administration of the methanol and alkaloid extracts of M. speciosa leaves in mice were 4.90 g/kg and 173.20 mg/kg, respectively. Oral administration (50, 100 and 200 mg/kg of the methanol extract of M. speciosa leaves significantly prolonged the latency of nociceptive response on hot plate test in mice. The alkaloid extract of M. speciosa also increased the pain response latency at the dose of 20 mg/kg but less potent than those of the methanol extract (100 mg/kg in mice (comparing 5-10 mg/kg alkaloid extract with corresponding to approximately 200 mg/kg of methanol extract. The antinociceptive action of either methanol extract (100 mg/kg, p.o. or alkaloid extract (20 mg/kg, p.o. of M. speciosa leaves was blocked by naloxone (2 mg/kg, i.p. in mice. Neither the methanol extract nor the alkaloid extract significantly prolonged latency of nociceptive response on tail flick test in rats. Both of the extracts had no significant change on spontaneous motor activity or pentobarbital-induced sleep in mice, respectively. These results suggest that the methanol and alkaloid extracts of M. speciosa leaves possess the analgesic activity which partly acted at opioid receptors in the supraspinal opioid system.

  4. Intrathecal tramadol added to bupivacaine as spinal anesthetic increases analgesic effect of the spinal blockade after major gynecological surgeries

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    Chakraborty Susmita

    2008-01-01

    Full Text Available The analgesic effect of the centrally acting opioid, tramadol, is well-known. It has been shown in clinical studies that using tramadol epidurally can provide longer duration of analgesia, without the common side effects of opioids. The study was undertaken to evaluate the duration of analgesia and/or pain free period produced by intrathecal tramadol added to bupivacaine in patients undergoing major gynecological surgery in a randomized double blind placebo controlled protocol. Fifty patients ASA I & II scheduled for Wardmayo′s operation and Fothergill′s operation were randomly allocated to two equal groups. Group A (n=25 received 3 ml of 0.5% hyperbaric bupivacaine (15 mg with 0.2 ml of normal saline and Group B (n=25 received 3 ml 0.5% hyperbaric bupivacaine and 0.2 ml (20 mg tramadol by intrathecal route at L3-4 inter space. Standard monitoring of the vital parameters was done during the study period. Levels of sensory block and sedation score were recorded every two minutes for the first 20 minutes, and then every ten minutes for the rest of the surgical procedure. Assessment of pain was done using Visual Analogue Scale (VAS. The study was concluded when the VAS was more than 40 mm, postoperatively. The patient was medicated and the time was recorded. Duration of analgesia or pain free period was estimated from the time of completion of spinal injection to administration of rescue analgesic or when the VAS score was greater than 40 mm. In Group B patients, the VAS score was significantly lower, as compared to Group A patients. The duration of analgesia was 210 ± 10.12 min in Group A; whereas, in Group B, it was 380 ± 11.82 min, which was found to be significant.

  5. Venom-based biotoxins as potential analgesics.

    Science.gov (United States)

    Gazerani, Parisa; Cairns, Brian Edwin

    2014-11-01

    Chronic pain is a common debilitating condition with negative social and economic consequences. Management of chronic pain is challenging and the currently available medications do not yet yield satisfactory outcomes for many patients. Venom-derived biotoxins from various venomous species consist of several substances with different structures and compositions that include peptides. A unique characteristic of some venom-based biotoxins is the ability to block essential components of the pain signaling system, notably ion channels. This property is leading to the evaluation of the potential of biotoxins as analgesics to manage chronic pain. In addition to their therapeutic potential, biotoxins have also been essential tools to probe mechanisms underlying pain signaling, channelopathies and receptor expression. This review discusses venom-derived peptidergic biotoxins that are in preclinical stages or already in clinical trials. Some promising results from preliminary in vitro studies, ongoing challenges and unmet needs will also be discussed. PMID:25234848

  6. Opioid Painkiller May Be New Treatment for Heroin Addicts

    Science.gov (United States)

    ... html Opioid Painkiller May Be New Treatment for Heroin Addicts Study finds hydromorphone an effective, widely available, ... opioid painkiller -- may be another treatment option for heroin addiction, a new Canadian study suggests. The research ...

  7. Many Addicts Going without Meds That Curb Opioid Abuse

    Science.gov (United States)

    ... addicted to opioids such as Oxycontin, Vicodin, Percocet, fentanyl and even heroin. In fact, the U.S. Centers ... an overdose of one powerful synthetic opioid painkiller, fentanyl, was behind the April 21 death of music ...

  8. Many Addicts Going without Meds That Curb Opioid Abuse

    Science.gov (United States)

    ... Many Addicts Going Without Meds That Curb Opioid Abuse In 2013, just 17 percent were given drugs ... in the grip of an epidemic of opioid abuse. However, new research suggests that drugs that help ...

  9. Morphine-induced antinociception and reward in "humanized" mice expressing the mu opioid receptor A118G polymorphism.

    Science.gov (United States)

    Henderson-Redmond, Angela N; Yuill, Matthew B; Lowe, Tammy E; Kline, Aaron M; Zee, Michael L; Guindon, Josée; Morgan, Daniel J

    2016-05-01

    The rewarding and antinociceptive effects of opioids are mediated through the mu-opioid receptor. The A118G single nucleotide polymorphism in this receptor has been implicated in drug addiction and differences in pain response. Clinical and preclinical studies have found that the G allele is associated with increased heroin reward and self-administration, elevated post-operative pain, and reduced analgesic responsiveness to opioids. Male and female mice homozygous for the "humanized" 118AA or 118GG alleles were evaluated to test the hypothesis that 118GG mice are less sensitive to the rewarding and antinociceptive effects of morphine. We found that 118AA and 118GG mice of both genders developed conditioned place preference for morphine. All mice developed tolerance to the antinociceptive and hypothermic effects of morphine. However, morphine tolerance was not different between AA and GG mice. We also examined sensitivity to the antinociceptive and hypothermic effects of cumulative morphine doses. We found that 118GG mice show reduced hypothermic and antinociceptive responses on the hotplate for 10mg/kg morphine. Finally, we examined basal pain response and morphine-induced antinociception in the formalin test for inflammatory pain. We found no gender or genotype differences in either basal pain response or morphine-induced antinociception in the formalin test. Our data suggests that homozygous expression of the GG allele in mice blunts morphine-induced hypothermia and hotplate antinociception but does not alter morphine CPP, morphine tolerance, or basal inflammatory pain response. PMID:26521067

  10. Analgesic and anti-inflammatory activities of a fraction rich in gaultherin isolated from Gaultheria yunnanensis (FRANCH.) REHDER.

    Science.gov (United States)

    Zhang, Bin; Li, Jian-Bei; Zhang, Dong-Ming; Ding, Yi; Du, Guan-Hua

    2007-03-01

    The analgesic and anti-inflammatory activities of a salicylate derivatives fraction (SDF) isolated from Gaultheria yunnanensis (FRANCH.) REHDER and the mechanisms of actions were investigated in the present study. The major constituent of SDF, which represented around 50% of this fraction, was a methyl salicylate diglycoside named gaultherin. SDF showed a significant inhibition on the hind paw edema in rats (200, 400 mg/kg body wt., p.o.) and ear swelling in mice (200, 400, 800 mg/kg body wt., p.o.) caused by carrageenin and croton oil, respectively. In addition, SDF (400, 800 mg/kg body wt., p.o.) inhibited only the second phase (inflammatory) in the formalin test, and showed no effect in the hot-plate test in mice. The antinociceptive activity of SDF was predominantly peripheral and independent of the opioid system. These findings demonstrate that SDF from Gaultheria yunnanensis (FRANCH.) REHDER possesses analgesic and anti-inflammatory activities, which may be mediated, at least partly, through the suppression of inflammatory mediators or their release suggested by the animal experiment. The observed effects of SDF are probably due to the presence of high content of salicylate derivatives (80%), including gaultherin, MSTG-A and MSTG-B. PMID:17329839

  11. Proceedings of the AMCP Partnership Forum: Breaking the Link Between Pain Management and Opioid Use Disorder.

    Science.gov (United States)

    2015-12-01

    Prescription drug misuse and abuse, especially with opioid analgesics, is the fastest growing drug problem in the United States. Addressing this public health crisis demands the coordinated efforts and actions of all stakeholders to establish a process of improving patient care and decreasing misuse and abuse. On September 9, 2014, the Academy of Managed Care Pharmacy (AMCP) convened a meeting of multiple stakeholders to recommend activities and programs that AMCP can promote to improve pain management, prevent opioid use disorder (OUD), and improve medication-assisted treatment outcomes. The speakers and panelists recommended that efforts to improve pain management outcomes and reduce the potential for OUD should rely on demonstrated evidence and best practices. It was recommended that AMCP promote a more holistic and evidence-based approach to pain management and OUD treatment that actively engages the patient in the decision-making process and includes care coordination with medical, pharmacy, behavioral, and mental health aspects of organizations, all of which is seamlessly supported by a technology infrastructure. To accomplish this, it was recommended that AMCP work to collaborate with organizations representing these stakeholders. Additionally, it was recommended that AMCP conduct continuing pharmacy education programs, develop a best practices toolkit on pain management, and actively promote quality standards for OUD prevention and treatment. PMID:26679961

  12. Effects of constant rate infusion of anesthetic or analgesic drugs on general anesthesia with isoflurane: A retrospective study in 200 dogs
    Efeitos da infusão intravenosa contínua de fármacos anestésicos ou analgésicos sobre a anestesia geral com isoflurano: Estudo retrospectivo em 200 cães

    OpenAIRE

    Sofia de Amorim Cerejo; Ewaldo de Mattos Júnior; Lilian Toshiko Nishimura; Carolina Quarterone; Leandro Guimarães Franco

    2013-01-01

    Constant rate infusion (CRI) shows several advantages in balanced anesthesia, such as reduction of requirement for inhaled anesthetics and control of pain. The most commonly used drugs in these protocols are local anesthetics, dissociative, and opioids, which may be administered alone or in combinations. We evaluated the records of 200 dogs that underwent various surgical procedures with anesthetic or analgesic CRI in the perioperative period during 2011 and 2012 at the Veterinary Hospital of...

  13. Evidence of CNIH3 involvement in opioid dependence

    OpenAIRE

    Nelson, Elliot C.; Agrawal, Arpana; Heath, Andrew C; Bogdan, Ryan; Sherva, Richard; Zhang, Bo; Al-Hasani, Ream; Bruchas, Michael R.; Chou, Yi-Ling; Demers, Catherine H.; Carey, Caitlin E.; Emily D Conley; Fakira, Amanda K.; Farrer, Lindsay A.; Goate, Alison

    2015-01-01

    Opioid dependence, a severe addictive disorder and major societal problem, has been demonstrated to be moderately heritable. We conducted a genome-wide association study in Comorbidity and Trauma Study data comparing opioid dependent daily injectors (N=1167) with opioid misusers who never progressed to daily injection (N=161). The strongest associations, observed for CNIH3 SNPs, were confirmed in two independent samples, the Yale-Penn genetic studies of opioid, cocaine, and alcohol dependence...

  14. Noribogaine is a G-protein biased κ-opioid receptor agonist.

    Science.gov (United States)

    Maillet, Emeline L; Milon, Nicolas; Heghinian, Mari D; Fishback, James; Schürer, Stephan C; Garamszegi, Nandor; Mash, Deborah C

    2015-12-01

    Noribogaine is the long-lived human metabolite of the anti-addictive substance ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to 20 μM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine displays atypical opioid-like components in vivo, anti-addictive effects and potent modulatory properties of the tolerance to opiates for which the mode of action remained uncharacterized thus far. Our binding experiments and computational simulations indicate that noribogaine may bind to the orthosteric morphinan binding site of the opioid receptors. Functional activities of noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid receptors were characterized. Noribogaine was a weak mu antagonist with a functional inhibition constants (Ke) of 20 μM at the G-protein and β-arrestin signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) but only 12% as efficacious at recruiting β-arrestin, which could contribute to the lack of dysphoric effects of noribogaine. In turn, noribogaine functionally inhibited dynorphin-induced kappa β-arrestin recruitment and was more potent than its G-protein agonistic activity with an IC50 of 1 μM. This biased agonist/antagonist pharmacology is unique to noribogaine in comparison to various other ligands including ibogaine, 18-MC, nalmefene, and 6'-GNTI. We predict noribogaine to promote certain analgesic effects as well as anti-addictive effects at effective concentrations>1 μM in the brain. Because elevated levels of dynorphins are commonly observed and correlated with anxiety, dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant functional inhibition bias to endogenously released dynorphins by noribogaine might be worthy of consideration for treating anxiety and substance related disorders. PMID:26302653

  15. EXPERIMENTAL EVALUATION FOR ANALGESIC ACTIVITY OF MAMSYADI KWATHA

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    Shreevathsa

    2011-04-01

    Full Text Available Siddha Yoga Sangraha of Yadavji Trikamji Acharya, states about Mamsyadi kwatha, an Ayurvedic formulation which is said to be effective in minor mental disorders. The ingredients of Mamsyadi kwatha are Jatamamsi (Nardistachys jatamansi DC, Ashwagandha (Withania somnifera Linn and Parasika yavani (Hyoscymus niger Linn, in 8:4:1 ratio respectively. The test formulation was subjected to assess its analgesic effect. The model selected for the assessment of analgesic effect was tail flick test, in albino mice. The test formulation possesses analgesic effect, which is mainly due to its component Parasika yavani.

  16. FDA Boxed Warning for Immediate-Release Opioids.

    Science.gov (United States)

    Food And Drug Administration Public Health Service U S Department Of Health And Human Services

    2016-06-01

    On March 22, 2016, the Food and Drug Administration (FDA) announced enhanced warnings for immediate-release opioid pain medications related to risks of misuse, abuse, addiction, overdose, and death. The new safety warnings also added to all prescription opioid medications to inform prescribers and patients of additional risks related to opioid use. PMID:27301692

  17. Evaluation of analgesic effect of local administration of morphine after iliac crest bone graft harvesting: A double blind study

    Directory of Open Access Journals (Sweden)

    Devinder Singh

    2013-01-01

    Full Text Available Background and Objective: Pain is a complex process influenced by both physiological and psychological factors. In spite of an armamentarium of analgesic drugs and techniques available to combat post-operative pain, appropriate selection, and effective management for relief of post-operative pain still poses unique challenges. The discovery of peripheral opioid receptors has led to growing interest in the use of locally applied opioids (intra-articular, intra-pleural, intra-peritoneal, and perineural for managing acute pain. As bone graft harvesting is associated with significant post-operative pain and there is a paucity of literature on the use of peripheral opioids at the iliac crest bone harvesting site, the present study was planned to evaluate the analgesic efficacy of local administration of morphine after iliac crest bone graft harvesting. Materials and Methods: A total of 60 patients, 20-50 years of age scheduled to undergo elective surgery for delayed and non-union fracture both bone leg with bone grafting under general anaesthesia (GA were randomly assigned to one of the four groups of 15 patients each: group 1: 2.5 ml normal saline (NS +2.5 ml NS infiltrated into the harvest site at 2 sites + 1 ml NS intramuscularly (i/m; Group 2: 2.5 ml NS + 2.5 ml NS infiltrated into the harvest site at 2 sites + 5 mg morphine in 1 ml i/m.; Group 3: 2.5 mg (2.5 ml morphine + 2.5 mg (2.5 ml morphine infiltrated into the harvest site at 2 sites + 1 ml NS i/m; Group 4: 0.5 mg naloxone (2.5 ml +5 mg (2.5 ml morphine infiltrated into the harvest site at 2 sites + 1 ml NS i/m. Pain from the bone graft site and operative site was assessed for 24 h post-operatively. Results: The patients who had received morphine infiltration (Group 3 had significantly less pain scores at the graft site at 4, 6, and 10 post-operative hours. They also had significantly less morphine consumption and overall better pain relief as compared to the other groups. Conclusions

  18. Treatment of acute opioid withdrawal with ibogaine.

    Science.gov (United States)

    Alper, K R; Lotsof, H S; Frenken, G M; Luciano, D J; Bastiaans, J

    1999-01-01

    Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting. PMID:10506904

  19. Patient-controlled intravenous analgesia as an alternative to epidural analgesia during labor: questioning the use of the short-acting opioid remifentanil. Survey in the French part of Belgium (Wallonia and Brussels).

    Science.gov (United States)

    Lavand'homme, P; Roelants, F

    2009-01-01

    Childbirth ranks among the most intense experiences of acute pain. Neuraxial analgesia (i.e. epidural or combined spinal-epidural technique) is the most effective way to relieve that pain but it is contraindicated or impossible to perform for some parturients. We designed a survey of the current use of analgesic alternatives to epidural analgesia (EA) for labor pain, specifically the use of opioid patient-controlled intravenous analgesia (PCIA), in the French part of Belgium (Wallonia and Brussels). A questionnaire was mailed to the departmental chair of the hospitals with an obstetric unit, both in university and non-university centers (total of 53 centers). The questionnaire evaluated the availability of EA, the alternatives used when EA was contraindicated, the use of opioid-based PCIA for labor analgesia as well as opioid preference and doses, and finally the reasons for not using opioid PCIA. The response rate was 67.5% (36 centers). Among the responding hospitals, EA was available for 68% (range 25-85%) of labors and deliveries. When EA was not available or contraindicated, a parenteral opioid (piritramide, tramadol or pethidine) was proposed in 19% (7/36) of the centers, Entonox in 11% (4/36), a pudendal block by obstetricians in 28% (10/36) and non-pharmacologic alternatives (i.e. hypnosis, sophrology, baths and massages) in 19% (7/36). In 28% (10/36) of the centers however, no analgesic alternative was proposed. Opioid PCIA was employed in 36% (13/36) of the centers and for an additional 11% (4/36) only in case of intrauterine death. Remifentanil was the first choice (76.5% of the PCIA), followed by sufentanil (23.5%). Other opioids (piritramide, morphine, fentanyl) and ketamine were also administered by PCIA. Forty-five percents of the centers reported never using opioid PCIA by either lack of knowledge (7%), fear of maternal or fetal side effects (48%) and unability to provide a correct supervision of the parturient during PCIA use (48%), opposition from

  20. Tapentadol in the management of opioid-naïve patients with cancer pain

    Directory of Open Access Journals (Sweden)

    E. López Ramírez

    2016-02-01

    Full Text Available Introduction: Tapentadol is a centrally acting analgesic with two mechanisms of action (μ opioid agonism and norepinephrine reuptake inhibition. Patients and methods: Tapentadol in 53 cancer opioid-naïve patients with chronic and/or acute pain treated with tapentadol in 3 Radiotherapy Departments from October 2011 to February 2013. Results: Patients included 18 women (33.96 % and 35 men (66.04 % aged 28-85 years (mean: 62.7. Treatment was suspended due to death in 16.98 %, improvement in 5.66 %, pruritus in 1.9 % and dizziness in 1.9 %. Treatment was continued in 66.03 %, and doses increased in 26.41 % to achieve analgesia while 7.5 % were switched to another drug. a The most common cancers were head and neck in 32.1 %, lung in 24.5 % and breast in 13.2 %. b Pain was due to: 47.16 % tumor, 18.7 % bone metastases, 13.21 % radiation therapy, 7.55 % benign processes, 7.55 % neuropathic pain and 3.77 % visceral metastases. c Visual Analog Scale pain pre-treatment was 7.2 and post-treatment 3.3 (difference: 3.9 points, while 71.8 % progressed to mild pain (VAS ≤ 4. d The dose most used was: 50 mg (50.9 %. e Associated medications were: none (22.64 %, rapid-onset fentanyl (60.38 %, anticonvulsants (17 %, steroids (17 %, NSAIDs (13.2 %, morphine (5.66 %, anxiolytics (1.9 %, antidepressants (1.9 %, lidocaine 5 % (1.9 % and acupuncture (1.9 %. f Analgesic efficacy was achieved in 94.34 % of cases. Mean analgesia was reached by 58 % of patients and maximum analgesia was 87.5 % in one patient. g Tapentadol was well tolerated with mild side effects (pruritus, constipation and dizziness in 4 cases (10.7 %. Conclusions: Our data support the use of Tapentadol in cancer opioid-naïve patients with moderate-to-severe chronic or acute pain (VAS > 5. Tapentadol is an effective pain reliever with few side effects.

  1. Intrathecal morphine attenuates acute opioid tolerance secondary to remifentanil infusions during spinal surgery in adolescents

    Directory of Open Access Journals (Sweden)

    Tripi PA

    2015-09-01

    Full Text Available Paul A Tripi,1 Matthew E Kuestner,1 Connie S Poe-Kochert,2 Kasia Rubin,1 Jochen P Son-Hing,2 George H Thompson,2 Joseph D Tobias3 1Division of Pediatric Anesthesiology, 2Division of Pediatric Orthopaedic Surgery, Rainbow Babies and Children's Hospital, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, 3Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital, Columbus, OH, USA Introduction: The unique pharmacokinetic properties of remifentanil with a context-sensitive half-life unaffected by length of infusion contribute to its frequent use during anesthetic management during posterior spinal fusion in children and adolescents. However, its intraoperative administration can lead to increased postoperative analgesic requirements, which is postulated to be the result of acute opioid tolerance with enhancement of spinal N-methyl-D-aspartate receptor function. Although strategies to prevent or reduce tolerance have included the coadministration of longer acting opioids or ketamine, the majority of these studies have demonstrated little to no benefit. The current study retrospectively evaluates the efficacy of intrathecal morphine (ITM in preventing hyperalgesia following a remifentanil infusion.Methods: We retrospectively analyzed 54 patients undergoing posterior spinal fusion with segmental spinal instrumentation, to evaluate the effects of ITM on hyperalgesia from remifentanil. Patients were divided into two groups based on whether they did or did not receive remifentanil during the surgery: no remifentanil (control group (n=27 and remifentanil (study group (n=27. Data included demographics, remifentanil dose and duration, Wong–Baker visual analog scale postoperative pain scores, and postoperative intravenous morphine consumption in the first 48 postoperative hours.Results: The demographics of the two study groups were similar. There were no differences in the Wong–Baker visual analog

  2. Primary care for opioid use disorder

    Directory of Open Access Journals (Sweden)

    Mannelli P

    2016-08-01

    Full Text Available Paolo Mannelli,1 Li-Tzy Wu1–41Department of Psychiatry and Behavioral Sciences, 2Department of Medicine, 3Duke Clinical Research Institute, Duke University Medical Center, 4Center for Child and Family Policy, Sanford School of Public Policy, Duke University, Durham, NC, USARecent reports on prescription opioid misuse and abuse have described unprecedented peaks of a national crisis and the only answer is to expand prevention and treatment, including different levels of care.1 Nonetheless, concerns remain about the ability of busy primary care settings to manage problem opioid users along with other patients. In particular, proposed extensions of buprenorphine treatment, a critically effective intervention for opioid use disorder (OUD, are cautiously considered due to the potential risk of misuse or abuse.2 General practitioners are already facing this burden daily in the treatment of chronic pain, and expert supervision and treatment model adjustment are needed to help improve outcomes. Approximately 20% of patients in primary care have noncancer pain symptoms, with most of them receiving opioid prescriptions by their physicians, and their number is increasing.3 Pain diagnoses are comparable in severity to those of tertiary centers and are complicated by significant psychiatric comorbidity, with a measurable lifetime risk of developing OUD.4,5 Some primary care physicians report frustration about opioid abuse and diversion by their patients; support from pain specialists would improve their competence, the quality f their performance, and the ability to identify patients at risk of opioid misuse.6 Thus, buprenorphine treatment should not be adding to a complex clinical scenario. To this end, the promising models of care emphasize the integration of medical with psychological and pharmacological expertise for the management of OUD. 

  3. Cell death sensitization of leukemia cells by opioid receptor activation

    Science.gov (United States)

    Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

    2013-01-01

    Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

  4. Phytochemical Screening and Evaluation of Analgesic Activity of Oroxylum indicum

    Science.gov (United States)

    Das, B. K.; Al-Amin, M. M.; Russel, S. M.; Kabir, S.; Bhattacherjee, R.; Hannan, J. M. A.

    2014-01-01

    We aimed to study phytochemical screening and analgesic activity of ethanol extract of Oroxylum indicum. The dried powder of the barks of the plant was extracted with 95% ethanol and was subjected to various phytochemical tests to ascertain the principle constituents contained in the extract. The result revealed the presence of alkaloids, flavonoids, tannins, glycosides in the ethanol extract of Oroxylum indicum. The extract was screened for analgesic activity by using hot plate, acetic acid-induced writhing and formalin test. The ethanol extract of the plant at two different doses (250 and 500 mg/kg) showed significant (Pflavonoids and tannins might be responsible for the analgesic activity. We suggest that ethanol extract of Oroxylum indicum might have potential chemical constituents that could be used in the future for the development of novel analgesic agent. PMID:25593396

  5. Opioid receptors: Structural and mechanistic insights into pharmacology and signaling.

    Science.gov (United States)

    Shang, Yi; Filizola, Marta

    2015-09-15

    Opioid receptors are important drug targets for pain management, addiction, and mood disorders. Although substantial research on these important subtypes of G protein-coupled receptors has been conducted over the past two decades to discover ligands with higher specificity and diminished side effects, currently used opioid therapeutics remain suboptimal. Luckily, recent advances in structural biology of opioid receptors provide unprecedented insights into opioid receptor pharmacology and signaling. We review here a few recent studies that have used the crystal structures of opioid receptors as a basis for revealing mechanistic details of signal transduction mediated by these receptors, and for the purpose of drug discovery. PMID:25981301

  6. Caffeine Accelerates Absorption and Enhances the Analgesic Effect of Acetaminophen

    OpenAIRE

    Renner, Bertold; Clarke, Geoff; Grattan, Tim; Beisel, Angelika; Mueller, Christian; Werner, Ulrike; Kobal, Gerd; Brune, Kay

    2013-01-01

    The aim of this study was to determine the analgesic effect of acetaminophen compared to a combination of both caffeine and acetaminophen or caffeine alone using tonic and phasic pain stimulation. Twenty-four subjects were treated orally with 1000 mg acetaminophen, 130 mg caffeine, and a combination of both in a 4-way crossover, double-blind, placebo-controlled study. Pharmacokinetics and analgesic effects were assessed by means of an experimental pain model based on pain-related cortical pot...

  7. Analgesic use - prevalence, biomonitoring and endocrine and reproductive effects

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Mazaud-Guittot, Sverine; Gaudriault, Pierre;

    2016-01-01

    policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have......Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental...

  8. Comparison of the Risks of Shopping Behavior and Opioid Abuse Between Tapentadol and Oxycodone and Association of Shopping Behavior and Opioid Abuse

    OpenAIRE

    Cepeda, M. Soledad; Fife, Daniel; Kihm, Mary A.; Mastrogiovanni, Greg; Yuan, Yingli

    2014-01-01

    Objectives: This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. Materials and Methods: This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial ex...

  9. Prescription opioid abuse in patients presenting for methadone maintenance treatment.

    Science.gov (United States)

    Brands, Bruna; Blake, Joan; Sproule, Beth; Gourlay, Douglas; Busto, Usoa

    2004-02-01

    To characterize prescription opioid dependent patients in a methadone maintenance treatment (MMT) program, a detailed retrospective chart review of new admissions (1997-1999, n=178, mean age=34.5+/-0.7 years, 65% male) was conducted. At admission most patients (83%) had been using prescription opioids (+/-heroin). Four groups were identified: 24% had used prescription opioids only; 24% used prescription opioids initially and heroin later; 35% used heroin first and prescription opioids subsequently; and 17% had used heroin only (this group was significantly younger: mean age 26+/-1 years, P=0.0001). Subjects reported regular use of prescription opioids at higher than therapeutic dosages. For example, in the 'prescription opioid only' group the reported mean (+/-S.E.) number of codeine or oxycodone-containing tablets consumed daily was 23 (+/-6) tablets and 21 (+/-3) tablets, respectively. There were no significant differences found amongst the groups in measures of social stability. Those dependent on prescription opioids alone were less likely to use illicit non-opioid drugs or to be associated with injection drug use. Those that used prescription opioids only or initially were more likely to have ongoing pain problems and to be involved in psychiatric treatment. Further research is required to better elucidate the complex relationships between pain, mental health and addiction in order to develop optimal prevention and treatment strategies for prescription opioid dependence. PMID:14725960

  10. Uma breve história do ópio e dos opióides Una historia breve del opio y de los opioides Opium and opioids: a brief history

    Directory of Open Access Journals (Sweden)

    Danilo Freire Duarte

    2005-02-01

    alcaloides del opio y las facilidades para el empleo de esas substancias por vía parenteral, hubo aumento del interés por el uso criterioso de los opioides en la área médica y del análisis de las consecuencias sociales de su uso abusivo. Se justifica, por lo expuesto, una revisión histórica del opio y de sus derivados. CONTENIDO: La evolución de los conocimientos sobre el opio, producto natural extraído del Papaver somniferum, y sobre los opioides, substancias naturales, semi-sintéticas y sintéticas extraídas del opio, bien como las principales referencias a esas substancias desde la Antiguedad fueron evaluadas. Fue enfatizado el progreso logrado desde los trabajos de Setürner que resultaron en el aislamiento de la morfina. Las averiguaciones acarreadas por otros autores en la busca de substancias sintéticas que presentasen ventajas sobre los productos naturales fueron mencionadas. La importancia del hallazgo de los receptores opioides y de sus ligantes endógenos fue subrayada. CONCLUSIONES: En el amanecer del tercer milenio, a despecho de las pesquisas realizadas con drogas analgésicas de otros grupos farmacológicos, los opioides continúan siendo los analgésicos más potentes, aunque su eficacia sea contestada en ciertos tipos de dolor. Los actuales conocimientos de Farmacología Clínica permiten seleccionar el opioide a ser administrado, considerando la enfermedad y las condiciones del paciente, en la busca de la mejor relación costo-beneficio.BACKGROUND AND OBJECTIVES: In addition to their major influence on human behavior, opium and opioids have been used for a long time as sedative and analgesic drugs. As from the 19th century, with the isolation of opium alkaloids and easy parenteral administration of these substances, there has been increased interest in the judicious medical use of opioids and in the analysis of social consequences of their abuse, which has justified a historical review of opium and opioids. CONTENTS: Further understanding of

  11. Announcing the CDC guideline for prescribing opioids for chronic pain.

    Science.gov (United States)

    Houry, Debra; Baldwin, Grant

    2016-06-01

    This guideline provides recommendations for primary care providers who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses: (a) when to initiate or continue opioids for chronic pain; (b) opioid selection, dosage, duration, follow-up, and discontinuation; and (c) assessing risk and addressing harms of opioid use. This guideline is intended to improve communication between providers and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including abuse, dependence, overdose, and death (Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep 2016;65:1-49. DOI: http://dx.doi.org/10.15585/mmwr.rr6501e1.). PMID:27178083

  12. Opioides en el dolor raquídeo: Relación riesgo/beneficio y estrategia apropiada para su utilización Opioids in spinal pain: Risk/benefit ratio and an appropriate strategy for their use

    Directory of Open Access Journals (Sweden)

    M.A. Caramés

    2010-04-01

    Full Text Available En los últimos años se ha observado un incremento notable en el uso de los opioides en España, por lo que queda ampliamente superada nuestra tradicional posición en el furgón de cola de los prescriptores de opioides en Europa. Este crecimiento se ha reflejado también en el tratamiento de uno de los síndromes dolorosos de mayor prevalencia: el dolor raquídeo. Sin embargo, la eficacia de los opioides administrados de forma crónica para el tratamiento del dolor raquídeo no está clara, aunque cada vez sí son más patentes los riesgos que hemos de asumir: adicción, conductas aberrantes, probable incremento en el tiempo de incapacidad laboral y múltiples efectos secundarios, como la hiperalgesia o el estreñimiento rebelde al tratamiento. Teniendo en cuenta una relación riesgo/beneficio estrecha para este tratamiento, planteamos que estos fármacos sólo los han de prescribir facultativos que puedan realizar un seguimiento atento de los pacientes, pacientes en los que se han agotado otras opciones terapéuticas, incluidas diferentes técnicas antiálgicas y a los cuales habremos informado ampliamente de su correcta utilización y posibles efectos secundarios.In the last few years there has been a notable increase in the use of opioids in our country, overcoming our traditional position at the end of the queue of opioid prescribers in Europe. This growth has also been reflected in the treatment of highly prevalent pain syndromes, such as spinal pain. However, the efficacy of opioids administered chronically for spinal pain is not clear, due to the risks that have to be assumed being obvious: addiction, aberrant behaviour, probable increase in time off sick and the many secondary effects, such as hyperalgesia or persistent constipation with treatment. Taking into account the narrow risk/benefit ratio for this treatment, we assume that these drugs have been prescribed only by physicians who can closely follow up the patients, patients in

  13. Comparison of craving for opioid in opioid-dependent individuals and people under methadone maintenance treatment

    Directory of Open Access Journals (Sweden)

    Azita Chehri

    2014-02-01

    Full Text Available Background: Methadone Maintenance Therapy (MMT is the most important treatment for opioid -dependency recurrence. The aim of this study was to compare the craving level in opioid-dependent individuals and people under methadone maintenance therapy. Methods: In this case – control study, 120 men with opioid dependency were selected through cluster sampling method. They were divided into two groups, 60 people in opioid-dependent group and 60 people in MMT group. Both groups were matched for age, sex, marital status, education, duration of opioid dependency and method of consumption. Then, they completed INCAS Substance Abuse Profile (ISAP, opiate withdrawal symptoms checklist, self–report of craving, Desire for Drug Questionnaire (DDQ, Obsessive Compulsive Drug Use Scale (OCDUS and visual cue-induced craving questionnaire. Data were analyzed by SPSS 15 using t-test and ANOVA. Results: Mean craving for drug significantly was lower in MMT group comparing opioid-dependent group (P<0.01. Conclusion: Methadone Maintenance Therapy decreased the craving for drugs and substances This can have an important role in relapse prevention.

  14. Who Benefits from Chronic Opioid Therapy? Rethinking the Question of Opioid Misuse Risk.

    Science.gov (United States)

    Huber, Elizabeth; Robinson, Richard C; Noe, Carl E; Van Ness, Olivia

    2016-01-01

    Beginning in the late 1990s, a movement began within the pain management field focused upon the underutilization of opioids, thought to be a potentially safe and effective class of pain medication. Concern for addiction and misuse were present at the start of this shift within pain medicine, and an emphasis was placed on developing reliable and valid methods and measures of identifying those at risk for opioid misuse. Since that time, the evidence for the safety and effectiveness of chronic opioid therapy (COT) has not been established. Rather, the harmful, dose-dependent deleterious effects have become clearer, including addiction, increased risk of injuries, respiratory depression, opioid induced hyperalgesia, and death. Still, many individuals on low doses of opioids for long periods of time appear to have good pain control and retain social and occupational functioning. Therefore, we propose that the question, "Who is at risk of opioid misuse?" should evolve to, "Who may benefit from COT?" in light of the current evidence. PMID:27417617

  15. The Prescription Opioid Pain Medication Overdose Epidemic

    Centers for Disease Control (CDC) Podcasts

    2016-04-19

    Overdose related to prescription opioids has become an epidemic. This podcast discusses the risks of this type of drug sometimes used to treat pain, and how to protect yourself. .  Created: 4/19/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/19/2016.

  16. Opioider påvirker immunsystemet

    DEFF Research Database (Denmark)

    Gundestrup, Svend; Sjøgren, Per

    2014-01-01

    Opioids can modulate and suppress the immune system through central mediated mechanisms. Morphine increases replication and spread of HIV-1. Evidence suggests that morphine can also enhance growth and spread of some cancer diagnoses like breast-, prostate- and non-small cell lung cancer. The...

  17. Release of opioid peptides in anaesthetized cats?

    OpenAIRE

    Dashwood, M. R.; Feldberg, W.

    1980-01-01

    1 The effect on arterial blood pressure of intravenous injections of naloxone (200 μg) was examined in cats anaesthetized with chloralose. Usually these injections have no effect on blood pressure unless morphine or opioid peptides have been injected, when they produce a pressor response with tachycardia.

  18. Actualizaciones en el manejo clínico de los opioides espinales en el dolor agudo postoperatorio Up to date in clinical management of neuraxial opioids for the treatment of postoperative pain

    Directory of Open Access Journals (Sweden)

    B. Mugabure Bujedo

    2012-04-01

    -200 μg.Opioids are the strongest drugs currently used for the treatment of pain. Over the last 40 years, because of the discovery of the spinal cord opioid receptors, the use of spinal opioids has become a standard for producing intense segmental analgesia without side effects associated with systemic administration. There is a widespread misconception that any opioid administered epidurally or intrathecally will always produce analgesia by a selective mechanism without central adverse effects. This is simply not true because multiple of these opioids produce analgesia by uptake into the systemic circulation or cerebrospinal fluid (CSF, with subsequent redistribution to brain opioid receptors. The findings indicate that increasing lipid solubility decreases the spinal cord bioavailability, therefore morphine is the most spinally selective opioid currently used in the epidural and intrathecal spaces. Extended release epidural morphine (EREM utilizes a proprietary liposomal carrier to provide prolonged analgesia without the need for an indwelling catheter. Fentanyl is the best option for ambulatory surgery and it becomes apparent that epidural fentanyl acts predominantly spinally when administered as a bolus, and predominantly supraspinally as a continuous infusion. Epidural methadone and hydromorphone are valid alternatives for improve analgesia in the postoperative setting. All opioids injected intrathecally can be expected to produce analgesia, at last in part, by a spinal mechanism. The principal difference among opioids is in their duration of analgesic action, speed of re-distribution and the mechanism by which the drug reaches brainstem sites. In general, lipophilic opioids produce short durations of action (1-4 hours, which makes them attractive for short-term postoperative states. However, morphine doses of only 100 to 200 μg produce potent analgesia lasting as long as 24 hours.

  19. Hiperalgesia asociada al tratamiento con opioides

    Directory of Open Access Journals (Sweden)

    A. Gil Martín

    2014-10-01

    Full Text Available La hiperalgesia inducida por opioides es una reacción paradójica caracterizada por una percepción intensificada de dolor relacionada con el uso de estos medicamentos en ausencia de progresión de la enfermedad o de síndrome de retirada. A diferencia de los casos de tolerancia, definida como pérdida de potencia analgésica durante el uso prolongado de opioides, no se produce mejoría con el escalado de dosis. La hiperalgesia inducida por opioides se ha manifestado en pacientes con dosis de mantenimiento y retirada, pacientes con dosis elevadas o escalado de dosis y pacientes con dosis ultra bajas. Para establecer un diagnóstico diferencial es importante tener en cuenta que un incremento de dosis puede producir una mejoría temporal en pacientes con tolerancia pero no en los que han desarrollado hiperalgesia. La prevalencia de dicho fenómeno es desconocida, pero puede ser más frecuente de lo esperado y muchas veces no reconocido. El mecanismo subyacente no está bien definido, pero existen diversos estudios experimentales tanto en modelos animales como en humanos en los que se observa que la hiperalgesia no está desencadenada por un único factor, sino que son muchos los implicados. Entre los mecanismos propuestos destacan: la mediación del receptor NMDA (N-metil-D-aspartato activado por la liberación presináptica de glutamato, la modulación por la proteína-kinasa de calcio/calmodulina, el aumento en el número de nociceptores o la liberación de neurotransmisores excitadores. Se han realizado diversos estudios para describir la expresión y la relevancia de la hiperalgesia inducida por opioides en distintos grupos de pacientes: ex-adictos a opioides en tratamiento de mantenimiento con metadona, en exposición perioperatoria, en voluntarios sanos o en dolor crónico. Existen diferentes estrategias de tratamiento disponibles; entre las más aceptadas se encuentra la reducción en la dosis del opioide utilizado, la rotación del

  20. Tramadol: a new centrally acting analgesic.

    Science.gov (United States)

    Lewis, K S; Han, N H

    1997-03-15

    The pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of tramadol are reviewed. Tramadol is a synthetic analogue of codeine that binds to mu opiate receptors and inhibits norepinephrine and serotonin reuptake. It is rapidly and extensively absorbed after oral doses and is metabolized in the liver. Analgesia begins within one hour and starts to peak in two hours. In patients with moderate postoperative pain, i.v. or i.m. tramadol is roughly equal in efficacy to meperidine or morphine; for severe acute pain, tramadol is less effective than morphine. Oral tramadol can also be effective after certain types of surgery. Tramadol and meperidine are equally effective in postoperative patient-controlled analgesia. In epidural administration for pain after abdominal surgery, tramadol is more effective than bupivacaine but less effective than morphine. In patients with ureteral calculi, both dipyrone and butylscopolamine are more effective than tramadol. For labor pain, i.m. tramadol works as well as meperidine and is less likely to cause neonatal respiratory depression. Oral tramadol is as effective as codeine for acute dental pain. In several types of severe or refractory cancer pain, tramadol is effective, but less so than morphine; for other types of chronic pain, such as low-back pain, oral tramadol works as well as acetaminophen-codeine. Common adverse effects of tramadol include dizziness, nausea, dry mouth, and sedation. The abuse potential seems low. The recommended oral dosage is 50-100 mg every four to six hours. Tramadol is an effective, if expensive, alternative to other analgesics in some clinical situations. PMID:9075493

  1. PET imaging of human cardiac opioid receptors

    International Nuclear Information System (INIS)

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image μ and δ opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65±8 years old) underwent PET scanning of the chest with [11C]carfentanil ([11C]CFN) and [11C]-N-methyl-naltrindole ([11C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [11C]CFN or [11C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [11C]CFN and [11C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37±0.91 with [11C]CFN and 3.86±0.60 with [11C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [11C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [11C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  2. The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism

    OpenAIRE

    Coluzzi, Flaminia

    2015-01-01

    Flaminia Coluzzi,1,2 Joseph Pergolizzi,3,4 Robert B Raffa,5 Consalvo Mattia1,2 1Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anesthesiology, Intensive Care Medicine and Pain Therapy, Faculty of Pharmacy and Medicine – Polo Pontino, Sapienza University of Rome, Latina, Italy; 2SIAARTI Study Group on Acute and Chronic Pain, Rome, Italy; 3Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 4Naples Anesthesia and Pain Associat...

  3. Non-medical use of opioids among HIV-infected opioid dependent individuals on opioid maintenance treatment: the need for a more comprehensive approach

    Directory of Open Access Journals (Sweden)

    Roux Perrine

    2011-11-01

    Full Text Available Abstract Background Opioid maintenance treatment (OMT has a positive impact on substance use and health outcomes among HIV-infected opioid dependent patients. The present study investigates non-medical use of opioids by HIV-infected opioid-dependent individuals treated with buprenorphine or methadone. Methods The MANIF 2000 study is a longitudinal study that enrolled a cohort of 476 HIV-infected opioid-dependent individuals. Data were collected in outpatient hospital services delivering HIV care in France. The sample comprised all patients receiving OMT (either methadone or buprenorphine who attended at least one follow-up visit with data on adherence to OMT (N = 235 patients, 1056 visits. Non-medical use of opioids during OMT was defined as having reported use of opioids in a non-medical context, and/or the misuse of the prescribed oral OMT by an inappropriate route of administration (injection or sniffing. After adjusting for the non-random assignment of OMT type, a model based on GEE was then used to identify predictors of non-medical use of opioids. Results Among the 235 patients, 144 (61.3% and 91 (38.9% patients were receiving buprenorphine and methadone, respectively, at baseline. Non-medical use of opioids was found in 41.6% of visits for 83% of individual patients. In the multivariate analysis, predictors of non-medical use of opioids were: cocaine, daily cannabis, and benzodiazepine use, experience of opioid withdrawal symptoms, and less time since OMT initiation. Conclusions Non-medical use of opioids was found to be comparable in OMT patients receiving methadone or buprenorphine. The presence of opioid withdrawal symptoms was a determinant of non-medical use of opioids and may serve as a clinical indicator of inadequate dosage, medication, or type of follow-up. Sustainability and continuity of care with adequate monitoring of withdrawal symptoms and polydrug use may contribute to reduced harms from ongoing non-medical use of opioids.

  4. Role of serotonin in pathogenesis of analgesic induced headache

    Energy Technology Data Exchange (ETDEWEB)

    Srikiatkhachorn, A.

    1999-12-16

    Analgesic abuse has recently been recognized as a cause of deterioration in primary headache patients. Although the pathogenesis of this headache transformation is still obscure, and alteration of central pain control system is one possible mechanism. A number of recent studies indicated that simple analgesics exert their effect by modulating the endogenous pain control system rather than the effect at the peripheral tissue, as previously suggested. Serotonin (5-hydroxytryptamine ; 5-HT) has long been known to play a pivotal role in the pain modulatory system in the brainstem. In the present study, we investigated the changes in 5-HT system in platelets and brain tissue. A significant decrease in platelet 5-HT concentration (221.8{+-}30.7, 445.3{+-}37.4 and 467.2{+-}38.5 ng/10{sup 9} platelets, for patients with analgesic-induced headache and migraine patients, respectively, p<0.02) were evident in patients with analgesic induced headache. Chronic paracetamol administration induced a decrease in 5-HT{sub 2} serotonin receptor in cortical and brain stem tissue in experimental animals (B{sub max}=0.93{+-}0.04 and 1.79{+-}0.61 pmol/mg protein for paracetamol treated rat and controls, respectively, p<0.05). Our preliminary results suggested that chronic administration of analgesics interferes with central and peripheral 5-HT system and therefore possibly alters the 5-HT dependent antinociceptive system. (author)

  5. Heat stroke: opioid-mediated mechanisms.

    Science.gov (United States)

    Romanovsky, A A; Blatteis, C M

    1996-12-01

    In our previous study in guinea pigs, intensive and prolonged intraperitoneal heating (IPH) caused heat stroke characterized by high mortality and accompanied by two paradoxical phenomena: ear skin vasoconstriction at a high body temperature (Tb) (hyperthermia-induced vasoconstriction) and a post-IPH Tb fall at an ambient temperature (Ta) below thermoneutrality (hyperthermia-induced hypothermia). In this study, we tested the hypothesis that the mechanisms of the two phenomena involve endogenous opioid agonists. Experiments were conducted in 24 unanesthetized, lightly restrained guinea pigs, each chronically implanted with an intraperitoneal thermode and intrahypothalamic thermocouple. The thermoregulatory effects of a wide-spectrum opioid-receptor antagonist, naltrexone (NTX; 50 or 0 mumol/kg sc), were studied in IPH-induced heat stroke and under normal conditions. IPH was accomplished by perfusing (50 ml/min; 80 min) water (45 degrees C) through the thermode. Ta was maintained at approximately 24 degrees C. Skin vasodilation occurred at the onset of IPH but later changed to vasoconstriction despite high Tb and continuing IPH. IPH-induced hyperthermia (1.8 +/- 0.1 degrees C) was followed by a post-IPH Tb fall (-5.1 +/- 0.7 degree C; calculated for the survivors only). The 48-h mortality rate was 50%. NTX prevented the hyperthermia-induced vasoconstriction and attenuated the hyperthermia-induced hypothermia (-1.8 +/- 0.4 degree C). None of the NTX-treated animals died. The effects of NTX on Tb regulation under normal conditions were minor. These results indicate that the phenomena of both hyperthermia-induced vasoconstriction and hyperthermia-induced hypothermia are opioid dependent. The latter is speculated to reflect opioid-mediated inhibition of metabolism; the former is thought to result from opioid-induced hemodynamic alterations. Because both phenomena did not occur in the NTX-treated survivors, the skin vasoconstriction at high Tb and the posthyperthermia Tb

  6. [Clinical and economical evaluation of new analgesics for the management of chronic pain].

    Science.gov (United States)

    Coluzzi, Flaminia; Ruggeri, Matteo

    2014-11-01

    The management of chronic pain still represent a challenge for physicians. Opioids are the main stem in the treatment of chronic severe pain, not only for their potency, but as they act as central drugs. The main limit to their utilization in clinical practice is the prevalence of side effects, in particular in the gastrointestinal tract, whose constipation represents the most common. Two new formulations are nowadays available on the market: tapentadol PR (TAP PR) and oxycodone/naloxone (OXN). A recent meta-analysis showed that both drugs have a better tolerability profile than a tradizional opioid, such as oxycodone CR (OXY CR), but TAP PR reduces by 47% (RR=0.53) the percentage of patients discontinuing treatment because of side effects, compared to 24% (RR=0.76) of OXN. A similar advantage has been reported in the reduction of the risk of developing nausea and/or vomiting: TAP PR reduces the risk by 47% (RR=0.53), while OXN reduces the risk by only by 10% (RR=0.90). Both drugs reduced by about 40% the risk of constipation (RR=0.61 for TAP PR and for OXN). These results have been recently confirmed by a direct comparison of the two formulations (TAP PR vs OXN) in patients with chronic low back pain with neuropathic component. Both drugs were reported to be effective in reducing pain intensity and neuropathic symptoms, however TAP PR resulted superior to OXN in terms of analgesic efficacy, quality of life, and tolerability, in particular regarding constipation and adherence to treatment. A pharmacoeconomic analysis can be useful to understand the costs of these clinical advantages, and can be done by using a probabilistic analisys and by populating a Markov model that simulates the transition in time of 100 patients through 4 different possible health states: 1) still on treatment; 2) presence of adverse events; 3) discontinuation; 4) death. Both treatments (TAP PR and OXN) have been shown to have an excellent cost-effectiveness profile. In the case of OXN, in

  7. Fluoxetine, a selective inhibitor of serotonin uptake, potentiates morphine analgesia without altering its discriminative stimulus properties or affinity for opioid receptors

    International Nuclear Information System (INIS)

    The analgesic effect of morphine in the rat tail jerk assay was enhanced by the serotonin uptake inhibitor, fluoxetine. Tail jerk latency was not affected by fluoxetine alone. Morphine's affinity for opioid receptors labeled in vitro with 3H-naloxone or 3H-D-Ala2-D-Leu5-enkephalin was not altered by fluoxetine, which has no affinity for these sites at concentrations as high as 1000 nM. In rats trained to discriminate morphine from saline, fluoxetine at doses of 5 or 10 mg/kg were recognized as saline. Increasing the fluoxetine dose to 20 mg/kg did not result in generalization to either saline or morphine. The dose response curve for morphine generalization was not significantly altered by fluoxetine doses of 5 or 10 mg/kg. Those rats treated with the combination of morphine and 20 mg/kg of fluoxetine did not exhibit saline or morphine appropriate responding. Fluoxetine potentiates the analgesic properties of morphine without enhancing its affinity for opioid receptors or its discriminative stimulus properties. 30 references, 2 figures, 2 tables

  8. Fluoxetine, a selective inhibitor of serotonin uptake, potentiates morphine analgesia without altering its discriminative stimulus properties or affinity for opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Hynes, M.D.; Lochner, M.A.; Bemis, K.G.; Hymson, D.L.

    1985-06-17

    The analgesic effect of morphine in the rat tail jerk assay was enhanced by the serotonin uptake inhibitor, fluoxetine. Tail jerk latency was not affected by fluoxetine alone. Morphine's affinity for opioid receptors labeled in vitro with /sup 3/H-naloxone or /sup 3/H-D-Ala/sup 2/-D-Leu/sup 5/-enkephalin was not altered by fluoxetine, which has no affinity for these sites at concentrations as high as 1000 nM. In rats trained to discriminate morphine from saline, fluoxetine at doses of 5 or 10 mg/kg were recognized as saline. Increasing the fluoxetine dose to 20 mg/kg did not result in generalization to either saline or morphine. The dose response curve for morphine generalization was not significantly altered by fluoxetine doses of 5 or 10 mg/kg. Those rats treated with the combination of morphine and 20 mg/kg of fluoxetine did not exhibit saline or morphine appropriate responding. Fluoxetine potentiates the analgesic properties of morphine without enhancing its affinity for opioid receptors or its discriminative stimulus properties. 30 references, 2 figures, 2 tables.

  9. Síndrome de neurotoxicidad inducido por opioides (NIO Opioid induced-neurotoxicity syndrome (OIN

    Directory of Open Access Journals (Sweden)

    M. L. Cid

    2008-12-01

    Full Text Available El síndrome de neurotoxicidad inducido por opioides (NIO es uno de los efectos adversos del uso de estos fármacos descrito en los últimos años. Su aparición de debe a la acumulación de metabolitos tóxicos, principalmente el M3 Glucurónido de la morfina; los cuáles pueden provocar hiperexcitabilidad neuronal, con desarrollo de alteraciones cognitivas, delirium, alucinaciones, mioclonias, convulsiones e hiperalgesia. Especialmente vulnerables a estos efectos son los pacientes mayores o con factores de riesgo como insuficiencia renal o deshidratación. Su manejo incluye principalmente la prevención de su aparición, con el manejo de factores precipitantes; disminución o rotación de opioides y manejo sintomático, intentando mantener siempre un buen control del dolor.The opioid induced neurotoxicity (OIN is an adverse effect for opioids use, described in the last years. Because the accumulation of toxic metabolites, especially M3 Glucuronide of morphine, cause neuronal hiperexcitability, patients can develop cognitive failure, delirium, hallucinations, myoclonus, seizures and hyperalgesia. The most vulnerable patients are old people, patients with dehydration and renal failure. Its treatment include prevention, with the management of trigger factors, decrease or change opioids and symptomatic management, trying to keep the good control of pain.

  10. Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neuronal systems in brain

    International Nuclear Information System (INIS)

    Using adjacent section autoradiography-immunocytochemistry, the distribution of [3H]naloxone binding sites was studied in relation to neuronal systems containing [Leu]enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of [3H]naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand [3H]D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between [3H]naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed. Within regions, the relationship was complex. The complexity of the association between [3H]naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission

  11. Switching from high doses of pure u-opioid agonists to transdermal buprenorphine in patients with cancer

    DEFF Research Database (Denmark)

    Lundorff, Lena; Sjøgren, Per; Hansen, Ole Bo;

    2013-01-01

    BACKGROUND: Several myths on buprenorphine's pharmacology exist: possible analgesic ceiling effect, feasibility of combination with other opioid agonists, and the reversibility of side effects. Aim to evaluate: 1) if cancer patients receiving high doses of pure agonists could obtain adequate pain...... relief after switching to transdermal (TD) buprenorphine and 2) whether the numbers of breakthrough pain episodes after switching increased and whether they could be treated with the same doses of pure agonist as before switching. DESIGN: The prospective open multicenter study included outpatients with...... moderate-to-severe cancer pain satisfactorily controlled. SETTING: Patients were switched from the usual pure agonist to TD buprenorphine and were titrated to a stable dose. The assessments were: 1) daily self-assessment of pain intensity, numbers of rescue medications, and pain interference with sleep; 2...

  12. Anti-inflammatory and analgesic activities of Melanthera scandens

    Institute of Scientific and Technical Information of China (English)

    Jude E Okokon; Anwanga E Udoh; Samuel G Frank; Louis U Amazu

    2012-01-01

    Objective: To evaluate the anti-inflammatory and analgesic activities of leaf extract of Melanthera scandens (M. scandens). Methods: The crude leaf extract (39-111 mg/kg) of M. scandens was investigated for anti-inflammatory and analgesic activities using various experimental models. The anti-inflammatory activity was investigated using carragenin, egg-albumin induced oedema models, while acetic acid, formalin-induced paw licking and thermal-induced pain models were used to evaluate the antinociceptive property. Results: The extract caused a significant (P<0.05 - 0.001) dose-dependent reduction of inflammation and pains induced by different agents used. Conclusions: The leaf extract possesses anti-inflammatory and analgesic effects which may be mediated through the phytochemical constituents of the plant.

  13. Analgesic activity of various extracts of Punica granatum (Linn flowers

    Directory of Open Access Journals (Sweden)

    Chakraborthy Guno

    2008-01-01

    Full Text Available The extracts of flowers of Punica granatum (Linn. (N.O. Family Punicaceae were investigated for analgesic activity in mice using hot plate method. The flowers of Punica granatum (Linn were collected from the local market of Mumbai, Maharashtra and were in a dried condition. The dried powdered flowers (500 gm were extracted in a soxhlet apparatus by using different solvents. Mice weighing 15-25 gm were taken for the experiment. The reaction time of animals in all the groups was noted at 30, 60 and 120 min after drug administration. All data were analyzed with Student-t test. The various extract of the flowers of Punica granatum (Linn showed significant analgesic activity at a dose of 50 mg/kg body weight. A maximum analgesic activity was found at 60 min, after drug administration, which was equivalent to the standard drug used as morphine sulphate.

  14. Drug Repurposing for the Development of Novel Analgesics.

    Science.gov (United States)

    Sisignano, Marco; Parnham, Michael J; Geisslinger, Gerd

    2016-03-01

    Drug development consumes huge amounts of time and money and the search for novel analgesics, which are urgently required, is particularly difficult, having resulted in many setbacks in the past. Drug repurposing - the identification of new uses for existing drugs - is an alternative approach, which bypasses most of the time- and cost-consuming components of drug development. Recent, unexpected findings suggest a role for several existing drugs, such as minocycline, ceftriaxone, sivelestat, and pioglitazone, as novel analgesics in chronic and neuropathic pain states. Here, we discuss these findings as well as their proposed antihyperalgesic mechanisms and outline the merits of pathway-based repurposing screens, in combination with bioinformatics and novel cellular reprogramming techniques, for the identification of novel analgesics. PMID:26706620

  15. Cytotoxic and analgesic potentials of papaver pavoninum fisch and mey

    International Nuclear Information System (INIS)

    Ethanolic extract of whole plant of Papaver pavoninum was used to investigate its cytotoxic and analgesic potentials. Brine Shrimp Cytotoxic bioassay showed that 100 and 1000 micro g/ml doses produced highly significant cytotoxicities causing 83.3 ± 1.924 percentage and 96.7 ± 1.924 percentage lethalities respectively, with LD50 value of 2.54 micro g/ml. The analgesic bioassay, using acetic acid induced writhing behavior in mice showed that all the three doses of the extract (50, 100 and 150 mg/kg) were highly effective and even more effective than the standard analgesic drug (Diclofenic Sodium), which reduced the number of writhes by 13.54 percentage, while the three doses of the plant extract reduced the writhing by 36.91 percentage, 57.01 percentage and 68.39 percentage respectively. (author)

  16. A short history of anti-rheumatic therapy - V. Analgesics

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available The pharmacological treatment of pain has very ancient origins, when plant-derived products were used, including mandrake extracts and opium, a dried latex obtained from Papaver somniferum. In the XVI and XVII centuries opium came into the preparation of two compounds widely used for pain relief: laudanum and Dover’s powder. The analgesic properties of extracts of willow bark were then recognized and later, in the second half of the XIX century, experimental studies on chemically synthesized analgesics were planned, thus promoting the marketing of some derivatives of para-amino-phenol and pyrazole, the predecessors of paracetamol and metamizol. In the XX century, nonsteroidal anti-inflammatory drugs were synthesized, such as phenylbutazone, which was initially considered primarily a pain medication. The introduction on the market of centrally acting analgesics, such as tramadol, sometimes used in the treatment of rheumatic pain. is quite recent.

  17. Treatment Practice and Research Issues in Improving Opioid Treatment Outcomes

    OpenAIRE

    JACKSON, T. RON

    2002-01-01

    Providers of treatment for opioid addiction have entered a new era of accountability, as Federal and State regulators increasingly demand objective evidence of treatment effectiveness. Since the length of treatment is associated with success of treatment, opioid treatment programs that demonstrate an ability to retain patients can make a strong case that they are effective. The challenge to opioid treatment providers is to examine their practices and begin organizational change to incorporate...

  18. The multiple facets of opioid receptor function: implications for addiction

    OpenAIRE

    Lutz, Pierre-Eric; Kieffer, Brigitte L.

    2013-01-01

    Addiction is characterized by altered reward processing, disrupted emotional responses and poor decision-making. Beyond a central role in drug reward, increasing evidence indicate that opioid receptors are more generally involved in all these processes. Recent studies establish the mu opioid receptor as a main player in social reward, which attracts increasing attention in psychiatric research. There is growing interest in blocking the kappa opioid receptor to prevent relapse, and alleviate t...

  19. Opioids Switching with Transdermal Systems in Chronic Cancer Pain

    OpenAIRE

    Barbarisi M; Sansone P; Pota V; Pace MC; Aurilio C; Grella E; Passavanti MB

    2009-01-01

    Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switche...

  20. Modulation of opioid receptor function by protein-protein interactions

    OpenAIRE

    Alfaras-Melainis, Konstantinos; Gomes, Ivone; Rozenfeld, Raphael; Zachariou, Venetia; Devi, Lakshmi,

    2009-01-01

    Opioid receptors, MORP, DORP and KORP, belong to the family A of G protein coupled receptors (GPCR), and have been found to modulate a large number of physiological functions, including mood, stress, appetite, nociception and immune responses. Exogenously applied opioid alkaloids produce analgesia, hedonia and addiction. Addiction is linked to alterations in function and responsiveness of all three opioid receptors in the brain. Over the last few years, a large number of studies identified pr...

  1. Functional modulation of human delta opioid receptor by neuropeptide FF

    Directory of Open Access Journals (Sweden)

    Panula Pertti

    2005-04-01

    Full Text Available Abstract Background Neuropeptide FF (NPFF plays a role in physiological pain sensation and opioid analgesia. For example, NPFF potentiates opiate-induced analgesia and the delta opioid receptor antagonist naltrindole inhibits NPFF-induced antinociception. The nature of the interactions between NPFF and opioid receptors seems to be complex and the molecular mechanisms behind the observed physiological effects are not known. Results We used a stable Chinese hamster ovary cell line expressing c-MYC-tagged human delta opioid receptor to study the interactions at the molecular level. Our results imply that NPFF can directly modulate the activation of delta opioid receptor in the absence of NPFF receptors. The modulatory effect, though only moderate, was consistently detected with several methods. The agonist-induced receptor trafficking was changed in the presence of (1DMeNPYF, a stable NPFF-analogue. (1DMeNPYF enhanced the receptor activation and recovery; opioid antagonists inhibited the effects, indicating that they were delta opioid receptor-mediated. The binding experiments with a novel ligand, Terbium-labeled deltorphin I, showed that (1DMeNPYF modulated the binding of delta opioid receptor ligands. The levels of phosphorylated mitogen-activated protein kinase and intracellular cAMP were studied to clarify the effects of NPFF on the opioid signaling mechanisms. Application of (1DMeNPYF together with a delta opioid receptor agonist enhanced the signaling via both pathways studied. Concomitantly to the receptor trafficking, the time-course of the activation of the signaling was altered. Conclusion In addition to working via indirect mechanisms on the opioid systems, NPFF may exert a direct modulatory effect on the delta opioid receptor. NPFF may be a multi-functional neuropeptide that regulates several neuronal systems depending on the site of action.

  2. Preference or fat? Revisiting opioid effects on food intake

    OpenAIRE

    Taha, Sharif A.

    2010-01-01

    It is well established that opioid signaling in the central nervous system constitutes a powerful stimulus for food intake. The role of opioids in determining food preference, however, is less well defined. Opioids have been proposed to promote intake of preferred foods, or, alternatively, to preferentially increase consumption of fat. In the present manuscript, I comprehensively review results from previous studies investigating this issue. Data from these studies suggests a mechanism for op...

  3. Computer Modeling of Human Delta Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Tatyana Dzimbova

    2013-04-01

    Full Text Available The development of selective agonists of δ-opioid receptor as well as the model of interaction of ligands with this receptor is the subjects of increased interest. In the absence of crystal structures of opioid receptors, 3D homology models with different templates have been reported in the literature. The problem is that these models are not available for widespread use. The aims of our study are: (1 to choose within recently published crystallographic structures templates for homology modeling of the human δ-opioid receptor (DOR; (2 to evaluate the models with different computational tools; and (3 to precise the most reliable model basing on correlation between docking data and in vitro bioassay results. The enkephalin analogues, as ligands used in this study, were previously synthesized by our group and their biological activity was evaluated. Several models of DOR were generated using different templates. All these models were evaluated by PROCHECK and MolProbity and relationship between docking data and in vitro results was determined. The best correlations received for the tested models of DOR were found between efficacy (erel of the compounds, calculated from in vitro experiments and Fitness scoring function from docking studies. New model of DOR was generated and evaluated by different approaches. This model has good GA341 value (0.99 from MODELLER, good values from PROCHECK (92.6% of most favored regions and MolProbity (99.5% of favored regions. Scoring function correlates (Pearson r = -0.7368, p-value = 0.0097 with erel of a series of enkephalin analogues, calculated from in vitro experiments. So, this investigation allows suggesting a reliable model of DOR. Newly generated model of DOR receptor could be used further for in silico experiments and it will give possibility for faster and more correct design of selective and effective ligands for δ-opioid receptor.

  4. Primary care for opioid use disorder

    OpenAIRE

    Wu, Li-Tzy; Mannelli, Paolo

    2016-01-01

    Paolo Mannelli,1 Li-Tzy Wu1–41Department of Psychiatry and Behavioral Sciences, 2Department of Medicine, 3Duke Clinical Research Institute, Duke University Medical Center, 4Center for Child and Family Policy, Sanford School of Public Policy, Duke University, Durham, NC, USARecent reports on prescription opioid misuse and abuse have described unprecedented peaks of a national crisis and the only answer is to expand prevention and treatment, including different levels of care.1 Noneth...

  5. Opioid ligands and receptors of the joint

    OpenAIRE

    Bergström, Jonas

    2006-01-01

    The aim was to explore the occurrence of an opioid system in joints. Thus, joint tissues from rats with and without arthritis and also from patients with knee osteoarthrosis were investigated by EM, immunohistochemistry, RIA, HPLC, receptor binding assay and RT-PCR. In rat joints, EM demonstrated the occurrence of met-enkephalin (ME) in nerve fibers, but also in osteoblasts, osteocytes, endothelial, synovial and monoblastic cells. The novel finding of multiple sources of op...

  6. Serial Analgesic Consumptions and Predictors of Intravenous Patient-controlled Analgesia with Cluster Analysis

    Science.gov (United States)

    Lin, Shih-Pin; Chang, Kuang-Yi; Tsou, Mei-Yung

    2016-01-01

    Objectives: To elucidate the dynamics of analgesic consumption regarding intravenous patient controlled analgesia (IVPCA) during postoperative period is rather complex partly due to between-patient variation and partly due to within-patient variation. A statistical method was proposed to classify serial analgesic consumption into different classifications that were further taken as the multiple outcomes on which to explore the associated predictors. Methods: We retrospectively included 3284 patients administrated by IVPCA for 3 days after surgery. A repeated measurement design corresponding to serial analgesic consumption variables defined as six-hour total analgesic consumptions was adopted. After determining the numbers of clusters, serial analgesic consumptions were classified into several homogeneous subgroups. Factors associated with new classifications were identified and quantified with a multinominal logistic regression model. Results: Three distinct analgesic classifications were aggregated, including “high”, ”middle” and “low” level of analgesic consumption of IVPCA. The mean analgesic consumptions on 12 successive analgesic consumptions at 6-hour interval of each classification consistently revealed a decreasing trend. As the trends were almost parallel with time, this suggests the time-invariant proportionality of analgesic consumption between the levels of analgesic consumption of IVPCA. Patient’s characteristics, like age, gender, weight, height, and cancer status, were significant factors associated with analgesic classifications. Surgical sites had great impacts on analgesic classifications. Discussion: The serial analgesic consumptions were simplified into 3 analgesic consumptions classifications. The identified predictors are useful to recognize patient’s analgesic classifications before using IVPCA. This study explored a new approach to analysing dynamic changes of postoperative analgesic consumptions. PMID:26710218

  7. Analgesic effect of clove essential oil in mice

    OpenAIRE

    Mahmoud Hosseini; Mina Kamkar Asl; Hassan Rakhshandeh

    2011-01-01

    Objective: Results obtained from literature reviews and human studies have shown the analgesic effects of clove plant in toothache. The present work was undertaken in order to investigate the possible analgesic effect of clove oil in mice. Materials and Methods: Fifty mice were divided into 5 groups: 1) Saline; 2) Essential oil (Ess) 2%, 3) Ess 5%, 4) Ess10% and 5) Ess 20%. The hot plate test (55±0.2 °C; Cut-off 60 sec) was performed as a base record 15 min before injection of drugs (Salin...

  8. [Analgesic effects of cannabinoids on central pain syndrome].

    Science.gov (United States)

    Igon'kina, S I; Churiukanov, M V; Churiukanov, V V; Kukushkin, M L

    2011-01-01

    It was shown that cannabinoids anandamide, HU210 and WIN 55,212-2 inhibit both spontaneous episodes of pain and mechanical allodynia in rats with central pain syndrome caused by disturbance of inhibitory processes in the dorsal horns of lumbar spinal cord. The analgesic effect is most pronounced in the intrathecal route of administration. The intensity of analgesic actions of cannabinoids on the central pain syndrome in rats, depending on the drug is as follows: HU210 > WIN 55,212-2 > anandamide. PMID:22359935

  9. Analgesic profile of hydroalcoholic extract obtained from Marrubium vulgare.

    Science.gov (United States)

    de Souza, M M; de Jesus, R A; Cechinel-Filho, V; Schlemper, V

    1998-04-01

    Marrubium vulgare L. is a medicinal plant used in folk medicine to cure a variety of diseases. Recently we have demonstrated that a hydroalcoholic extract of this plant showed significant, nonspecific antispasmodic effects on isolated smooth muscle. In this report, we have investigated the possible analgesic effects of the same hydroalcoholic extract in different models of pain in mice. The results suggest that this extract exhibits significant analgesic activity, antagonizing chemically-induced acute pain. Such effects may be related to the presence of steroids and terpenes, which were detected by TLC analysis. PMID:23195761

  10. The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine.

    Science.gov (United States)

    Cooper, S A; Kupperman, A

    1991-01-01

    In a single-dose, parallel group, randomized block treatment allocation study, the relative analgesic efficacy of flurbiprofen, a nonsteroidal antiinflammatory drug, was compared to acetaminophen 650 mg with codeine 60 mg, zomepirac sodium 100 mg, and placebo. A total of 226 post-surgical dental patients (146 females and 80 males) participated in the study. Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination. The results of this study support previous work on flurbiprofen. PMID:1930699

  11. Ethical Considerations for Analgesic Use in Sports Medicine.

    Science.gov (United States)

    Matava, Matthew J

    2016-04-01

    This article provides an overview of commonly used analgesics in athletes and the ethical implications of their use in athletic settings. Given the highly competitive nature of modern-day sports and the economic impact of athletic performance at elite levels, athletes feel more compelled than ever to play with injury, which has led to the widespread use of a variety of analgesic agents. An ethical dilemma often ensues for team physicians who must balance the medical implications of these drugs with pressure from players, coaches, and management. The most commonly used agents and their ethical and rational use are discussed. PMID:26832973

  12. κ-Opioid receptor participates of NSAIDs peripheral antinociception.

    Science.gov (United States)

    Silva, Lívia Caroline Resende; Castor, Marina Gomes Miranda E; Navarro, Larissa Caldeira; Romero, Thiago Roberto Lima; Duarte, Igor Dimitri Gama

    2016-05-27

    NSAIDs represent some of the most widely prescribed drugs for relief of short-term fever, pain and inflammation. The participation of the opioid system in the peripheral is poorly understood. The aim of this study was evaluate the role of opioid system in the peripheral antinociception by diclofenac and dipyrone. To test this hypothesis, opioid receptor antagonists were evaluated using the rat paw pressure test, in which pain sensitivity is increased by intraplantar injection of prostaglandin E2 (PGE2, 2μg). Diclofenac (20μg/paw) and Dipyrone (40μg/paw) administered locally into the right paw elicited an antinociceptive effect. It was used naloxone (50μg/paw), a non-selective opioid receptor antagonist, which antagonized peripheral antinociception induced by diclofenac and dipyrone. Selectively, it was evaluated the μ-, δ- and κ-opioid receptor antagonists, respectively, clocinnamox (40μg/paw), naltrindole (50μg/paw) and nor-binaltorphimine (20, 40 and 80μg/paw). Our data indicated that only the κ-opioid antagonist was capable to reverse the peripheral antinociception by NSAIDs. The present results provide evidence that the opioid system participated in the diclofenac and dipyrone-induced peripheral antinociception by indirect activation of κ-opioid receptor probable by release of endogenous opioids such as dynorphins. PMID:27091501

  13. Effect of Opioid on Adult Hippocampal Neurogenesis

    Science.gov (United States)

    Zhang, Yue; Loh, Horace H.; Law, Ping-Yee

    2016-01-01

    During the past decade, the study of the mechanisms and functional implications of adult neurogenesis has significantly progressed. Many studies focus on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells, including addictive drugs such as opioid. Here, we review the most recent works on opiate drugs' effect on different developmental stages of adult hippocampal neurogenesis, as well as the possible underlying mechanisms. We conclude that opiate drugs in general cause a loss of newly born neural progenitors in the subgranular zone of dentate gyrus, by either modulating proliferation or interfering with differentiation and maturation. We also discuss the consequent impact of regulation of adult neurogenesis in animal's opioid addiction behavior. We further look into the future directions in studying the convergence between the adult neurogenesis field and opioid addiction field, since the adult-born granular cells were shown to play a role in neuroplasticity and may help to reduce the vulnerability to drug craving and relapse. PMID:27127799

  14. Optimizing treatment with opioids and beyond.

    Science.gov (United States)

    Clark, Michael R; Treisman, Glenn J

    2011-01-01

    Patients with both chronic pain and substance use disorders offer special challenges and opportunities. They represent a large number of patients with significant costs to themselves and society that translate into poor outcome. The challenges in defining addiction in patients with chronic pain, particularly in those treated with chronic opioid therapy, have distracted the healthcare community from designing effective treatment programs. Traditional treatment programs for chronic pain disorders or substance use disorders are incapable of addressing the issues of the patients' 'other' problem. Treatment devolves to prescribing opioid medications with the belief that both disorders will be treated at least in part, which is deemed better than receiving no treatment at all. Patients are actually concerned about the risks of this type of treatment, and even if it did offer significant benefits, physicians demonstrate a lack of knowledge and skill in administering opioids to these patients. The inadequate treatment of either chronic pain or addiction interferes with the treatment of the other condition and necessitates the design of new treatment paradigms. A new approach to patients with both chronic pain and addiction should start with an evaluation and formulation of these patients to determine the different domains that contribute to their disability (diseases, dimensions, behaviors, life stories). A comprehensive formulation provides the appropriate platform for the implementation of an integrated program of therapy for both conditions that can be intensified to provide more, rather than less, care for the patient that does not meet the goals of functional rehabilitation. PMID:21508627

  15. Effect of Opioid on Adult Hippocampal Neurogenesis.

    Science.gov (United States)

    Zhang, Yue; Loh, Horace H; Law, Ping-Yee

    2016-01-01

    During the past decade, the study of the mechanisms and functional implications of adult neurogenesis has significantly progressed. Many studies focus on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells, including addictive drugs such as opioid. Here, we review the most recent works on opiate drugs' effect on different developmental stages of adult hippocampal neurogenesis, as well as the possible underlying mechanisms. We conclude that opiate drugs in general cause a loss of newly born neural progenitors in the subgranular zone of dentate gyrus, by either modulating proliferation or interfering with differentiation and maturation. We also discuss the consequent impact of regulation of adult neurogenesis in animal's opioid addiction behavior. We further look into the future directions in studying the convergence between the adult neurogenesis field and opioid addiction field, since the adult-born granular cells were shown to play a role in neuroplasticity and may help to reduce the vulnerability to drug craving and relapse. PMID:27127799

  16. Correlation versus causation? Pharmacovigilance of the analgesic flupirtine exemplifies the need for refined spontaneous ADR reporting.

    Directory of Open Access Journals (Sweden)

    Nora Anderson

    Full Text Available Annually, adverse drug reactions result in more than 2,000,000 hospitalizations and rank among the top 10 causes of death in the United States. Consequently, there is a need to continuously monitor and to improve the safety assessment of marketed drugs. Nonetheless, pharmacovigilance practice frequently lacks causality assessment. Here, we report the case of flupirtine, a centrally acting non-opioid analgesic. We re-evaluated the plausibility and causality of 226 unselected, spontaneously reported hepatobiliary adverse drug reactions according to the adapted Bradford-Hill criteria, CIOMS score and WHO-UMC scales. Thorough re-evaluation showed that only about 20% of the reported cases were probable or likely for flupirtine treatment, suggesting an incidence of flupirtine-related liver injury of 1∶100,000 when estimated prescription data are considered, or 0.8 in 10,000 on the basis of all 226 reported adverse drug reactions. Neither daily or cumulative dose nor duration of treatment correlated with markers of liver injury. In the majority of cases (151/226, an average of 3 co-medications with drugs known for their liver liability was observed that may well be causative for adverse drug reactions, but were reported under a suspected flupirtine ADR. Our study highlights the need to improve the quality and standards of ADR reporting. This should be done with utmost care taking into account contributing factors such as concomitant medications including over-the-counter drugs, the medical history and current health conditions, in order to avoid unjustified flagging and drug warnings that may erroneously cause uncertainty among healthcare professionals and patients, and may eventually lead to unjustified safety signals of useful drugs with a reasonable risk to benefit ratio.

  17. PET imaging of human cardiac opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Villemagne, Patricia S.R.; Dannals, Robert F. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ravert, Hayden T. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Frost, James J. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2002-10-01

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image {mu} and {delta} opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65{+-}8 years old) underwent PET scanning of the chest with [{sup 11}C]carfentanil ([{sup 11}C]CFN) and [{sup 11}C]-N-methyl-naltrindole ([{sup 11}C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [{sup 11}C]CFN or [{sup 11}C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [{sup 11}C]CFN and [{sup 11}C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37{+-}0.91 with [{sup 11}C]CFN and 3.86{+-}0.60 with [{sup 11}C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [{sup 11}C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [{sup 11}C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  18. Evaluation of analgesic activity of Aegle marmelos steam bark in experimental animals

    Directory of Open Access Journals (Sweden)

    Sarang Gajanan Ghodki

    2016-06-01

    Conclusions: AMSBAE has analgesic activity. The analgesic activity of AMSBAE was comparable to that of tramadol and Aspirin. Hence, AMSBAE could be a possible alternative to NSAIDs. [Int J Basic Clin Pharmacol 2016; 5(3.000: 1081-1086

  19. Stability and Analgesic Efficacy of Di-acetyl Morphine (Diamorphine) Compared with Morphine in Implanted Intrathecal Pumps In Vivo.

    Science.gov (United States)

    Raphael, Jon H; Palfrey, Stephen M; Rayen, Arasu; Southall, Jane L; Labib, Maurad H

    2004-07-01

    The objective of this study was to investigate di-acetyl morphine as an alternative opioid analgesic for use in implanted intrathecal drug delivery systems because of its greater solubility through evaluation of its stability in vivo and analgesic efficacy in the period between pump refills. Contents of intrathecal drug delivery system reservoirs (SynchroMed, Medtronic, Inc., Minneapolis, MN) that had been filled with di-acetyl morphine dissolved in saline (21), bupivacaine (9), or in both bupivacaine and clonidine (19) were sampled in vivo between 1 and 125 days after refill. The samples were assayed for di-acetyl morphine and its breakdown products by micellar electrokinetic capillary chromatography. Prospective daily numerical pain scores between pump refills, using 11-point Likert scales, on 24 patients with implanted SynchroMed pumps (12 delivering di-acetyl morphine in saline, 12 were delivering morphine in saline) were collected. Results showed that di-acetyl morphine immediately started to decay to mono-acetyl morphine in implanted Synchromed pumps with half-life of 50 days. Mono-acetyl morphine decayed to morphine with a maxima estimated at 125 days. There was no clinically significant change in average weekly pain scores for up to ten weeks in either group (range, 2.5 to 2.8 for diamorphine and 2.7 to 3.1 for morphine) (2-way repeated ANOVA, F(9,220) = 0.98, n.s.). We conclude that di-acetyl morphine and its breakdown products, 6 mono-acetyl morphine and morphine, provide similar analgesia to morphine alone when administered by intrathecal pump for a period of at least ten weeks and may be a useful alternative when a more soluble agent is favored. PMID:22151270

  20. Analgesic and antisympathetic effects of clonidine in burn patients, a randomized, double-blind, placebo-controlled clinical trial

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    Ostadalipour Abbas

    2007-01-01

    Full Text Available Objectives: Unlike most other Analgesic drugs, α2 adrenoceptor agonists are capable of producing analgesia. The aim of this study was to evaluate the Analgesic and antisympathetic effects of clonidine, an α2 adrenoceptor agonist in burn patients. Materials and Methods: This randomized, double-blind, placebo-controlled clinical trial performed on one hundred burn patients in Zarea Hospital, Mazandaran, Iran from august 2004 to July 2005. All patients divided in two groups. Case group (n=50 received oral clonidine, 3.3μg/kg TDS and controls (n=50 received placebo. Heart rate and systolic blood pressure and pain severity Visual analogue score (VAS, were recorded after clonidine administration. Statistical analysis was done by means of Mann Witney U test. Results: 50 patients (mean age 28.96±10 years in case group, and 50 patients (mean age 27.60±11.4 years in control group were studied. VAS pain scores and heart rate in the clonidine group were significantly lower than the control group (P< 0.0001, P< 0.02.there were no significant difference in systolic blood pressure between the two groups on the first and second day but on third day the systolic blood pressure in clonidine group, was lower than controls significantly (P=0.002. Conclusion: This study demonstrates that the use of oral clonidine affects the hemodynamic response to pain in burn patients. Our study demonstrated that clonidine can produce good analgesia and decreased in sympathetic over activity in burn patients, and also reduce opioid dose requirements.

  1. Pharmacological properties of novel cyclic pentapeptides with µ-opioid receptor agonist activity.

    Science.gov (United States)

    Perlikowska, Renata; Piekielna, Justyna; Fichna, Jakub; do-Rego, Jean Claude; Toth, Geza; Janecki, Tomasz; Janecka, Anna

    2014-03-01

    In our previous paper we have reported the synthesis and biological activity of a cyclic analog, Tyr-c(D-Lys- Phe-Phe-Asp)-NH2, based on endomorphin-2 (EM-2) structure. This analog displayed high affinity for the µ-opioid receptor, was much more stable than EM-2 in rat brain homogenate and showed remarkable antinociceptive activity after intracerebroventricular (i.c.v.) injection. Even more importantly, the cyclic analog elicited weak analgesia also after peripheral administration, giving evidence that it was able to cross, at least to some extent, the blood-brain barrier (BBB). Here we describe further modifications of this analog aimed at enhancing brain delivery by increasing lipophilicity. Two new cyclic pentapeptides, Tyr-c(D-Lys-D-1-Nal-Phe-Asp)-NH2 and Tyr-c(D-Lys-D-2-Nal-Phe-Asp)-NH2 (where 1-Nal=1- naphthyl-3-alanine, 2-Nal=2-naphthyl-3-alanine) were synthesized and evaluated in biological assays. Both analogs showed high µ-opioid receptor affinity and agonist activity and were stable in the rat brain homogenates. Unfortunately, the increase of lipophilicity was achieved at the expense of water solubility. The analog with D-2-Nal residue showed strong analgesic effect when given i.c.v. but could not be tested after intravenous (i.v.) administration where higher concentrations of the compound are required. However, this analog showed inhibitory effect on gastrointestinal (GI) motility in vivo, providing an interesting approach to the development of peripherally restricted agents that could be useful for studying gastrointestinal disorders in animal models. PMID:23628088

  2. Beneficial properties of maraviroc on neuropathic pain development and opioid effectiveness in rats.

    Science.gov (United States)

    Kwiatkowski, Klaudia; Piotrowska, Anna; Rojewska, Ewelina; Makuch, Wioletta; Jurga, Agnieszka; Slusarczyk, Joanna; Trojan, Ewa; Basta-Kaim, Agnieszka; Mika, Joanna

    2016-01-01

    Targeting chemokine signaling pathways is crucial in neuropathy development. In this study, we investigated the influence of chronic administration of maraviroc (CCR5 antagonist) on nociception and opioid effectiveness during neuropathy, which develops as a result of chronic constriction injury (CCI) of the sciatic nerve. To investigate the mechanism of action of maraviroc, we measured the expression of glial cell markers, CCR5 and certain CCR5 ligands (CCL3, CCL4, CCL5, CCL7, CCL11), in the spinal cord and dorsal root ganglia (DRG) of vehicle- and maraviroc-treated, CCI-exposed rats. Our results demonstrate that chronic intrathecal administration of maraviroc diminished neuropathic pain symptoms on day 7 post-CCI. Western blot analysis showed that maraviroc diminished protein level of Iba-1 and GFAP and reversed the up-regulated CCR5 expression observed in spinal cord and DRG after CCI. Additionally, using qRT-PCR, we demonstrated that CCR5 and some of its pronociceptive ligands (CCL3, CCL4, CCL5) increased in the spinal cord after nerve injury, and maraviroc effectively diminished those changes. However, CCL11 spinal expression was undetectable, even after injury. In vitro primary culture studies showed that CCL3, CCL4, CCL5 and CCL7 (but not CCL11) were of microglial and astroglial origin and were up-regulated after LPS stimulation. Our results indicate that maraviroc not only attenuated the development of neuropathic pain symptoms due to significant modulation of neuroimmune interactions but also intensified the analgesic properties of morphine and buprenorphine. In sum, our results suggest the pharmacological modulation of CCR5 by maraviroc as a novel therapeutic approach for co-treatment of patients receiving opioid therapy for neuropathy. PMID:26190414

  3. Laser acupuncture and analgesia: preliminary evidence for a transient and opioid-mediated effect

    Science.gov (United States)

    Whittaker, Peter

    2006-02-01

    Acupuncture is frequently used to treat pain. Although human pain quantification is difficult and often subjective, in rodent models the tail-flick test provides a well-established and objective assessment of analgesia. This test measures the time taken before a rat withdraws its tail from a heat source. Needle and electroacupuncture at the acupuncture point Spleen-6, located at the tibia's posterior margin above the medial malleolus, has been found to increase tail-flick time in rats. The aim of the current study was to determine if laser acupuncture had a similar effect. A 550 μm diameter optic fiber was used to irradiate Spleen-6 for 2 minutes (690 nm, 130 mW) in female Sprague-Dawley rats. In addition, control experiments were performed in which rats were subjected to sham treatment (restraint but no irradiation) or irradiation of an non-acupuncture point (the tail's dorsal surface, 1cm from the base) using the same laser parameters. The baseline tail-flick time was measured and 15 minutes later the laser acupuncture or the control protocols were performed and tail-flick time re-measured 10 minutes after treatment. Additional experiments were done in which the opioid-blocker naloxone (20 mg/kg, intraperitoneal injection) was administered one hour before laser acupuncture. Tailflick time increased after laser acupuncture (P = 0.0002), but returned to baseline values one hour later. In contrast, no increase was found after either sham treatment or tail irradiation. Pretreatment with naloxone attenuated the increase in tail-flick time. In summary, laser acupuncture exerts a transient analgesic effect which may act via an opioid-mediated mechanism.

  4. Managing cancer pain at the end of life with multiple strong opioids: a population-based retrospective cohort study in primary care.

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    Wei Gao

    Full Text Available BACKGROUND: End-of-life cancer patients commonly receive more than one type of strong opioid. The three-step analgesic ladder framework of the World Health Organisation (WHO provides no guidance on multiple opioid prescribing and there is little epidemiological data available to inform practice. This study aims to investigate the time trend of such cases and the associated factors. METHODS: Strong opioid prescribing in the last three months of life of cancer patients were extracted from the General Practice Research Database (GPRD. The outcome variable was the number of different types of prescribed non-rescue doses of opioids (1 vs 2-4, referred to as a complex case. Associated factors were evaluated using prevalence ratios (PR derived from multivariate log-binomial model, adjusting for clustering effects and potential confounding variables. RESULTS: Overall, 26.4% (95% CI: 25.6-27.1% of 13,427 cancer patients (lung 41.7%, colorectal 19.1%, breast 18.6%, prostate 15.5%, head and neck 5.0% were complex cases. Complex cases increased steadily over the study period (1.02% annually, 95%CI: 0.42-1.61%, p = 0.048 but with a small dip (7.5% reduction, 95%CI: -0.03 to 17.8% around the period of the Shipman case, a British primary care doctor who murdered his patients with opioids. The dip significantly affected the correlation of the complex cases with persistent increasing background opioid prescribing (weighted correlation coefficients pre-, post-Shipman periods: 0.98(95%CI: 0.67-1.00, p = 0.011; 0.14 (95%CI: -0.85 to 0.91, p = 0.85. Multivariate adjusted analysis showed that the complex cases were predominantly associated with year of death (PRs vs 2000: 1.05-1.65, not other demographic and clinical factors except colorectal cancer (PR vs lung cancer: 1.24, 95%CI: 1.12-1.37. CONCLUSION: These findings suggest that prescribing behaviour, rather than patient factors, plays an important role in multiple opioid prescribing at the end of life

  5. N-terminal guanidinylation of TIPP (Tyr-Tic-Phe-Phe) peptides results in major changes of the opioid activity profile.

    Science.gov (United States)

    Weltrowska, Grazyna; Nguyen, Thi M-D; Chung, Nga N; Wilkes, Brian C; Schiller, Peter W

    2013-09-15

    Derivatives of peptides of the TIPP (Tyr-Tic-Phe-Phe; Tic=1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) family containing a guanidino (Guan) function in place of the N-terminal amino group were synthesized in an effort to improve their blood-brain barrier permeability. Unexpectedly, N-terminal amidination significantly altered the in vitro opioid activity profiles. Guan-analogues of TIPP-related δ opioid antagonists showed δ partial agonist or mixed δ partial agonist/μ partial agonist activity. Guanidinylation of the mixed μ agonist/δ antagonists H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) and H-Dmt-TicΨ[CH2NH]Phe-Phe-NH2 (DIPP-NH2[Ψ]) converted them to mixed μ agonist/δ agonists. A docking study revealed distinct positioning of DIPP-NH2 and Guan-DIPP-NH2 in the δ receptor binding site. Lys(3)-analogues of DIPP-NH2 and DIPP-NH2[Ψ] (guanidinylated or non-guanidinylated) turned out to be mixed μ/κ agonists with δ antagonist-, δ partial agonist- or δ full agonist activity. Compounds with some of the observed mixed opioid activity profiles have therapeutic potential as analgesics with reduced side effects or for treatment of cocaine addiction. PMID:23932788

  6. Stress and use of over-the-counter analgesics

    DEFF Research Database (Denmark)

    Koushede, Vibeke Jenny; Ekholm, Ola; Holstein, Bjørn E; Andersen, Anette; Hansen, Ebba Holme

    2011-01-01

    To examine the prevalence of over-the-counter analgesic (OTCA) use and perceived stress among 25 to 44-year-old men and women from 1994 to 2005; to examine the association between stress and OTCA use over time, and to explore whether the association attenuates when controlled by stress...

  7. Antiinflammatory, analgesic and antipyretic activities of Mimusops elengi Linn

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    Purnima A

    2010-01-01

    Full Text Available In the present study, 70% ethanol extract of Mimusops elengi Linn. bark was assessed for antiinflammatory, analgesic and antipyretic activities in animals. The antiinflammatory activity of ethanol extract of Mimusops elengi (200 mg/kg, p.o was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma models. Analgesic effect was evaluated using acetic acid-induced writhing and Eddy′s hot plate models and antipyretic activity was assessed by Brewer′s yeast-induced pyrexia in rats. The ethanol extract of Mimusops elengi (200 mg/kg, p.o significantly inhibited the carrageenan-induced paw oedema at 3rd and 4th h and in cotton pellet model it reduced the transudative weight and little extent of granuloma weight. In analgesic models the ethanol extract of Mimusops elengi decreases the acetic acid-induced writhing and it also reduces the rectal temperature in Brewer′s yeast induced pyrexia. However, Mimusops elengi did not increase the latency time in the hot plate test. These results show that ethanol extract of Mimusops elengi has an antiinflammatory, analgesic and antipyretic activity.

  8. Evaluation of analgesic activity of Emblica officinalis in albino rats

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    Bhomik Goel

    2014-04-01

    Results: Emblica officinalis extract did not produced statistically significant (p>0.05 analgesia when compared with the control group in hot plate latency, but produced a statistically significant reduction in 6% NaCl induced abdominal writhing (pEmblica officinalis exhibit analgesic activity involving peripheral mechanisms. [Int J Basic Clin Pharmacol 2014; 3(2.000: 365-368

  9. [Analgesic abuse and psychiatric comorbidity in headache patients].

    Science.gov (United States)

    Radat, F; Irachabal, S; Swendsen, J; Henry, P

    2002-01-01

    Headache patients frequently overuse analgesic medications: 20% of the patients from headache centers is concerned by this problem, which has been estimated to occur in four percent of the community migrainers. Frequent use of various types of headache medication may paradoxically cause an increase in headache attack frequency as well as their chronicisation due to potentially complex mechanisms of sensitization. Patients will enter into a self- perpetuating cycle of daily headaches and use of symptomatic medications which can lead to addiction and to social and occupational impairement. Indeed, many patients will experience pharmacological tolerance and dependence but also by some kind of craving. International Headache Society qualify these patients as abusers referring mostly to the amount of substance ingested. Hence patients are labelled analgesic abusers . However, as many of these analgesic medications contained psychotropic substances (i.e. caffeine, codeine.), these patients may fulfill DSM IV criteria of dependance. Nevertheless, the dependance criteria should be adapted to chronic pain patients. Indeed, if pharmacological dependence and tolerance criteria are easy to apply in such patients, it is not the case for the criteria a great deal of time spent to obtain substances, to use substances or to recover from substances effects . As analgesic medications are legally obtained from medical practitioners, drug seeking behaviours are mostly: obtaining medications from multiple providers, repeating episodes of prescription loss and multiplying requests for early refills. Moreover the detrimental effects of analgesic abuse on psychosocial functioning is likely to be related to pain rather than to medication overuse. Finally the best indicator of addictive behaviors in such patients, is the loss of control over the use of analgesic medication despite the adverse consequences over pain. Comorbidity with addiction to other substances has never been specifically

  10. Innovations in agonist maintenance treatment of opioid-dependent patients

    NARCIS (Netherlands)

    C. Haasen; W. van den Brink

    2006-01-01

    Purpose of review To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients. Recent findings The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid depe

  11. Who will prescribe? A proposal for specialized opioid management clinics.

    Science.gov (United States)

    Loder, Elizabeth

    2003-09-01

    There is currently no uniform system of providing care for patients with chronic nonmalignant pain who require ongoing opioid maintenance therapy. Some patients receive care in a general practice setting, while others are managed in pain clinics where opioid management is only one of many services provided. Current events involving increased abuse and diversion of opioid medications suggest the need for improved case management and coordination when opioids are used for chronic nonmalignant pain. Based on the model of anticoagulation clinics, the author proposes the development of specialized opioid management clinics. These clinics would: 1) evaluate patient-specific risks and benefits of therapy; 2) supervise the mechanics of opioid prescribing; 3) provide systematic and secure monitoring of patient adherence to therapy; 4) assess goals of therapy and progress towards them; 5) coordinate opioid treatment with other pain-related treatment; 6) supply education to patients, family members and caregivers about the appropriate use of opioids; 7) maintain communication with other caregivers and pharmacists; and 8) provide regular psychological assistance and support for patients. PMID:17147670

  12. Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D Symptoms in an Opioid-Receptor Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Chunqiu Chen

    Full Text Available Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI tract and cortical neurons using animal models and in vitro tests.The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D symptoms. Then the opioid antagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons.In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR and delta- (DOR opioid receptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons.Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions.

  13. Chronic pain, opioid prescriptions, and mortality in Denmark

    DEFF Research Database (Denmark)

    Ekholm, Ola; Kurita, Geana Paula; Højsted, Jette; Juel, Knud; Sjøgren, Per

    2014-01-01

    were caused by accidents or suicides, although opioid users had higher risks of injuries and toxicity/poisoning resulting in hospital inpatient admissions than individuals without chronic pain. The risk of all-cause mortality was significantly higher among long-term opioid users, but no obvious...... the previous year and at least 1 prescription in the previous year, respectively). The risk of all-cause mortality was 1.72 (95% confidence interval [CI]=1.23-2.41) times higher among long-term opioid users than among individuals without chronic pain. The risk of death was lower, but still...... associations between long-term opioid use and cause-specific mortality were observed. However, opioid use increased the risk of injuries and toxicity/poisoning resulting in hospital inpatient admissions....

  14. Opioid receptors and legal highs: Salvia divinorum and Kratom.

    Science.gov (United States)

    Babu, Kavita M; McCurdy, Christopher R; Boyer, Edward W

    2008-02-01

    Salvia divinorum and Mitragyna speciosa ("Kratom"), two unscheduled dietary supplements whose active agents are opioid receptor agonists, have discrete psychoactive effects that have contributed to their increasing popularity. Salvia divinorum contains the highly selective kappa- opioid receptor agonist salvinorin A; this compound produces visual hallucinations and synesthesia. Mitragynine, the major alkaloid identified from Kratom, has been reported as a partial opioid agonist producing similar effects to morphine. An interesting minor alkaloid of Kratom, 7-hydroxymitragynine, has been reported to be more potent than morphine. Both Kratom alkaloids are reported to activate supraspinal mu- and delta- opioid receptors, explaining their use by chronic narcotics users to ameliorate opioid withdrawal symptoms. Despite their widespread Internet availability, use of Salvia divinorum and Kratom represents an emerging trend that escapes traditional methods of toxicologic monitoring. The purpose of this article is to familiarize toxicologists and poison control specialists with these emerging psychoactive dietary supplements. PMID:18259963

  15. Opioid prescriptions before and after high-energy trauma

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Hallas, Jesper; Larsen, Morten S;

    2015-01-01

    OBJECTIVE: To describe the legal use of opioids in adult patients before and after high-energy trauma. DESIGN: The study was a retrospective database study. SETTING: Clinical care outside hospitals. PATIENTS: All patients who suffered high-energy trauma and were brought to Odense University...... Hospital (OUH), Denmark, in 2007 and 2008 were retrieved from the trauma database. These patients were linked with data on opioid use from the regional prescription database. In all, 938 patients were included. MAIN OUTCOME MEASURE: Redemption of opioid prescription during the 6 months prior to a...... multitrauma or redemption of two or more prescriptions for opioids 6 months or later after a multitrauma. RESULTS: Of the 938 patients brought to OUH with severe trauma within the study period, 61 patients died (7 percent) and six of these had redeemed prescriptions for opioids within 6 months prior to the...

  16. Avoiding Opioids and Their Harmful Side Effects in the Postoperative Patient: Exogenous Opioids, Endogenous Endorphins, Wellness, Mood, and Their Relation to Postoperative Pain.

    Science.gov (United States)

    Stephan, Bradley C; Parsa, Fereydoun D

    2016-03-01

    Prescribed opioids are routinely used for many postoperative patients. However, these medications have daunting adverse effects on the body's innate pain management system - the action of the beta-endorphins. The prescribed opioids not only severely impair the function of the mu-opioid receptors, but also inhibit the release of beta-endorphin. This is unfortunate, because beta-endorphin appears to be a much more potent agonist of the mu-opioid receptor than opioids. In addition, beta-endorphin indirectly elevates dopamine, a neurotransmitter related to feelings of euphoria. Therefore, by prescribing opioids, practitioners may inadvertently prolong and increase the overall intensity of the postoperative patients' pain as well as herald anhedonia. This article highlights the relationships between prescribed (exogenous) opioids, beta-endorphins, mu-opioid receptors, wellness, mood, and postoperative pain. The role of patient education, opioid alternatives, and additional recommendations regarding pain control in the postoperative patient are also discussed. PMID:27011886

  17. Consideraciones sobre el empleo de opioides en el dolor crónico del paciente geriátrico Considerations on the use of opioids in chronic pain of elderly patients

    Directory of Open Access Journals (Sweden)

    A. B. Mencías

    2008-10-01

    manejo del dolor moderado-severo con una clara eficacia y alto perfil de seguridad.The number of elderly patients is increasing every day in our society. Old age, formerly a privilege of the few, is now reached by many people, who often lead social and active lives and who are also in good health. However, as one reaches sixtyfive years of age and beyond, there is a gradual reduction in one’s functional abilities and, as a result, chronic diseases are common leading to disabilities. Medical care seeks to extend the lives of the elderly but, more importantly, to improve their quality of life. We believe, as the main objective of our work, that it is essential to learn the physiological, pharmacokinetic and pharmacodynamic characteristics of elderly patients for the proper management and control of analgesic use while ensuring minimal risk. Similarly, we believe that increasing an elderly patient’s functional abilities and quality of life are also of the utmost importance. Opioid analgesics represent a key therapeutic weapon in the management of moderate-severe pain. Despite the reluctance to use opioids in dealing with the chronic pain of elderly patients, its analgesic efficacy and high safety profile have now been proven. Thus, we must be guided by the risk-benefit equation when it comes to considering analgesic treatments for elderly patients, always mindful of their physiological, pharmacokinetic and pharmacodynamic characteristics. As a final thought, we acknowledge the high prevalence of pain in the elderly but would like to stress that many of them do not receive proper treatment. Pharmacological research has helped to develop a great amount of therapeutic drugs for pain treatment, demonstrating that opioid analgesics represent a key therapeutic weapon in the management of moderate-severe pain with a high rate of analgesic efficacy and a high safety profile.

  18. Avaliação da analgesia de opioide tópico em úlcera de perna de paciente falcêmico Evaluation of the topical application of opioid analgesia for a leg ulcer of a sickle cell disease patient

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    Alexandre F. Neves

    2010-01-01

    Full Text Available A doença falciforme é caracterizada por apresentar várias alterações clinicas e fisiopatológicas nos pacientes que por ela são acometidos. Uma dessas alterações é presença de úlceras de perna dolorosas e de difícil cicatrização, sendo necessário o apoio de equipe multiprofissional no seu manejo e tratamento. Com o objetivo de reduzir a dor associada a úlcera de perna, o paciente falcêmico faz uso de opioides parenterais e enterais que normalmente estão associados a efeitos colaterais indesejados. Com o objetivo de reduzir o uso desses opioides sistêmicos, avaliamos um gel de morfina, de fácil manipulação e baixo custo, que foi utilizado antes e após o processo de troca de curativo das úlceras de perna dos pacientes falcêmicos atendidos em nossa instituição. Baseados na escala analógica da dor foi avaliado o efeito analgésico do gel em 28 pacientes. Todos apresentavam dor grau 7 ou 8 antes da aplicação do gel. Vinte e quatro pacientes (85,7% apresentaram total ausência de dor por um período de 24 horas, não sendo necessário o uso de analgésicos sistêmicos. Em três pacientes (10,7% a ausência de dor durou um periodo de 12horas. Somente um paciente (3,6% não relatou analgesia apos o uso do gel. Os resultados demonstraram que o gel é altamente eficaz no controle da dor das úlceras de perna de pacientes falcêmicos.Sickle cell disease is characterized by several clinical and pathophysiological changes including painful leg ulcers. These are difficult to heal and require the support of a multidisciplinary team in their management. The treatment of pain in these patients usually involves the use of opioids. In order to reduce the use of systemic opioids, we evaluated an easy-to-use low-cost morphine gel (0.12% that was applied before and after changing leg ulcer dressings of sickle cell patients treated in Hemorio hospital. Based on the Analogue Pain Scale (APS we evaluated the analgesic effect of the gel with

  19. Medication-Assisted Treatment For Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43

    Science.gov (United States)

    Tinkler, Emily; Vallejos Bartlett, Catalina; Brooks, Margaret; Gilbert, Johnatnan Max; Henderson, Randi; Shuman, Deborah, J.

    2005-01-01

    TIP 43 provides best-practice guidelines for medication-assisted treatment of opioid addiction in opioid treatment programs (OTPs). The primary intended audience for this volume is substance abuse treatment providers and administrators who work in OTPs. Recommendations in the TIP are based on both an analysis of current research and determinations…

  20. Analgesic and antiinflammatory activity of kaur-16-en-19-oic acid from Annona reticulata L. bark.

    Science.gov (United States)

    Chavan, Machindra J; Kolhe, Dinesh R; Wakte, Pravin S; Shinde, Devanand B

    2012-02-01

    Kaur-16-en-19-oic acid was isolated from the bark of Annona reticulata and studied for its analgesic and antiinflammatory activity. Analgesic activity was assessed using the hot plate test and acetic acid-induced writhing, and the antiinflammatory activity using the carrageenan induced rat paw oedema method. Kaur-16-en-19-oic acid, at doses of 10 and 20 mg/kg, exhibited significant (p < 0.05) analgesic and antiinflammatory activity. These activities were comparable to the standard drugs used, and furthermore the analgesic effect of kaur-16-en-19-oic acid was blocked by naloxone (2 mg/kg) in both analgesic models. PMID:21674631

  1. Combination analgesic efficacy: individual patient data meta-analysis of single-dose oral tramadol plus acetaminophen in acute postoperative pain.

    Science.gov (United States)

    Edwards, Jayne E; McQuay, Henry J; Moore, R Andrew

    2002-02-01

    The primary aims of this study were to assess the analgesic efficacy and adverse effects of single-dose oral tramadol plus acetaminophen in acute postoperative pain and to use meta-analysis to demonstrate the efficacy of the combination drug compared with its components. Individual patient data from seven randomized, double blind, placebo controlled trials of tramadol plus acetaminophen were supplied for analysis by the R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey, USA. All trials used identical methods and assessed single-dose oral tramadol (75 mg or 112.5 mg) plus acetaminophen (650 mg or 975 mg) in adult patients with moderate or severe postoperative pain. Summed pain intensity and pain relief data over six and eight hours and global evaluations of treatment effect after eight hours were extracted. Number-needed-to-treat (NNT) for one patient to obtain at least 50% pain relief was calculated. NNTs derived from pain relief data were compared with those derived from pain intensity data and global evaluations. Information on adverse effects was collected. Combination analgesics (tramadol plus acetaminophen) had significantly lower (better) NNTs than the components alone, and comparable efficacy to ibuprofen 400 mg. This could be shown for dental but not postsurgical pain, because more patients were available for the former. Adverse effects were similar for the combination drugs and the opioid component alone. Common adverse effects were dizziness, drowsiness, nausea, vomiting, and headache. In sum, this meta-analysis demonstrated analgesic superiority of the combination drug over its components, without additional toxicity. PMID:11844632

  2. Patrones de uso de los opioides mayores en el dolor de origen neuropático

    Directory of Open Access Journals (Sweden)

    Mª V. Ribera

    2007-05-01

    change was inefficacy of the previous treatment. As regards the rest of treatments, 76.7% of the patients were receiving antiseizure drugs, 64.6% used antidepressants, and 96.1% received analgesics. Of the latter, 43.6% were prescribed minor opioids, of which tramadol accounted for 95.5%, while 36.9% were receiving major opioids. A total of 77.3% of the patients receiving tramadol used doses in excess of 150 mg/day. In this study, 47.2% of the patients presented a pain VAS score of over. Conclusions: The treatment of neuropathic pain follows a multimodal scheme in which antiseizure drugs and antidepressants play an important role. However, major opioids, particularly fentanyl TTS, are seen as a first line treatment for pain of this kind.

  3. Im10A, a short conopeptide isolated from Conus imperialis and possesses two highly concentrated disulfide bridges and analgesic activity.

    Science.gov (United States)

    Yu, Shuo; Du, Tianpeng; Liu, Zhuguo; Wu, Qiaoling; Feng, Guixue; Dong, Mingxin; Zhou, Xiaowei; Jiang, Ling; Dai, Qiuyun

    2016-07-01

    In the present study, we isolated, synthesized and NMR structurally characterized a novel conopeptide Im10A consisting of 11 amino acids (NTICCEGCMCY-NH2) from Conus imperialis. Unlike other conopeptides with four cysteine residues, Im10A had only two residues in loop 1 and one residue in loop 2 (CC-loop1-C-loop2-C), which formed a stable disulfide connectivity "I-IV, II- III" (framework X) with a type I β-turn. Interestingly, Im10A exhibited 50.7% analgesic activity on rat partial sciatic nerve ligation (PNL) at 2h after Im10A administration. However, 10μM Im10A exhibited no apparent effect on neuronal nicotinic acetylcholine receptor, and it did not target DRG voltage-dependent sodium, potassium and calcium ion channels and opioid receptor. To our knowledge, Im10A had the most concentrated disulfide bridges among conopeptides with four cysteine residues. This finding provided a new motif for the future development of biomimetic compounds. PMID:27131596

  4. DYNAMICS OF OPIOID SUBSTITUTION TREATMENTIN DIFFERENT INITIAL SUBSTANCE USER OPIOID DEPENDENT PATIENTS.

    Science.gov (United States)

    Todadze, Kh; Mosia, S

    2016-05-01

    Injecting drug user size estimation studies carried out in 2009, 2012 and 2015 revealed growing trends of drug abuse in Georgia:estimated number of people who inject drugs (PWID) have been increased from 40000 and 45000 to 50000. Since Soviet period the most popular injective narcotics have been opioids: home-made opium, heroine, buprenorphine and home-made desomorphine ("Krokodile") replacing each other on the black market. Self-made desomorphine typically contains big amounts of different toxic substances and causes significant somatic disorders, especially skin, bone, blood infections, liver and kidney failure; is highly addictive, associates with frequent injections that enhance injecting-related harm, including the risk of HIV transmission, in comparison with typical opioids. The aim of the study was to determine the effectiveness of opioid substitution treatment (OST) on depression and anxiety in opioid dependent clients with history of different opioid substance use. 104 opioid drug users undergoing OST with intensive psychological counseling have been divided in 5 groups according to the principal opioid drug that was abused during past 6 months before starting treatment: heroine, desomorphine, illicit methadone injectors, illicit buprenorphine injectors, and multiple drug abusers consuming opioids as primary drugs. Level of depression (Beck Depression Inventory), anxiety (Spielberger Anxiety Inventory) as well as clinical symptoms, risky behavior, quality of life (WHO), and other data were measured before starting and after 3, 9, 15, 21 months of treatment. The illegal use of psychotropic-narcotics was checked through random urine-testing 1-2 times per patient per month. In all five groups remarkable decrease of depression and anxiety was observed in comparison with the starting data. Before inclusion desomorphine and poly-drug users had the highest scores of depression and anxiety while buprenorphine users manifested the lowest rate. Improvement of

  5. Developing Items to Measure Theory of Planned Behavior Constructs for Opioid Administration for Children: Pilot Testing.

    Science.gov (United States)

    Vincent, Catherine; Riley, Barth B; Wilkie, Diana J

    2015-12-01

    The Theory of Planned Behavior (TpB) is useful to direct nursing research aimed at behavior change. As proposed in the TpB, individuals' attitudes, perceived norms, and perceived behavior control predict their intentions to perform a behavior and subsequently predict their actual performance of the behavior. Our purpose was to apply Fishbein and Ajzen's guidelines to begin development of a valid and reliable instrument for pediatric nurses' attitudes, perceived norms, perceived behavior control, and intentions to administer PRN opioid analgesics when hospitalized children self-report moderate to severe pain. Following Fishbein and Ajzen's directions, we were able to define the behavior of interest and specify the research population, formulate items for direct measures, elicit salient beliefs shared by our target population and formulate items for indirect measures, and prepare and test our questionnaire. For the pilot testing of internal consistency of measurement items, Cronbach alphas were between 0.60 and 0.90 for all constructs. Test-retest reliability correlations ranged from 0.63 to 0.90. Following Fishbein and Ajzen's guidelines was a feasible and organized approach for instrument development. In these early stages, we demonstrated good reliability for most subscales, showing promise for the instrument and its use in pain management research. Better understanding of the TpB constructs will facilitate the development of interventions targeted toward nurses' attitudes, perceived norms, and/or perceived behavior control to ultimately improve their pain behaviors toward reducing pain for vulnerable children. PMID:26527107

  6. Analgesic Efficiency of Propacetamol Hydrochlorid after Lumbar Disc Surgery

    OpenAIRE

    Hans, Pol; Brichant, Jean-François; Bonhomme, Vincent; Triffaux, M.

    1993-01-01

    The influence of intravenous propacetamol hydrochlorid administration on postoperative analgesia and intramuscular opioid consumption was assessed in a randomized placebo-controlled study. Fourty patients scheduled for lumbar disc surgery were randomly allocated to two groups. They were given either propacetamol 2 g or saline every 6 hours, starting at the end of procedure for a 24 hours period. The pain intensity (VAS) was not significantly different between the two groups except 3 and 4 hou...

  7. New development of drugs against opioid addiction

    Institute of Scientific and Technical Information of China (English)

    LiJin; SuRui-bin; LuXin-qiang; LiuYin

    2004-01-01

    Opioid addiction has been a big trouble for human being for several centuries. In China, it also has become a main direct threat against national safety, society advancement, economic development and public health. Based on the national report in 2002, the number of addicts registered in due form is over 1 million, which are distributed in 2148 counties and cities in China. The real number of addicts, however, is much more than those as mentioned above. Money used for buying opioids each year in China might be over 10 billion except for other payment. Base on the statistics, 20 - 50% crimes are commited by addicts. On the other hand, drug abuse often induces contagion spread, such as tuberculosis, hepatitis and HIV disease. About 70% HIV positive subjects in China are related to drug abuse. We are very happy to see more andmore attention has been paid to the problem in our country. Recently, a program on neurobiological basis and medical biological measures of addiction has been supported by National Science and Technology Ministry as a 973 program.

  8. Analgesic use - prevalence, biomonitoring and endocrine and reproductive effects.

    Science.gov (United States)

    Kristensen, David M; Mazaud-Guittot, Séverine; Gaudriault, Pierre; Lesné, Laurianne; Serrano, Tania; Main, Katharina M; Jégou, Bernard

    2016-07-01

    Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have endocrine disruptive properties capable of altering animal and human reproductive function from fetal life to adulthood in both sexes. Medical and public awareness about these health concerns should be increased, particularly among pregnant women. PMID:27150289

  9. Opioides como coadyuvantes de la analgesia epidural en pediatría Opiates as co-adjuvants of epidural analgesia in pediatrics

    Directory of Open Access Journals (Sweden)

    M. A. Vidal

    2005-09-01

    Full Text Available Hay un elevado número de receptores opioides localizados en la sustancia gelatinosa del asta dorsal medular. La inyección epidural de opioides permite la unión de forma saturable y competitiva con estos receptores, con lo que se consigue analgesia y disminución del riesgo de efectos adversos asociados a la administración parenteral de los mismos. No obstante, es importante tener en cuenta los posibles efectos adversos que pueden aparecer, siendo la depresión respiratoria la complicación más importante. La morfina es el opioide agonista mu más utilizado para el tratamiento del dolor agudo o crónico y constituye el analgésico estándar con el que se comparan los nuevos analgésicos. El fentanilo es un agonista opioide derivado de la fenilpiperidina que posee una alta afinidad por los receptores mu, lo que le confiere una potencia analgésica 50-100 veces superior a la morfina. El tramadol es el más reciente de los opioides sintéticos empleados en España. Tiene baja afinidad por los receptores mu, kappa y delta, no obstante su potencia analgésica respecto a la morfina es 1/10 por vía parenteral y 1/30 por vía espinal. Los opioides por vía epidural se han empleado ampliamente en adultos, pero con una frecuencia mucho menor en pediatría. En este artículo se repasan los distintos estudios que han evaluado sus efectos en pediatría, haciendo referencia a la farmacocinética, consideraciones clínicas y posibles efectos adversos tras la administración de morfina, fentanilo o tramadol por vía epidural.There is a high number of opiate receptors located at the gelatinous substance of the medullar dorsal horn. Epidural injection of opiates allows saturable and competitive binding to these receptors, thus providing analgesia and reducing the risk of side effects associated to their parenteral administration. However, potential side effects must be taken into account, the major complication being respiratory depression. Morphine is the

  10. Trends and predictors of opioid use after total knee and total hip arthroplasty.

    Science.gov (United States)

    Goesling, Jenna; Moser, Stephanie E; Zaidi, Bilal; Hassett, Afton L; Hilliard, Paul; Hallstrom, Brian; Clauw, Daniel J; Brummett, Chad M

    2016-06-01

    Few studies have assessed postoperative trends in opioid cessation and predictors of persistent opioid use after total knee arthroplasty (TKA) and total hip arthroplasty (THA). Preoperatively, 574 TKA and THA patients completed validated, self-report measures of pain, functioning, and mood and were longitudinally assessed for 6 months after surgery. Among patients who were opioid naive the day of surgery, 8.2% of TKA and 4.3% of THA patients were using opioids at 6 months. In comparison, 53.3% of TKA and 34.7% of THA patients who reported opioid use the day of surgery continued to use opioids at 6 months. Patients taking >60 mg oral morphine equivalents preoperatively had an 80% likelihood of persistent use postoperatively. Day of surgery predictors for 6-month opioid use by opioid-naive patients included greater overall body pain (P = 0.002), greater affected joint pain (knee/hip) (P = 0.034), and greater catastrophizing (P = 0.010). For both opioid-naive and opioid users on the day of surgery, decreases in overall body pain from baseline to 6 months were associated with decreased odds of being on opioids at 6 months (adjusted odds ratio [aOR] = 0.72, P = 0.050; aOR = 0.62, P = 0.001); however, change in affected joint pain (knee/hip) was not predictive of opioid use (aOR = 0.99, P = 0.939; aOR = 1.00, P = 0.963). In conclusion, many patients taking opioids before surgery continue to use opioids after arthroplasty and some opioid-naive patients remained on opioids; however, persistent opioid use was not associated with change in joint pain. Given the growing concerns about chronic opioid use, the reasons for persistent opioid use and perioperative prescribing of opioids deserve further study. PMID:26871536

  11. Correlates and Consequences of Opioid Misuse among High-Risk Young Adults

    OpenAIRE

    Schrager, Sheree M.; Aleksandar Kecojevic; Karol Silva; Jennifer Jackson Bloom; Ellen Iverson; Lankenau, Stephen E.

    2014-01-01

    Background. Prescription opioids are the most frequently misused class of prescription drug among young adults aged 18–25, yet trajectories of opioid misuse and escalation are understudied. We sought to model opioid misuse patterns and relationships between opioid misuse, sociodemographic factors, and other substance uses. Methods. Participants were 575 young adults age 16–25 who had misused opioids in the last 90 days. Latent class analysis was performed with models based on years of misuse,...

  12. Cellular mechanisms underlying the interaction between cannabinoid and opioid system.

    Science.gov (United States)

    Parolaro, D; Rubino, T; Viganò, D; Massi, P; Guidali, C; Realini, N

    2010-04-01

    Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to modulate immune system and emotions) and the combined use of the two drugs by drug abusers is becoming largely diffuse, only few papers focused on cellular and molecular mechanisms underlying this interaction. This review updates the biochemical and molecular underpinnings of opioid and cannabinoid interaction, both within the central nervous system and periphery. The most convincing theory for the explanation of this reciprocal interaction involves (i) the release of opioid peptides by cannabinoids or endocannabinoids by opioids, (ii) the existence of a direct receptor-receptor interaction when the receptors are co-expressed in the same cells, and (iii) the interaction of their intracellular pathways. Finally, the cannabinoid/opioid interaction might be different in the brain rewarding networks and in those accounting for other pharmacological effects (antinociception, modulation of emotionality and cognitive behavior), as well as between the central nervous system and periphery. Further insights about the cannabinoid/opioid interaction could pave the way for new and promising therapeutic approaches. PMID:20017730

  13. Evidence of CNIH3 involvement in opioid dependence.

    Science.gov (United States)

    Nelson, E C; Agrawal, A; Heath, A C; Bogdan, R; Sherva, R; Zhang, B; Al-Hasani, R; Bruchas, M R; Chou, Y-L; Demers, C H; Carey, C E; Conley, E D; Fakira, A K; Farrer, L A; Goate, A; Gordon, S; Henders, A K; Hesselbrock, V; Kapoor, M; Lynskey, M T; Madden, P A F; Moron, J A; Rice, J P; Saccone, N L; Schwab, S G; Shand, F L; Todorov, A A; Wallace, L; Wang, T; Wray, N R; Zhou, X; Degenhardt, L; Martin, N G; Hariri, A R; Kranzler, H R; Gelernter, J; Bierut, L J; Clark, D J; Montgomery, G W

    2016-05-01

    Opioid dependence, a severe addictive disorder and major societal problem, has been demonstrated to be moderately heritable. We conducted a genome-wide association study in Comorbidity and Trauma Study data comparing opioid-dependent daily injectors (N=1167) with opioid misusers who never progressed to daily injection (N=161). The strongest associations, observed for CNIH3 single-nucleotide polymorphisms (SNPs), were confirmed in two independent samples, the Yale-Penn genetic studies of opioid, cocaine and alcohol dependence and the Study of Addiction: Genetics and Environment, which both contain non-dependent opioid misusers and opioid-dependent individuals. Meta-analyses found five genome-wide significant CNIH3 SNPs. The A allele of rs10799590, the most highly associated SNP, was robustly protective (P=4.30E-9; odds ratio 0.64 (95% confidence interval 0.55-0.74)). Epigenetic annotation predicts that this SNP is functional in fetal brain. Neuroimaging data from the Duke Neurogenetics Study (N=312) provide evidence of this SNP's in vivo functionality; rs10799590 A allele carriers displayed significantly greater right amygdala habituation to threat-related facial expressions, a phenotype associated with resilience to psychopathology. Computational genetic analyses of physical dependence on morphine across 23 mouse strains yielded significant correlations for haplotypes in CNIH3 and functionally related genes. These convergent findings support CNIH3 involvement in the pathophysiology of opioid dependence, complementing prior studies implicating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate system. PMID:26239289

  14. Comparison of periodontal manifestations in amphetamine and opioids' consumers

    Directory of Open Access Journals (Sweden)

    Masoome Eivazi

    2016-03-01

    Full Text Available Background: Drug abuse is one of the most important etiologic and deteriorating factors in periodontal disease. Amphetamines and opioids, the most commonly used drugs worldwide, play an important role in this regard. The aim of this study was to compare the periodontal status of amphetamines and opioids consumers in Kermanshah city, Iran in 1393. Methods: Three drug rehabilitation clinics were selected randomly in Kermanshah. According to inclusion and exclusion criteria, 20 amphetamine consumers and 20 opioid consumers were selected randomly and participated in this study. A questionnaire for drug use and periodontal variables was designed. The collected data were entered into SPSS-18 software and Mann-Whitney and t-test were used for statistical analysis. Results: Pocket depth, gingival index and gingival bleeding in amphetamines users were more than those in opioids consumers (P<0.021. Plaque index and gingival recession in opioids users were more than those of amphetamines consumers (P<0.001. The number of periodontal disease cases in amphetamines group were 13 persons (65% and in opioids group 8 persons (40%. Conclusion: Our study showed that periodontal hygine in amphetamine consumers was worse than opioid consumers.

  15. A Novel Behavioral Fish Model of Nociception for Testing Analgesics

    OpenAIRE

    E. Don Stevens; Cunha, Sérgio R.; Martin Scholze; Correia, Ana D.

    2011-01-01

    Pain is a major symptom in many medical conditions, and often interferes significantly with a person's quality of life. Although a priority topic in medical research for many years, there are still few analgesic drugs approved for clinical use. One reason is the lack of appropriate animal models that faithfully represent relevant hallmarks associated with human pain. Here we propose zebrafish (Danio rerio) as a novel short-term behavioral model of nociception, and analyse its sensitivity and ...

  16. Open Source Patient-Controlled Analgesic Pump Requirements Documentation

    OpenAIRE

    Larson, Brian R.; Hatcliff, John; Chalin, Patrice

    2013-01-01

    The dynamic nature of the medical domain is driving a need for continuous innovation and improvement in techniques for developing and assuring medical devices. Unfortunately, research in academia and communication between academics, industrial engineers, and regulatory authorities is hampered by the lack of realistic non-proprietary development artifacts for medical devices. In this paper, we give an overview of a detailed requirements document for a Patient-Controlled Analgesic (PCA) pump de...

  17. Analgesic Effects of Intrathecal Curcumin in the Rat Formalin Test

    OpenAIRE

    Han, Yong Ku; Lee, Seong Heon; Jeong, Hye Jin; Kim, Min Sun; Yoon, Myung Ha; Kim, Woong Mo

    2012-01-01

    Background Curcumin has been reported to have anti-inflammatory, antioxidant, antiviral, antifungal, antitumor, and antinociceptive activity when administered systemically. We investigated the analgesic efficacy of intrathecal curcumin in a rat model of inflammatory pain. Methods Male Sprague Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, 50 µl) into the hind paw. Curcumin doses of 62.5, 125, 250, and 500 µg were delivered thr...

  18. Sound can enhance the analgesic effect of virtual reality

    OpenAIRE

    Johnson, Sarah,; Coxon, Matthew

    2016-01-01

    Virtual reality (VR) technology may serve as an effective non-pharmacological analgesic to aid pain management. During VR distraction, the individual is immersed in a game presented through a head-mounted display (HMD). The technological level of the HMD can vary, as can the use of different input devices and the inclusion of sound. While more technologically advanced designs may lead to more effective pain management the specific roles of individual components within such systems are not yet...

  19. Pharmacokinetics and analgesic potency of [Delta]9-tetrahydrocannabinol (THC)

    OpenAIRE

    Näf, Myrtha

    2004-01-01

    It is known from the folk medicine that Cannabis may reduce pain. The aim of the pain study was to compare analgesic effects of oral delta-9-tetrahydrocannabinol (THC, dronabinol, Marinol‚, main psychoactive component of the Cannabis plant) and a THC-morphine combination to morphine and placebo. This pain study was performed with 12 healthy volunteers in four different experimental models of acute pain. Additionally, side effects and vital functions were monitored and blood sam...

  20. ANALGESIC ACTIVITY OF ROOT EXTRACT OF SOLANUM MELONGENA LINN ROOT

    OpenAIRE

    Srivastava Ashish; Sanjay Yadav

    2011-01-01

    The present study was aimed at Pharmacognostic study and biological evaluation of analgesic activity of plants roots. The roots of plants were studies for Pharmacognostic characteristics namely, morphology, microscopy, physicochemical parameters, which can be of utilized in identification/authentication of the plant and/or its roots in crude drug form. The preliminary phytochemical screening of the dry residue was carried out by the chemical test and thin layer chromatographic method. The p...

  1. Post Tonsillectomy Pain: Can Honey Reduce the Analgesic Requirements?

    OpenAIRE

    Boroumand, Peyman; Zamani, Mohammad Mahdi; Saeedi, Masoumeh; Rouhbakhshfar, Omid; Hosseini Motlagh, Seyed Reza; Aarabi Moghaddam, Fatemeh

    2013-01-01

    Background Tonsillectomy with or without adenoidectomy is one of the most common surgical procedures performed worldwide, especially for children. Oral honey administration following tonsillectomy in pediatric cases may reduce the need for analgesics via relieving postoperative pain. Objectives The aim of this study was to evaluate the effects of honey on the incidence and severity of postoperative pain in patients undergoing tonsillectomy. Patients and Methods A randomized, double blind, pla...

  2. Overuse of non-prescription analgesics by dental clinic patients

    OpenAIRE

    Zallen Richard D; Bogdan Gregory M; Dart Richard C; Ries Nicole L; Heard Kennon J; Daly Frank

    2008-01-01

    Abstract Background Many patients present to dental clinics for treatment of painful conditions. Prior to seeking treatment, many of these patients will self-medicate with non-prescription analgesics (NPA), and some will unintentionally overdose on these products. The objective of this study is to describe the use of NPA among dental patients. Methods All adult patients presenting to an urban dental clinic during a two-week period in January and February of 2001 were approached to participate...

  3. Development and validation of the Patient Opioid Education Measure

    Directory of Open Access Journals (Sweden)

    Wallace LS

    2013-09-01

    Full Text Available Lorraine S Wallace,1 Randell K Wexler,1 W Frederick Miser,1 Leon McDougle,1 J David Haddox2,3 1The Ohio State University, Department of Family Medicine, Columbus, OH, 2Purdue Pharma LP, One Stanford Forum, Stanford, CT, 3Tufts University School of Medicine, Department of Public Health and Community Medicine, Boston, MA, USA Background: Although there are screening tools to aid clinicians in assessing the risk of opioid misuse, an instrument to assess opioid-related knowledge is not currently available. The purpose of this study was to develop a content-valid, understandable, readable, and reliable Patient Opioid Education Measure (POEM. Methods: Using concept mapping, clinicians caring for patients with chronic pain participated in brainstorming, sorting, and rating need-to-know information for patients prescribed opioids. Concept mapping analyses identified seven clusters addressing knowledge and expectations associated with opioid use, including medicolegal issues, prescribing policies, safe use and handling, expected outcomes, side effects, pharmacology, and warnings. Results: The 49-item POEM was verbally administered to 83 patients (average age 51.3 ± 9.8 years, 77.1% female, 47.1% African American taking opioids for chronic nonmalignant pain. Patients averaged in total 63.9% ± 14.3% (range 23%–91% correct responses on the POEM. The POEM demonstrated substantial test-retest reliability (interclass correlation coefficient 0.87. The POEM had a mean readability Lexile (L score of 805.9 ± 257.3 L (equivalent to approximately a US fifth grade reading level, with individual items ranging from 280 L to 1370 L. Conclusion: The POEM shows promise for rapidly identifying patients' opioid-related knowledge gaps and expectations. Correcting misunderstandings and gaps could result in safer use of opioids in a clinical care setting. Keywords: opioid, knowledge, pain, questionnaire

  4. Analgesic and anti-arthritic effect of Corallocarpus epigaeus

    Directory of Open Access Journals (Sweden)

    Subashini Uthrapathy

    2011-12-01

    Full Text Available Rheumatoid arthritis is a chronic inflammatory joint disease associated with the development of oxidative stress and inflammation. The safety and efficacy profile of 85% methanolic extract of Corallocarpus epigaeus (CE was evaluated in the present study. In safety profile LD50 value was determined by carrying out an acute toxicity study. In efficacy profile, the analgesic activity was evaluated by both hot plate and tail immersion tests. The anti-inflammatory activity was assessed by carrageenan-induced paw edema and anti-arthritic effect by complete Freund's adjuvant induced arthritis. Phytochemical screening of different CE extracts and quantitative analysis of both raw herb and 85% methanolic extract have been also carried out. The methanolic extract displayed analgesic activity by increasing the response time in both hot plate and tail immersion method. Extract exhibited 23,19% of anti-inflammatory activity and 33,59% of anti-arthritic effect in complete Freund's adjuvant induced paw edema. The CE extract increased the antioxidant level, along with a decrease of the oxidative stress developed by complete Freund's adjuvant induced arthritis. In conclusion, CE is a rich source of phytochemicals with analgesic, anti-inflammatory and antioxidant activities.

  5. Analgesic and Anti-inflammatory Effects of Ginger Oil

    Institute of Scientific and Technical Information of China (English)

    JIA Yong-liang; XIE Qiang-min; ZHAO Jun-ming; ZHANG Lin-hui; SUN Bao-shan; BAO Meng-jing; LI Fen-fen; SHEN Jian; SHEN Hui-jun; ZHAO Yu-qing

    2011-01-01

    Objective Ginger (Zingiber officinale) is widely used as a spice in cooking and as a medicinal herb in traditional herbal medicine. The present study was to investigate the analgesic and anti-inflammatory activities of ginger oil in experimental animal models. Methods The analgesic effect of the oils was evaluated by the "acetic acid" and "hot-plate" test models of pain in mice. The anti-inflammatory effect of the oil was investigated in rats, using rat paw edema induced by carrageenan, adjuvant arthritis, and vascular permeability induced by bradykinin, arachidonic acid, and histamine. Indomethacin (1 mg/kg), Aspirin (0.5 g/kg) and Dexamethasone (2.5 mg/kg) were used respectively as reference drugs for comparison. Results The ginger oil (0.25-1.0 g/kg) produced significant analgesic effect against chemically- and thermally-induced nociceptive pain stimuli in mice (P < 0.05, 0.01). And the ginger oil (0.25-1.0 g/kg) also significantly inhibited carrageenan-induced paw edema, adjuvant arthritis, and inflammatory mediators-induced vascular permeability in rats (P < 0.05, 0.001). Conclusion These findings confirm that the ginger oil can be used to treat pain and chronic inflammation such as rheumatic arthritis.

  6. [Oral exposure testing in non-aspirin-induced analgesic intolerance].

    Science.gov (United States)

    Wiedow, O; Brasch, J; Christophers, E

    1996-12-01

    Although intolerance reaction to analgesics are not uncommon, there is still a lack of standardized procedures to diagnose the problem. We retrospectively analyzed results of scratch tests as well as oral challenges with analgesics in order to evaluate risk and diagnostic relevance of these procedures. In 1987-1992 a total of 650 patients with supposed intolerance to drugs were tested by oral challenge. Among them were 98 patients with a positive history of intolerance to non-aspirin analgesics. In 56 patients the intolerance could be verified by oral challenge. In order of decreasing frequency, the most likely agents were propyphenazone, diclofenac, metamizole, ibuprofen, carbamazepine, indomethacin, phenazone (antipyrine), and paracetamol (acteaminophen). Oral provocation showed clear dose-response relationships. For propyphenazone, the half-effective provocation dose was the same for all symptoms (cutaneous, nasal, bronchial, anaphylactoid). Scratch testing was not of diagnostic significance. Standardized test protocols starting with low dose oral challenges are suitable and helpful in minimizing the risk of severe side effects. PMID:9081936

  7. ANALGESIC ACTIVITY OF ROOT EXTRACT OF SOLANUM MELONGENA LINN ROOT

    Directory of Open Access Journals (Sweden)

    Srivastava Ashish

    2011-05-01

    Full Text Available The present study was aimed at Pharmacognostic study and biological evaluation of analgesic activity of plants roots. The roots of plants were studies for Pharmacognostic characteristics namely, morphology, microscopy, physicochemical parameters, which can be of utilized in identification/authentication of the plant and/or its roots in crude drug form. The preliminary phytochemical screening of the dry residue was carried out by the chemical test and thin layer chromatographic method. The preliminary phytochemical screening of dry residue showed the presence of Saponins, Alkaloids, Glycoside, and Flavonoids in various extracts. However most of the medicinally potential phytoconstituents were present in methanolic and aqueous extracts. The Hydroalcoholic extract was selected for Biological screening due to high alcoholic-soluble extractive value, high yield of successive alcoholic extract and TLC results. The analgesic screening was done using Hot plate method, Tail immersion methods and acetic acid induced in rats and mice. Hydroalcoholic extract was administered orally at the acute doses of 200mg/kg and 400mg/kg b.w. Several activities on these doses have already been reported. Both the doses showed significant (p<0.05 analgesic activity.

  8. Analgesic effect of clove essential oil in mice

    Directory of Open Access Journals (Sweden)

    Mahmoud Hosseini

    2011-07-01

    Full Text Available Objective: Results obtained from literature reviews and human studies have shown the analgesic effects of clove plant in toothache. The present work was undertaken in order to investigate the possible analgesic effect of clove oil in mice.Materials and Methods: Fifty mice were divided into 5 groups: 1 Saline; 2 Essential oil (Ess 2%, 3 Ess 5%, 4 Ess10% and 5 Ess 20%. The hot plate test (55±0.2 °C; Cut-off 60 sec was performed as a base record 15 min before injection of drugs (Saline or 2, 5, 10 and 20% concentrations of Essential oil and consequently repeated every 15 minutes after injection. Results: Repeated measures ANOVA test showed that maximal percent effect (MPE in animal groups treated by 5, 10 and 20% essential oil was significantly higher than saline group. Comparison between 4 treated groups showed that MPE in 10% essential group was higher than 2 and 5% groups however; there was no significant difference between 10% and 20% groups.Conclusion: The result of present study showed that clove essential oil has analgesic effect inmice using hot plate test. More investigations are needed to elucidate the exact mechanism (s.

  9. Evaluation of analgesic activity of perindopril in albino mice

    Directory of Open Access Journals (Sweden)

    R N Suresha

    2014-01-01

    Full Text Available The aim was to evaluate the analgesic activity of perindopril in chemical, thermal and mechanical pain on Swiss albino mice. A total of 54 albino mice (Swiss strain weighing 25-30 g were allocated to each experimental model and in each model there were three groups. The control group received normal saline (25 ml/kg per orally, standard group received pentazocine (10 mg/kg intra-peritoneal and test groups received perindopril (1 mg/kg per orally. Perindopril and normal saline was administered 2 h before, whereas the pentazocine was administered 15 min prior to Eddy′s hot plate, writhing and tail clip methods. The decrease in number of writhes, the delay in reaction time in tail clip and Eddy′s hot plate method denoted the analgesic activity. Perindopril decreased the number of writhes, delayed the reaction time in tail clip and Eddy′s hot plate method considerably when compared with control (normal saline, but less when compared with standard (pentazocine. Perindopril exhibits analgesic activity in thermal, chemical, and mechanical pain models in albino mice.

  10. Tratamiento del dolor en el anciano: opioides y adyuvantes

    OpenAIRE

    M.P. Sáez López; N. Sánchez Hernández; N. Alonso García; J.A. Valverde García

    2016-01-01

    Se dispone de pocos estudios sobre el uso de opioides en ancianos. En pacientes seleccionados, los opioides pueden proporcionar una adecuada analgesia en el marco de un abordaje integral. Se ha revisado la utilización de opioides fuertes en ancianos con dolor oncológico o no oncológico. Se ha demostrado eficacia en dolor músculo-esquelético a corto plazo y algunos tipos de dolor neuropático. No obstante, no se dispone de datos sobre eficacia y seguridad a largo plazo. Aunque los antidepresivo...

  11. CE: Appropriate Use of Opioids in Managing Chronic Pain.

    Science.gov (United States)

    Denenberg, Risa; Curtiss, Carol P

    2016-07-01

    : Over the past two decades, the use of opioids to manage chronic pain has increased substantially, primarily in response to the recognized functional, emotional, and financial burden associated with chronic pain. Within this same period, unintentional death related to prescription opioids has been identified as a public health crisis, owing in part to such factors as insufficient professional training and medication overprescription, misuse, and diversion. The authors discuss current best practices for prescribing opioids for chronic pain, emphasizing patient assessment and essential patient teaching points regarding safe medication use, storage, and disposal. PMID:27294667

  12. The Central Reinforcing Properties of Ethanol Are Mediated by Endogenous Opioid Systems: Effects of Mu and Kappa Opioid Antagonists.

    Directory of Open Access Journals (Sweden)

    Norman E. Spear

    2009-09-01

    Full Text Available Endogenous opioid systems are implicated in the reinforcing effects of ethanol and may play a substantial role in modulating the central reinforcing effects of ethanol early in ontogeny. This possibility was explored in the present study through the use of an olfactory conditioning paradigm with centrally administered ethanol serving as an unconditioned stimulus (US. In Experiment 1, newborn rat pups were treated with either a selective mu antagonist CTOP or kappa selective antagonist nor-BNI prior to olfactory conditioning. Experiment 2 tested the effectiveness of an alternative, shorter-duration kappa opioid antagonist GNTI in altering ethanol reinforcement. Experiment 3 investigated whether the effectiveness of pharmacological blockade of opioid receptors was due to the disruption of learning per se using an olfactory aversive conditioning paradigm with intraoral quinine serving as a US. Central administration of either mu or kappa opioid antagonists prior to conditioning disrupted the reinforcing effects of ethanol in newborn rats. The kappa opioid antagonist GNTI was as effective as nor-BNI. These effects of opioid antagonists on ethanol reinforcement are unlikely to be due to a disruption of all types of conditioning, since CTOP did not affect aversive reinforcement to intraoral infusions of quinine. The present results support the hypothesis that in newborn rats, the reinforcing properties of ethanol are mediated by the endogenous activity at mu and kappa opioid receptors.

  13. The Central Reinforcing Properties of Ethanol Are Mediated by Endogenous Opioid Systems: Effects of Mu and Kappa Opioid Antagonists

    Science.gov (United States)

    Nizhnikov, Michael E.; Varlinskaya, Elena I.; Spear, Norman E.

    2010-01-01

    Endogenous opioid systems are implicated in the reinforcing effects of ethanol and may play a substantial role in modulating the central reinforcing effects of ethanol early in ontogeny. This possibility was explored in the present study through the use of an olfactory conditioning paradigm with centrally administered ethanol serving as an unconditioned stimulus (US). In Experiment 1, newborn rat pups were treated with either a selective mu antagonist CTOP or kappa selective antagonist nor-BNI prior to olfactory conditioning. Experiment 2 tested the effectiveness of an alternative, shorter-duration kappa opioid antagonist GNTI in altering ethanol reinforcement. Experiment 3 investigated whether the effectiveness of pharmacological blockade of opioid receptors was due to the disruption of learning per se using an olfactory aversive conditioning paradigm with intraoral quinine serving as a US. Central administration of either mu or kappa opioid antagonists prior to conditioning disrupted the reinforcing effects of ethanol in newborn rats. The kappa opioid antagonist GNTI was as effective as nor-BNI. These effects of opioid antagonists on ethanol reinforcement are unlikely to be due to a disruption of all types of conditioning, since CTOP did not affect aversive reinforcement to intraoral infusions of quinine. The present results support the hypothesis that in newborn rats, the reinforcing properties of ethanol are mediated by the endogenous activity at mu and kappa opioid receptors. PMID:22267966

  14. A benefit-risk assessment of caffeine as an analgesic adjuvant.

    Science.gov (United States)

    Zhang, W Y

    2001-01-01

    Caffeine has been an additive in analgesics for many years. However, the analgesic adjuvant effects of caffeine have not been seriously investigated since a pooled analysis conducted in 1984 showed that caffeine reduces the amount of paracetamol (acetaminophen) necessary for the same effect by approximately 40%. In vitro and in vivo pharmacological research has provided some evidence that caffeine can have anti-nociceptive actions through blockade of adenosine receptors, inhibition of cyclo-oxygenase-2 enzyme synthesis, or by changes in emotion state. Nevertheless, these actions are only considered in some cases. It is suggested that the actual doses of analgesics and caffeine used can influence the analgesic adjuvant effects of caffeine, and doses that are either too low or too high lead to no analgesic enhancement. Clinical trials suggest that caffeine in doses of more than 65 mg may be useful for enhancement of analgesia. However, except for in headache pain, the benefits are equivocal. While adding caffeine to analgesics increases the number of patients who become free from headache [rate ratio = 1.36, 95% confidence interval (CI) 1.17 to 1.58], it also leads to more patients with nervousness and dizziness (relative risk = 1.60, 95% CI 1.26 to 2.03). It is suggested that long-term use or overuse of analgesic medications is associated with rebound headache. However, there is no robust evidence that headache after use or withdrawal of caffeine-containing analgesics is more frequent than after other analgesics. Case-control studies have shown that caffeine-containing analgesics are associated with analgesic nephropathy (odds ratio = 4.9, 95% CI 2.3 to 10.3). However, no specific contribution of caffeine to analgesic nephropathy can be identified from these studies. Whether caffeine produces nephrotoxicity on its own, or increases nephrotoxicity due to analgesics, is yet to be established. PMID:11772146

  15. Efficacy and tolerability of oral oxycodone and oxycodone/naloxone combination in opioid-naïve cancer patients: a propensity analysis

    Science.gov (United States)

    Lazzari, Marzia; Greco, Maria Teresa; Marcassa, Claudio; Finocchi, Simona; Caldarulo, Clarissa; Corli, Oscar

    2015-01-01

    Background World Health Organization step III opioids are required to relieve moderate-to-severe cancer pain; constipation is one of the most frequent opioid-induced side effects. A fixed combination, prolonged-release oxycodone/naloxone (OXN), was developed with the aim of reducing opioid-related gastrointestinal side effects. The objective of this study was to compare the efficacy and safety of prolonged-release oxycodone (OXY) alone to OXN in opioid-naïve cancer patients with moderate-to-severe pain. Methods Propensity analysis was utilized in this observational study, which evaluated the efficacy, safety, and quality of life. Results Out of the 210 patients recruited, 146 were matched using propensity scores and included in the comparative analysis. In both groups, pain intensity decreased by ≈3 points after 60 days, indicating comparable analgesic efficacy. Responder rates were similar between groups. Analgesia was achieved and maintained with similarly low and stable dosages over time (12.0–20.4 mg/d for OXY and 11.5–22.0 mg/d for OXN). Bowel Function Index (BFI) and laxative use per week improved from baseline at 30 days and 60 days in OXN recipients (−16, P<0.0001 and −3.5, P=0.02, respectively); BFI worsened in the OXY group. The overall incidence of drug-related adverse events was 28.9% in the OXY group and 8.2% in the OXN group (P<0.01); nausea and vomiting were two to five times less frequent with OXN. Quality of life improved to a significantly greater extent in patients receiving OXN compared to OXY (increase in Short Form-36 physical component score of 7.1 points vs 3.2 points, respectively; P<0.001). Conclusion In patients with chronic cancer pain, OXN provided analgesic effectiveness that is similar to OXY, with early and sustained benefits in tolerability. The relationship between responsiveness to OXN and clinical characteristics is currently being investigated. PMID:26586937

  16. Dynorphin A (1-13) Neurotoxicity In Vitro: Opioid and Non-Opioid Mechanisms in Mouse Spinal Cord Neurons

    Science.gov (United States)

    Hauser, Kurt F.; Foldes, Jane K.; Turbek, Carol S.

    2016-01-01

    Dynorphin A is an endogenous opioid peptide that preferentially activates κ opioid receptors and is antinociceptive at physiological concentrations. Levels of dynorphin A and a major metabolite, dynorphin A (1-13), increase significantly following spinal cord trauma and reportedly contribute to neurodegeneration associated with secondary injury. Interestingly, both κ opioid and N-methyl-D-aspartate (NMDA) receptor antagonists can modulate dynorphin toxicity, suggesting that dynorphin is acting (directly or indirectly) through κ opioid and/or NMDA receptor (NMDAR) types. Despite these findings, few studies have systematically explored dynorphin toxicity at the cellular level in defined populations of neurons co-expressing κ opioid and NMDA receptors. To address this question, we isolated populations of neurons enriched in both κ opioid and NMDA receptors from embryonic mouse spinal cord and examined the effects of dynorphin A (1-13) on intracellular calcium concentration ([Ca2+]i) and neuronal survival in vitro. Time-lapse photography was used to repeatedly follow the same neurons before and during experimental treatments. At micromolar concentrations, dynorphin A (1-13) elevated [Ca2+]i and caused a significant loss of neurons. The excitotoxic effects were prevented by MK-801 (Dizocilpine) (10 μM), 2-amino-5-phosphopentanoic acid (AP-5) (100 μM), or 7-chlorokynurenic acid (100 μM)— suggesting that dynorphin A (1-13) was acting (directly or indirectly) through NMDA receptors. In contrast, co-treatment with (−)-naloxone (3 μM), or the more selective κ opioid receptor antagonist nor-binaltorphimine (3 μM), exacerbated dynorphin A (1-13)-induced neuronal loss; however, cell losses were not enhanced by the inactive stereoisomer (+)-naloxone (3 μM). Neuronal losses were not seen with exposure to the opioid antagonists alone (10 μM). Thus, opioid receptor blockade significantly increased toxicity, but only in the presence of excitotoxic levels of

  17. Inhibition of Opioid Transmission at the μ-Opioid Receptor Prevents Both Food Seeking and Binge-Like Eating

    OpenAIRE

    Giuliano, Chiara; Robbins, Trevor W.; Nathan, Pradeep J; Bullmore, Edward T.; Everitt, Barry J.

    2012-01-01

    Endogenous opioids, and in particular μ-opioid receptors, have been linked to hedonic and rewarding mechanisms engaged during palatable food intake. The aim of this study was to investigate the effects of GSK1521498, a novel μ-opioid receptor antagonist, on food-seeking behavior and on binge-like eating of a highly preferred chocolate diet. Food seeking was measured in rats trained to respond for chocolate under a second-order schedule of reinforcement, in which prolonged periods of food-seek...

  18. Addiction Risk Low for Seniors Taking Post-Op Opioids

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160358.html Addiction Risk Low for Seniors Taking Post-Op Opioids: ... many worry that post-surgical use might trigger addiction. But a new study suggests that painkiller abuse ...

  19. Addiction to opioids in chronic pain patients: a literature review

    DEFF Research Database (Denmark)

    Højsted, Jette; Sjøgren, Per

    2007-01-01

    , incidence and prevalence of addiction in opioid treated pain patients, screening tools for assessing opioid addiction in chronic pain patients and recommendations regarding addiction problems in national and international guidelines for opioid treatment in cancer patients and chronic non-malignant pain...... patients. The review indicates that the prevalence of addiction varied from 0% up to 50% in chronic non-malignant pain patients, and from 0% to 7.7% in cancer patients depending of the subpopulation studied and the criteria used. The risk of addiction has to be considered when initiating long-term opioid...... treatment as addiction may result in poor pain control. Several screening tools were identified, but only a few were thoroughly validated with respect to validity and reliability. Most of the identified guidelines mention addiction as a potential problem. The guidelines in cancer pain management are...

  20. Facts about Buprenorphine for Treatment of Opioid Addiction

    Science.gov (United States)

    the facts about BUPRENORPHINE for Treatment of Opioid Addiction U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Substance ... escape from the misery and risks of drug addiction? Most people cannot do it on their own. ...

  1. Addictive behaviors related to opioid use for chronic pain

    DEFF Research Database (Denmark)

    Højsted, Jette; Ekholm, Kim Ola Michael; Kurita, Geana Paula;

    2013-01-01

    The growing body of research showing increased opioid use in patients with chronic pain coupled with concerns regarding addiction encouraged the development of this population-based study. The goal of the study was to investigate the co-occurrence of indicators of addictive behaviors in patients......, 13,281 individuals were analyzed through multiple logistic regression analyses to assess the association between chronic pain (lasting ⩾6 months), opioid use, health behavior, and body mass index. Six potential addictive behaviors were identified: daily smoking; high alcohol intake; illicit drug use...... in the past year; obesity; long-term use of benzodiazepines; and long-term use of benzodiazepine-related drugs. At least 2 of the 6 addictive behaviors were observed in 22.6% of the long-term opioid users with chronic pain compared with 11.5% of the non-opioid users with chronic pain and 8.9% of the...

  2. Managing Opioid Abuse in Older Adults: Clinical Considerations and Challenges.

    Science.gov (United States)

    Loreck, David; Brandt, Nicole J; DiPaula, Bethany

    2016-04-01

    Opioid use disorder is a public health epidemic. There is increasing attention being given to opioid abuse and overdose in the United States. The overall use of illicit substances by older adults is on the rise and in part can be attributed to the aging of Baby Boomers. Furthermore, much attention is being given to prescription opioid drug overdose, but it is important to note that heroin-related deaths have also increased sharply. Heroin use is part of a larger substance abuse problem, with more than nine in 10 individuals who use heroin also using at least one other drug (e.g., cocaine, prescription opioid medication). The current article highlights treatment approaches, namely buprenorphine, buprenorphine/naloxone, and naltrexone; insurance considerations; and resources to aid in understanding and managing this public health crisis. PMID:27027362

  3. Many Take Opioids Months After Hip, Knee Replacements

    Science.gov (United States)

    ... the United States. Common prescription opioid painkillers include drugs such as OxyContin, Vicodin and Percocet. In fact, an autopsy report released Thursday showed that music legend Prince died in April after taking fentanyl, ...

  4. Comparison of Buprenorphine Treatment for Opioid Dependence in Three Settings

    OpenAIRE

    Miotto, Karen; Hillhouse, Maureen; Donovick, Roger; Cunningham-Rathner, Jerry; Charuvastra, Charlie; Torrington, Matthew; Esagoff, Asher E.; Ling, Walter

    2012-01-01

    Although use of buprenorphine in the treatment of opioid dependence is expected to continue to increase, little is known about the optimal setting for providing the medical and psychosocial care required with buprenorphine pharmacotherapy.

  5. Neurobiology of opioid dependence in creating addiction vulnerability.

    Science.gov (United States)

    Evans, Christopher J; Cahill, Catherine M

    2016-01-01

    Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses of euphoria and analgesia that societies have coveted for centuries. Repeated, or chronic, use of opioids induces adaptive or allostatic changes that modify neuronal circuitry and create an altered normality - the "drug-dependent" state. This state, at least that exhibited by those maintained continuously on long-acting opioid drugs such as methadone or buprenorphine, is generally indistinguishable from the drug-naïve state for most overt behaviors. The consequences of the allostatic changes (cellular, circuit, and system adaptations) that accompany the drug-dependent state are revealed during drug withdrawal. Drug cessation triggers a temporally orchestrated allostatic re-establishment of neuronal systems, which is manifested as opposing physiological and psychological effects to those exhibited by acute drug intoxication. Some withdrawal symptoms, such as physical symptoms (sweating, shaking, and diarrhea) resolve within days, whilst others, such as dysphoria, insomnia, and anxiety, can linger for months, and some adaptations, such as learned associations, may be established for life. We will briefly discuss the cellular mechanisms and neural circuitry that contribute to the opioid drug-dependent state, inferring an emerging role for neuroinflammation. We will argue that opioid addictive behaviors result from a learned relationship between opioids and relief from an existing or withdrawal-induced anxiogenic and/or dysphoric state. Furthermore, a future stressful life event can recall the memory that opioid drugs alleviate negative affect (despair, sadness, and anxiety) and thereby precipitate craving, resulting in relapse. A learned association of relief of aversive states would fuel drug craving in vulnerable people living in an increasingly stressful society. We suggest that this route to addiction is contributive to

  6. Pain relief and clinical outcome: from opioids to balanced analgesia

    DEFF Research Database (Denmark)

    Kehlet, H

    1996-01-01

    If it is generally accepted that adequate postoperative pain relief will improve outcome from surgery, several controlled trials demonstrated this only for lower body surgical procedures with epidural and spinal anesthetics. Important effects on outcome were not shown when postoperative opioids...... were administered with patient controlled (PCA) or epidural techniques. However, the most optimal pain relief seems to be best achieved with balanced analgesia techniques using combinations of epidural opioids and local anesthetics and systemic non-steroidal antiinflammatory drugs. Future efforts...

  7. Role of Opioid Ligands in the Irritable Bowel Syndrome

    OpenAIRE

    Corazziari, Enrico

    1999-01-01

    Endogenous opioid peptides – enkephalins, beta-endorphin and dynorphins – are located in specific sites of the brain, the spinal cord, the autonomic ganglia and the enteric nervous system. Endogenous opioids participate in the regulation of nervous visceral afference and sensitivity as well as of several visceral motor function induced by the central nervous system and through the enteroenteric and the myoenteric reflexes. Their final effect on gut physiology is the net and harmonically balan...

  8. Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence

    OpenAIRE

    Yang, Cheng; Chen, Yan; Tang, Lei; Wang, Zaijie Jim

    2011-01-01

    Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and depend...

  9. A practical and ethical solution to the opioid scheduling conundrum

    OpenAIRE

    Schatman ME; Darnall BD

    2013-01-01

    Michael E Schatman,1 Beth D Darnall21Foundation for Ethics in Pain Care, Bellevue, WA, USA; 2Stanford University School of Medicine, Division of Pain Medicine, Palo Alto, CA, USAAbuse-deterrent formulations (ADFs) of opioids have been in existence since the 1970s,1 with abuse-deterrent mechanisms including physical barriers (eg, barriers to crushing), chemical additives such as opioid antagonists or irritants, and prodrugs that require conversion of the medication into their active forms in t...

  10. Structure of the [delta]-opioid receptor bound to naltrindole

    Energy Technology Data Exchange (ETDEWEB)

    Granier, Sébastien; Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun; Thian, Foon Sun; Weis, William I.; Kobilka, Brian K. (Stanford-MED)

    2012-07-11

    The opioid receptor family comprises three members, the {mu}-, {delta}- and {kappa}-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The {delta}-opioid receptor ({delta}-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the {mu}-OR and {kappa}-OR have recently been solved. Here we report the crystal structure of the mouse {delta}-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the {mu}-OR and {kappa}-OR, the {delta}-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the {delta}-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.

  11. 灯笼草镇痛作用及其机理的研究%Experimental Study on the Analgesic Effect and Its Mechanism of Physalis peruviana L.

    Institute of Scientific and Technical Information of China (English)

    单立冬; 俞光第; 印其章; 郭试瑜; 久光正

    2001-01-01

    目的:观察灯笼草的镇痛作用。方法:采用扭体法、电刺激鼠尾-嘶叫法、钾离子透入法和辐射热-缩腿法等行为学指标以及丘脑束旁核神经元对伤害性刺激的放电反应的电生理指标。结果:灯笼草能剂量依赖地提高大鼠电刺激鼠尾-嘶叫法的痛阈,剂量依赖地抑制醋酸引起的小鼠扭体反应,对炎症性痛敏及神经源性痛敏灯笼草也有镇痛作用,灯笼草还能明显抑制丘脑束旁核神经元对伤害性刺激的放电反应。纳洛酮能翻转灯笼草的镇痛作用,反复给予灯笼草能产生耐受,但与吗啡镇痛之间不存在交叉耐受。结论:灯笼草具有镇痛作用,其镇痛作用可能涉及中枢阿片受体。%Objective: The experiment was performed to study the analgesic effect of Physalis peruviana L. (PPL.) Methods: The behavioral algesic measurements and the electrophysiological method were used to record extracellularly the nociceptive response of thalamic parafascicular neurons. Results: 1) PPL could dose-dependently raise the pain threshold in tail stimulation-vocalization test in rats and inhibit the writhing reaction induced by acetic acid in mice. PPL could decrease the hyperalgesia in adjuvant arthritis as well was in neuropathic pain in rats. 2) PPL could inhibit the nociceptive response of thalamic parafascicular neurons in rats evoked by sciatic nerve stimulation. 3) The analgesic effect of PPL could be reversed by naloxone; tolerance could develop after repeated administrations of PPL, but no cross-tolerance was observed with morphine analgesia. Conclusion: PPL has a dose-dependent analgesic effect and its analgesic effect might be mediated by central opioid receptor.

  12. Opioid Treatment of Migraine: Risk Factors and Behavioral Issues.

    Science.gov (United States)

    Stone, Melissa T; Weed, Valerie; Kulich, Ronald J

    2016-09-01

    Migraine can impact every aspect of a person's functioning. Psychological comorbidities, cognitive constructs, and behavioral responses to pain greatly impact the perception of migraine pain, treatment efficacy and outcome, and overall quality of life and functioning. Current considerations for migraine treatment emphasize the utility of the biopsychosocial model in understanding and treating migraine, noting both the importance of addressing psychological factors such as cognitive beliefs as well as psychiatric comorbidities. The guidelines for migraine treatment implicate opioid therapy as a second or third tier treatment. Guidelines and recommendations for the safe use of opioid medications among patients with chronic pain emphasize the importance of screening prior to prescribing opioid medications. Chronic opioid therapy has been shown to further levels of disability, decrease quality of life, and correlate to psychiatric comorbidities, concerns that are already present in migraine patients. While opioid treatment provides an alternative for persons with contraindications for alternative migraine treatments, it is critical that opioids be used sparingly and exclusively in conjunction with comprehensive assessment and integration of psychological treatment. PMID:27474093

  13. Developmental patterns for pancreatic opioids in the rat.

    Science.gov (United States)

    Powell, A M; Voyles, N R; Wilkins, S D; Zalenski, C M; Timmers, K I; Recant, L

    1989-01-01

    Developmental patterns for rat pancreatic opioid peptides and islet hormones were studied from gestational day 20 through adulthood. Fetal tissue was obtained as well as pancreas at birth (day 0), and postnatal days 3, 7, 14, and 21, and 7 weeks. The hormones measured included insulin, glucagon, and somatostatin. The opioids measured were beta-endorphin, Met- and Leu-enkephalins, and the high molecular weight enkephalin precursors. Pancreata were pooled as necessary and extracted (acid alcohol, or hot acetic acid), and opioids were further purified on reversed-phase C-18 (Sep-pak) cartridges. In all instances measurements were made by radioimmunoassays. Precursor peptides were first digested (with trypsin and carboxypeptidase B) prior to immunoassay. All opioids and hormones except the precursors for enkephalins showed a well-defined surge in pancreatic concentration during the first postnatal week. In contrast, the precursors had the highest concentration in the fetus, and by the seventh day of life had decreased by greater than 50%. This progressive decrease may represent maturation of the enkephalin convertase and trypsin-like enzymes in the islets. The opioid and hormonal surges that we have described are similar to the surge in islet concentration of thyroid-releasing hormone (TRH) previously described in neonatal rat islets. It is suggested that these postnatal alterations in opioid and hormone concentration relate to a specific function in the development of the endocrine pancreas. PMID:2530576

  14. Opioid modulation of taste hedonics within the ventral striatum.

    Science.gov (United States)

    Kelley, A E; Bakshi, V P; Haber, S N; Steininger, T L; Will, M J; Zhang, M

    2002-07-01

    There is a long-standing interest in the role of endogenous opioid peptides in feeding behavior and, in particular, in the modulation of food reward and palatability. Since drugs such as heroin, morphine, alcohol, and cannabinoids, interact with this system, there may be important common neural substrates between food and drug reward with regard to the brain's opioid systems. In this paper, we review the proposed functional role of opioid neurotransmission and mu opiate receptors within the nucleus accumbens and surrounding ventral striatum. Opioid compounds, particularly those selective for the mu receptor, induce a potent increase in food intake, sucrose, salt, saccharin, and ethanol intake. We have explored this phenomenon with regard to macronutrient selection, regional specificity, role of output structures, Fos mapping, analysis of motivational state, and enkephalin gene expression. We hypothesize that opioid-mediated mechanisms within ventral striatal medium spiny neurons mediate the affective or hedonic response to food ('liking' or food 'pleasure'). A further refinement of this hypothesis is that activation of ventral striatal opioids specifically encodes positive affect induced by tasty and/or calorically dense foods (such as sugar and fat), and promotes behaviors associated with this enhanced palatability. It is proposed that this brain mechanism was beneficial in evolutionary development for ensuring the consumption of relatively scarce, high-energy food sources. However, in modern times, with unlimited supplies of high-calorie food, it has contributed to the present epidemic of obesity. PMID:12117573

  15. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    International Nuclear Information System (INIS)

    The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced [3H]-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of [3H]-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand [3H]-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity

  16. Modulation of opioid receptor function by protein-protein interactions.

    Science.gov (United States)

    Alfaras-Melainis, Konstantinos; Gomes, Ivone; Rozenfeld, Raphael; Zachariou, Venetia; Devi, Lakshmi

    2009-01-01

    Opioid receptors, MORP, DORP and KORP, belong to the family A of G protein coupled receptors (GPCR), and have been found to modulate a large number of physiological functions, including mood, stress, appetite, nociception and immune responses. Exogenously applied opioid alkaloids produce analgesia, hedonia and addiction. Addiction is linked to alterations in function and responsiveness of all three opioid receptors in the brain. Over the last few years, a large number of studies identified protein-protein interactions that play an essential role in opioid receptor function and responsiveness. Here, we summarize interactions shown to affect receptor biogenesis and trafficking, as well as those affecting signal transduction events following receptor activation. This article also examines protein interactions modulating the rate of receptor endocytosis and degradation, events that play a major role in opiate analgesia. Like several other GPCRs, opioid receptors may form homo or heterodimers. The last part of this review summarizes recent knowledge on proteins known to affect opioid receptor dimerization. PMID:19273296

  17. Pattern self-medication use of analgesics in Pune, Maharashtra, India

    OpenAIRE

    Shruti Jaiswal; Yogendra N. Keche; Radha Yegnanarayan; Giriraj Gajendra; Kshitija Chandanwale; Vinaya Lanke; Surabhi Jain; Aditi Dakua; Gourav Das; Aishwarya Bhat; Sailee Belvi; Anandita Desai

    2014-01-01

    Background: Objective of current study was to find out self-medication pattern and to study awareness of ADRs to analgesics self-medication. Methods: II MBBS students collected the information of names of analgesics self-medication, dose, frequency of administration, health related problem for use of self-medication, source of information for the use of self-medication and information about ADRs. Students also educated the population about ADRs to analgesics with the help of ADR checklist....

  18. Intraoperative esmolol infusion reduces postoperative analgesic consumption and anaesthetic use during septorhinoplasty: a randomized trial

    OpenAIRE

    Nalan Celebi; Elif A. Cizmeci; Ozgur Canbay

    2014-01-01

    Background and objectives: Esmolol is known to have no analgesic activity and no anaesthetic properties; however, it could potentiate the reduction in anaesthetic requirements and reduce postoperative analgesic use. The objective of this study is to evaluate the effect of intravenous esmolol infusion on intraoperative and postoperative analgesic consumptions as well as its effect on depth of anaesthesia. Methods: This randomized-controlled double blind study was conducted in a tertiary care ...

  19. Selective antagonism of opioid-induced ventilatory depression by an ampakine molecule in humans without loss of opioid analgesia.

    Science.gov (United States)

    Oertel, B G; Felden, L; Tran, P V; Bradshaw, M H; Angst, M S; Schmidt, H; Johnson, S; Greer, J J; Geisslinger, G; Varney, M A; Lötsch, J

    2010-02-01

    Ventilatory depression is a significant risk associated with the use of opioids. We assessed whether opioid-induced ventilatory depression can be selectively antagonized by an ampakine without reduction of analgesia. In 16 healthy men, after a single oral dose of 1,500 mg of the ampakine CX717, a target concentration of 100 ng/ml alfentanil decreased the respiratory frequency by only 2.9 +/- 33.4% as compared with 25.6 +/- 27.9% during placebo coadministration (P CX717 than with placebo. In contrast, CX717 did not affect alfentanil-induced analgesia in either electrical or heat-based experimental models of pain. Both ventilatory depression and analgesia were reversed with 1.6 mg of naloxone. These results support the use of ampakines as selective antidotes in humans to counter opioid-induced ventilatory depression without affecting opioid-mediated analgesia. PMID:19907420

  20. Characteristics of opioid-users whose death was related to opioid-toxicity: a population-based study in Ontario, Canada.

    Directory of Open Access Journals (Sweden)

    Parvaz Madadi

    Full Text Available BACKGROUND: The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity. METHODS: This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed. RESULTS: Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359. Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch, 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer. SIGNIFICANCE/CONCLUSION: These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users.

  1. Potential analgesic, anti-inflammatory and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut.

    Science.gov (United States)

    Bhandare, Amol M; Kshirsagar, Ajay D; Vyawahare, Neeraj S; Hadambar, Avinash A; Thorve, Vrushali S

    2010-12-01

    The hydroalcoholic extract of Areca catechu L. (ANE) nut was screened for its analgesic, anti-inflammatory and in vitro antioxidant potential. Three doses of ANE (250, 500 and 1000 mg/kg orally) were tested for analgesic and anti-inflammatory activities. Evaluation of analgesic activity of ANE was performed using hot plate and formalin test in mice. ANE showed maximum increase in hot plate reaction time (56.27%, pAreca catechu could be considered as a potential analgesic, anti-inflammatory and antioxidant agent. PMID:20849907

  2. 76 FR 22404 - Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative

    Science.gov (United States)

    2011-04-21

    ... Networks (ACTION) Initiative AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food... Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative. The goal of...

  3. Etodolac: analgesic effects in musculoskeletal and postoperative pain.

    Science.gov (United States)

    Pena, M

    1990-01-01

    Numerous clinical trials have shown etodolac to be an effective analgesic. The purpose of the present report is to review results of 14 studies that demonstrate the effectiveness of etodolac in a variety of painful conditions. Presented are the results of four postsurgical pain studies, one study of acute gouty arthritis and nine studies of acute musculoskeletal disorders: acute low back pain, acute painful shoulder, tendinitis and bursitis, and acute sports injuries. A single oral dose of etodolac (25, 50, 100, 200, or 400 mg) was compared with aspirin (650 mg) or a combination of acetaminophen (600 mg) plus codeine (60 mg) for the relief of pain up to 12 h following oral, urogenital or orthopedic surgery. In multiple dose studies of acute gouty arthritis and musculoskeletal conditions, etodolac 200 or 300 mg twice a day (b.i.d.) or 200 mg three times a day (t.i.d.) was compared with naproxen 500 mg b.i.d. or t.i.d., diclofenac 50 mg b.i.d. or t.i.d., and piroxicam 20 or 40 mg once a day (o.d.) administered over 5 to 14 days. The efficacy of etodolac was at least equal and in some ways superior to aspirin and acetaminophen plus codeine in the relief of postsurgical pain. In studies of acute gouty arthritis, significant improvement from baseline were seen for all efficacy parameters evaluated for both the etodolac- and naproxen-treated patients. All the present studies of musculoskeletal conditions have shown etodolac to be effective and comparable in analgesic efficacy to naproxen, diclofenac or piroxicam. In summary, etodolac therapy for pain following surgery, in acute gouty arthritis and in acute musculoskeletal conditions resulted in analgesia comparable to that provided by several well-established analgesic or anti-inflammatory agents. PMID:2150571

  4. Analgesic oral efficacy of tramadol hydrochloride in postoperative pain.

    Science.gov (United States)

    Sunshine, A; Olson, N Z; Zighelboim, I; DeCastro, A; Minn, F L

    1992-06-01

    Tramadol hydrochloride is a synthetic opiate agonist with a plasma elimination half-life of 5 to 6 hours and peak plasma levels at about 1 1/2 hours. It derives its activity from attachment to the mu-receptor and blockage of norepinephrine reuptake. The purpose of this single-dose, double-blind, placebo-controlled study was to determine the analgesic effectiveness of an oral administration of two dose levels of tramadol hydrochloride (75 or 150 mg) compared with the combination of 650 mg acetaminophen plus 100 mg propoxyphene napsylate in 161 patients with severe postoperative pain after cesarean section. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard scales for pain intensity and relief and a number of derived variables based on these data. A global rating of the study medication was also used to compare treatments. The three active treatments were effective analgesics, statistically superior to placebo for many hourly and summary measures. A dose response was seen between the two tramadol doses, with the 150 mg dose providing significantly greater analgesia over the lower dose. The 75 mg dose of tramadol was generally more effective than the acetaminophen-propoxyphene combination after hour 2, and significantly so for some hourly time points, as well as for the global rating of the medication. The 150 mg dose of tramadol was significantly more effective than the acetaminophen-propoxyphene combination from hour 2 through hour 6 for the sum of pain intensity differences and total pain relief scores, as well as for the global rating of the medication. Tramadol hydrochloride at both dose levels is an effective analgesic agent and at 150 mg is statistically superior to the acetaminophen-propoxyphene combination. No serious adverse effects were observed; however, dizziness was more frequently reported with 150 mg tramadol. PMID:1351804

  5. Discovery of the First Small-Molecule Opioid Pan Antagonist with Nanomolar Affinity at Mu, Delta, Kappa, and Nociceptin Opioid Receptors

    OpenAIRE

    Zaveri, Nurulain T.; Journigan, V. Blair; Polgar, Willma E.

    2015-01-01

    The trans-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine scaffold is a known pharmacophore for mu opioid (MOP), kappa opioid (KOP), and delta opioid (DOP) receptor antagonists; however, it has not been explored in nociceptin opioid (NOP/ORL-1) receptor ligands. We recently found that the selective KOP antagonist JDTic, (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide, containing this opioid a...

  6. Analgesic action of laser therapy (LLLT) in an animal model

    OpenAIRE

    Daniel Pozza; Patricia Fregapani; João Weber; Marília Gerhardt de Oliveira; Marcos André de Oliveira; Nelson Ribeiro Neto; João Macedo Sobrinho

    2008-01-01

    OBJECTIVES: To evaluate the analgesic effect of laser therapy on healthy tissue of mice.STUDY DESIGN: Forty-five animals were divided in three groups of 15: A--infrared laser irradiation (830 nm, Kondortech, São Carlos, SP, Brazil); B--red laser irradiation (660 nm, Kondortech, São Carlos, SP, Brazil); C-- ham irradiation with laser unit off. After laser application, the mice remained immobilized for the injection of 30 microl of 2% formalin in the plantar pad of the irradiated hind paw. The ...

  7. Coffee drinking enhances the analgesic effect of cigarette smoking

    DEFF Research Database (Denmark)

    Nastase, Anca; Ioan, Silvia; Braga, Radu I;

    2007-01-01

    Nicotine (from cigarette smoke) and caffeine (from coffee) have analgesic effects in humans and experimental animals. We investigated the combined effects of coffee drinking and cigarette smoking on pain experience in a group of moderate nicotine-dependent, coffee drinking, young smokers. Pain...... threshold and pain tolerance were measured during cold pressor test following the habitual nocturnal deprivation of smoking and coffee drinking. Smoking increased pain threshold and pain tolerance in both men and women. Coffee drinking, at a dose that had no independent effect, doubled the increase in pain...

  8. Evaluation of analgesic activity of perindopril in albino mice

    OpenAIRE

    Suresha, R. N.; Siddamma Amoghimath; Vaibhavi, P. S.; Shruthi, S L; M.K. Jayanthi; H L Kalabharathi

    2014-01-01

    The aim was to evaluate the analgesic activity of perindopril in chemical, thermal and mechanical pain on Swiss albino mice. A total of 54 albino mice (Swiss strain) weighing 25-30 g were allocated to each experimental model and in each model there were three groups. The control group received normal saline (25 ml/kg) per orally, standard group received pentazocine (10 mg/kg) intra-peritoneal and test groups received perindopril (1 mg/kg) per orally. Perindopril and normal saline was administ...

  9. Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

    LENUS (Irish Health Repository)

    Fanning, Rebecca A

    2013-01-05

    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

  10. Anular o acortar los primeros peldaños de la Escalera Analgésica de la OMS To annul or to shorten the first steps of the WHO Analgesic Leader

    Directory of Open Access Journals (Sweden)

    A. Rubio

    2008-02-01

    Full Text Available Objetivo: Consideramos la posibilidad de anular o acortar el segundo peldaño de la escalera analgésica de la OMS, con el propósito de controlar el dolor crónico de nuestros pacientes en el menor tiempo posible. Material y métodos: Presentamos un estudio sobre 74 pacientes, divididos en tres grupos, para valorar si existen diferencias entre ellos. Un primer grupo pasó a tratarse con fentanilo TTS sin tratamiento previo con opioides débiles, los otros dos se trataron anteriormente con tramadol a dosis distintas. Un grupo a dosis previas de tramadol comprendidas entre 1 y 3 mg/Kg y otro grupo con dosis comprendidas entre 3.5 y 6 mg/Kg. Resultados: Los resultados han sido similares, clínica y estadísticamente, en cuanto a efectos secundarios, control del dolor y abandonos. Conclusiones: Concluimos que es posible acortar el tiempo necesario para controlar el dolor crónico en pacientes con patologías severas y que se presuponga necesitarán la prescripción de opioides mayores y que se puede anular el primer escalón de la OMS y también acortar el segundo.Objective: This study was designed to evalúate the possibility of either shorten or annul the first and second level of the WHO-analgesic ladder; in order to achieve pain control in patientes suffering from OA within the shortest period of time. Material and Methods: - First group pain was not adequately controlled by non-opioid analgesic and afterwards treated with TD-Fentanyl. - The second group was treated with TDF after not being adequately controlled by weak opoids, with a dose that ranged between 1 mg up to 3 mg/kg. - The third group was treated with TDF after a dose of weak opioids (tramadol which ranged between 3,5 mg up to 6 mg/kg. Results: Results related to pain control, adverse effects and therapy discontinuing, were statistically and clinically similar among the three groups. Conclusion: It is possible to shorten the period of time necessary to achieve pain control in

  11. Opioid profiles of Cys2-containing enkephalin analogues.

    Science.gov (United States)

    Pencheva, Nevena; Milanov, Peter; Vezenkov, Lubomir; Pajpanova, Tamara; Naydenova, Emilia

    2004-09-13

    To elucidate the structural features determining delta-opioid receptor properties of enkephalin analogues containing Cys(O2NH2) in position 2, a series of Cys2-containing derivatives were synthesized and tested for their effectiveness in depressing electrically evoked contractions of the mouse vas deferens (predominantly enkephalin-selective delta-opioid receptors) and the guinea-pig ileum (mu- and kappa-opioid receptors). The peptidase resistance of the compounds was also tested. The ratio IC50 in the guinea-pig ileum/IC50 in the mouse vas deferens, indicating selectivity for delta-opioid receptors, was high for Cys(O2NH2)2-containing analogues and especially for [Cys(O2NH2)2, Leu5]enkephalin, which was about seven times more selective than delta-opioid receptor selective ligand cyclic [D-Pen2, D-Pen5]enkephalin (DPDPE). The dissociation constant (KA) and relative efficacy (e(rel)) of the compounds in the mouse-isolated vas deferens were determined using explicit formulae derived by fitting of the data points with two-parametric hyperbolic function. The obtained values for KA and e(rel) suggest that: (i) incorporation of Cys(O2NH2)2 in the molecule of [Leu5]enkephalin highly increases the efficacy and does not change significantly the affinity of the respective analogues to delta-opioid receptors; [Cys(O2NH2)2, Leu5]enkephalin has higher affinity than DPDPE, but is less resistant to enzyme degradation; the effect of this modification on the efficacy is decreased when methionine is in position 5; (ii) D-configuration of Cys(O2NH2)2-containing analogues increases their peptidase resistance, but reduces efficacy and affinity of the peptides towards delta-opioid receptors; (iii) the substitution of Cys(O2NH2) with Hcy(O2NH2) reduces the efficacy, affinity and potency of the respective analogues and maintains their sensitivity to endogenous peptidases; (iv) the substitution of the sulfonamide group with benzyl group in the molecule of Cys in position 2 decreases their

  12. PROSPECTIVE STUDY TO COMPARE THE EFFICACY OF ANALGESIC AGENTS USED FOR THE PAIN MANAGEMENT DURING EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY

    Directory of Open Access Journals (Sweden)

    Abhirudra

    2016-05-01

    intrarenal surgery was done for residual stones after 3 sessions of SWL. Post ESWL complications like pyelonephritis, steinstrasse and renal stone migrating to ureter were 2%, 4.5%, 1.9% respectively. CONCLUSIONS With regard to pain scores, the EMLA cream provided better analgesic effect as compared to other groups. Oral NSAID and occlusive dressing of EMLA offers an effective mode for achieving analgesia with minimal morbidity. This therapy avoids the need for general anaesthesia, injectable analgesics, and opioids along with their side effects.

  13. Analgesics use in competitive triathletes: its relationship to doping and on predicting its usage.

    Science.gov (United States)

    Dietz, Pavel; Dalaker, Robert; Letzel, Stephan; Ulrich, Rolf; Simon, Perikles

    2016-10-01

    The two major objectives of this study were (i) to assess variables that predict the use of analgesics in competitive athletes and (ii) to test whether the use of analgesics is associated with the use of doping. A questionnaire primarily addressing the use of analgesics and doping was distributed among 2,997 triathletes. Binary logistic regression analysis was performed to predict the use of analgesics. Moreover, the randomised response technique (RRT) was used to estimate the prevalence of doping in order to assess whether users of analgesics have a higher potential risk for doping than non-users. Statistical power analyses were performed to determine sample size. The bootstrap method was used to assess the statistical significance of the prevalence difference for doping between users and non-users of analgesics. Four variables from a pool of 16 variables were identified that predict the use of analgesics. These were: "version of questionnaire (English)", "gender (female)", "behaviour in case of pain (continue training)", and "hours of training per week (>12 h/week)". The 12-month prevalence estimate for the use of doping substances (overall estimate 13.0%) was significantly higher in athletes that used analgesics (20.4%) than in those athletes who did not use analgesics (12.4%). The results of this study revealed that athletes who use analgesics prior to competition may be especially prone to using doping substances. The predictors of analgesic use found in the study may be of importance to prepare education material and prevention models against the misuse of drugs in athletes. PMID:26911564

  14. Comparison of Buprenorphine Treatment for Opioid Dependence in Three Settings

    Science.gov (United States)

    Hillhouse, Maureen; Donovick, Roger; Cunningham-Rathner, Jerry; Charuvastra, Charlie; Torrington, Matthew; Esagoff, Asher E.; Ling, Walter

    2011-01-01

    Although use of buprenorphine in the treatment of opioid dependence is expected to continue to increase, little is known about the optimal setting for providing the medical and psychosocial care required with buprenorphine pharmacotherapy. OBJECTIVE This study compared buprenorphine therapy delivered in three distinct treatment settings: an opioid-treatment program (OTP) offering individual counseling; a group counseling program utilizing the manualized Matrix Model (MMM) of cognitive-behavioral treatment; and a private clinic setting mirroring standard medical management for buprenorphine treatment provided specifically at a psychiatrist’s private practice (PCS). METHOD Participants were inducted on buprenorphine and provided with treatment over a 52-week study duration. All participants were scheduled for weekly treatment visits for the first 6 study weeks, and two sites reduced treatment to monthly visits for dispensing of medication and psychosocial counseling. Outcomes include opioid use, participant retention in treatment, and treatment participation. RESULTS Participants presenting for treatment at the sites differed only by race/ethnicity, and opioid use did not differ by site. Retention differed by treatment site, with the number of participants who stayed in the study until the end of 20 weeks significantly associated with treatment site. The mean number of minutes spent in each individual counseling session also differed by site. Although no difference in opioid use by treatment site was found, results document a significant association between opioid use and buprenorphine dose. DISCUSSION These results show some differences by treatment site, although the similarity and relative ease in which the sites were able to recruit participants for treatment with buprenorphine, and minor implementation problems reported suggests the feasibility of treatment with buprenorphine across various treatment settings. CONCLUSION Similar rates of continued opioid use

  15. Five-factor model personality traits in opioid dependence

    Directory of Open Access Journals (Sweden)

    Nordvik Hilmar

    2007-08-01

    Full Text Available Abstract Background Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether there is a distinct personality pattern associated with opioid dependence. Methods We compared FFM personality traits in 65 opioid dependent persons (mean age 27 years, 34% females in outpatient counselling after a minimum of 5 weeks in buprenorphine replacement therapy, with those in a non-clinical, age- and sex-matched sample selected from a national database. Personality traits were assessed by a Norwegian version of the Revised NEO Personality Inventory (NEO PI-R, a 240-item self-report questionnaire. Cohen's d effect sizes were calculated for the differences in personality trait scores. Results The opioid-dependent sample scored higher on Neuroticism, lower on Extraversion and lower on Conscientiousness (d = -1.7, 1.2 and 1.7, respectively than the controls. Effects sizes were small for the difference between the groups in Openness to experience scores and Agreeableness scores. Conclusion We found differences of medium and large effect sizes between the opioid dependent group and the matched comparison group, suggesting that the personality traits of people with opioid dependence are in fact different from those of non-clinical peers.

  16. ANTIOXIDANT, ANALGESIC AND CYTOTOXIC ACTIVITIES OF MIMUSOPS ELENGI LINN. LEAVES

    Directory of Open Access Journals (Sweden)

    Utpal Kumar Karmakar et al.

    2011-11-01

    Full Text Available Mimusops elengi Linn. (Family: Sapotaceae is a tree which is traditionally used against a number of diseases including ulcers, headache, dental diseases, wound and fever. In the present study crude methanolic extract of Mimusops elengi Linn. leaf was investigated for possible antioxidant, analgesic and cytotoxic activity. The extract exhibited statistically significant antioxidant activity in DPPH free radical scavenging and Nitric oxide scavenging test. The analgesic activity of the sample was studied using acetic acid induced writhing of white albino mice and hot plate test. The extract produced 45.61% and 63.85% (P<0.001 writhing inhibition at the doses of 250mg/kg and 500 mg/kg body weight respectively which is comparable to the standard drug diclofenac sodium was found to be 76.69% at a dose of 25 mg/kg body weight. In hot plate test the extract exerted significant (P<0.001 prolongation in the response of latency time to the heat stimulus. The cytotoxic activity of the extract was assessed by brine shrimp lethality bioassay as an indicator of toxicity in which LC50= 80μg/ml and LC90 = 320μg/ml for sample. All the results tend to justify the traditional uses of the plant and require further investigation to identify the chemicals.

  17. Ethical Tensions in the Pain Management of an End-Stage Cancer Patient with Evidence of Opioid Medication Diversion.

    Science.gov (United States)

    Venkat, Arvind; Kim, David

    2016-06-01

    At the end of life, pain management is commonly a fundamental part of the treatment plan for patients where curative measures are no longer possible. However, the increased recognition of opioid diversion for secondary gain coupled with efforts to treat patients in the home environment towards the end of life creates the potential for ethical dilemmas in the palliative care management of terminal patients in need of continuous pain management. We present the case of an end-stage patient with rectal cancer who required a continuous residential narcotic infusion of fentanyl for pain control due to metastatic disease. His functional status was such that he had poor oral intake and ability to perform other activities of daily living, but was able to live at home with health agency nursing care. The patient presented to this institution with a highly suspect history of having lost his fentanyl infusion in a residential accident and asking for a refill to continue home therapy. The treating physicians had concerns of diversion of the infusion medication by caregivers and were reluctant to continue the therapeutic relationship with the patient. This case exemplifies the tension that can exist between wanting to continue with palliative care management of an end-stage patient and the fear of providers when confronted by evidence of potential diversion of opioid analgesic medications. We elucidate how an ethical framework based on a combination of virtue and narrative/relationship theories with reference to proportionality can guide physicians to a pragmatic resolution of these difficult situations. PMID:25381648

  18. Influence of opioid peptides on human neutrophil apoptosis and activation in vitro

    Directory of Open Access Journals (Sweden)

    Zofia Sulowska

    2002-01-01

    Full Text Available Background: It has been shown that cells of the immune system release opioid peptides and possess receptors for them. The concentrations of opioid peptides in the peripheral circulation rapidly increase during inflammation and acute stress response.

  19. Vital Statistics: Opioid-Related Deaths by Gender and Race/Ethnicity: Beginning 2003

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset contains opioid-related death counts and adjusted mortality rates by gender, race/ethnicity, and selected cause of death. The opioid-related deaths...

  20. Social costs of untreated opioid dependence.

    Science.gov (United States)

    Wall, R; Rehm, J; Fischer, B; Brands, B; Gliksman, L; Stewart, J; Medved, W; Blake, J

    2000-12-01

    Using cost-of-illness methodology applied to a comprehensive survey of 114 daily opiate users not currently in or seeking treatment for their addiction, we estimated the 1996 social costs of untreated opioid dependence in Toronto (Ontario, Canada). The survey collected data on social and demographic characteristics, drug use history, physical and mental health status, the use of health care and substance treatment services, drug use modality and sex-related risks of infectious diseases, sources of income, as well as criminality and involvement with the law enforcement system. The annual social cost generated by this sample, calculated at Canadian $5.086 million, is explained mostly by crime victimization (44.6%) and law enforcement (42.4%), followed by productivity losses (7.0%) and the utilization of health care (6.1%). Applying the $13,100 cost to the estimated 8,000 to 13,000 users and 2.456 million residents living in Toronto yields a range of social cost between $43 and $69 per capita. PMID:11194311