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Sample records for analgesics opioid

  1. Opioid analgesics: does potency matter?

    Science.gov (United States)

    Passik, Steven D; Webster, Lynn

    2014-01-01

    Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

  2. Structural comparisons of meptazinol with opioid analgesics

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Jing-lai HAO; Yun TANG; Yan CHEN; Zhui-bai QIU

    2005-01-01

    Aim: To investigate the mechanism of action of a potent analgesic, (±)-meptazinol.Methods: The structures of meptazinol enantiomers were compared with opioid pharmacophore and tramadol. Results: Neither enantiomer of meptazinol fitted any patterns among the opioid pharmacophore and tramadol, although they did share some structural and pharmacological similarities. However, the structure superpositions implied that both enantiomers of meptazinol might share some similar analgesic mechanisms with typical opiate analgesics. Conclusion:Meptazinol should have a different mechanism of action to known analgesics,which would be helpful in further investigations of meptazinol in the search for non-addictive analgesics.

  3. Opioid Analgesics and Nicotine: More Than Blowing Smoke.

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    Yoon, Jin H; Lane, Scott D; Weaver, Michael F

    2015-09-01

    Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs. PMID:26375198

  4. 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...... patients only using controlled studies were updated. Fourteen controlled studies on the cognitive effects of opioids in chronic non-cancer pain patients and eleven controlled studies in cancer pain patients were included and analyzed. Opioid treatment involved slightly opposite outcomes in the two patient...

  5. Non-analgesic effects of opioids: opioids and the endocrine system.

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    Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E

    2012-01-01

    Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

  6. 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

  7. Prescription Opioid Analgesics: Promoting Patient Safety with Better Patient Education.

    Science.gov (United States)

    Costello, Margaret

    2015-11-01

    Patients expect and deserve adequate postoperative pain relief. Opioid analgesics are widely used and effective in controlling postoperative pain, but their use poses risks that many patients don't understand and that all too often result in adverse outcomes. Inappropriate and often dangerous use of prescription medication has increased sharply in the past two decades in the United States. Patients and caregivers must have an adequate understanding of safe use, storage, and disposal of opioids to prevent adverse drug events in patients and others. Nurses play a key role in providing this patient education. This article provides a case study that highlights the risks and important aspects of opioid medication use in the postoperative patient.

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

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    Merab G Tsagareli

    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.

  9. 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

  10. 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

  11. 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.

  12. Clinical Research on Nourishing Yin and Unblocking Meridians Recipe Combined with Opioid Analgesics in Cancer Pain Management

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ting; MA Sheng-lin; XIE Guang-ru; DENG Qing-hua; TANG Zhong-zhu; PAN Xiao-chan; ZHANG Min; XU Su

    2006-01-01

    Objective: To investigate the analgesic effects of Nourishing yin and Unblocking meridians Receipe (NUR) combined with opioid analgesics in managing cancer pain. Methods: All the patients enrolled were differentiated as of yin deficiency and meridian blocked syndrome type of TCM. Forty-one of them in the treated group were treated with NUR combined with opioid analgesics, while 43 of them in the control group were given opioid analgesics alone with successive 14 days as one treatment course for both groups. Results:The indexes of the treated group were superior to those in the control group as to the degree of pain-relieving, the therapeutic effect of analgesia, the occurrence frequency of cancer pain every day and its duration each time, the analgesic initial time, and the quality of life. Conclusion: NUR combined with opioid analgesics in cancer pain management was more effective than opioid analgesics alone.

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

    Science.gov (United States)

    2016-02-01

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

  14. Impact of a Mandatory Prescription Drug Monitoring Program on Prescription of Opioid Analgesics by Dentists.

    Directory of Open Access Journals (Sweden)

    Linda Rasubala

    Full Text Available Prescription Drug Monitoring Programs (PDMP are statewide databases that collect data on prescription of controlled substances. New York State mandates prescribers to consult the PDMP registry before prescribing a controlled substance such as opioid analgesics. The effect of mandatory PDMP on opioid drug prescriptions by dentists is not known. This study investigates the impact of mandatory PDMP on frequency and quantity of opioid prescriptions by dentists in a dental urgent care center. Based on the sample size estimate, we collected patient records of a 3-month period before and two consecutive 3-month periods after the mandatory PDMP implementation and analyzed the data on number of visits, treatment types and drug prescriptions using Chi-square tests. For patients who were prescribed pain medications, 452 (30.6%, 190 (14.1%, and 140 (9.6% received opioid analgesics in the three study periods respectively, signifying a statistically significant reduction in the number of opioid prescriptions after implementation of the mandatory PDMP (p<0.05. Total numbers of prescribed opioid pills in a 3-month period decreased from 5096 to 1120, signifying a 78% reduction in absolute quantity. Prescriptions for non-opioid analgesics acetaminophen increased during the same periods (p<0.05. We conclude that the mandatory PDMP significantly affected the prescription pattern for pain medications by dentists. Such change in prescription pattern represents a shift towards the evidence-based prescription practices for acute postoperative pain.

  15. Abuse-deterrent formulations of prescription opioid analgesics in the management of chronic noncancer pain.

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    Hale, Martin E; Moe, Derek; Bond, Mary; Gasior, Maciej; Malamut, Richard

    2016-10-01

    Misuse, abuse and diversion of prescription opioid analgesics represent a global public health concern. The development of abuse-deterrent formulations (ADFs) of prescription opioid analgesics is an important step toward reducing abuse and diversion of these medications, as well as potentially limiting medical consequences when misused or administered in error. ADFs aim to hinder extraction of the active ingredient, prevent administration through alternative routes and/or make abuse of the manipulated product less attractive, less rewarding or aversive. However, opioid ADFs may still be abused via the intended route of administration by increasing the dose and/or dosing frequency. The science of abuse deterrence and the regulatory landscape are still relatively new and evolving. This paper reviews the current status of opioid ADFs, with particular focus on different approaches that can be used to deter abuse, regulatory considerations and implications for clinical management.

  16. Adverse selection? A multi-dimensional profile of people dispensed opioid analgesics for persistent non-cancer pain.

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    Kris D Rogers

    Full Text Available OBJECTIVES: This study investigates utilisation patterns for prescription opioid analgesics in the Australian community and how these are associated with a framework of individual-level factors related to healthcare use. METHODS: Self-reported demographic and health information from participants in the 45 and Up Study cohort were linked to pharmaceutical claims from 2006-2009. Participants comprised 19,816 people with ≥1 opioid analgesic dispensing in the 12-months after recruitment to the cohort and 79,882 people not dispensed opioid analgesics. All participants were aged ≥45 years, were social security pharmaceutical beneficiaries, with no history of cancer. People dispensed opioid analgesics were classified as having acute (dispensing period <90 days, episodic (≥90 days and <3 'authority' prescriptions for increased quantity supply or long-term treatment (≥90 days and ≥3 authority prescriptions. RESULTS: Of participants dispensed opioid analgesic 52% received acute treatment, 25% episodic treatment and 23% long-term treatment. People dispensed opioid analgesics long-term had an average of 14.9 opioid analgesic prescriptions/year from 2.0 doctors compared with 1.5 prescriptions from 1.1 doctors for people receiving acute treatment. People dispensed opioid analgesics reported more need-related factors such as poorer physical functioning and higher psychological distress. Long-term users were more likely to have access-related factors such as low-income and living outside major cities. After simultaneous adjustment, association with predisposing health factors and access diminished, but indicators of need such as osteoarthritis treatment, paracetamol use, and poor physical function were the strongest predictors for all opioid analgesic users. CONCLUSIONS: People dispensed opioid analgesics were in poorer health, reported higher levels of distress and poorer functioning than people not receiving opioid analgesics. Varying dispensing

  17. 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 ...

  18. Prediction formulas for individual opioid analgesic requirements based on genetic polymorphism analyses.

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    Kaori Yoshida

    Full Text Available The analgesic efficacy of opioids is well known to vary widely among individuals, and various factors related to individual differences in opioid sensitivity have been identified. However, a prediction model to calculate appropriate opioid analgesic requirements has not yet been established. The present study sought to construct prediction formulas for individual opioid analgesic requirements based on genetic polymorphisms and clinical data from patients who underwent cosmetic orthognathic surgery and validate the utility of the prediction formulas in patients who underwent major open abdominal surgery.To construct the prediction formulas, we performed multiple linear regression analyses using data from subjects who underwent cosmetic orthognathic surgery. The dependent variable was 24-h postoperative or perioperative fentanyl use, and the independent variables were age, gender, height, weight, pain perception latencies (PPL, and genotype data of five single-nucleotide polymorphisms (SNPs. To examine the utility of the prediction formulas, we performed simple linear regression analyses using subjects who underwent major open abdominal surgery. Actual 24-h postoperative or perioperative analgesic use and the predicted values that were calculated using the multiple regression equations were incorporated as dependent and independent variables, respectively.Multiple linear regression analyses showed that the four SNPs, PPL, and weight were retained as independent predictors of 24-h postoperative fentanyl use (R² = 0.145, P = 5.66 × 10⁻¹⁰ and the two SNPs and weight were retained as independent predictors of perioperative fentanyl use (R² = 0.185, P = 1.99 × 10⁻¹⁵. Simple linear regression analyses showed that the predicted values were retained as an independent predictor of actual 24-h postoperative analgesic use (R² = 0.033, P = 0.030 and perioperative analgesic use (R² = 0.100, P = 1.09 × 10⁻⁴, respectively.We constructed

  19. 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......: This 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...

  20. Possible analgesic and anti-inflammatory interactions of aspartame with opioids and NSAIDs.

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    Sharma, Sameer; Jain, N K; Kulkarni, S K

    2005-06-01

    The purpose of the present study was to investigate analgesic and anti-inflammatory properties of aspartame, an artificial sweetner and its combination with various opioids and NSAIDs for a possible synergistic response. The oral administration of aspartame (2-16mg/kg, po) significantly increased the pain threshold against acetic acid-induced writhes in mice. Co-administration of aspartame (2mg/kg, po) with nimesulide (2 mg/kg, po) and naproxen (5 mg/kg, po) significantly reduced acetic acid-induced writhes as compared to effects per se of individual drugs. Similarly when morphine (1 mg/kg, po) or pentazocine (1 mg/kg, po) was co-administered with aspartame it reduced the number of writhes as compared to their effects per se. Aspartame (4,8,16 mg/kg, po) significantly decreased carrageenan-induced increase in paw volume and also reversed the hyperalgesic effects in rats in combination with nimesulide (2 mg/kg, po). The study indicated that aspartame exerted analgesic and anti-inflammatory effects on its own and have a synergistic analgesic response with conventional analgesics of opioid and non-opioid type, respectively.

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

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    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

  2. Conformational re-analysis of (+)-meptazinol: an opioid with mixed analgesic pharmacophores

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Xing-hai WANG; Choi-wan LAU; Yun TANG; Qiong XIE; Zhui-bai QIU

    2006-01-01

    Aim: To further investigate the analgesic pharmacophore of (+)-meptazinol. Methods: Two different opioid pharmacophores, Pharm-Ⅰ and Pharm-Ⅱ, were established from structures of nine typical opiates and meperidine by using molecular modeling approaches according to their different structure activity relationship properties. They were further validated by a set of conformationally constrained arylpiperidines. Two conformers of (+)-meptazinol (Conformer-Ⅰ and Con-former-Ⅱ) detected in solution were then fitted into the pharmacophores, respectively, by Fit Atoms facilities available in SYBYL, a computational modeling tool kit for molecular design and analysis. Results: Conformer-Ⅰ fit Pharm-Ⅰ from typical opiates well. However, Conformer-Ⅱ fit none of these pharmacophores. Instead, it was found to be similar to another potent analgesic, benzofuro[2,3-c] pyridin-6-ol, whose pharmacophore was suggested to hold the transitional state between the two established pharmacophores. Unlike typical analgesics derived from 4-aryl piperidine (eg, meperidine) with one conformer absolutely overwhelming, the (+)-meptazinol exists in two conformers with similar amounts in solution. Furthermore, both conformers can not transform to each other freely in ordinary conditions based on our NMR results. Conclusion: (+)-meptazinol was suggested to be an opioid with mixed analgesic pharmacophores, which may account for the complicated pharmacological properties of meptazinol.

  3. 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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common 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-based recommendations developed......Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared...

  5. 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 ...

  6. Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations.

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    Gasior, Maciej; Bond, Mary; Malamut, Richard

    2016-01-01

    Prescription opioid analgesics are an important treatment option for patients with chronic pain; however, misuse, abuse and diversion of these medications are a major global public health concern. Prescription opioid analgesics can be abused via intended and non-intended routes of administration, both intact or after manipulation of the original formulation to alter the drug-delivery characteristics. Available data indicate that ingestion (with or without manipulation of the prescribed formulation) is the most prevalent route of abuse, followed by inhalation (snorting, smoking and vaping) and injection. However, reported routes of abuse vary considerably between different formulations. A number of factors have been identified that appear to be associated with non-oral routes of abuse, including a longer duration of abuse, younger age, male sex and a rural or socially deprived location. The development of abuse-deterrent formulations of prescription opioid analgesics is an important step toward reducing abuse of these medications. Available abuse-deterrent formulations aim to hinder extraction of the active ingredient, prevent administration through alternative routes and/or make abuse of the manipulated product less attractive, less rewarding or even aversive. There are currently five opioid analgesics with a Food and Drug Administration abuse-deterrent label, and a number of other products are under review. A growing body of evidence suggests that introduction of abuse-deterrent opioid analgesics in the USA has been associated with decreased rates of abuse of these formulations. The availability of abuse-deterrent formulations therefore appears to represent an important step toward curbing the epidemic of abuse of prescription opioid analgesics, while ensuring the availability of effective pain medications for patients with legitimate medical need.

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

    Science.gov (United States)

    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

  8. 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.

  9. Non-Opioid Analgesics Consumption At The Surgery Departments Of A Secondary Care Hospital In General Hospital In Kraljevo, Serbia

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    Aleksic Dejan

    2015-09-01

    Full Text Available The aim of this study was to determine the amount of non-opioid analgesics consumed at the surgical departments of a secondary care hospital in Serbia, a developing country undergoing a socioeconomic transition that thus lacks sufficient funds to finance and invest in the healthcare system.

  10. 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).

  11. Sudden unexpected nocturnal death in Chiari type 1 malformation and potential role of opioid analgesics

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    Fereydoon Roohi

    2014-01-01

    Full Text Available Background: Chiari malformation type 1 (CM1 is a common congenital anomaly of the craniocervical junction. CM1 is reported to run a usually benign course and patients typically experience no symptoms or chronic, slowly progressive symptoms. However, recent reports indicate that a subset of patients with CM1 may present with acute deterioration and sudden unexpected death (SUD. We report a case of SUD during sleep in a young man with CM1, which we believe was related to the administration of common and therapeutic doses of narcotic analgesics for the management of pain. We will clarify the pathophysiology of acute deterioration and SUD in CM1 and the possibility that the adverse effects of opiate analgesics likely were the leading cause of death in our patient. Case Description: In this review, we present a 29-year-old male with worsening headache secondary to previously diagnosed CM1. The patient died suddenly and unexpectedly after administration of common and therapeutic doses of narcotic analgesics for the management of pain. Conclusion: The mechanism(s of acute neurological deterioration and sudden death in patients with CM1 remains poorly understood. We believe the rapid fatal deterioration in our patient following administration of opioids suggests that this category of medication may cause sudden unexpected "neurogenic" cardiac death in CM1 patients by inducing sleep-related breathing difficulties and associated hypercapnia. Hypercapnia by further increasing intracranial pressure can result in a sudden pressure-induced decompensation of the cardiopulmonary control centers in the brain stem and cause instantaneous cardiorespiratory arrest.

  12. Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior.

    Science.gov (United States)

    Váradi, András; Marrone, Gina F; Eans, Shainnel O; Ganno, Michelle L; Subrath, Joan J; Le Rouzic, Valerie; Hunkele, Amanda; Pasternak, Gavril W; McLaughlin, Jay P; Majumdar, Susruta

    2015-11-18

    3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 double bond and various N-17 alkyl substituents. The structural modifications resulted in analogs with picomolar affinities for opioid receptors. The lead compound (MP1104) was found to exhibit approximately 15-fold greater antinociceptive potency (ED50 = 0.33 mg/kg) compared with morphine, mediated through the activation of kappa- and delta-opioid receptors. Despite its kappa agonism, this lead derivative did not cause place aversion or preference in mice in a place-conditioning assay, even at doses 3 times the analgesic ED50. However, pretreatment with the lead compound prevented the reward behavior associated with cocaine in a conditioned place preference assay. Together, these results suggest the promise of dual acting kappa- and delta-opioid receptor agonists as analgesics and treatments for cocaine addiction.

  13. 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...

  14. 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.

  15. Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2.

    Science.gov (United States)

    Váradi, András; Marrone, Gina F; Palmer, Travis C; Narayan, Ankita; Szabó, Márton R; Le Rouzic, Valerie; Grinnell, Steven G; Subrath, Joan J; Warner, Evelyn; Kalra, Sanjay; Hunkele, Amanda; Pagirsky, Jeremy; Eans, Shainnel O; Medina, Jessica M; Xu, Jin; Pan, Ying-Xian; Borics, Attila; Pasternak, Gavril W; McLaughlin, Jay P; Majumdar, Susruta

    2016-09-22

    Natural products found in Mitragyna speciosa, commonly known as kratom, represent diverse scaffolds (indole, indolenine, and spiro pseudoindoxyl) with opioid activity, providing opportunities to better understand opioid pharmacology. Herein, we report the pharmacology and SAR studies both in vitro and in vivo of mitragynine pseudoindoxyl (3), an oxidative rearrangement product of the corynanthe alkaloid mitragynine. 3 and its corresponding corynantheidine analogs show promise as potent analgesics with a mechanism of action that includes mu opioid receptor agonism/delta opioid receptor antagonism. In vitro, 3 and its analogs were potent agonists in [(35)S]GTPγS assays at the mu opioid receptor but failed to recruit β-arrestin-2, which is associated with opioid side effects. Additionally, 3 developed analgesic tolerance more slowly than morphine, showed limited physical dependence, respiratory depression, constipation, and displayed no reward or aversion in CPP/CPA assays, suggesting that analogs might represent a promising new generation of novel pain relievers.

  16. 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

  17. 阿片类镇痛药物的不良反应%Adverse Drug Reactions of Opioid Analgesics

    Institute of Scientific and Technical Information of China (English)

    赵文亭

    2015-01-01

    Objective To investigate the side effects of opioid analgesics.Methods The clinical data of 38 patients with opioid analgesic drugs used in District,Linzi District,January 2015 to January 2014, were colected and analyzed.Results The adverse reactions of opioid analgesics were the most common in patients aged 70 to 70 years,and the incidence of adverse reactions was 60 to years old.The highest adverse reaction rate of opioid analgesics was fentanyl,folowed by the treatment of the pain,and the main adverse reactions were constipation.Conclusion The main adverse reactions of opioid analgesics are constipation, so that the elderly patients can be seen,the clinical application should take ful account of the patient's constitution and tolerance,reduce the incidence of adverse reactions,improve the clinical rational drug use.%目的:探讨阿片类镇痛药物的不良反应。方法收集2014年1月至2015年1月临淄区妇幼保健院使用阿片类镇痛药物出现不良反应的38例患者的临床资料,统计患者的性别、年龄、用药类型、不良反应的类型等,分析导致不良反应发生的原因。结果阿片类镇痛药物的不良反应以>70岁患者最常见,其次为60~70岁;发生率最高的为芬太尼,其次为哌替啶;主要不良反应为便秘。结论阿片类镇痛药物主要不良反应为便秘,以老年患者多见,临床应用要充分考虑患者体质和耐受性,以降低不良反应的发生率,提高临床合理用药。

  18. 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

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

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    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.

  20. DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic and inflammatory pain.

    Science.gov (United States)

    Rajagopalan, Parthasarathi; Tracey, Heather; Chen, Zhoumou; Bandyopadhyaya, Acintya; Veeraraghavan, Sridhar; Rajagopalan, Desikan R; Salvemini, Daniela; McPhee, Ian; Viswanadha, Srikant; Rajagopalan, Raghavan

    2014-07-15

    DDD-028 (4), a novel pentacyclic pyridoindolobenzazepine derivative was evaluated in vitro for receptor binding affinity and in vivo for analgesic activity using rodent models of neuropathic and inflammatory pain. DDD-028 does not bind to opioid, cannabinoid, dopamine, or histamine receptors. DDD-028 is very active even at the low oral dose of 1-5 mg/kg in both neuropathic, (spinal nerve ligation and chronic constriction injury) and inflammatory (Complete Freund's Adjuvant Induced) models of pain. DDD-028 appears to be about 6-fold more potent than pregabalin and indomethacin. Visual observation of all the animals used in these studies indicated that DDD-028 is well tolerated without any sedation. Thus, DDD-028 seems to be a promising candidate for the treatment of neuropathic and inflammatory pain without the possible side effects or abuse potential associated with opioid or cannabinoid activities.

  1. Non-analgesic effects of opioids: opioid-induced nausea and vomiting: mechanisms and strategies for their limitation.

    Science.gov (United States)

    Coluzzi, Flaminia; Rocco, Alessandra; Mandatori, Ilenia; Mattia, Consalvo

    2012-01-01

    Nausea and vomiting are common gastrointestinal symptoms following opioid administration, for either chronic or acute pain management. As a consequence, patients' dissatisfaction has a negative impact on treatment efficacy. A number of mechanisms have been identified, involving both central and peripheral sites. This article will review the pathophysiology of opioid-induced nausea and vomiting and the various pharmacological treatments currently available for its management. Preventive strategies and therapeutic approaches are evaluated in the perioperative setting and in chronic pain. Newer drugs include second generation serotonin receptor antagonists (palonosetron) and neurokinin-1 (NK-1) antagonists (aprepitant).

  2. 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 ...

  3. Pharmacological evaluation of opioid and non-opioid analgesics in a murine bone cancer model of pain.

    NARCIS (Netherlands)

    ElMouedden, M.; Meert, T.F.

    2007-01-01

    The intramedulary injection of osteosarcoma cells in the mouse femur has served as a laboratory model to study bone cancer pain. However, the efficacy of different classes of analgesics has not fully been analyzed in this model. Therefore, the acute antinociceptive properties of different classes of

  4. Analgesic

    Directory of Open Access Journals (Sweden)

    Bian Juhua

    2016-05-01

    Full Text Available This study is to establish a model of rat tibial osteocarcinoma pain, intrathecally inject specific ERK1/2 inhibitors SCH772984, observe the analgesic effect, and discuss the influence of ERK-P90RSK-Fos signal path in bone cancer pain. Forty female SD rats were randomly divided into 5 groups. Establish a bone cancer pain model after putting the intrathecal tube 5d and determine the rats’ mechanical withdrawal threshold (MWT after tube 5d; 40 SD rats with intrathecal tube back 5d were randomly divided into 5 groups. Sham Group receives no medication, the other four respectively receive 5% DMSO 10 μl, SCH 0.1, 1.0, 10 μg (SCH dissolved in 10 μl 5% DMSO intrathecally. Determine the rats’ mechanical withdrawal threshold (MWT before and after giving medication 1, 3, 6, 9, 12, 15, 18, 24 h, and 2 min spontaneous paw withdrawal. Western blot and immuno-fluorescence determine the expression condition of spinal cord dorsal horn of p-ERK, p-p90RSK and Fos protein. Intrathecal injection of SCH772984 has analgesic effects on rats with bone cancer pain, and the effects enhance with increasing dose; intrathecal injection of SCH772984 10 μg could greatly reduce the expression of spinal dorsal horn Fos protein. Injecting walker 256 tumor cells into rats’ tibia could cause behavior changes, such as idiopathic pain sensitivity and pain; the intrathecal tube almost has no effect on motor function of rats; ERK1/2 is involved in bone cancer pain, and intrathecal injection of ERK1/2 specific inhibitors SCH772984 10 μg may effectively relieve bone cancer pain.

  5. Local analgesic effect of tramadol is mediated by opioid receptors in late postoperative pain after plantar incision in rats

    Science.gov (United States)

    de Oliveira Junior, José Oswaldo; de Freitas, Milena Fernandes; Bullara de Andrade, Carolina; Chacur, Marucia; Ashmawi, Hazem Adel

    2016-01-01

    Tramadol is a drug used to treat moderate to severe pain. It is known to present a peripheral effect, but the local mechanisms underlying its actions remain unclear. The role of peripheral opioid receptors in postoperative pain is not well understood. In the present study, we examined the peripheral opioid receptors to determine the local effect of tramadol in a plantar incision pain model. Rats were subjected to plantar incision and divided into four groups on postoperative day (POD) 1: SF_SF, 0.9% NaCl injected into the right hindpaw; SF_TraI, 0.9% NaCl and tramadol injected into the right hindpaw; SF_TraC, 0.9% NaCl and tramadol injected into the contralateral hindpaw; and Nal_Tra, naloxone and tramadol injected into the ipsilateral hindpaw. To determine the animals’ nociceptive threshold, mechanical hyperalgesia was measured before incision, on POD1 before treatment and at 15, 30, 45, and 60 minutes after the incision. The same procedure was repeated on the POD2. The expression levels of μ-opioid receptor (MOR) and δ-opioid receptor (DOR) were obtained through immunoblotting assays in the lumbar dorsal root ganglia (L3–L6) in naïve rats and 1, 2, 3, and 7 days after the incision. Our results showed that the plantar incision was able to cause an increase in mechanical hyperalgesia and that tramadol reversed this hyperalgesia on POD1 and POD2. Tramadol injections in the contralateral paw did not affect the animals’ nociceptive threshold. Naloxone was able to antagonize the tramadol effect partially on POD1 and completely on POD2. The DOR expression increased on POD2, POD3, and POD7, whereas the MOR expression did not change. Together, our results show that tramadol promoted a local analgesic effect in the postoperative pain model that was antagonized by naloxone in POD2, alongside the increase of DOR expression. PMID:27799813

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

    DEFF Research Database (Denmark)

    Ebert, B; Thorkildsen, C; Andersen, S;

    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......, in order to obtain complete analgesia, a combination of an NMDA receptor antagonist and an opioid receptor agonist is needed. Recent in vitro data have demonstrated that methadone, ketobemidone, and dextropropoxyphene, in addition to being opioid receptor agonists, also are weak noncompetitive NMDA...... receptor antagonists. Clinical anecdotes suggest that the NMDA receptor antagonism of these opioids may play a significant role in the pharmacological action of these compounds; however, no clinical studies have been conducted to support this issue. In the present commentary, we discuss evidence...

  7. 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.

  8. 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

  9. Progress of Non-opioid Analgesics in Perioperative Analgesia%非阿片类镇痛药的围术期应用进展

    Institute of Scientific and Technical Information of China (English)

    闫东来(综述); 于泳浩(审校)

    2015-01-01

    阿片类药物被广泛地应用于手术患者围术期镇痛,但其不良反应明显,且大剂量阿片类药物可能引起急性耐受和痛觉过敏,最终导致更严重的疼痛反应。因此,各种非阿片类药物和新技术逐渐被研发和应用于临床,目的是改善患者疼痛和减少阿片类药物的使用,降低阿片相关的不良反应。该文就几种主要非阿片类镇痛药围术期镇痛的应用进展做一综述,以期对患者围术期疼痛进行精确管理,避免过度使用镇痛药物。%Opioids are a kind of classic perioperative analgesics with several dose-related side-effects. Furthermore,large doses of opioids may cause acute tolerance and hyperalgesia,resulting in more serious pain.Therefore various non-opioids and techniques have been explored as part of multimodal analgesia in order to improve pain management and reduce opioid consumption and opioid-related side-effects.Here is to make a review of recent progresses in the study on these non-opioid analgesics,and remind our readers of pre-cise management of perioperative pain and avoid overuse of analgesic drugs .

  10. 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 ...

  11. Molecular docking and structural analysis of non-opioid analgesic drug acemetacin with halogen substitution: A DFT approach

    Science.gov (United States)

    Leenaraj, D. R.; Manimaran, D.; Joe, I. Hubert

    2016-11-01

    Acemetacin is a non-opioid analgesic which belongs to the class, the non-steroidal anti-inflammatory drug. The bioactive conformer was identified through potential energy surface scan studies. Spectral features of acemetacin have been probed by the techniques of Fourier transform infrared, Raman and Nuclear magnetic resonance combined with density functional theory calculations at the B3LYP level with 6-311 + G(d,p) basis set. The detailed interpretation of vibrational spectral assignments has been carried out on the basis of potential energy distribution method. Geometrical parameters reveal that the carbonyl substitution in between chlorophenyl and indole ring leads to a significant loss of planarity. The red-shifted Cdbnd O stretching wavenumber describe the conjugation between N and O atoms. The shifted Csbnd H stretching wavenumbers of Osbnd CH3 and Osbnd CH2 groups depict the back-donation and induction effects. The substitution of halogen atoms on the title molecule influences the charge distribution and the geometrical parameters. Drug activity and binding affinity of halogen substitution in title molecule with target protein were undertaken by molecular docking study. This study enlightens the effects of bioefficiency due to the halogen substitution in the molecule.

  12. Non-analgesic effects of opioids: the cognitive effects of opioids in chronic pain of malignant and non-malignant origin. An update.

    Science.gov (United States)

    Højsted, Jette; Kurita, Geana Paula; Kendall, Sally; Lundorff, Lena; de Mattos Pimenta, Cibele Andrucioli; Sjøgren, Per

    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 patients only using controlled studies were updated. Fourteen controlled studies on the cognitive effects of opioids in chronic non-cancer pain patients and eleven controlled studies in cancer pain patients were included and analyzed. Opioid treatment involved slightly opposite outcomes in the two patient 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 quality of evidence opioid induced deficits in cognitive functioning were associated with dose increase and the use of supplemental doses of opioids in cancer patients. Future perspectives should comprise the conduction of high quality randomized controlled trials (RCTs) involving relevant control groups and validated neuropsychological assessments tools before and after opioid treatment in order to further explore the complex interaction between pain, opioids and cognition.

  13. [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

  14. Determination of opioid analgesics in hair samples using liquid chromatography/tandem mass spectrometry and application to patients under palliative care.

    Science.gov (United States)

    Musshoff, Frank; Lachenmeier, Katrin; Trafkowski, Jens; Madea, Burkhard; Nauck, Friedemann; Stamer, Ulrike

    2007-10-01

    Hair testing procedures allow a cumulative reflection of long-term drug abuse and are useful as a test for compliance in clinical toxicology. In the present study, liquid chromatography coupled with tandem mass spectrometry was used to determine analgesic opioid drugs in hair samples. The procedure used a simple methanolic extraction, and the evaporated extract was analyzed directly. A selective and sensitive procedure for the simultaneous determination of bisnortilidine, nortilidine, tilidine, buprenorphine, codeine, oxycodone, fentanyl, norfentanyl, hydromorphone, morphine, normorphine, oxymorphone, methadone, piritramide, and tramadol was developed and fully validated. The method fulfilled validation criteria and was shown to be sensitive, with limits of detection ranging from 0.008 to 0.017 ng/mg hair matrix, and precision ranging between 3.1% and 14.9 %. The applicability of the method was shown by analysis of authentic hair samples from patients receiving opioids for the treatment of cancer pain (eg, fentanyl was detected in concentrations up to 0.292 ng/mg, tramadol in concentrations up to 0.612 ng/mg of hair of 1 patient). Hair analysis was shown to be a complementary and useful tool in monitoring the drug-taking behavior of patients consuming opioid analgesics for the treatment of pain. In self-reports and medical records especially, the ingestion of tramadol and methadone was found to be dramatically underreported. In summary, hair analyses gave important additional information for the medical treatment of patients, the results often coming as a surprise to even the attending physicians.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Analgesic tolerance without demonstrable opioid-induced hyperalgesia: a double-blinded, randomized, placebo-controlled trial of sustained-release morphine for treatment of chronic nonradicular low-back pain.

    Science.gov (United States)

    Chu, Larry F; D'Arcy, Nicole; Brady, Caitlin; Zamora, Abigail Kathleen; Young, Chelsea Anne; Kim, Julie Eunwoo; Clemenson, Anna Marie; Angst, Martin S; Clark, J David

    2012-08-01

    Although often successful in acute settings, long-term use of opioid pain medications may be accompanied by waning levels of analgesic response not readily attributable to advancing underlying disease, necessitating dose escalation to attain pain relief. Analgesic tolerance, and more recently opioid-induced hyperalgesia, have been invoked to explain such declines in opioid effectiveness over time. Because both phenomena result in inadequate analgesia, they are difficult to distinguish in a clinical setting. Patients with otherwise uncomplicated low-back pain were titrated to comfort or dose-limiting side effects in a prospective, randomized, double-blind, placebo-controlled clinical trial using sustained-release morphine or weight-matched placebo capsules for 1 month. A total of 103 patients completed the study, with an average end titration dose of 78 mg morphine/d. After 1 month, the morphine-treated patients developed tolerance to the analgesic effects of remifentanil, but did not develop opioid-induced hyperalgesia. On average, these patients experienced a 42% reduction in analgesic potency. The morphine-treated patients experienced clinically relevant improvements in pain relief, as shown by a 44% reduction in average visual analogue scale pain levels and a 31% improvement in functional ability. The differences in visual analogue scale pain levels (P = .003) and self-reported disability (P = .03) between both treatment groups were statistically significant. After 1 month of oral morphine therapy, patients with chronic low-back pain developed tolerance but not opioid-induced hyperalgesia. Improvements in pain and functional ability were observed.

  2. 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...

  3. 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

  4. 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.

  5. [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

  6. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.

    Science.gov (United States)

    Caraceni, Augusto; Hanks, Geoffrey; Kaasa, Stein; Bennett, Michael I; Brunelli, Cinzia; Cherny, Nathan; Dale, Ola; De Conno, Franco; Fallon, Marie; Hanna, Magdi; Haugen, Dagny Faksvåg; Juhl, Gitte; King, Samuel; Klepstad, Pål; Laugsand, Eivor A; Maltoni, Marco; Mercadante, Sebastiano; Nabal, Maria; Pigni, Alessandra; Radbruch, Lukas; Reid, Colette; Sjogren, Per; Stone, Patrick C; Tassinari, Davide; Zeppetella, Giovambattista

    2012-02-01

    Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common 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-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system.

  7. 我院2005~2009年阿片类镇痛药应用分析%Analysis on the use of the Opioid Analgesics in our hospital from 2005 to 2009

    Institute of Scientific and Technical Information of China (English)

    杨青; 齐海燕; 张震; 宋军俊

    2011-01-01

    Objective: To know the use of Opioid Analgesics in our hospital, providing the references for clinical using. Methods: The data of opioid Analgesics were analyzed and compared in respect to the sorting of amount of money, defined daily dose system (DDDs), defined daily drug cost (DDDc) and other indicators in our hospital from 2005 to 2009. Results: In the last 5 years, the DDDs and amount of money of Morphine Tablets were continuously increasing year by year, while Morphine Injection and Fentanyl Injection remained relatively steady, Pethidine Injection was declining year by year. Conclusion: The use of Opioid Analgesics in our hospital are reasonable primitively. Morphine is become the main medication in oral Analgesic. We should need to introduce more preparations and dosage forms, for example Fentanyl Patch for meeting the clinical application.%目的:了解我院阿片类镇痛药的应用情况,为临床合理用药提供参考.方法:采用金额比例排序、用药频度(DDDs)、日限定费用(DDDc)等指标,对我院2005~2009年阿片类镇痛药进行统计、分析.结果:5年来我院吗啡缓释片的用药频度和金额呈逐年上升趋势,吗啡注射液和芬太尼注射液保持相对稳定,哌替啶则逐年下降.结论:我院阿片类镇痛药使用基本合理,口服吗啡已成为镇痛类用药主流,还应引进芬太尼贴剂等更多品种和剂型以满足临床用药需求.

  8. 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.

  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

    Directory of Open Access Journals (Sweden)

    Svetlana Vladislavovna Doubova

    2007-12-01

    Full Text Available 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 (FCB sobre ANOP. Se realizó análisis descriptivo y bivariado. RESULTADOS: Del total de participantes, 64.2% tuvo FCB; 28% desconocía la forma correcta de tomar ANOP y 48% sabía que ocasionan trastornos gastrointestinales. Factores asociados con la FCB: no recibir información sobre ANOP (RM= 2.22; IC95% 1.32-3.70, escolaridad OBJECTIVE: To describe patients’ knowledge of non-opioid analgesics (NOA and to identify factors associated with patients’ lack of basic knowledge (LBN on this type of medication. MATERIAL AND METHODS: A total of 629 ambulatory patients older than 50 years of age, with non-malignant pain syndrome, attended to two family medicine clinics and received seven day prescriptions for NOA. The data on patients’ general characteristics, the information they received and their actual knowledge of NOA were analyzed using descriptive statistics and bivariate analysis. RESULTS: A total of 64.2% had LBN; 28% did not know how to take NOA properly, and 48% knew that these drugs cause gastrointestinal adverse effects. The factors significantly associated with LBN on NOA included: failure to receive information on NOA (OR:2.22, 95%CI 1.32-3.70, education <7 years (OR:1.87, 95%CI 1.33-2.63 and pain duration <4 years (OR:1.70, 95%CI 1.22-2.37. CONCLUSION: Patients lack knowledge and receive little information on NOA. It is important to encourage actions to tackle this problem.

  10. 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.

  11. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

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

    2011-01-01

    studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... 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. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

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

    2011-01-01

    studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... 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....

  13. 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

  14. 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.

  15. Peripherally applied opioids for postoperative pain

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June...... 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...... postoperative analgesia. CONCLUSION: Evidence of a clinically relevant analgesic effect of peripherally applied opioids for acute postoperative pain is lacking. The analgesic effect of peripherally applied opioids may depend on the presence of preoperative inflammation....

  16. 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

  17. 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.

    Science.gov (United States)

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

    2012-11-01

    H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA) is a synthetic tetrapeptide with extraordinary selectivity for the mu-opioid receptor and is an extremely potent analgesic. [Dmt(1) ]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, [Dmt(1) ]DALDA inhibits norepinephrine re-uptake and is a mitochondria-targeted antioxidant. Such characteristics may make [Dmt(1)]DALDA particularly effective against neuropathic pain. The present study was designed to compare the effects of [Dmt(1)]DALDA and morphine on thermal hyperalgesia in an experimental neuropathic pain model. Neuropathic pain was induced in rats by surgical ligation of the L5 spinal nerve, and thermal pain thresholds were assessed by latencies of paw withdrawal to radiant heat. The increase in paw withdrawal latency was greater after the administration of [Dmt(1) ]DALDA than that of morphine in neuropathic rats at doses that were equianalgesic in naïve animals. We conclude that [Dmt(1)]DALDA is more effective than morphine against thermal hyperalgesia in this experimental model of neuropathic pain.

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...... better analgesic effects, and also fewer unwanted side effects. Although opioids have played a prominent role in postoperative analgesia for centuries and are still often administered as a matter of routine, their frequent minor side effects and the increasing availability of suitable alternatives may...... relief-what is the issue? Br J Anaesth 1994;72:375-8)] provide an opportunity for a reappraisal of opioid use in these settings. For this debate, controlled clinical studies on the opioid-sparing effect of different analgesic techniques are mentioned, and preferably studies with multiple dosing...

  3. 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

  4. 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.

  5. Opioid induced nausea and vomiting.

    Science.gov (United States)

    Smith, Howard S; Laufer, Andras

    2014-01-01

    Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the palliative care population. Unfortunately, among the adverse effects of opioids that may be experienced along with analgesia is nausea, vomiting, and/or retching. Although it is conceivable that in the future, using combination agents (opioids combined with agents which may nullify emetic effects), currently nausea/vomiting remains a significant issue for certain patients. However, there exists potential current strategies that may be useful in efforts to diminish the frequency and/or intensity of opioid-induced nausea/vomiting (OINV).

  6. 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 (...

  7. 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

  8. Attentional Bias For Prescription Opioid Cues Among Opioid Dependent Chronic Pain Patients

    OpenAIRE

    GARLAND, ERIC L.; Froeliger, Brett; Passik, Steven D.; Howard, Matthew O

    2012-01-01

    Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioidrelated cues. Opioid-dependent c...

  9. Intravenous analgesia with opioids versus femoral nerve block with 0.2% ropivacaine as preemptive analgesic for fracture femur: A randomized comparative study

    Science.gov (United States)

    Singh, Arvinder Pal; Kohli, Vaneet; Bajwa, Sukhminder Jit Singh

    2016-01-01

    Background and Objective: Femoral fractures are extremely painful and pain invariably worsens on any movement. Anesthesia for fracture femur surgery is usually provided by spinal block. This study was undertaken to compare the analgesic effects of femoral nerve block (FNB) using nerve stimulator with 0.2% ropivacaine (15 ml) and intravenous (I.V.) fentanyl before patient positioning for fracture femur surgery under spinal anesthesia. Materials and Methods: A prospective, randomized, double-blind, comparative study was conducted on 60 American Society of Anesthesiologists I and II patients (18–60 years) scheduled for femur surgery under combined spinal epidural anesthesia. Patients in Group I (n = 30), were administered FNB using nerve stimulator with 0.2% ropivacaine (15 ml) and in Group II patients (n = 30), I.V. fentanyl 0.5 μg/kg was given as preemptive analgesia. Parameters observed included time to spinal anesthesia, intra-operative and postoperative visual analog scale (VAS) for any pain and postoperative epidural top-ups dosages. Results: Demographic profile was comparable in both the groups. VAS at 2 min in Group I was 5.63 and in Group II it was 8.00. Satisfaction score was better in Group I as compared to Group II patients. Time to administer subarachnoid block was 17.80 min in patients of Group I as compared to 25.03 min in Group II patients. Postoperatively, VAS scores were lower in Group I than Group II patients. The frequency of epidural top-ups was higher in Group II than in Group I patients. Conclusions: FNB is comparatively better in comparison to I.V. fentanyl when used as preemptive and postoperative analgesic in patients being operated for fracture femur. PMID:27212771

  10. Clinical interpretation of opioid tolerance versus opioid-induced hyperalgesia.

    Science.gov (United States)

    Chen, Lucy; Sein, Michael; Vo, Trang; Amhmed, Shihab; Zhang, Yi; Hilaire, Kristin St; Houghton, Mary; Mao, Jianren

    2014-01-01

    Opioid analgesics are commonly used to manage moderate to severe pain. However, the long-term use of opioids could lead to opioid tolerance (OT) and opioid-induced hyperalgesia (OIH). Distinguishing OIH from OT would impact the practice of opioid therapy because opioid dose adjustment may differentially influence OT and OIH. Currently, there are no standard criteria of OT versus OIH causing considerable ambiguity in clinical interpretation and management of these conditions. The authors designed a practitioner-based survey consisting of 20 targeted questions. Answering these questions would require responders' actual clinical experiences with opioid therapy. The survey was conducted between 2011 and 2012 through direct mails or e-mails to 1,408 physicians who are currently practicing in the United States. The authors find that certain clinical characteristics (eg, increased pain despite opioid dose escalation) are often used by practitioners to make differential diagnosis of OT and OIH despite some overlap in their clinical presentation. A key difference in clinical outcome is that OT and OIH could be improved and exacerbated by opioid dose escalation, respectively. Our survey results revealed a significant knowledge gap in some responders regarding differential diagnosis and management of OT and OIH. The results also identified several issues, such as opioid dose adjustment and clinical comorbidities related to OT and OIH, which require future patient-based studies.

  11. 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.

  12. Opioid intoxication

    Science.gov (United States)

    Intoxication - opioids ... In the United States, the most commonly abused opioids are heroin and methadone. People who become addicted ... of these drugs. Also, the use of prescription opioids for nonmedical reasons is an extensive and growing ...

  13. The opioid ketobemidone has a NMDA blocking effect

    DEFF Research Database (Denmark)

    Andersen, S; Dickenson, A H; Kohn, M;

    1996-01-01

    There are clinical observations that neurogenic pain can respond well to the opioid ketobemidone, in contrast to pethidine and morphine. This has led us to the hypothesis that the analgesic effect of ketobemidone in neurogenic pain may be due to both opioid as well as additional non-opioid effects...... with a Ki value of 26 microM. Therefore, ketobemidone appears to possess both mu opioid agonist as well as NMDA blocking effects....

  14. 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 ...

  15. Opioid rotation with extended-release opioids: where should we begin?

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2011-12-01

    Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation

  16. 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.

  17. Chronic Opioid Therapy and Opioid Tolerance: A New Hypothesis

    Directory of Open Access Journals (Sweden)

    Joel S. Goldberg

    2013-01-01

    Full Text Available Opioids are efficacious and cost-effective analgesics, but tolerance limits their effectiveness. This paper does not present any new clinical or experimental data but demonstrates that there exist ascending sensory pathways that contain few opioid receptors. These pathways are located by brain PET scans and spinal cord autoradiography. These nonopioid ascending pathways include portions of the ventral spinal thalamic tract originating in Rexed layers VI–VIII, thalamocortical fibers that project to the primary somatosensory cortex (S1, and possibly a midline dorsal column visceral pathway. One hypothesis is that opioid tolerance and opioid-induced hyperalgesia may be caused by homeostatic upregulation during opioid exposure of nonopioid-dependent ascending pain pathways. Upregulation of sensory pathways is not a new concept and has been demonstrated in individuals impaired with deafness or blindness. A second hypothesis is that adjuvant nonopioid therapies may inhibit ascending nonopioid-dependent pathways and support the clinical observations that monotherapy with opioids usually fails. The uniqueness of opioid tolerance compared to tolerance associated with other central nervous system medications and lack of tolerance from excess hormone production is discussed. Experimental work that could prove or disprove the concepts as well as flaws in the concepts is discussed.

  18. Mu Opioid Splice Variant MOR-1K Contributes to the Development of Opioid-Induced Hyperalgesia.

    Directory of Open Access Journals (Sweden)

    Folabomi A Oladosu

    Full Text Available A subset of the population receiving opioids for the treatment of acute and chronic clinical pain develops a paradoxical increase in pain sensitivity known as opioid-induced hyperalgesia. Given that opioid analgesics are one of few treatments available against clinical pain, it is critical to determine the key molecular mechanisms that drive opioid-induced hyperalgesia in order to reduce its prevalence. Recent evidence implicates a splice variant of the mu opioid receptor known as MOR-1K in the emergence of opioid-induced hyperalgesia. Results from human genetic association and cell signaling studies demonstrate that MOR-1K contributes to decreased opioid analgesic responses and produces increased cellular activity via Gs signaling. Here, we conducted the first study to directly test the role of MOR-1K in opioid-induced hyperalgesia.In order to examine the role of MOR-1K in opioid-induced hyperalgesia, we first assessed pain responses to mechanical and thermal stimuli prior to, during, and following chronic morphine administration. Results show that genetically diverse mouse strains (C57BL/6J, 129S6, and CXB7/ByJ exhibited different morphine response profiles with corresponding changes in MOR-1K gene expression patterns. The 129S6 mice exhibited an analgesic response correlating to a measured decrease in MOR-1K gene expression levels, while CXB7/ByJ mice exhibited a hyperalgesic response correlating to a measured increase in MOR-1K gene expression levels. Furthermore, knockdown of MOR-1K in CXB7/ByJ mice via chronic intrathecal siRNA administration not only prevented the development of opioid-induced hyperalgesia, but also unmasked morphine analgesia.These findings suggest that MOR-1K is likely a necessary contributor to the development of opioid-induced hyperalgesia. With further research, MOR-1K could be exploited as a target for antagonists that reduce or prevent opioid-induced hyperalgesia.

  19. 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.

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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...

  5. 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...

  6. 从1例肺癌伴疼痛患者探讨克唑替尼与阿片类止痛药物的相互作用%Investigation of the interaction between crizotinib and opioid analgesics through a lung cancer patient with pain

    Institute of Scientific and Technical Information of China (English)

    王伟兰; 张超; 朱曼

    2014-01-01

    1例肺癌伴疼痛男性患者,因确诊“左肺腺癌多发骨转移1年余”入院,入院后同时服用克唑替尼与阿片类止痛药物。临床药师结合相关资料分析克唑替尼与不同止痛药物之间的相互作用、临床意义及防治措施。根据相关研究文献分析,芬太尼透皮贴在小剂量缓慢释放的止痛剂量下,受到克唑替尼影响产生显著临床意义的可能性小。该患者更换为芬太尼透皮贴后未出现呼吸抑制症状,且便秘反应明显减轻。提示临床药师遇到酶抑制剂与酶底物同时使用的医嘱时,不应一律否定,而应根据药物特性、剂量以及用药安全等方面权衡利弊。%One male lung cancer patient with pain was hospitalized for left lung adenocarcinoma with multiple bone metastases more than one year. Crizotinib and opioid analgesics were taken simultaneously by the patient after admission. Clinical pharmacists analyzed drug interactions, clinical significance and prevention measures between crizotinib and opioid analgesics according to relevant reference data. According to research literature, we inferred a small dose slow-release fentanyl transdermal patches which only play analgesic role produced small possibility of clinical signiifcance by the impact of crizotinib. The patient didn't appear respiratory depression symptoms and constipation significantly reduced when he was administrated with fentanyl transdermal patches again. The case suggested that clinical pharmacists should not always reject combination use of enzyme inhibitors and enzyme substrate, should weigh the advantages and disadvantages of these kinds of drug combination according to drug properties, dosage and safety.

  7. Opioids for cancer pain: the challenge of optimizing treatment.

    Science.gov (United States)

    Plante, Gérard E; VanItallie, Theodore B

    2010-10-01

    During 2007, 11.7 million US men and women of all ages suffered from some form of invasive cancer. During their illness, at least 70% (8.2 million) will experience pain sufficiently severe to require chronic opioid treatment. Cancer-induced pain is usually described under 3 headings: acute pain, chronic pain, and breakthrough pain. Among patients with chronic, persistent cancer pain controlled by around-the-clock analgesics, there is a high prevalence of breakthrough pain-often precipitated by some form of physical activity. Breakthrough pain seems best treated by a powerful, fast-acting opioid such as intravenous morphine or transmucosal fentanyl. At present, opioids are virtually the only analgesics capable of controlling moderate and severe cancer pain. In recent years, a veritable arsenal of opioids with a wide range of pharmacologic properties has become available for use in different pain situations. The World Health Organization has developed a 3-step "analgesic ladder" to guide management of cancer pain, based on the pain's severity, estimated by means of a 1 to 10 numeric rating scale. As the severity of the pain escalates, more potent (World Health Organization Step III) opioids are used. When faced with a difficult case of cancer pain, the physician must choose-from an array of options-the safest and most effective opioid analgesic and the most appropriate delivery system. Such decisions require an adequate understanding of the available opioids and experience with their use. The pharmacodynamic response to a given opioid depends on the nature of the receptor to which the opioid binds and its affinity for the receptor. Morphine activates the μ-opioid receptors, resulting in not only analgesia and sedation, but also euphoria, respiratory depression, constipation, and pruritus. The existence of a number of opioid receptor subtypes, each with its own repertoire of responses, has given rise to the hope (as yet unrealized) that an opioid can be found (or

  8. 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.

  9. [Opioid tolerance and dependence--pharmacological aspects].

    Science.gov (United States)

    Jaba, I M; Luncanu, I; Mungiu, O C

    2001-01-01

    Prolonged opioids administration leads inevitably to tolerance and dependence, a phenomenon we meet more often in healthy people than in ill patients. Tolerance means a hypersensibility of neuronal membranes as well as changes in the number and affinity of opioid receptors, which implies intake of larger doses to obtain the initial effect. Physical dependence, quite different of the psychological one, is the appearance of abstinence syndrome on sudden interruption of opioid administration or on administration of an antagonist. There is usually cross-tolerance in opioids, but it can also be incomplete, when the initial opioid can be replaced with another one that produces a milder abstinence syndrome. Classically, metadone is used in long time therapy, after detoxification with an antagonist is performed (naloxon, naltrexon). Modern pharmacological alternatives are levo-alpha-acetyl-methadol (LAAM) and agonists-antagonists (butorphanol, buprenorphine, pentazocine, nalbuphine). An antagonist can also be used if associated with an alpha--stimulant (clonidine), in order to remove noradrenergic manifestations of abstinence syndrome. Now other therapeutical principles are being studied: enkephalinaze inhibitors to reduce the abstinence syndrome, NMDA receptor antagonists, NO sintetasis inhibitors, that facilitates opioid analgesia and hinders tolerance development; colecystokinin-receptors agonists or antagonists to reduce tolerance on morphine. A recent study showed that the concomitant administration of an opioid agonist (sufentanil) and a calcium channels blocker (nimodipine) not only prevents from tolerance development but also triggers hypersensibility to analgesic effects of the opioid. PMID:12092171

  10. Opioid-Induced Hyperalgesia: A Diagnostic Dilemma.

    Science.gov (United States)

    Carullo, Veronica; Fitz-James, Ingrid; Delphin, Ellise

    2015-01-01

    Opioids are utilized frequently for the treatment of moderate to severe acute pain in the perioperative setting, as well as in the treatment of cancer-related pain. When prescribing chronic opioid therapy to patients with chronic pain, it is crucial for the practitioner to be aware not only of the issues of tolerance and withdrawal, but also to have knowledge of the possibility for opioid-induced hyperalgesia (OIH). An understanding of the differences between tolerance and OIH when escalating opioid therapy allows the titration of opioid as well as nonopioid analgesics in order to obtain maximum control of both chronic and acute pain. A case study is described to highlight the importance of judicious utilization of opioids in the treatment of cancer-related pain. In this case, high-dose opioid therapy did not improve chronic pain and contributed to a hyperalgesic state in which a young man experienced severe intractable pain postoperatively after two routine thoracotomies, despite aggressive pharmacologic measures to manage his perioperative pain. Furthermore, it illustrates the potential advantages of opioid rotation to methadone when OIH is suspected.

  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. Chronic pre-operative opioid use and acute pain after fast-track total knee arthroplasty

    DEFF Research Database (Denmark)

    Aasvang, E K; Lunn, T H; Hansen, T B;

    2016-01-01

    available for final analysis (93% follow-up rate). Post-operative pain during walk was significantly increased in both opioid-treated groups vs. non-opioid-treated patients (P ...BACKGROUND: Pre-operative opioid use has been suggested to increase post-operative pain and opioid consumption after total knee arthroplasty (TKA), but previous studies are either retrospective or inhomogeneous with regard to surgical procedures or control of analgesic regimes, or with few opioid...... had well-defined multimodal opioid-sparring perioperative analgesic therapy, and continued any pre-operative opioid medication. The primary outcome was differences between groups in pain at rest and during walk for the first 6 post-operative days. RESULTS: Among 123 patients included, 115 were...

  13. Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations.

    Science.gov (United States)

    Arout, Caroline A; Edens, Ellen; Petrakis, Ismene L; Sofuoglu, Mehmet

    2015-06-01

    Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.

  14. 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

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

    Science.gov (United States)

    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

  16. Suspected opioid-induced hyperalgesia in an infant.

    Science.gov (United States)

    Hallett, B R; Chalkiadis, G A

    2012-01-01

    One explanation for diminished opioid analgesic efficacy is opioid-induced hyperalgesia (OIH). We report a case of OIH in an infant with gastroschisis, requiring multiple surgical interventions and prolonged sedation for ventilation. This is the first report of OIH in an infant. On day 41 of life after nine separate surgical interventions, the patient's pain scores increased and remained elevated, despite increasing opioid administration. The patient also developed hyperalgesia, allodynia, and photophobia and became extremely irritable upon handling. Other possible causes were excluded, including interruption to opioid delivery, sepsis, acid-base and electrolyte disturbance, and ongoing surgical pathology. An opioid rotation to hydromorphone was initiated and ketamine was commenced. Sedation for ventilation was achieved with dexmedetomidine and midazolam infusions. Over a period of 24 h after opioid de-escalation, pain scores reduced rapidly and the patient became significantly less irritable with handling. All infusions were gradually weaned and eventually ceased.

  17. Preoperative low-dose ketamine has no preemptive analgesic effect in opioid-naïve patients undergoing colon surgery when nitrous oxide is used - a randomized study [v1; ref status: indexed, http://f1000r.es/4bp

    Directory of Open Access Journals (Sweden)

    Beatriz Nistal-Nuño

    2014-09-01

    Full Text Available Background: The analgesic properties of ketamine are associated with its non-competitive antagonism of the N-methyl-D-aspartate receptor; these receptors exhibit an excitatory function on pain transmission and this binding seems to inhibit or reverse the central sensitization of pain. In the literature, the value of this anesthetic for preemptive analgesia in the control of postoperative pain is uncertain. The objective of this study was to ascertain whether preoperative low-dose ketamine reduces postoperative pain and morphine consumption in adults undergoing colon surgery. Methods: In a double-blind, randomized trial, 48 patients were studied. Patients in the ketamine group received 0.5 mg/kg intravenous ketamine before surgical incision, while the control group received normal saline. The postoperative analgesia was achieved with a continuous infusion of morphine at 0.015 mg∙kgˉ¹∙hˉ¹ with the possibility of 0.02 mg/kg bolus every 10 min. Pain was assessed using the Visual Analog Scale (VAS, morphine consumption, and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively. We quantified times to rescue analgesic (Paracetamol, adverse effects and patient satisfaction. Results: No significant differences were observed in VAS scores between groups (P>0.05, except at 4 hours postoperatively (P=0.040. There were no differences in cumulative consumption of morphine at any time point (P>0.05. We found no significant differences in incremental postoperative doses of morphine consumption in bolus, except at 12 h (P =0.013 and 24 h (P =0.002. The time to first required rescue analgesia was 70 ± 15.491 min in the ketamine group and 44 ± 19.494 min in the control (P>0.05. There were no differences in hemodynamic parameters or patient satisfaction (P>0.05. Conclusions: Preoperative low-dose-ketamine did not show a preemptive analgesic effect or efficacy as an adjuvant for decreasing opioid requirements for postoperative pain

  18. 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

    In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no w......In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice......, and no 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...... reduced 24 h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h...

  19. 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 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.

  20. [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

  1. [Opioid receptors of the CNS: function, structure and distribution].

    Science.gov (United States)

    Slamberová, R

    2004-01-01

    Even though the alkaloids of opium, such as morphine and codeine, were isolated at the beginning of 19th century, the opioid receptors were not determined until 1970's. The discovery of endogenous opioid peptides, such as endorphins, enkephalins and dynorphins, has helped to differentiate between the specific opioid receptor subtypes, mu, delta and kappa, that are used up to now. Opioid receptors are distributed in the central nervous system unevenly. Each receptor subtype has its own specific and nonspecific agonists and antagonists. Opioides, as exogenous opioid receptor agonists, are drugs that are often used in medicine for their analgesic effects, but they are also some of the most heavily abused drugs in the world. Opioides may also induce long-term changes in the numbers and binding activities of opioid receptors. Some of our studies in fact demonstrate that prenatal morphine exposure can alter opioid receptors of adult rats. This may begin to provide insight into the sources of some of the morphological and behavioral changes in the progeny of mothers that received or abused opioides during pregnancy.

  2. 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

  3. 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...

  4. 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...

  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. 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

  7. The pharmacology of topical analgesics.

    Science.gov (United States)

    Barkin, Robert L

    2013-07-01

    Pain management of patients continues to pose challenges to clinicians. Given the multiple dimensions of pain--whether acute or chronic, mild, moderate, or severe, nociceptive or neuropathic--a multimodal approach may be needed. Fortunately, clinicians have an array of nonpharmacologic and pharmacologic treatment choices; however, each modality must be chosen carefully, because some often used oral agents are associated with safety and tolerability issues that restrict their use in certain patients. In particular, orally administered nonsteroidal antiinflammatory drugs, opioids, antidepressants, and anticonvulsants are known to cause systemic adverse effects in some patients. To address this problem, a number of topical therapies in various therapeutic classes have been developed to reduce systemic exposure and minimize the risks of patients developing adverse events. For example, topical nonsteroidal anti-inflammatory drug formulations produce a site-specific effect (ie, cyclo-oxygenase inhibition) while decreasing the systemic exposure that may lead to undesired effects in patients. Similarly, derivatives of acetylsalicylic acid (ie, salicylates) are used in topical analgesic formulations that do not significantly enter the patient's systemic circulation. Salicylates, along with capsaicin, menthol, and camphor, compose the counterirritant class of topical analgesics, which produce analgesia by activating and then desensitizing epidermal nociceptors. Additionally, patches and creams that contain the local anesthetic lidocaine, alone or co-formulated with other local anesthetics, are also used to manage patients with select acute and chronic pain states. Perhaps the most common topical analgesic modality is the cautious application of cutaneous cold and heat. Such treatments may decrease pain not by reaching the target tissue through systemic distribution, but by acting more directly on the affected tissue. Despite the tolerability benefits associated with avoiding

  8. [The clinical relevance of opioid-induced hyperalgesia remains unresolved].

    Science.gov (United States)

    Sørensen, Jakob; Sjøgren, Per

    2011-03-28

    Opioids are widely used as analgesics in chronic pain of malignant as well as non-malignant origin. During opioid treatment, pain is occasionally worsened. This could be due to progression of the disease or tolerance or opioid-induced hyperalgesia (OIH). The present article summarizes the preclinical and clinical data in support of the existence of OIH. Further, possible mechanisms and potential treatments are outlined. We conclude that only a few clinical studies on OIH are available. However, a growing body of experimental data supports the presence of OIH in clinical settings. Diagnostic tools for assessment of OIH have yet to be developed.

  9. 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...

  10. 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

  11. 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

  12. Association Between Prescription Opioid Use and Biomarkers of Kidney Disease in US Adults

    Directory of Open Access Journals (Sweden)

    Celestina Barbosa-Leiker

    2016-06-01

    Full Text Available Background/Aims: Prescription opioid use is increasing despite concerns about drug safety. We examined relationships between use of analgesics with biomarkers of chronic kidney disease (CKD in a representative sample of adults in the United States (US. Methods: Participants (n=3980 were from the National Health and Nutrition Examination Survey (NHANES 2009-2010. Use of any analgesic, prescription opioids, and NSAIDs were compared to referent groups with use of non-analgesic prescription medication or use of no prescription medication. CKD biomarkers including urine albumin-to-creatinine ratio (UACR and serum-creatinine-based estimated glomerular filtration rate (eGFR; CKD Epidemiology Collaboration: CKD-EPI equation were analyzed as continuous and binary variables (UACR ≥30 mg/g or eGFR 2; median splits. Results: Frequencies of use were: any prescription analgesic 12.7% (507/3980; prescription opioids 5.1% (204/3980; NSAIDs 5.6% (224/3980; non-analgesic medication 38.7% (1540/3980; no medication 48.6% (1933/3980. Prescription analgesic use (β=0.17, p=0.021 and opioid use (β=0.19, p=0.002 were associated with higher UACR values, while NSAID use was not (β=0.17, p=0.105. Prescription analgesic use was related to UACR ≥5.98 mg/g (median, (OR=1.34, 95%CI=1.01-7.79, p=0.045. No type of analgesic use was related to CKD-EPI eGFR. Conclusion: In a representative US population, prescription opioid use associated with higher albuminuria levels compared to non-opioid-users.

  13. 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.

  14. 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

  15. High-affinity naloxone binding to filamin a prevents mu opioid receptor-Gs coupling underlying opioid tolerance and dependence.

    Directory of Open Access Journals (Sweden)

    Hoau-Yan Wang

    Full Text Available Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs by the mu opioid receptor (MOR, although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [(3H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [(3H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A(2561-2565 as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A(2561-2565 abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor-Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence.

  16. 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

  17. The impact of opioid-induced hyperalgesia for postoperative pain.

    Science.gov (United States)

    Koppert, Wolfgang; Schmelz, Martin

    2007-03-01

    Clinical evidence suggests that--besides their well known analgesic activity - opioids can increase rather than decrease sensitivity to noxious stimuli. Based on the observation that opioids can activate pain inhibitory and pain facilitatory systems, this pain hypersensitivity has been attributed to a relative predominance of pronociceptive mechanisms. Acute receptor desensitization via uncoupling of the receptor from G-proteins, upregulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA)-receptor system, as well as descending facilitation, have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. Numerous reports exist demonstrating that opioid-induced hyperalgesia is observed both in animal and human experimental models. Brief exposures to micro-receptor agonists induce long-lasting hyperalgesic effects for days in rodents, and also in humans large-doses of intraoperative micro-receptor agonists were found to increase postoperative pain and morphine consumption. Furthermore, the prolonged use of opioids in patients is often associated with a requirement for increasing doses and the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs like NMDA-antagonists, alpha2-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor/selectivity.

  18. [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

  19. 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 ...

  20. Efficacy of opioid switching in asian 51-year-old-man with a phenomenon of pharmacokinetics tolerance: case report

    Directory of Open Access Journals (Sweden)

    Carmelo Costa

    2012-05-01

    Full Text Available Opioid switching is a therapeutic procedure used in pain management as a method to improve analgesic response and/or reduce adverse side effects. The rationale behind opioid substitution is the incomplete cross-tolerance between opioid. We report the case of an asian 51-year-old man with cancer pain unresponsive to oxycodone. In this case we hypothesize that the lack of response to oxycodone is linked to a phenomenon of pharmacokinetics tolerance.

  1. Clinical observation of analgesic effect of strong opioid drugs for moderate and severe cancer pain in patients with different gastrointestinal function%强阿片类药物对不同胃肠功能状态的晚期中-重度癌痛患者的镇痛效果观察

    Institute of Scientific and Technical Information of China (English)

    朱士合; 王晓丽; 李平; 孔令娟

    2015-01-01

    为主要维持用药。%Objective To investigate the analgesic effect of strong opioid drugs for moderate and severe cancer pain in patients with different gastrointestinal function. Methods One hundred and two advanced cancer patients with moderate and severe cancer pain were divided into digestive cancer group (n=46) and non-digestive cancer group (n=56), and then according to the different condition of gastrointestinal function, further divided into defecation interval less than 3 days group and more than 3 days group. All patients received analgesic treatment in our department. The proportion of severe pain , pain classification, morphine equivalent daily consumption , pain relief rate and total pain control efficiency were compared between the two groups. Results There was no significant difference in the total pain control efficiency between the digestive and non-digestive cancer groups (93.48% vs. 91.07%, P>0.05). The proportions of the patients with defecation interval more than 3 days (69.57% vs. 37.50%,P0.05). The total pain control efficiency was significantly higher(all P0.05). Conclusions Strong opioids or transdermal fentanyl patch can achieve better control effect for moderate and severe cancer pain. Defecation interval more than 3days is negatively associated with the analgesic effect. The terminal digestive cancer patients with defecation interval over 3 days were suitable for accepting fentanyl patch as main maintenance medication.

  2. Nonnarcotic analgesics and hypertension.

    Science.gov (United States)

    Gaziano, J Michael

    2006-05-01

    In 2004, individuals in the United States spent >$2.5 billion on over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) and filled >100 million NSAID prescriptions. The most commonly used OTC analgesics include aspirin, acetaminophen, and nonaspirin NSAIDs. Nonnarcotic analgesics are generally considered safe when used as directed but do have the potential to increase blood pressure in patients with hypertension treated with antihypertensives. This is important because hypertension alone has been correlated with an increased risk of cardiovascular disease or stroke. Small increases in blood pressure in patients with hypertension also have been shown to increase cardiovascular morbidity and mortality. Therefore, when nonnarcotic analgesics are taken by patients with hypertension, there may be important implications. This review explores the potential connection among analgesic agents, blood pressure, and hypertension, and discusses possible mechanisms by which analgesics might cause increases in blood pressure. This is followed by a summary of data on the relation between analgesics and blood pressure from both observational and randomized trials.

  3. 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

  4. 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.

  5. 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...

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

    DEFF Research Database (Denmark)

    Andersen, Lasse Østergaard; Kehlet, H

    2014-01-01

    were selected for inclusion in the review. In THA, no additional analgesic effect of LIA compared with placebo was reported in trials with low risk of bias when a multimodal analgesic regimen was administered perioperatively. Compared with intrathecal morphine and epidural analgesia, LIA was 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 analgesia...

  7. [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

  8. Dietary methyl content regulates opioid responses in mice

    Directory of Open Access Journals (Sweden)

    Liang DY

    2013-03-01

    Full Text Available De-Yong Liang,1,2 Yuan Sun,1,2 J David Clark1,2 1Department of Anesthesiology, Veterans Affairs Palo Alto Health Care System, Palo Alto, 2Stanford University School of Medicine, Stanford, CA, USA Background: Large interindividual differences in clinical responses to opioids and the variable susceptibility to abuse of this class of drugs make their use problematic. We lack a full understanding of the factors responsible for these differences. Dietary factors including methyl donor content have been noted to alter multiple physiological and behavioral characteristics of laboratory animals. The purpose of this research was to determine the effects of dietary methyl donor content on opioid responses in mice. Methods: Groups of male C57BL/6J mice were treated with high and low methyl donor diets either in the perinatal period or after weaning. Analgesic responses to morphine, as well as tolerance, opioid-induced hyperalgesia, and physical dependence were assessed. Results: Mice fed high and low methyl donor diets showed equal weight gain over the course of the experiments. Exposure to a high methyl donor diet in the perinatal period enhanced physical dependence. Dietary methyl donor content also altered analgesic responses to low doses of morphine when the dietary treatments were given to the mice after weaning. Opioid-induced hyperalgesia was unaltered by dietary methyl donor content. Conclusion: High and low methyl donor diet treatment has selective effects on opioid responses depending on the timing of exposure. These findings suggest that examination of DNA methylation patterns in specific brain regions linked to opioid analgesia and dependence may provide specific explanations for dietary effects on opioid responses. Keywords: opioid, methylation, tolerance, hyperalgesia, dependence

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

    Science.gov (United States)

    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 blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system (CNS) often accelerate the opioid’s adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects. PMID:24829664

  10. 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.

  11. Is mechanism and symptom-based analgesia an answer to opioid-induced hyperalgesia?

    Science.gov (United States)

    Gupta, Mayank; Gupta, Priyanka

    2015-01-01

    "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.

  12. 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

  13. 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

  14. 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

  15. Complications of long-term opioid therapy for management of chronic pain: the paradox of opioid-induced hyperalgesia.

    Science.gov (United States)

    Brush, D Eric

    2012-12-01

    While opioids remain a valid and effective analgesic strategy for patients suffering from a wide variety of painful conditions, they are not a panacea. Increasingly, physicians must balance patient expectations of adequate pain control with known limitations of opioid pharmaceuticals including adverse effects, tolerance, addiction, withdrawal, and drug diversion. Further complicating the issue over the last decade is a growing body of evidence suggesting chronic opioid use may unexpectedly worsen the perception of pain in some individuals. This syndrome, termed opioid-induced hyperalgesia (OIH), fundamentally changes our understanding of opioid pharmacodynamics and may influence our approach to management of chronic pain. This manuscript describes the concept OIH and provides an overview of basic science and clinical research to date attempting to characterize this syndrome, as well as ascertain its clinical relevance. The potential existence of OIH in humans is framed within the context of our current understanding of opioids and our prescribing patterns so that physicians may begin to incorporate these ideas into their philosophy of pain management as further information develops. Animal studies reliably validate OIH in controlled models. Rigorous research protocols in humans are lacking, and we cannot yet confidently conclude that OIH manifests in clinically significant ways. However, clinicians should consider the possibility of OIH when evaluating outcomes of patients on chronic opioid therapy.

  16. 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.

  17. Opioid abuse-deterrent strategies: role of clinicians in acute pain management.

    Science.gov (United States)

    Webster, Lynn R; Brennan, Michael J; Kwong, Louis M; Levandowski, Richard; Gudin, Jeffrey A

    2016-01-01

    Opioid abuse is a healthcare and societal problem that burdens individuals, their families and the healthcare professionals who care for them. Restricting access to opioid analgesics is one option to deter abuse, but this may prevent pain patients in need from obtaining effective analgesics. Therefore, strategies that mitigate the risk of opioid abuse while maintaining access are being pursued by several stakeholders including federal agencies, state governments, payors, researchers, the pharmaceutical industry and clinicians. Federal agency efforts have included required licensure and documentation for prescribing opioids, implementation of risk evaluation and mitigation strategies, and guidance on assessment and labeling of opioid abuse-deterrent formulations. In addition, state governments and payors have enacted monitoring programs, and pharmaceutical companies continue to develop abuse-deterrent opioid formulations. Strategies for clinicians to mitigate opioid abuse include comprehensive patient assessment and universal precautions (e.g. use of multimodal analgesia and abuse-deterrent opioid formulations, urine toxicology screening, participation in prescription drug monitoring and risk evaluation and mitigation strategy programs).

  18. 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

  19. 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.)

  20. 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...

  1. 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...

  2. 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....

  3. Analgesic Efficacy of Firocoxib, a Selective Inhibitor of Cyclooxygenase 2, in a Mouse Model of Incisional Pain

    OpenAIRE

    Reddyjarugu, Balagangadharreddy; Pavek, Todd; Southard, Teresa; Barry, Jason; Singh, Bhupinder

    2015-01-01

    Pain management in laboratory animals is generally accomplished by using opioids and NSAIDs. However, opioid use is hindered by controlled substance requirements and a relatively short duration of action. In this study, we compared the analgesic efficacy of firocoxib (a cyclooxygenase-2-selective NSAID) with that of buprenorphine in the mouse model of plantar incisional pain by objective measurement of mechanical allodynia and thermal hyperalgesia using von Frey and Hargreaves equipment, resp...

  4. 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.

  5. 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...

  6. 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...

  7. 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...

  8. Interaction of the mu-opioid receptor with GPR177 (Wntless inhibits Wnt secretion: potential implications for opioid dependence

    Directory of Open Access Journals (Sweden)

    Stagljar Igor

    2010-03-01

    Full Text Available Abstract Background Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR. Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs may help to elucidate the underlying mechanisms involved in the development of opioid dependence. Results GPR177, the mammalian ortholog of Drosophila Wntless/Evi/Sprinter, was identified as a MORIP in a modified split ubiquitin yeast two-hybrid screen. GPR177 is an evolutionarily conserved protein that plays a critical role in mediating Wnt protein secretion from Wnt producing cells. The MOR/GPR177 interaction was validated in pulldown, coimmunoprecipitation, and colocalization studies using mammalian tissue culture cells. The interaction was also observed in rodent brain, where MOR and GPR177 were coexpressed in close spatial proximity within striatal neurons. At the cellular level, morphine treatment caused a shift in the distribution of GPR177 from cytosol to the cell surface, leading to enhanced MOR/GPR177 complex formation at the cell periphery and the inhibition of Wnt protein secretion. Conclusions It is known that chronic morphine treatment decreases dendritic arborization and hippocampal neurogenesis, and Wnt proteins are essential for these processes. We therefore propose that the morphine-mediated MOR/GPR177 interaction may result in decreased Wnt secretion in the CNS, resulting in atrophy of dendritic arbors and decreased neurogenesis. Our results demonstrate a previously unrecognized role for GPR177 in regulating cellular response to opioid drugs.

  9. μ受体介导靶向毁损脑干下行易化神经元对骨癌痛大鼠的镇痛效应%Analgesic effects of the selective blocking of descending facilitation targeting μ, opioid receptor positive neurons in a rat model of bone cancer pain

    Institute of Scientific and Technical Information of China (English)

    曹菲; 梅伟; 田玉科; 陈莎莎; 刘希江; 肖兴鹏; 杨少兵; 许爱军; 高峰; 杨辉; 田学愎

    2009-01-01

    目的 探讨μ受体介导靶向毁损脑干下行易化神经元对骨癌痛大鼠的镇痛效应.方法 成年雌性Wistar大鼠48只,体重180~200 g,随机分为6组,对照组(n=3):不给予任何处理;骨癌痛组(n=9):于右下肢胫骨中部骨髓腔内注射Walker 256乳腺癌细胞10 μl制备骨癌痛模型;PBS组(n=9):乳腺细胞接种前28 d时延髓头端腹内侧(RVM)区单次微注射PBS;皮啡肽组(n=9):乳腺癌细胞接种前28 d时RVM区单次微注射皮啡肽;皂角素组(n=9):乳腺癌细胞接种前28 d时RVM区单次微注射皂角素;皮啡肽-皂角素耦联体组(n=9):乳腺癌细胞接种前28 d时RVM区单次微注射皮啡肽-皂角素耦联体.于乳腺癌细胞接种前1 d、乳腺癌细胞接种后3、5、7、9、11、14、16、18、20 d时测定机械痛阈.C组于乳腺癌细胞接种后20 d时,其余各组于乳腺癌细胞接种后7、14和20 d时,各处死3只大鼠,测定脊髓背角Fos蛋白表达水平.结果 与对照组比较,骨癌痛组、皮啡肽组和皂角素组接种侧机械痛阈乳腺癌细胞接种后7~20 d时降低,接种对侧机械痛阈乳腺癌细胞接种后9~20 d时降低,接种侧和接种对侧脊髓背角Fos蛋白表达上调,皮啡肽-皂角素组接种侧机械痛阈乳腺癌细胞接种后7~14 d时降低,接种对侧机械痛阈乳腺癌细胞接种后9~14 d时降低,皮啡肽组-皂角素组乳腺癌细胞接种后7 d时接种侧和接种对侧脊髓背角Fos蛋白表达上调(P0.05),皮啡肽-皂角素组接种侧机械痛阈乳腺癌细胞接种后11~20 d时升高,接种对侧机械痛阈乳腺癌细胞接种后4~20 d时升高,乳腺癌细胞接种后14、20 d时接种侧和接种对侧脊髓背角Fos蛋白表达下调(p<0.05).结论 μ受体介导靶向毁损脑干下行易化神经元可有效降低骨癌痛大鼠痛觉超敏的程度.%Objective To investigate analgesic effects of the selective blocking of descending facilitation targeting μ opioid receptor positive neurons in

  10. 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

  11. Structural and functional interactions between six-transmembrane μ-opioid receptors and β2-adrenoreceptors modulate opioid signaling

    Science.gov (United States)

    Samoshkin, Alexander; Convertino, Marino; Viet, Chi T.; Wieskopf, Jeffrey S.; Kambur, Oleg; Marcovitz, Jaclyn; Patel, Pinkal; Stone, Laura S.; Kalso, Eija; Mogil, Jeffrey S.; Schmidt, Brian L.; Maixner, William; Dokholyan, Nikolay V.; Diatchenko, Luda

    2015-01-01

    The primary molecular target for clinically used opioids is the μ-opioid receptor (MOR). Besides the major seven-transmembrane (7TM) receptors, the MOR gene codes for alternatively spliced six-transmembrane (6TM) isoforms, the biological and clinical significance of which remains unclear. Here, we show that the otherwise exclusively intracellular localized 6TM-MOR translocates to the plasma membrane upon coexpression with β2-adrenergic receptors (β2-ARs) through an interaction with the fifth and sixth helices of β2-AR. Coexpression of the two receptors in BE(2)-C neuroblastoma cells potentiates calcium responses to a 6TM-MOR ligand, and this calcium response is completely blocked by a selective β2-antagonist in BE(2)-C cells, and in trigeminal and dorsal root ganglia. Co-administration of 6TM-MOR and β2-AR ligands leads to substantial analgesic synergy and completely reverses opioid-induced hyperalgesia in rodent behavioral models. Together, our results provide evidence that the heterodimerization of 6TM-MOR with β2-AR underlies a molecular mechanism for 6TM cellular signaling, presenting a unique functional responses to opioids. This signaling pathway may contribute to the hyperalgesic effects of opioids that can be efficiently blocked by β2-AR antagonists, providing a new avenue for opioid therapy. PMID:26657998

  12. 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

  13. Remifentanil-acute opioid tolerance and opioid-induced hyperalgesia: a systematic review.

    Science.gov (United States)

    Kim, Sang Hun; Stoicea, Nicoleta; Soghomonyan, Suren; Bergese, Sergio D

    2015-01-01

    The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

  14. 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.

  15. 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.

  16. [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

  17. ANALYSIS OF PHARMACEUTICAL SUPPORRT OF ONCOLOGICAL PATIENTS WITH NARCOTIC ANALGESICS IN THE OUTPATIENT SETTING IN NIZHNI NOVGOROD

    Directory of Open Access Journals (Sweden)

    S. V. Kononova

    2015-01-01

    Full Text Available The article presents the analysis of pharmaceutical support of oncological patients with narcotic analgesics for reversal of chronic pain syndrome at the terminal stage, at the outpatient treatment in Nizhni Novgorod oblast for 2011-2013. Injection forms of morphine hydrochloride and promedol were the principal drugs which are applied by this patient group. We have noted the deficit of strong opioid analgesics in non-invasive forms. The support of incurable oncological patients with narcotic analgesics for the analyzed period averagely amounted to 6.33%. 

  18. Intercambiabilidad de opioides y moléculas bioequivalentes Opioid switching and bioequivalent molecules

    Directory of Open Access Journals (Sweden)

    M.D. Rodrigo

    2010-03-01

    Full Text Available Ante la alerta creada por dos situaciones que inciden, de manera significativa, en el entorno de la actividad clínica de los médicos que tratan el dolor, y que son: por un lado, la intercambiabilidad de moléculas bioequivalentes y, por el otro, las directrices emitidas por alguna consejería de salud en el fomento del uso de morfina frente a otros opioides como analgésico opioide de primera elección, el Grupo de Trabajo de Opioides de la Sociedad Española del Dolor -considerando que ambas pueden llevar a actuaciones en la práctica clínica que no se ajustan a la evidencia científica disponible- analiza estos dos hechos a partir del informe de experto del Dr. Cecilio Álamo, realizado en mayo de 2009, sobre la intercambiabilidad clínica de opioides potentes. Tras una revisión en profundidad de la bibliografía disponible a nivel nacional e internacional, así como de la posición de instituciones sanitarias europeas, entre otras, la Agencia Francesa del Medicamento y la Royal Pharmaceutical Society del Reino Unido, emite las conclusiones siguientes: 1. No creemos justificada la intercambiabilidad de opioides potentes entre sí, ya sean genéricos o de marca. 2. Ante las ventajas que aportan las nuevas moléculas con diferentes formulaciones (tanto por vía oral como por vía transdérmica, podemos afirmar que hay otras opciones terapéuticas frente al uso de morfina como analgésico opioide de primera elección.Due to the alert created due to two important incidents that took place involving the clinical activity of doctors who treat pain (one is the switching of bioequivalent molecules, and the other is the directives issued by a Health Department on encouraging the use of morphine instead of other opioids as first choice analgesic opioid, the Working Group of the Spanish Pain Society, considering that both can affect the activities in clinical practices that do not adapt to the available scientific evidence, analysed these two facts

  19. Electroacupuncture-Induced Dynamic Processes of Gene Expression Levels of Endogenous Opioid Peptide Precursors and Opioid Receptors in the CNS of Goats

    Directory of Open Access Journals (Sweden)

    Li-Li Cheng

    2013-01-01

    Full Text Available In order to investigate the dynamic processes of mRNA levels of proenkephalin, proopiomelanocortin, prodynorphin, and opioid receptors (δ-, μ-, and κ-receptor induced by electroacupuncture (EA in the central nerve system, goats were stimulated by EA of 60 Hz for 0.5 h at a set of Baihui, Santai, Ergen, and Sanyangluo points. The pain threshold was measured using the method of potassium iontophoresis. The mRNA levels of the three opioid peptide precursors and three opioid receptors were determined with quantitative real-time PCR and the levels of Met-enkephalin with SABC immunohistochemistry at 0.5 h before and at 0, 2, 4, 6, 8, 12, and 24 h after EA. The results showed that the pain threshold correlated (P<0.01 with Met-enkephalin immunoactivities in the measured nuclei and areas of goats. The analgesic aftereffect lasted for 12 h at least. The mRNA levels of the three opioid peptide precursors and three opioid receptors began to increase at 0 h, reached the peak during the time from 4 h to 6 h or at 12 h, and remained higher at 24 h after EA was discontinued. These results suggested that the initiation of gene expression of opioid peptides and the three receptors may be associated with EA-induced analgesic aftereffect.

  20. 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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    /or pharmacodynamics (eg opioid receptor and catechol-O-methyltransferase enzymes). We present recent experimentally induced pain, postoperative pain, and cancer pain and chronic non-malignant pain conditions studies in humans, focusing on the association between genetic variation and analgesic response assessed...

  2. 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 ...

  3. Opioid Use and Storage Patterns by Patients after Hospital Discharge following Surgery.

    Directory of Open Access Journals (Sweden)

    Karsten Bartels

    Full Text Available Opioid-based analgesic therapy represents a cornerstone of pain management after surgery. The recent rise in opioid sales and opioid overdoses suggests it is important to maximize the safety of opioid prescribing after surgery. Given that patients may live with other family members in the home, safe storage and appropriate disposal of excess opioids after hospital discharge are necessary to prevent unintended secondary exposures. Identifying characteristics of patients who are likely to be prescribed excess opioids after surgery may enable more targeted prescription practices and safety interventions. Our study aimed to elucidate patient-reported opioid use patterns and modes of home storage of opioids among patients discharged home after Cesarean section (C-section and thoracic surgery. Specifically, we sought to identify characteristics of patients who reported using about half or more versus less of the opioids prescribed to them for use after hospital discharge.For this cohort study, we developed a survey on quality of analgesia following hospital discharge, amounts of opioids taken relative to the amount prescribed, reasons for not taking all prescribed medications, and storage and disposal methods for leftover opioids. Adult patients, who had C-section or thoracic surgery at a tertiary academic medical center, were given a web-based self-administered survey after discharge. Descriptive statistics (means and standard deviations, proportions were used to describe the study sample and survey results. Comparisons between patients who reported taking about half or more versus less of the opioids prescribed to them for use after hospital discharge were made using unpaired t-tests, Mann-Whitney tests, and Chi-square tests as appropriate.The majority (53% of respondents after C-section (N = 30 reported taking either no or very few (less than 5 prescribed opioid pills; 83% reported taking half or less; and 17% of women, reported taking all or

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. Prescription pattern of analgesics in orthopedics outpatient department at a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    R. Bhaskar

    2015-04-01

    Conclusions: The results of the present study show frequent use of selective COX-2 inhibitors, although non-selective NSAIDs topped the list of various selective NSAIDs, non-selective NSAIDs, and opioid analgesics. This suggests that gastrointestinal safety was an important concern while prescribing these drugs. Many FDCs were found to be irrational. [Int J Basic Clin Pharmacol 2015; 4(2.000: 250-253

  10. 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...

  11. 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...

  12. Combinations of opioid agonist and opioid antagonist%阿片受体激动剂和拮抗剂的联用

    Institute of Scientific and Technical Information of China (English)

    石靖; 许真玉

    2013-01-01

    The opioid agonists employed primarily as moderate to strong analgesics have many pharmacological effects including vomiting,respiratory depression,constipation,and also have high possibility of addiction and dependence.Combinations of opioid agonists and opioid antagonists have been developed in recent years,and many clinical trials showed that such kind of drug combinations could moderate the side effects of opioid agonists and decrease the risk of drug abuse.Successful development of these combinations gives new options for the clinical application of opioid analgesics.%阿片受体激动剂是临床常用的镇痛药,通常用于中重度疼痛的治疗,但是此类药物常伴有明显的不良反应,如恶心、呕吐、便秘和呼吸抑制等,同时存在较高的成瘾性和依赖性,大大影响了药物的临床应用.近年来,阿片受体拮抗剂与阿片受体激动剂组成的复方药物陆续上市,临床试验显示此类复方制剂可以减轻不良反应,降低药物滥用的风险,为阿片类镇痛的临床应用提供了新的思路和选择.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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

  15. Liposome bupivacaine for improvement in economic outcomes and opioid burden in GI surgery: IMPROVE Study pooled analysis

    Directory of Open Access Journals (Sweden)

    Cohen SM

    2014-06-01

    Full Text Available Stephen M Cohen,1 Jon D Vogel,2 Jorge E Marcet,3 Keith A Candiotti4 1Atlanta Colon and Rectal Surgery, PA, Atlanta, GA, USA; 2General Surgery Clinic, University of Colorado, Aurora, CO, USA; 3Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; 4Department of Anesthesiology, University of Miami Leonard Miller School of Medicine, Miami, FL, USA Abstract: Postsurgical pain management remains a significant challenge. Liposome bupivacaine, as part of a multimodal analgesic regimen, has been shown to significantly reduce postsurgical opioid consumption, hospital length of stay (LOS, and hospitalization costs in gastrointestinal (GI surgery, compared with intravenous (IV opioid-based patient-controlled analgesia (PCA. Pooled results from open-label studies comparing a liposome bupivacaine-based multimodal analgesic regimen with IV opioid PCA were analyzed. Patients (n=191 who underwent planned surgery and received study drug (IV opioid PCA, n=105; multimodal analgesia, n=86 were included. Liposome bupivacaine-based multimodal analgesia compared with IV opioid PCA significantly reduced mean (standard deviation [SD] postsurgical opioid consumption (38 [55] mg versus [vs] 96 [85] mg; P<0.0001, postsurgical LOS (median 2.9 vs 4.3 days; P<0.0001, and mean hospitalization costs (US$8,271 vs US$10,726; P=0.0109. The multimodal analgesia group reported significantly fewer patients with opioid-related adverse events (AEs than the IV opioid PCA group (P=0.0027; there were no significant between-group differences in patient satisfaction scores at 30 days. A liposome bupivacaine-based multimodal analgesic regimen was associated with significantly less opioid consumption, opioid-related AEs, and better health economic outcomes compared with an IV opioid PCA-based regimen in patients undergoing GI surgery. Study registration: This pooled analysis is based on data from Phase IV clinical trials registered on the US National

  16. Opioid-induced hyperalgesia in chronic pain patients and the mitigating effects of gabapentin.

    Science.gov (United States)

    Stoicea, Nicoleta; Russell, Daric; Weidner, Greg; Durda, Michael; Joseph, Nicholas C; Yu, Jeffrey; Bergese, Sergio D

    2015-01-01

    Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH), wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. Gabapentin, a gamma-aminobutyric acid (GABA) analog anticonvulsant used to treat neuropathic pain, has been shown in animal models to reduce fentanyl hyperalgesia without compromising analgesic effect. Chronic pain patients have also exhibited lower opioid consumption and improved pain response when given gabapentin. However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.

  17. Opioid-Induced Hyperalgesia in Chronic Pain Patients and the Mitigating Effects of Gabapentin

    Directory of Open Access Journals (Sweden)

    Nicoleta eStoicea

    2015-05-01

    Full Text Available Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH, wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. Gabapentin, a gamma-aminobutyric acid (GABA analogue anticonvulsant used to treat neuropathic pain, has been shown in animal models to reduce fentanyl hyperalgesia without compromising analgesic effect. Chronic pain patients have also exhibited lower opioid consumption and improved pain response when given gabapentin. However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.

  18. 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

  19. 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.

  20. Overlapping mechanisms of stress-induced relapse to opioid use disorder and chronic pain: Clinical implications

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    Udi E Ghitza

    2016-05-01

    Full Text Available Over the past two decades, a steeply growing number of persons with chronic non-cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics which have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently-available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions which may be pursued to fill these gaps. Such research directions, if conducted through well-designed randomized controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions.

  1. 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

  2. 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.

  3. 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, p<0.05), current misuse (β=0.253, p<0.01), and symptoms of current opioid use disorder (OUD; β=0.206, p<0.05). Sensation 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

  4. The stigma of low opioid prescription in the hospitalized multimorbid elderly in Italy.

    Science.gov (United States)

    Marengoni, Alessandra; Nobili, Alessandro; Corli, Oscar; Djade, Codjo Djignefa; Bertoni, Diana; Tettamanti, Mauro; Pasina, Luca; Corrao, Salvatore; Salerno, Francesco; Marcucci, Maura; Mannucci, Pier Mannuccio

    2015-04-01

    The primary aim of this study was to evaluate the prevalence of opioid prescriptions in hospitalized geriatric patients. Other aims were to evaluate factors associated with opioid prescription, and whether or not there was consistency between the presence of pain and prescription. Opioid prescriptions were gathered from the REgistro POliterapie Societa` Italiana di Medicina Interna (REPOSI) data for the years 2008, 2010 and 2012. 1,380 in-patients, 65+ years old, were enrolled in the first registry run, 1,332 in the second and 1,340 in the third. The prevalence of opioid prescription was calculated at hospital admission and discharge. In the third run of the registry, the degree of pain was assessed by means of a numerical scale. The prevalence of patients prescribed with opioids at admission was 3.8% in the first run, 3.6% in the second and 4.1% in the third, whereas at discharge rates were slightly higher (5.8, 5.3, and 6.6%). The most frequently prescribed agents were mild opioids such as codeine and tramadol. The number of total prescribed drugs was positively associated with opioid prescription in the three runs; in the third, dementia and a better functional status were inversely associated with opioid prescription. Finally, as many as 58% of patients with significant pain at discharge were prescribed no analgesic at all. The conservative attitude of Italian physicians to prescribe opioids in elderly patients changed very little between hospital admission and discharge through a period of 5 years. Reasons for such a low opioid prescription should be sought in physicians' and patients' concerns and prejudices.

  5. Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain.

    Science.gov (United States)

    Doehring, Alexandra; Oertel, Bruno Georg; Sittl, Reinhard; Lötsch, Jörn

    2013-01-01

    Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics. A major epigenetic mechanism is methylation or demethylation at CpG-rich DNA islands. DNA methylation triggered by drugs has largely unexplored therapeutic consequences. Here we report increased methylation at a CpG rich island in the OPRM1 gene coding for μ-opioid receptors and at a global methylation site (LINE-1) in leukocytes of methadone-substituted former opiate addicts compared with matched healthy controls. Higher DNA methylation associated with chronic opioid exposure was reproduced in an independent cohort of opioid-treated as compared to non-opioid-treated pain patients. This suggests that opioids may stimulate DNA methylation. The OPRM1 methylation had no immediate effect on μ-opioid receptor transcription and was not associated with opioid dosing requirements. However, the global DNA methylation at LINE-1 was significantly correlated with increased chronic pain. This suggests inhibitory effects on the transcription of still unspecified nocifensive gene products. It further implies that opioids may be causally associated with increased genome-wide DNA methylation, although currently there is no direct evidence of this. This has phenotypic consequences for pain and may provide a new, epigenetics-associated mechanism of opioid-induced hyperalgesia. The results indicate a potential influence of opioid analgesics on the patients' epigenome. They emphasize the need for reliable and cost-effective screening tools and may imply that high-throughput screening for lead compounds in artificial expression systems may not provide the best tools for identifying new pain medications.

  6. 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.

  7. 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.

  8. 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.

  9. Impact of Intraoperative Acetaminophen Administration on Postoperative Opioid Consumption in Patients Undergoing Hip or Knee Replacement

    Science.gov (United States)

    Vaughan, Cathy; McGee, Ann

    2014-01-01

    Abstract Background: Opioid utilization for acute pain has been associated with numerous adverse events, potentially resulting in longer inpatient stays and increased costs. Objective: To examine the effect of intravenous (IV) acetaminophen administered intraoperatively on postoperative opioid consumption in adult subjects who underwent hip or knee replacement. Methods: This retrospective cohort study evaluated postoperative opioid consumption in 176 randomly selected adult subjects who underwent hip or knee replacement at Duke University Hospital (DUH). Eighty-eight subjects received a single, intraoperative, 1 g dose of IV acetaminophen. The other subjects did not receive any IV acetaminophen. This study evaluated mean opioid consumption (in oral morphine equivalents) during the 24-hour postoperative period in the 2 groups. Other endpoints included length of stay in the postanesthesia care unit (PACU), incidence of oversedation, need for acute opioid reversal, and adjunctive analgesic utilization. Results: Subjects who were given a single dose of intraoperative acetaminophen received an average of 149.3 mg of oral morphine equivalents during the 24 hours following surgery compared to 147.2 mg in participants who were not exposed to IV acetaminophen (P = .904). The difference in average length of PACU stay between the IV acetaminophen group (163 minutes) and those subjects not exposed to IV acetaminophen (169 minutes) was not statistically significant (P = .588). No subjects in the study experienced oversedation or required acute opioid reversal. Conclusion: There was not a statistically significant difference in postoperative opioid consumption between patients receiving and not receiving IV acetaminophen intraoperatively. PMID:25673891

  10. 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

  11. 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.

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

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    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.

  13. 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

  14. Effects of ginsenosides on opioid-induced hyperalgesia in mice.

    Science.gov (United States)

    Li, Peng; Tang, Minke; Li, Hui; Huang, Xinjie; Chen, Lei; Zhai, Haifeng

    2014-07-01

    Opioid-induced hyperalgesia (OIH) is characterized by nociceptive sensitization caused by the cessation of chronic opioid use. OIH can limit the clinical use of opioid analgesics and complicate withdrawal from opioid addiction. In this study, we investigated the effects of Re, Rg1, and Rb1 ginsenosides, the bioactive components of ginseng, on OIH. OIH was achieved in mice after subcutaneous administration of morphine for 7 consecutive days three times per day. During withdrawal (days 8 and 9), these mice were administered Re, Rg1, or Rb1 intragastrically two times per day. On the test day (day 10), mice were subjected to the thermal sensitivity test and the acetic acid-induced writhing test. Re (300 mg/kg) inhibited OIH in both the thermal sensitivity test and the acetic acid-induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid-induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH.

  15. 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 ...

  16. 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...

  17. The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine

    DEFF Research Database (Denmark)

    Kristensen, K; Christensen, C B; Christrup, Lona Louring

    1995-01-01

    The binding affinities of racemic methadone and its optical isomers R-methadone and S-methadone were evaluated for the opioid receptors mu1, mu2, delta and kappa, in comparison with that of morphine. The analgesic R-methadone had a 10-fold higher affinity for mu1 receptors than S-methadone (IC50 3...... receptors. This result suggests that S-methadone does not essentially contribute to opioid effect of racemic methadone. R-methadone has a receptor binding profile which resembles that of morphine....

  18. 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

  19. 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.

  20. 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...

  1. 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...

  2. 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? ...

  3. Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis

    Science.gov (United States)

    Arumugam, Sudha; Lau, Christine SM; Chamberlain, Ronald S

    2016-01-01

    Objectives Effective postoperative pain management is crucial in the care of surgical patients. Opioids, which are commonly used in managing postoperative pain, have a potential for tolerance and addiction, along with sedating side effects. Gabapentin’s use as a multimodal analgesic regimen to treat neuropathic pain has been documented as having favorable side effects. This meta-analysis examined the use of preoperative gabapentin and its impact on postoperative opioid consumption. Materials and methods A comprehensive literature search was conducted to identify randomized control trials that evaluated preoperative gabapentin on postoperative opioid consumption. The outcomes of interest were cumulative opioid consumption following the surgery and the incidence of vomiting, somnolence, and nausea. Results A total of 1,793 patients involved in 17 randomized control trials formed the final analysis for this study. Postoperative opioid consumption was reduced when using gabapentin within the initial 24 hours following surgery (standard mean difference −1.35, 95% confidence interval [CI]: −1.96 to −0.73; Pfentanyl, and tramadol consumption (P<0.05). While a significant increase in postoperative somnolence incidence was observed (relative risk 1.30, 95% CI: 1.10–1.54, P<0.05), there were no significant effects on postoperative vomiting and nausea. Conclusion The administration of preoperative gabapentin reduced the consumption of opioids during the initial 24 hours following surgery. The reduction in postoperative opioids with preoperative gabapentin increased postoperative somnolence, but no significant differences were observed in nausea and vomiting incidences. The results from this study demonstrate that gabapentin is more beneficial in mastectomy and spinal, abdominal, and thyroid surgeries. Gabapentin is an effective analgesic adjunct, and clinicians should consider its use in multimodal treatment plans among patients undergoing elective surgery. PMID

  4. 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

  5. [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

  6. 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...

  7. 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

  8. 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.

  9. 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 ...

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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 ...

  15. Cancer-Related Pain Management and the Optimal Use of Opioids.

    Science.gov (United States)

    Reis-Pina, Paulo; Lawlor, Peter G; Barbosa, António

    2015-01-01

    Pain relief is vital to the treatment of cancer. Despite the widespread use and recognition of clinical recommendations for the management of cancer-related pain, avoidable suffering is still prevalent in patients with malignant disease. A gap exists between what is known about pain medical management and actual practices of patients, caregivers, healthcare professionals and institutions. Opioids are the pillar of the medical management of moderate to severe pain. The prescription of opioid analgesics - by a registered medical practitioner for absolute pain control - is a legitimate practice. In this article we look at patients' fears and physicians' general hesitations towards morphine and alike. We examine misconceptions that yield fallacies on the therapeutically use of opioids and, therefore, sustain inadequate pain management.

  16. 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

    function/attention/mental flexibility were evaluated by continuous reaction time (CRT), verbal fluency test (VFT) and trail making test-B (TMT-B), respectively. In the 1st experiment, the cognitive effects of experimental tonic pain of mild and moderate intensities produced by a computer......RATIONALE: Studies have demonstrated that both pain and opioids have actions on the central nervous system that may interfere with cognitive function, but their effects have mainly been analysed separately and not as an integrated process. OBJECTIVE: The objective of this study is to test two...... 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...

  17. Potentiation of Opioid-Induced Analgesia by L-Type Calcium Channel Blockers: Need for Clinical Trial in Cancer Pain

    Directory of Open Access Journals (Sweden)

    S Basu Ray

    2008-01-01

    Full Text Available Previous reports indicate that the analgesic effect of opioids is due to both closure of specific voltage-gated calcium channels (N- and P/Q-types and opening of G protein-coupled inwardly rectifying potassium channels (GIRKs in neurons concerned with transmission of pain. However, administration of opioids leads to unacceptable levels of side effects, particularly at high doses. Thus, current research is directed towards simultaneously targeting other voltage-gated calcium channels (VGCCs like the L-type VGCCs or even other cell signaling mechanisms, which would aug-ment opioid-mediated analgesic effect without a concurrent increase in the side effects. Unfortunately, the results of these studies are often conflicting considering the different experimental paradigms (variable drug selection and their doses and also the specific pain test used for studying analgesia adopted by researchers. The present review focuses on some of the interesting findings regarding the analgesic effect of Opioids + L-VGCC blockers and suggests that time has come for a clinical trial of this combination of drugs in the treatment of cancer pain.

  18. Dual action mechanisms of KK-3, a newly synthesized leu-enkephalin derivative, in the production of spinal analgesic effects.

    Science.gov (United States)

    Takahashi, M; Senda, T; Kaneto, H

    1990-04-01

    The action mechanism for the production of spinal analgesia of KK-3, tyrosyl-N-methyl-gamma-aminobutylyl-phenylalaninol, was examined by the tail pinch and tail flick methods. Intrathecal KK-3, 2.5, 5 and 10 nmol/mouse, dose-dependently produced an analgesic effect in both methods. In the tail pinch method, the analgesia was suppressed by 2 mg/kg but not by 1 mg/kg of naloxone; however, the analgesic effect was significantly antagonized by 1 and 2 mg/kg Mr2266, a kappa-antagonist. Meanwhile, both naloxone and Mr2266 failed to block the analgesic effect of KK-3 in the tail flick test. Intrathecal capsaicin, 0.3, 3 and 15 nmol/mouse, also produced a dose-dependent analgesic effect in the tail flick test, whereas no appreciable analgesia could be found in the tail pinch test. Neither naloxone nor Mr2266 blocked the analgesic effect of capsaicin. The results indicate that KK-3 may possess two separate pharmacological mechanisms for the production of analgesic effects on the spinal level: one is the depletion of substance P following its release from the spinal cord, and the other is the mediation through kappa-opioid receptors. PMID:2342228

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. A biphasic opioid function modulator: agmatine%双向阿片功能调节剂:胍丁胺

    Institute of Scientific and Technical Information of China (English)

    苏瑞斌; 李锦; 秦伯益

    2003-01-01

    近年研究表明某些药物尽管不能与阿片受体发生相互作用,但能对阿片药理作用产生重要的调节.特别是有些药物能对阿片功能产生双向调节作用,即增强阿片镇痛,对抗阿片耐受和躯体依赖.我们将这些不与阿片受体发生作用,但具有双向调节阿片功能的药物称之为双向阿片功能调节剂(biphasic opioid function modulator,BOFM).基于我们的研究工作,可以认定胍丁胺就是一个典型的双向阿片功能调节剂.胍丁胺本身有弱的镇痛作用,它能增强吗啡镇痛,对抗吗啡耐受和依赖;胍丁胺产生上述作用的主要机制与抑制阿片长期作用下在阿片受体信号转导系统产生的代偿性适应过程相关.%Recently it has been revealed that some agents that are not able to interact with opioid receptors play animportant role in regulating the pharmacological actions of opioids. Especially, some of them show biphasicmodulation on opioid functions, which enhance opioid analgesia, but inhibit tolerance to and substance dependenceon opioids. We would like to call these agents which do not interact with opioid receptors, but do have biphasicmodulation on opioid functions as biphasic opioid function modulator (BOFM). Mainly based on our results,agmatine is a typical BOFM. Agmatine itself was a weak analgesic which enhanced analgesic action of morphineand inhibited tolerance to and dependence on opioid. The main mechanisms of agmatine were related to inhibitionof the adaptation of opioid receptor signal transduction induced by chronic treatment of opioid.

  5. The impact of the opioids fentanyl and morphine on nociception and bone destruction in a murine model of bone cancer pain.

    NARCIS (Netherlands)

    ElMouedden, M.; Meert, T.F.

    2007-01-01

    Chronic pain resulting from metastasis into skeleton of certain neoplastic diseases remains poorly understood and relatively resistant to analgesic treatment. Opioids are the principal axis in drug therapy for this type of pain, especially at the end stage of cancer. Our aim was to examine whether,

  6. 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

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

    DEFF Research Database (Denmark)

    Byager, N; Hansen, Mads; Mathiesen, Ole;

    2014-01-01

    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......-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....... The analgesic effect was evaluated in a qualitative analysis by assessment of significant difference between groups (P

  8. 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...

  9. Fentanyl tolerance in the treatment of cancer pain: a case of successful opioid switching from fentanyl to oxycodone at a reduced equivalent dose.

    Science.gov (United States)

    Sutou, Ichiro; Nakatani, Toshihiko; Hashimoto, Tatsuya; Saito, Yoji

    2015-06-01

    Opioids are not generally deemed to have an analgesic ceiling effect on cancer pain. However, there have been occasional reports of tolerance to opioid development induced by multiple doses of fentanyl. The authors report a case of suspected tolerance to the analgesic effect of opioid, in which an increasing dose of fentanyl failed to relieve the patient's cancer pain symptoms, but opioid switching to oxycodone injections enabled a dose reduction to below the equivalent dose conversion ratio. The patient was a 60-year-old man diagnosed with pancreatic body carcinoma with multiple metastases. The base dose consisted of 12 mg/day of transdermal fentanyl patches (equivalent to 3.6 mg/day, 150 μg/h fentanyl injection), and rescue therapy consisted of 10 mg immediate-release oxycodone powders. Despite the total daily dose of fentanyl reaching 5.6 mg (equivalent to 560 mg oral morphine), the analgesic effect was inadequate; thus, an urgent adjustment was necessary. Due to the moderate dose of fentanyl, the switch to oxycodone injection was done incrementally at a daily dose equivalent to 25% of the fentanyl injection. The total dose of oxycodone was replaced approximately 53.5% of the dose of fentanyl prior to opioid switching.

  10. Liquid chromatography-electrospray linear ion trap mass spectrometry analysis of targeted neuropeptides in Tac1(-/-) mouse spinal cords reveals significant lower concentration of opioid peptides.

    Science.gov (United States)

    Saidi, Mouna; Beaudry, Francis

    2015-08-01

    Tachykinin and opioid peptides play a central role in pain transmission, modulation and inhibition. The treatment of pain is very important in medicine and many studies using NK1 receptor antagonists failed to show significant analgesic effects in humans. Recent investigations suggest that both pronociceptive tachykinins and the analgesic opioid systems are important for normal pain sensation. The analysis of opioid peptides in Tac1(-/-) spinal cord tissues offers a great opportunity to verify the influence of the tachykinin system on specific opioid peptides. The objectives of this study were to develop an HPLC-MS/MRM assay to quantify targeted peptides in spinal cord tissues. Secondly, we wanted to verify if the Tac1(-/-) mouse endogenous opioid system is hampered and therefore affects significantly the pain modulatory pathways. Targeted neuropeptides were analyzed by high performance liquid chromatography linear ion trap mass spectrometry. Our results reveal that EM-2, Leu-Enk and Dyn A were down-regulated in Tac1(-/-) spinal cord tissues. Interestingly, Dyn A was almost 3 fold down-regulated (p<0.0001). No significant concentration differences were observed in mouse Tac1(-/-) spinal cords for Met-Enk and CGRP. The analysis of Tac1(-/-) mouse spinal cords revealed noteworthy decreases of EM-2, Leu-Enk and Dyn A concentrations which strongly suggest a significant impact on the endogenous pain-relieving mechanisms. These observations may have insightful impact on future analgesic drug developments and therapeutic strategies.

  11. 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.

  12. 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

  13. 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.

  14. Analgesic Activity of Sphaeranthus indicus Linn

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    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.

  15. The damage done by the war on opioids: the pendulum has swung too far

    Directory of Open Access Journals (Sweden)

    Atkinson TJ

    2014-05-01

    Full Text Available Timothy J Atkinson,1 Michael E Schatman,2 Jeffrey Fudin1,3–51PGY2 Pain and Palliative Care Pharmacy Residency, Stratton VA Medical Center, Albany, NY, 2Foundation for Ethics in Pain Care, Bellevue, WA, 3School of Pharmacy, University of Connecticut, Storrs, CT, 4Western New England University College of Pharmacy, Springfield, MA, 5Buffalo College of Pharmacy, State University of New York, Buffalo, NY, USAIn the United States, patterns of opioid use for the management of pain have drastically changed over the past 30 years. In the 1980s, the American pain medicine landscape was characterized by opiophobia, the fear to prescribe opioids. Around the turn of the millennium, however, we witnessed a fairly rapid shift to opiophilia, or the "overprescribing" of opioids. The ubiquitous undertreatment of pain was the catalyst for clinicians and pain societies to successfully lobby for increased use of opioids for all pain types, including non-cancer pain. The approval of new standards for pain management incorporating pain as the "fifth vital sign" by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO1 seemingly fueled this increase in opioid prescription. From 1991–2009, prescriptions for opioid analgesics tripled, with emergency department visits related to non-medical use of prescription opioid overdoses doubling from 2005–2009.2 In 2010, accidental overdose deaths associated with opioids increased for the eleventh consecutive year, highlighting the drastic shift in opioid use.3 The figurative pendulum began to swing toward opiophobia following the publication of data that demonstrated that the risk of addiction associated with chronic opioid use was likely underestimated.4 Guidelines for the use of controlled substances released by the Federation of State Medical Boards of the US in 1998 reflected this change in attitude.5 At present, there is a general consensus that opioids are over-prescribed and education among health

  16. Role of opioid system in verapamil-induced antinociception in a rat model of orofacial pain

    Directory of Open Access Journals (Sweden)

    Esmaeal Tamaddonfard

    2014-04-01

    Full Text Available Calcium, through its various channels involves in local, spinal and supra-spinal transmission of pain. In the present study, we investigated the separate and combined treatment effects of verapamil (a calcium channel blocker, morphine (an opioid agonist and naloxone (an opioid antagonist on pain in the orofacial region of rats. Orofacial pain was induced by subcutaneous (SC injection of formalin (50 µL, 1.5% into the left upper lip side, and the time durations spent face rubbing with epsilateral forepaw were recorded in three min blocks for a period of 45 min. Formalin induced a biphasic pattern (first phase: 0-3 min; second phase: 15-33 min of pain. Intraperitoneal (IP injections of verapamil (2 and 8 mg kg-1 and morphine (2 and 4 mg kg-1 suppressed orofacial pain. Co-administration of sub-analgesic doses of verapamil (0.5 mg kg-1 and morphine (1 mg kg-1 produced second phase analgesia. Both phases of formalin-induced pain were suppressed when an analgesic dose (2 mg kg-1 of verapamil co-administered with a sub-analgesic dose (1 mg kg-1 of morphine. The SC injection of naloxone (2 mg kg-1 alone with no effect on pain intensity, prevented the antinociceptive effects induced by morphine (2 mg kg-1, but not verapamil (2 mg kg-1. The obtained results showed antinociceptive effects for verapamli and morphine on orofacial pain. Co-administrations of verapamil and morphine produced antinociceptive effects. It seems that opioid analgesic system may not have a role in the verapamil-induced antinociception.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Opioids and their peripheral receptors

    Directory of Open Access Journals (Sweden)

    Francesco Amato

    2012-12-01

    Full Text Available The inflammation of peripheral tissues leads the primary afferent neurons, in particular at the cell bodies level located in the DRG (dorsal root ganglia, to an increased synthesis of opioid receptors: determining an “up-regulation”. After that opioid receptors are transported at the level of the nociceptive terminals, they are incorporated into the neuronal membrane becoming functional receptors. The above receptor proteins bind to opioid produced by immune cells or the exogenous ones. This leads to a direct or indirect suppression of the Ca2+ currents induced by TRPV1 or the currents of the Na+, resulting in neuronal reduced excitability and in transmitted signals decrease. The observation that the immune system is able to modulate the pain by ligands that interact with the opioid receptors located on sensory neurons, may have broad implications for the development of innovative and safer pain drugs.

  2. 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.

  3. 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 litera...... analgesic treatment in LRYGB surgery....

  4. 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 ...

  5. 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

  6. 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

  7. The Global Opioid Policy Initiative (GOPI) project to evaluate the availability and accessibility of opioids for the management of cancer pain in Africa, Asia, Latin America and the Caribbean, and the Middle East: introduction and methodology.

    Science.gov (United States)

    Cherny, N I; Cleary, J; Scholten, W; Radbruch, L; Torode, J

    2013-12-01

    Opioid analgesics are critical to the effective relief of cancer pain. Effective treatment is predicated on sound assessments, individually tailored analgesic therapy, and the availability and accessibility of the required medications. In some countries, pain relief is hampered by the lack of availability or barriers to the accessibility of opioid analgesics. As the follow-up to a successful project to evaluate the availability and accessibility of opioids and regulatory barriers in Europe, the European Society for Medical Oncology (ESMO) and the European Association for Palliative Care (EAPC) undertook to expand their research to those parts of the world where data were lacking regarding these aspects of care, in particular Africa, Asia, the Middle East, Latin America and the Caribbean, and the states of India. This project has been undertaken in collaboration with the Union for International Cancer Control (UICC), the Pain and Policy Studies Group (PPSG) of the University of Wisconsin, and the World Health Organization (WHO), together with a consortium of 17 international oncology and palliative care societies. This article describes the study methodology.

  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. 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 ...

  10. 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

  11. 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;...

  12. 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.

  13. Effect of pre-operative rectal diclofenac suppository on post-operative analgesic requirement in cleft palate repair: A randomised clinical trial

    Directory of Open Access Journals (Sweden)

    E S Adarsh

    2012-01-01

    Full Text Available Background: Opioid analgesics used for analgesia are associated with sedation, respiratory depression and post-operative nausea and vomiting. Non-steroidal anti-inflammatory drugs such as diclofenac are a safe and effective alternative with opioid-sparing effect. Objective: To evaluate the effectiveness of pre-operative rectal diclofenac suppository (1 mg/kg in cleft palate repair for post-operative analgesia and reduction in post-operative opioid requirements. Study Design: A randomized clinical trial. Methods: After obtaining approval from the institutional ethical committee, 60 children were allocated by a computer-generated randomisation into two groups of 30 each; group D (Diclofenac group and group C (Conventional group. Children in group D and group C were similar in all aspects except for the fact that group D children received 1 mg/kg diclofenac suppository after induction. Pain was evaluated using modification of the objective pain scale by Hannallah and colleagues for 6 h post-operatively by an anaesthesiology resident or nursing staff who was blinded to the group. If the pain score was more than 3, rescue analgesic I.V. fentanyl 0.5 μgm/kg was administered. The pain scores at different intervals, number of doses and quantity of rescue analgesic required were noted. Results: We observed that pre-operative rectal diclofenac provided effective analgesia in the immediate post-operative period, as evidenced by reduced pain scores and reduced opioid requirement (P=0.00002. There was no evidence of any increased perioperative bleeding in the diclofenac group. Conclusion: Pre-operative rectal diclofenac reduces opioid consumption and provides good post-operative analgesia.

  14. 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

  15. Pain Raises Risk of Opioid Addiction

    Science.gov (United States)

    ... prescription opioid painkillers, a new study suggests. "In light of the national opioid abuse epidemic, these new results underscore the importance of developing effective ... approaches to managing common painful medical conditions," said senior ...

  16. 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.

  17. Analgesic-antiinflammatory drugs inhibit orbicularis oculi reflexes in humans via a central mode of action.

    Science.gov (United States)

    Ferracuti, S; Leardi, M G; Cruccu, G; Fabbri, A; Itil, T M

    1994-01-01

    1. A cross-over single blind study examined the possible central effects of non-opioid analgesic drugs on the trigeminal reflexes. 2. The corneal reflex and blink reflex (R1, R2) were recorded electromyographically and response areas measured in healthy volunteers before and after intramuscular injection of piroxicam (40 mg); and after intravenous injection of lysine acetylsalicylate (500 mg). After the last drug recording the subjects received intravenous naloxone (2 mg) followed 5 minutes later by further reflex testing. Saline was used as a placebo in control experiments. 3. Both analgesics reduced the corneal reflex: piroxicam induced a 27% and lysine acetylsalicylate a 21% a reduction that naloxone did not reverse. Neither drug reduced the early or the late component of the blink reflex. 4. The marked inhibitory changes that the two non-narcotic analgesics produced on the corneal reflex--a nociceptive response--indicate a centrally-mediated action. 5. Naloxone's failure to reverse the induced analgesia argues against opiate receptor mediation. PMID:8115666

  18. 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.

  19. Analgesic-antiinflammatory drugs inhibit orbicularis oculi reflexes in humans via a central mode of action.

    Science.gov (United States)

    Ferracuti, S; Leardi, M G; Cruccu, G; Fabbri, A; Itil, T M

    1994-01-01

    1. A cross-over single blind study examined the possible central effects of non-opioid analgesic drugs on the trigeminal reflexes. 2. The corneal reflex and blink reflex (R1, R2) were recorded electromyographically and response areas measured in healthy volunteers before and after intramuscular injection of piroxicam (40 mg); and after intravenous injection of lysine acetylsalicylate (500 mg). After the last drug recording the subjects received intravenous naloxone (2 mg) followed 5 minutes later by further reflex testing. Saline was used as a placebo in control experiments. 3. Both analgesics reduced the corneal reflex: piroxicam induced a 27% and lysine acetylsalicylate a 21% a reduction that naloxone did not reverse. Neither drug reduced the early or the late component of the blink reflex. 4. The marked inhibitory changes that the two non-narcotic analgesics produced on the corneal reflex--a nociceptive response--indicate a centrally-mediated action. 5. Naloxone's failure to reverse the induced analgesia argues against opiate receptor mediation.

  20. 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

  1. Effects of Adjuvant Analgesics on Cerebral Ischemia-Induced Mechanical Allodynia.

    Science.gov (United States)

    Matsuura, Wataru; Harada, Shinichi; Tokuyama, Shogo

    2016-01-01

    Central post-stroke pain (CPSP), a potential sequela of stroke, is classified as neuropathic pain. Although we recently established a CPSP-like model in mice, the effects of adjuvant analgesics as therapeutic drugs for neuropathic pain in this model are unknown. Hence, the aim of the present study was to assess the usefulness of our model by evaluating the effects of adjuvant analgesics used for treating neuropathic pain in this mouse model of CPSP. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. The mechanical allodynia was significantly increased on day 3 after BCAO compared with that during the pre-BCAO assessment. BCAO-induced mechanical allodynia was significantly decreased by intraperitoneal injections of imipramine (a tricyclic antidepressant), mexiletine (an antiarrhythmic), gabapentin (an antiepileptic), or a subcutaneous injection of morphine (an opioid receptor agonist) compared with that following vehicle treatment in BCAO-mice. By contrast, milnacipran (a serotonin and norepinephrine reuptake inhibitor), paroxetine (selective serotonin reuptake inhibitor), carbamazepine (antiepileptic), and indomethacin (nonsteroidal anti-inflammatory drug) did not affect the BCAO-induced mechanical allodynia. Our results show that BCAO in mice may be useful as an animal model of CPSP. In addition, BCAO-induced mechanical allodynia may be suppressed by some adjuvant analgesics used to treat neuropathic pain. PMID:27150152

  2. 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...

  3. Opioid Tolerance and Physical Dependence: Role of Spinal Neuropeptides, Excitatory Amino Acids and Their Messengers

    Directory of Open Access Journals (Sweden)

    Khem Jhamandas

    2000-01-01

    Full Text Available Chronic opioid treatment results in the development of tolerance and physical dependence. The mechanisms underlying opioid tolerance and/or physical dependence are unclear. Recent studies suggest that opioid receptor or nociceptive, neural network-based adaptations contribute to this phenomenon. At the spinal level, the genesis of tolerance and physical dependence is associated with increased excitatory amino acid activity expressed through N-methyl-D-aspartate receptors in the dorsal horn. However, recent evidence also implicates spinal neuropeptide transmitters such as calcitonin gene-related peptide (CGRP and  substance P in the development of opioid tolerance. Long term spinal morphine treatment increases CGRP-like immunostaining in the dorsal horn, and coadministration of morphine with CGRP8-37, a competitive CGRP1 receptor antagonist, prevents this response as well as loss of the analgesic potency. CGRP8-37, like N-methyl-D-aspartate receptor antagonists, has the potential to restore morphine potency in experimental animals who are already tolerant to the opioid agonist. Recent evidence suggests that the effects of excitatory amino acid and neuropeptide receptor activity may be expressed through the generation of messengers such as nitric oxide and prostanoids. Agents that inhibit the synthesis of nitric oxide and prostanoids have the potential to inhibit and reverse spinal opioid tolerance, suggesting that this phenomenon may be expressed through the activity of these mediators. Nociceptive transmission in the dorsal horn of the spinal cord also involves activity of a number of other mediators including morphine modulatory neuropeptides, neuropeptide FF  and neuropeptide SF. The role of these mediators and their relationship with other factors implicated in tolerance remain to be determined.

  4. Effects of ketoprofen, morphine, and kappa opioids on pain-related depression of nesting in mice.

    Science.gov (United States)

    Negus, S Stevens; Neddenriep, Bradley; Altarifi, Ahmad A; Carroll, F Ivy; Leitl, Michael D; Miller, Laurence L

    2015-06-01

    Pain-related functional impairment and behavioral depression are diagnostic indicators of pain and targets for its treatment. Nesting is an innate behavior in mice that may be sensitive to pain manipulations and responsive to analgesics. The goal of this study was to develop and validate a procedure for evaluation of pain-related depression of nesting in mice. Male ICR mice were individually housed and tested in their home cages. On test days, a 5- × 5-cm Nestlet was subdivided into 6 pieces, the pieces were evenly distributed on the cage floor, and Nestlet consolidation was quantified during 100-minute sessions. Baseline nesting was stable within and between subjects, and nesting was depressed by 2 commonly used inflammatory pain stimuli (intraperitoneal injection of dilute acid; intraplantar injection of complete Freund adjuvant). Pain-related depression of nesting was alleviated by drugs from 2 classes of clinically effective analgesics (the nonsteroidal anti-inflammatory drug ketoprofen and the μ-opioid receptor agonist morphine) but not by a drug from a class that has failed to yield effective analgesics (the centrally acting kappa opioid agonist U69,593). Neither ketoprofen nor morphine alleviated depression of nesting by U69,593, which suggests that ketoprofen and morphine effects were selective for pain-related depression of nesting. In contrast to ketoprofen and morphine, the kappa opioid receptor antagonist JDTic blocked depression of nesting by U69,593 but not by acid or complete Freund adjuvant. These results support utility of this procedure to assess expression and treatment of pain-related depression in mice.

  5. Exploring the relationship between analgesic event rate and pain intensity in kidney stone surgery: A Repeated Time to Event Pilot Study

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Pedersen, Katja Venborg; Christrup, Lona Louring;

    been reported as an indirect measure of pain in postoperative pain trials. The rate of consecutive analgesic events can be described by repeated time-to-event (RTTE) modelling in order to analyse the dynamical changes and concentration-effect-relationships with analgesic consumption. However......III-60 Rasmus Juul Exploring the relationship between analgesic event rate and pain intensity in kidney stone surgery: A Repeated Time to Event Pilot Study RV Juul(1), KV Pedersen(2, 4), LL Christrup(1), AE Olesen(1, 3), AM Drewes(3), PJS Osther(4), TM Lund(1) 1) Department of Drug Design...... and Pharmacology, University of Copenhagen, Denmark. 2) Department of Clinical Genetics, Vejle Hospital, Denmark. 3) Mech-Sense, Aalborg University Hospital, Denmark, 4) Urological Research Center, Lillebaelt Hospital, University of Southern Denmark, Fredericia, Denmark Objectives: Opioid consumption has often...

  6. Anger regulation style, anger arousal and acute pain sensitivity: evidence for an endogenous opioid "triggering" model.

    Science.gov (United States)

    Burns, John W; Bruehl, Stephen; Chont, Melissa

    2014-08-01

    Findings suggest that greater tendency to express anger is associated with greater sensitivity to acute pain via endogenous opioid system dysfunction, but past studies have not addressed the role of anger arousal. We used a 2 × 2 factorial design with Drug Condition (placebo or opioid blockade with naltrexone) crossed with Task Order (anger-induction/pain-induction or pain-induction/anger-induction), and with continuous Anger-out Subscale scores. Drug × Task Order × Anger-out Subscale interactions were tested for pain intensity during a 4-min ischemic pain task performed by 146 healthy people. A significant Drug × Task Order × Anger-out Subscale interaction was dissected to reveal different patterns of pain intensity changes during the pain task for high anger-out participants who underwent pain-induction prior to anger-induction compared to those high in anger-out in the opposite order. Namely, when angered prior to pain, high anger-out participants appeared to exhibit low pain intensity under placebo that was not shown by high anger-out participants who received naltrexone. Results hint that people with a pronounced tendency to express anger may suffer from inadequate opioid function under simple pain-induction, but may experience analgesic benefit to some extent from the opioid triggering properties of strong anger arousal.

  7. PET imaging reveals sex differences in kappa opioid receptor availability in humans, in vivo.

    Science.gov (United States)

    Vijay, Aishwarya; Wang, Shuo; Worhunsky, Patrick; Zheng, Ming-Qiang; Nabulsi, Nabeel; Ropchan, Jim; Krishnan-Sarin, Suchitra; Huang, Yiyun; Morris, Evan D

    2016-01-01

    Opioid receptors may play critical roles in alcoholism and other addictions, addiction withdrawal, and depression and are considered pharmacological targets for treatment of these conditions. Sex differences have been demonstrated in mu (MOR) and delta (DOR) opioid receptors in humans, in vivo. In addition, sex differences have been observed in efficacy of treatment targeting kappa opioid receptors (KOR). Our goal in the present study was to compare the availability of KOR (1) between healthy control (HC) men and women. Twenty-seven subjects-18 males (M) and 9 females (F)-underwent PET scans with [(11)C] LY2795050, a selective kappa antagonist tracer. Partial volume correction was applied to all PET data. Volume of distribution (V T) of the tracer was estimated regionally as well as at the voxel level. V T values of males versus females were compared for 19 defined ROIs. Results at the regional and voxel levels were consistent. Males had significantly higher V T and thus a higher KOR availability than women in multiple brain regions. To our knowledge, this is the first report of sex differences in the KOR system in humans, in vivo. These findings could have implications for the treatment of pain with kappa opioid analgesics. The results may also have an impact on the diagnosis and treatment of addictive and other disorders. PMID:27648372

  8. 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 ...

  9. The Fentanyl Patch Boil-Up - A Novel Method of Opioid Abuse.

    Science.gov (United States)

    Schauer, Cameron K M W; Shand, James A D; Reynolds, Thomas M

    2015-11-01

    Fentanyl is a potent opioid analgesic used in the treatment of pain. Transdermal fentanyl patches are now widely utilized as an acceptable and efficacious method of medication delivery. Unfortunately, the potential for their abuse is well recognized. Previous case reports have documented deaths after intravenous (IV) misuse of fentanyl which had been extracted from Duragesic (liquid reservoir type) patches. We present a case of IV fentanyl abuse after the extraction from a Mylan (matrix type) patch. This method of abuse has not previously been described in the literature.

  10. 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...

  11. Place avoidance learning and stress-induced analgesia in the attacked mouse: role of endogenous opioids.

    Science.gov (United States)

    Siegfried, B; Frischknecht, H R

    1989-07-01

    In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradigm) were investigated in attacked, DBA/2 and C57BL/6, mice. During training, exposure of test animals to 10 or 30 bites by an aggressive, isolated ICR mouse situated in the dark half of a bright/dark conditioning box induced a significantly higher social conflict analgesia in DBA than in C57 mice. Naltrexone (0.5 and 2.0 mg/kg) reduced this response in DBA mice that received 30, but not 10, bites and was ineffective in C57 mice. This points to different, opioid versus naltrexone-insensitive nonopioid, analgesic mechanisms. During place choice testing in the same box 24 h later, DBA mice that had received 30, but not 10, bites showed a significant, naltrexone-reversible, avoidance of the attack place. No place avoidance learning was observed in C57 mice. The data provided unequivocal evidence that place avoidance learning was a result of associative conditioning, in that neither pairing nor social conflict per se significantly changed the preference for the dark side seen in experimentally naive DBA mice. Antagonism of place avoidance conditioning was observed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation for the naltrexone-induced impairment. Individual correlational analysis in saline-injected, attacked DBA mice revealed a negative relationship between the analgesic state immediately after training and the avoidance of attack place during testing. In summary, the results suggest strain-dependent analgesic and learning mechanisms and indicate that endogenous opioids released in attacked DBA mice support pain inhibition and modulate the memorization of attack place by their analgesic effects, as well as by mechanisms independent of pain inhibitory systems.

  12. 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.

  13. 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

  14. 3-(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides: potent, non-peptidic agonists of both the micro and delta opioid receptors.

    Science.gov (United States)

    Bishop, Michael J; Garrido, Dulce M; Boswell, G Evan; Collins, Mark A; Harris, Philip A; McNutt, Robert W; O'Neill, Scott J; Wei, Ke; Chang, Kwen-Jen

    2003-02-13

    Opioid analgesics with both micro and delta opioid receptor activation represent a new approach to the treatment of severe pain with an improved safety profile. Compounds with this profile may exhibit strong analgesic properties due to micro agonism, with a reduced side effect profile resulting from delta agonism. Replacing the p-diethylamide of the known potent delta opioid receptor selective agonist BW373U86 with a m-diethylamide resulted in a compound with agonist activity at both the micro and delta opioid receptors. Modifying the amide to an N-methyl-N-phenylamide increased agonist potency at both receptors. A series of 3-(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides have been made to explore the structure-activity relationship (SAR) around the N-methyl-N-phenylamide. Several potent agonists of both the micro and delta opioid receptors have been identified, including (+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-(4-fluorophenyl)-N-methylbenzamide (23), which has EC50 values of 0.67 and 1.1 nM at the micro (guinea pig ileum assay) and delta (mouse vas deferens assay) opioid receptors, respectively.

  15. A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics

    Directory of Open Access Journals (Sweden)

    T.R. Lavich

    2005-03-01

    Full Text Available It is widely accepted that the classical constant-temperature hot-plate test is insensitive to cyclooxygenase inhibitors. In the current study, we developed a variant of the hot-plate test procedure (modified hot-plate (MHP test to measure inflammatory nociception in freely moving rats and mice. Following left and right hind paw stimulation with a phlogogen and vehicle, respectively, the animals were placed individually on a hot-plate surface at 51ºC and the withdrawal latency for each paw was determined simultaneously in measurements performed at 15, 60, 180, and 360 min post-challenge. Plantar stimulation of rats (250 and 500 µg/paw and mice (125-500 µg/paw with carrageenan led to a rapid hyperalgesic response of the ipsilateral paw that reached a plateau from 15 to 360 min after challenge. Pretreatment with indomethacin (4 mg/kg, ip inhibited the phenomenon at all the times analyzed. Similarly, plantar stimulation of rats and mice with prostaglandin E2 (0.5 and 1 µg/paw also resulted in rapid hyperalgesia which was first detected 15 min post-challenge. Finally, we observed that the MHP test was more sensitive than the classical Hargreaves' test, being able to detect about 4- and 10-fold lower doses of prostaglandin E2 and carrageenan, respectively. In conclusion, the MHP test is a simple and sensitive method for detecting peripheral hyperalgesia and analgesia in rats and mice. This test represents a low-cost alternative for the study of inflammatory pain in freely moving animals.

  16. 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

  17. 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 ...

  18. 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.

  19. 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

  20. Opioid/naloxone prolonged release combinations for opioid induced constipation

    Institute of Scientific and Technical Information of China (English)

    Shailendra Kapoor

    2012-01-01

    I read with great interest the recent article by Chen et a/in a recent issue of your esteemed journal.The article is highly thought provoking.One emerging therapeutic alternative for opioid induced constipation is the emergence of opioid/naloxone prolonged release combinations.For instance,naloxone when administered in a 1∶2 ratio with oxycodone reverses the inhibitory effect of oxycodone on the gastrointestinal tract.The advantage of oxycodone/naloxone prolonged release (OXN) is that while its anti-nociceptive efficacy is equivalent to that of oxycodone prolonged release (OXC),it significantly decreases the "Bowel Function Index" thereby ameliorating symptoms of opioid induced constipation to a large extent.Schutter et al in a recent study have reported a decrease in the bowel function index from 38.2 to 15.1.Similarly,L(o)wenstein et al in another recent study have reported that following a month of therapy,complete spontaneous bowel movements per week is increased from one in OXC therapy to three in OXN therapy.

  1. 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

  2. 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.

  3. Dimethyltyrosine, the Viagra of Opioids

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Introduction The introduction of 2',6'-dimethyl-L-tyrosine (Dmt) [1] at the N-terminus of Tyr-Tic ( 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid )-containing δ-opioid antagonists[2-8] enhances receptor affinity and in vitro bioactivity to several orders of magnitude[1] and its application in the formation of ligands with new properties[9], such as potent inverse agonism[10].

  4. 76 FR 22404 - Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative

    Science.gov (United States)

    2011-04-21

    ... HUMAN SERVICES Food and Drug Administration Analgesic Clinical Trials Innovation, Opportunities, and... Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative. The goal of the... major gaps in scientific information, which can slow down analgesic clinical trials and analgesic...

  5. 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.

  6. 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.

  7. 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....

  8. 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...

  9. Intraoperative nitrous oxide as a preventive analgesic.

    Science.gov (United States)

    Stiglitz, D K; Amaratunge, L N; Konstantatos, A H; Lindholm, D E

    2010-09-01

    Preventive analgesia is defined as the persistence of the analgesic effects of a drug beyond the clinical activity of the drug. The N-methyl D-aspartate receptor plays a critical role in the sensitisation of pain pathways induced by injury. Nitrous oxide inhibits excitatory N-methyl D-aspartate sensitive glutamate receptors. The objective of our study was to test the efficacy of nitrous oxide as a preventive analgesic. We conducted a retrospective analysis of data from a subset of patients (n = 100) randomly selected from a previous major multicentre randomised controlled trial on nitrous oxide (ENIGMA trial). Data analysed included postoperative analgesic requirements, pain scores and duration of patient-controlled analgesia during the first 72 postoperative hours. There was no significant difference in postoperative oral morphine equivalent usage (nitrous group 248 mg, no nitrous group 289 mg, mean difference -43 mg, 95% confidence interval 141 to 54 mg). However, patients who received nitrous oxide had a shorter duration of patient-controlled analgesia use (nitrous group 35 hours, no nitrous group 51 hours, mean difference -16 hours, 95% confidence interval -29 to -2 hours, P = 0.022). There was no difference in pain scores between the groups. The shorter patient-controlled analgesia duration in the nitrous oxide group suggests that intraoperative nitrous oxide may have a preventive analgesic effect.

  10. Clinical consequences of nonnarcotic analgesic use.

    Science.gov (United States)

    Matzke, G R

    1997-02-01

    The accuracy of the economic analysis of the selected adverse events evaluated by McGoldrick and Bailie is questionable. The quantitative perspective on the economics of the adverse events associated with nonnarcotic analgesic use proposed by these authors is limited by the fact that they have combined data on over 30 different NSAIDs into a single value for comparison with two single-entity agents: acetaminophen and aspirin. The relative prevalence of major organ system toxicities varies markedly among the NSAIDs, and this variance invalidates the use of a class conclusion approach. Their conservative incidence estimates, the lack of data in some areas (i.e., hepatic injury), and the exclusion of combination analgesics further limit the utility of their conclusions. However, it is difficult to argue authoritatively that the relative costs of toxicities associated with the three analgesic classes they reviewed are not representative. The ultimate question is, "What is the optimal analgesic for a given patient?" This question can be addressed only if one considers the underlying cause of pain, its chronicity/acuity, the patient's concurrent disease states, if any, and the potential for drug interactions with the patient's concomitant medications. McGoldrick and Bailie concluded on an economic basis that acetaminophen is the analgesic of choice for most patients, including those with impaired renal function. This recommendation is in agreement with those of the Analgesics and the Kidney Ad Hoc Committee of the National Kidney Foundation. It also would seem prudent to use acetaminophen as the first-line agent for those patients in whom aspirin and NSAID use should be avoided or used only with caution along with frequent monitoring of renal function, blood pressure, electrolytes, and/or coagulation status. Thus, there is little to no controversy in their recommendation to initiate treatment with acetaminophen. The authors, however, also suggested that switching

  11. Opioid-induced hyperalgesia and rapid opioid detoxification after tacrolimus administration.

    Science.gov (United States)

    Siniscalchi, Antonio; Piraccini, Emanuele; Miklosova, Zuzana; Taddei, Stefania; Faenza, Stefano; Martinelli, Gerardo

    2008-02-01

    Opioids can induce central sensitization and hyperalgesia, referred to as "opioid-induced hyperalgesia." Our report describes a patient who underwent intestinal transplant followed by immunosuppressant-related neuropathic pain. Her pain was treated with limited success over the course of 3 yr with different therapies, including i.v. morphine. She developed opioid-induced hyperalgesia, which was successfully treated with rapid detoxification under general anesthesia. Detoxification improved her quality of life, including the ability to resume physiotherapy. Six months after treatment, she remained opioid free. Our experience suggests that rapid detoxification under general anesthesia may be an effective treatment for opioid-induced hyperalgesia and merits comparison to traditional detoxification methods.

  12. 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

  13. 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

  14. 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.

  15. Reduced consumption of analgesics in patients with diabetes mellitus admitted to hospital for acute myocardial infarction

    DEFF Research Database (Denmark)

    Nielsen, F E; Gram-Hansen, P; Christensen, J H;

    1991-01-01

    .05). There was no statistically significant trend for the duration of pain to be shorter in the diabetes group. There was no difference between the two groups with respect to number of patients with Q-wave infarct, initial heart rate-blood pressure product or body weight, all of which are possible confounders. We conclude......In a case-control study, the consumption of analgesics was analysed in 39 patients with diabetes, admitted with acute myocardial infarction (MI). The control group comprised of non-diabetics with MI was computer-matched to the diabetic group with respect to age and sex as well as enzyme......-estimated size of the infarction. The median number of injections of opioid analgesics in the diabetes and non-diabetes groups was 2 and 5, respectively (0.01 less than P less than 0.05), and the median consumption of morphine was 20 mg and 35 mg, respectively (0.01 less than P less than 0...

  16. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    Directory of Open Access Journals (Sweden)

    Hao Jiqing

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

  17. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    Science.gov (United States)

    Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

    2009-01-01

    Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

  18. 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

  19. Validation of a computer case definition for sudden cardiac death in opioid users

    Directory of Open Access Journals (Sweden)

    Kawai Vivian K

    2012-08-01

    Full Text Available Abstract Background To facilitate the use of automated databases for studies of sudden cardiac death, we previously developed a computerized case definition that had a positive predictive value between 86% and 88%. However, the definition has not been specifically validated for prescription opioid users, for whom out-of-hospital overdose deaths may be difficult to distinguish from sudden cardiac death. Findings We assembled a cohort of persons 30-74 years of age prescribed propoxyphene or hydrocodone who had no life-threatening non-cardiovascular illness, diagnosed drug abuse, residence in a nursing home in the past year, or hospital stay within the past 30 days. Medical records were sought for a sample of 140 cohort deaths within 30 days of a prescription fill meeting the computer case definition. Of the 140 sampled deaths, 81 were adjudicated; 73 (90% were sudden cardiac deaths. Two deaths had possible opioid overdose; after removing these two the positive predictive value was 88%. Conclusions These findings are consistent with our previous validation studies and suggest the computer case definition of sudden cardiac death is a useful tool for pharmacoepidemiologic studies of opioid analgesics.

  20. 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.

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

    Science.gov (United States)

    Aminian, Atefeh; Javadi, Shiva; Rahimian, Reza; Dehpour, Ahmad Reza; Asadi Amoli, Fahimeh; Moghaddas, Payman; Ejtemaei Mehr, Shahram

    2016-07-01

    Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg), animals received intraperitoneal injections of morphine (5 mg/kg/day) and/or naltrexone (20 mg/kg/day), an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH) concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy. PMID:27424012

  2. 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.

  3. Anti-hyperalgesic effect of a benzilidine-cyclohexanone analogue on a mouse model of chronic constriction injury-induced neuropathic pain: Participation of the κ-opioid receptor and KATP.

    Science.gov (United States)

    Ming-Tatt, Lee; Khalivulla, Shaik Ibrahim; Akhtar, Muhammad Nadeem; Lajis, Nordin; Perimal, Enoch Kumar; Akira, Ahmad; Ali, Daud Israf; Sulaiman, Mohd Roslan

    2013-12-01

    The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall-Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not β-funaltrexamine (β-FN, selective μ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening.

  4. 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

  5. Activation profiles of opioid ligands in HEK cells expressing δ opioid receptors

    Directory of Open Access Journals (Sweden)

    Clark J

    2002-11-01

    Full Text Available Abstract Background The aim of the present study was to characterize the activation profiles of 15 opioid ligands in transfected human embryonic kidney cells expressing only δ opioid receptors. Activation profiles of most of these ligands at δ opioid receptors had not been previously characterized in vitro. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cAMP production. Results Naltrexone and nalorphine were classified as antagonists at δ opioid receptor. The other ligands studied were agonists at δ opioid receptors and demonstrated IC50 values of 0.1 nM to 2 μM, maximal inhibition of 39–77% and receptor binding affinities of 0.5 to 243 nM. The rank order of efficacy of the ligands tested was metazocine = xorphanol ≥ fentanyl = SKF 10047 = etorphine = hydromorphone = butorphanol = lofentanil > WIN 44,441 = Nalbuphine = cyclazocine ≥ met-enkephalin >> morphine = dezocine. For the first time these data describe and compare the function and relative efficacy of several ligands at δ opioid receptors. Conclusions The data produced from this study can lead to elucidation of the complete activation profiles of several opioid ligands, leading to clarification of the mechanisms involved in physiological effects of these ligands at δ opioid receptors. Furthermore, these data can be used as a basis for novel use of existing opioid ligands based on their pharmacology at δ opioid receptors.

  6. 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

  7. 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

  8. 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; Vetter, Irina

    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

  9. Dmt and opioid peptides: a potent alliance.

    Science.gov (United States)

    Bryant, Sharon D; Jinsmaa, Yunden; Salvadori, Severo; Okada, Yoshio; Lazarus, Lawrence H

    2003-01-01

    The introduction of the Dmt (2',6'-dimethyl-L-tyrosine)-Tic pharmacophore into the design of opioid ligands produced an extraordinary family of potent delta-opioid receptor antagonists and heralded a new phase in opioid research. First reviewed extensively in 1998, the incorporation of Dmt into a diverse group of opioid molecules stimulated the opioid field leading to the development of unique analogues with remarkable properties. This overview will document the crucial role played by this residue in the proliferation of opioid peptides with high receptor affinity (K(i) equal to or less than 1 nM) and potent bioactivity. The discussion will include the metamorphosis between delta-opioid receptor antagonists to delta-agonists based solely on subtle structural changes at the C-terminal region of the Dmt-Tic pharmacophore as well as their behavior in vivo. Dmt may be considered promiscuous due to the acquisition of potent mu-agonism by dermorphin and endomorphin derivatives as well as by a unique class of opioidmimetics containing two Dmt residues separated by alkyl or pyrazinone linkers. Structural studies on the Dmt-Tic compounds were enhanced tremendously by x-ray diffraction data for three potent and biologically diverse Dmt-Tic opioidmimetics that led to the development of pharmacophores for both delta-opioid receptor agonists and antagonists. Molecular modeling studies of other unique Dmt opioid analogues illuminated structural differences between delta- and mu-receptor ligand interactions. The future of these compounds as therapeutic applications for various medical syndromes including the control of cancer-associated pain is only a matter of time and perseverance.

  10. 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 mechanisms behind the effects of morphine are mainly mediated by inhibiting apoptosis of cancer cells and by stimulation of angiogenesis. Some other opioid agonists seem to be depleted from these effects. Prospective studies are needed to clarify the immunosuppressive effects of opioids in cancer pain...

  11. 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.

  12. 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.

  13. 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...

  14. 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

  15. 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

  16. Opioid-Induced Glial Activation: Mechanisms of Activation and Implications for Opioid Analgesia, Dependence, and Reward

    Directory of Open Access Journals (Sweden)

    Mark R. Hutchinson

    2007-01-01

    Full Text Available This review will introduce the concept of toll-like receptor (TLR–mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward. Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine level of analysis. Moreover, a novel antagonism of TLR4 by (+- and (˗-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia and unwanted (tolerance, dependence, and reward actions of opioids, thereby improving the safety and efficacy of their use.

  17. Behavioural and morphological evidence for the involvement of glial cell activation in delta opioid receptor function: implications for the development of opioid tolerance

    Directory of Open Access Journals (Sweden)

    Taylor Anna MW

    2007-03-01

    Full Text Available Abstract Previous studies have demonstrated that prolonged morphine treatment in vivo induces the translocation of delta opioid receptors (δORs from intracellular compartments to neuronal plasma membranes and this trafficking event is correlated with an increased functional competence of the receptor. The mechanism underlying this phenomenon is unknown; however chronic morphine treatment has been shown to involve the activation and hypertrophy of spinal glial cells. In the present study we have examined whether activated glia may be associated with the enhanced δOR-mediated antinociception observed following prolonged morphine treatment. Accordingly, animals were treated with morphine with or without concomitant administration of propentofylline, an inhibitor of glial activation that was previously shown to block the development of morphine antinociceptive tolerance. The morphine regimen previously demonstrated to initiate δOR trafficking induced the activation of both astrocytes and microglia in the dorsal spinal cord as indicated by a significant increase in cell volume and cell surface area. Consistent with previous data, morphine-treated rats displayed a significant augmentation in δOR-mediated antinociception. Concomitant spinal administration of propentofylline with morphine significantly attenuated the spinal immune response as well as the morphine-induced enhancement of δOR-mediated effects. These results complement previous reports that glial activation contributes to a state of opioid analgesic tolerance, and also suggest that neuro-glial communication is likely responsible in part for the altered functional competence in δOR-mediated effects following morphine treatment.

  18. 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 ...

  19. 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 ...

  20. Endogenous Opioid-Masked Latent Pain Sensitization

    DEFF Research Database (Denmark)

    Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B;

    2015-01-01

    UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development...

  1. Opioid induced hyperalgesia in anesthetic settings.

    Science.gov (United States)

    Lee, Hyeon Jeong; Yeomans, David C

    2014-11-01

    Pain is difficult to investigate and difficult to treat, in part, because of problems in quantification and assessment. The use of opioids, combined with classic anesthetics to maintain hemodynamic stability by controlling responses to intraoperative painful events has gained significant popularity in the anesthetic field. However, several side effects profiles concerning perioperative use of opioid have been published. Over the past two decades, many concerns have arisen with respect to opioid-induced hyperalgesia (OIH), which is the paradoxical effect wherein opioid usage may decrease pain thresholds and increase atypical pain unrelated to the original, preexisting pain. This brief review focuses on the evidence, mechanisms, and modulatory and pharmacologic management of OIH in order to elaborate on the clinical implication of OIH.

  2. 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 ...

  3. 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...... 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....

  4. Opioid-induced androgen deficiency (OPIAD).

    Science.gov (United States)

    Smith, Howard S; Elliott, Jennifer A

    2012-07-01

    Opioid therapy is one of the most effective forms of analgesia currently in use. In the past few decades, the use of opioids as a long-term treatment for chronic pain has increased dramatically. Accompanying this upsurge in the use of long-term opioid therapy has been an increase in the occurrence of opioid associated endocrinopathy, most commonly manifested as an androgen deficiency and therefore referred to as opioid associated androgen deficiency (OPIAD). This syndrome is characterized by the presence of inappropriately low levels of gonadotropins (follicle stimulating hormone and luteinizing hormone) leading to inadequate production of sex hormones, particularly testosterone. Symptoms that may manifest in patients with OPIAD include reduced libido, erectile dysfunction, fatigue, hot flashes, and depression. Physical findings may include reduced facial and body hair, anemia, decreased muscle mass, weight gain, and osteopenia or osteoporosis. Additionally, both men and women with OPIAD may suffer from infertility. While the literature regarding OPIAD remains limited, it is apparent that OPIAD is becoming increasingly prevalent among chronic opioid consumers but often goes unrecognized. OPIAD can have a significant negative impact on the the quality of life of opioid users, and clinicians should anticipate the potential for its occurrence whenever long-term opioid prescribing is undertaken. Once diagnosed, treatment for OPIAD may be offered utilizing a number of androgen replacement therapy options including a variety of testosterone preparations and, for female patients with OPIAD, dehydroepiandrosterone (DHEA) supplementation. Follow-up evaluation of patients receiving androgen replacement therapy should include a review of any unresolved symptoms of hypogonadism, laboratory evaluation, and surveillance for potential adverse effects of androgen replacement therapy including prostate disease in males.: PMID:22786453

  5. Comparison of stably expressed rat UGT1.1 and UGT2B1 in the glucuronidation of opioid compounds.

    Science.gov (United States)

    King, C D; Rios, G R; Green, M D; MacKenzie, P I; Tephly, T R

    1997-02-01

    Opioids are important drugs used as analgesics, antitussives, antidiarrheals, and in the therapy of myocardial infarctions, and as antagonists of opioid intoxication. The glucuronidation of these compounds, catalyzed by UDP-glucuronosyltransferases (UGTs), is well known to be a primary step in their metabolism to hydrophilic products and in their ultimate excretion. The present study was designed to compare the reactivity and relative glucuronidation efficiencies of opioid agonists, antagonists, and partial agonists with two rat UGT isoforms; UGT1.1, which is generally considered the "bilirubin UGT," and UGT2B1, which has previously been shown to catalyze the glucuronidation of testosterone, chloramphenicol, and (-)-morphine. Rat UGT2B1, stably expressed in HK293 cells, exhibited high glucuronidation rates and catalytic efficiencies for many opioids, although values for (-)-morphine and nalorphine were the highest. In contrast, these compounds were very poor substrates for expressed rat UGT1.1. Comparably high glucuronidation rates and efficiencies were found for buprenorphine and diprenorphine with both UGT isoforms. These results suggest that opioids with morphinan-based chemical structures similar to (-)-morphine interact with UGTs differently than those with oripavine-based chemical structures similar to buprenorphine. To investigate the contribution of rat UGT1.1 and UGT2B1 in the overall rate of glucuronidation of buprenorphine in the rat liver, hepatic microsomes from Gunn rats (where UGT1.1 activity is absent) and Wistar rats (where UGT1.1 activity is present) were studied. Buprenorphine glucuronidation activity in Gunn rat liver microsomes exhibit approximately 25% of rates observed in Wistar rat liver microsomes, whereas (-)-morphine, naloxone, and naltrexone glucuronidation rates were not significantly different in microsomal preparations from Gunn and Wistar rats. These data suggest that UGT2B1 is the major hepatic enzyme involved in the glucuronidation

  6. Nicotine effects and the endogenous opioid system.

    Science.gov (United States)

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro

    2014-01-01

    Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR.

  7. 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

  8. 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...

  9. Analgesic effect of Persian Gulf Conus textile venom

    Directory of Open Access Journals (Sweden)

    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

  10. 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

  11. Analgesic Efficacy of Firocoxib, a Selective Inhibitor of Cyclooxygenase 2, in a Mouse Model of Incisional Pain.

    Science.gov (United States)

    Reddyjarugu, Balagangadharreddy; Pavek, Todd; Southard, Teresa; Barry, Jason; Singh, Bhupinder

    2015-07-01

    Pain management in laboratory animals is generally accomplished by using opioids and NSAIDs. However, opioid use is hindered by controlled substance requirements and a relatively short duration of action. In this study, we compared the analgesic efficacy of firocoxib (a cyclooxygenase-2-selective NSAID) with that of buprenorphine in the mouse model of plantar incisional pain by objective measurement of mechanical allodynia and thermal hyperalgesia using von Frey and Hargreaves equipment, respectively. Our experimental design included 5 treatment groups: firocoxib at 10 mg/kg IP every 24 h (F10 group); firocoxib at 20 mg/kg IP every 24 h (F20); buprenorphine at 0.2 mg/kg SC every 8 h; intraperitoneal normal saline every 24 h; and sham group (anesthesia, no incision) treated with firocoxib at 20 mg/kg IP every 24 h (sham+F20). All mice underwent nociceptive assays at 24 h before and 4, 24, 48, and 72 h after surgery. Buprenorphine alleviated allodynia at all time points after incision. The F10 treatment alleviated allodynia at 4, 24, and 48 h, whereas F20 alleviated allodynia at 24, 48, and 72 h. None of the treatments alleviated thermal hyperalgesia at 4h. Except for F10 and buprenorphine at 24 h, all treatments alleviated thermal hyperalgesia at 24, 48, and 72 h. No significant differences were noted between the 2 doses of firocoxib and buprenorphine regarding mechanical allodynia and thermal hyperalgesia at all time points. In conclusion, the analgesic efficacy of firocoxib is comparable to that of buprenorphine in this mouse pain model. PMID:26224441

  12. Effect of the analgesic butorphanol on activity behaviour in turkeys (Meleagris gallopavo).

    Science.gov (United States)

    Buchwalder, T; Huber-Eicher, B

    2005-12-01

    During fattening, the bodyweight of modern broad-breasted turkeys increases considerably within a very short space of time. In particular, the breast muscles increase disproportionately. This leads to a disadvantageous distribution in weight, and as a consequence, to a disturbed leg position and skeletal deformations like antitrochanteric degeneration, tibial dyschondroplasia, bending, twisting and rotation of the tibia, osteochondrosis, osteomyelitis, rickets, and epiphyseolysis of the femoral head increases. This cases of degenerative joint disease cause severe pain in humans and there are indications that this is also true for turkeys. The purpose of this study was to determine if behaviour indicative of such pain in turkeys of the B.U.T. Big 6 breeding line could be attenuated by administering a quick-acting analgesic, butorphanol. Twelve pairs of turkeys were tested at the ages of 7 and 12 weeks. One bird in each pair received an analgesic opioid injection, while the other one received a control injection of physiologically balanced saline solution. The time the birds spent putting weight on their legs, i.e., 'walking' and 'standing' and the distance covered by the birds were recorded during the 30 min periods before and after the application of the drug. At week seven the treated birds spent significantly more time putting weight on their legs than control birds. At week 12, the same tendency was observed. No significant differences were found in the distances covered by the animals. It is concluded that fattening turkeys reduce the time they are putting weight on their legs because these behaviours may be associated with pain.

  13. Countless Opioid Pills Unused by Dental-Surgery Patients

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_161184.html Countless Opioid Pills Unused by Dental-Surgery Patients Surplus may contribute to the opioid abuse epidemic, researchers say To use the sharing ...

  14. Most on Opioid Painkillers OK with Getting Overdose Antidote: Survey

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_160933.html Most on Opioid Painkillers OK With Getting Overdose Antidote: Survey More ... A new, small survey of people taking powerful opioid painkillers like OxyContin and Vicodin found that most ...

  15. Opioid Abuse Fueling Drug-Related Heart Infections

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160746.html Opioid Abuse Fueling Drug-Related Heart Infections: Study Injecting ... with heart infections caused by use of injected opioid drugs is on the rise, a new study ...

  16. 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 ...

  17. Antinociceptive effects of morphine and naloxone in mu-opioid receptor knockout mice transfected with the MORS196A gene

    Directory of Open Access Journals (Sweden)

    Tao Pao-Luh

    2010-04-01

    Full Text Available Abstract Background Opioid analgesics such as morphine and meperidine have been used to control moderate to severe pain for many years. However, these opioids have many side effects, including the development of tolerance and dependence after long-term use, which has limited their clinical use. We previously reported that mutations in the mu-opioid receptors (MOR S196L and S196A rendered them responsive to the opioid antagonist naloxone without altering the agonist phenotype. In MORS196A knock-in mice, naloxone and naltrexone were antinociceptive but did not cause tolerance or physical dependence. In this study we delivery this mutated MOR gene into pain related pathway to confirm the possibility of in vivo transfecting MORS196A gene and using naloxone as a new analgesic agent. Methods The MOR-knockout (MOR-KO mice were used to investigate whether morphine and naloxone could show antinociceptive effects when MORS196A gene was transfected into the spinal cords of MOR-KO mice. Double-stranded adeno-associated virus type 2 (dsAAV2 was used to deliver the MORS196A-enhanced green fluorescence protein (EGFP gene by microinjected the virus into the spinal cord (S2/S3 dorsal horn region. Tail-flick test was used to measure the antinociceptive effect of drugs. Results Morphine (10 mg/kg, s.c. and naloxone (10 mg/kg, s.c. had no antinociceptive effects in MOR-KO mice before gene transfection. However, two or three weeks after the MOR-S196A gene had been injected locally into the spinal cord of MOR-KO mice, significant antinociceptive effects could be induced by naloxone or morphine. On the other hand, only morphine but not naloxone induced significant tolerance after sub-chronic treatment. Conclusion Transfecting the MORS196A gene into the spinal cord and systemically administering naloxone in MOR-KO mice activated the exogenously delivered mutant MOR and provided antinociceptive effect without causing tolerance. Since naloxone will not activate natural

  18. A case of topical opioid-induced delirium mistaken as behavioural and psychological symptoms of dementia in demented state.

    Science.gov (United States)

    Ito, Go; Kanemoto, Kousuke

    2013-06-01

    In Japan, indications for opioid analgesics, once exclusively used as pain killers for patients suffering from malignant cancer, have been expanded for a wide range of pain. Herein we report a patient with opioid-induced delirium associated with the administration of buprenorphine patches that was well below the indicated therapeutic range limit. An 82-year-old woman was referred to us from an orthopaedic practitioner for uncontrollable behavioural problems apparently caused by the beginning of dementia; the patient had gradually developed disorientation, visual hallucinations, and delusions. Laboratory and imaging findings excluded common causes of delirium including Alzheimer's disease and diffuse Lewy body disease. Detailed questioning revealed that the patient's confused state appeared following a buprenorphine patch dose increase and subsequently disappeared after administration was stopped. Delirium has not been reported as a side-effect in clinical trials of buprenorphine patches. However, our findings in this case show that even topical opioids can precipitate the development of a delirious state in elderly patients.

  19. YFa and analogs: Investigation of opioid receptors in smooth muscle contraction

    Institute of Scientific and Technical Information of China (English)

    Krishan Kumar; Ritika Goyal; Annu Mudgal; Anita Mohan; Santosh Pasha

    2011-01-01

    AIM: To study the pharmacological profile and inhibition of smooth muscle contraction by YFa and its analogs in conjunction with their receptor selectivity. METHODS: The effects of YFa and its analogs (D-Ala2) YFa, Y (D-Ala2) GFMKKKFMRF amide and Des-Phe- YGGFMKKKFMR amide in guinea pig ileum (GPI) and mouse vas deferens (MVD) motility were studied using an isolated tissue organ bath system, and morphine and DynA (1-13) served as controls. Acetylcholine was used for muscle stimulation. The observations were validated by specific antagonist pretreatment experiments using naloxonazine, naltrindole and norbinaltorphimine norBNI. RESULTS: YFa did not demonstrate significant inhibition of GPI muscle contraction as compared with morphine (15% vs 62%, P = 0.0002), but moderate inhibition of MVD muscle contraction, indicating the role of κ opioid receptors in the contraction. A moderate inhibition of GPI muscles by (Des-Phe) YFa revealed the role of anti-opiate receptors in the smooth muscle contraction. (D-Ala-2) YFa showed significant inhibition of smooth muscle contraction, indicating the involvement of mainly d receptors in MVD contraction. These results were supported by specific antagonist pretreatment assays. CONCLUSION: YFa revealed its side-effect-free analgesic properties with regard to arrest of gastrointestinal transit. The study provides evidences for the involvement of κ and anti-opioid receptors in smooth muscle contraction.

  20. 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...

  1. When medications make pain worse: opioid-induced hyperalgesia.

    Science.gov (United States)

    Martin, Caren McHenry

    2011-08-01

    Opioid medications are commonly used to treat moderate-to-severe pain. While these medications are generally an effective means of pain control, they can, in rare cases, actually exacerbate the pain. This paradoxical reaction is called opioid-induced hyperalgesia (OIH). Patients experiencing OIH may benefit from decreasing or discontinuing the opioid, switching to an alternative opioid, and/or using a nonopioid medication for pain.

  2. Effects of opioid peptides on thermoregulation

    Energy Technology Data Exchange (ETDEWEB)

    Clark, W.G.

    1981-11-01

    In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate that stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic peptide analogs do not necessarily evoke the same response as does the related endogenous peptide. The lack of effect of naloxone on body temperature of subjects housed at usual laboratory temperature or on pyrogen-induced increases in body temperature indicates that an action of endogenous peptides on naloxone-sensitive receptors plays little, if any, role in normal thermoregulation or in fever. However, there is some evidence that such an action may be involved in responses to restraint or ambient temperature-induced stress. Further evaluation of possible physiological roles of endogenous opioid peptides will be facilitated when specific antagonists at other types of opioid receptors become available.

  3. 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

  4. Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis.

    Directory of Open Access Journals (Sweden)

    Li He

    Full Text Available It is well known that the mu-opioid receptor (MOR plays an important role in the rewarding properties of ethanol. However, it is less clear how chronic ethanol consumption affects MOR signaling. Here, we demonstrate that rats with prolonged voluntary ethanol consumption develop antinociceptive tolerance to opioids. Signaling through the MOR is controlled at many levels, including via the process of endocytosis. Importantly, agonists at the MOR that promote receptor endocytosis, such as the endogenous peptides enkephalin and β-endorphin, show a reduced propensity to promote antinociceptive tolerance than do agonists, like morphine, which do not promote receptor endocytosis. These observations led us to examine whether chronic ethanol consumption produced opioid tolerance by interfering with MOR endocytosis. Indeed, here we show that chronic ethanol consumption inhibits the endocytosis of MOR in response to opioid peptide. This loss of endocytosis was accompanied by a dramatic decrease in G protein coupled receptor kinase 2 (GRK2 protein levels after chronic drinking, suggesting that loss of this component of the trafficking machinery could be a mechanism by which endocytosis is lost. We also found that MOR coupling to G-protein was decreased in ethanol-drinking rats, providing a functional explanation for loss of opioid antinociception. Together, these results suggest that chronic ethanol drinking alters the ability of MOR to endocytose in response to opioid peptides, and consequently, promotes tolerance to the effects of opioids.

  5. 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

  6. 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...

  7. Endocytosis of μ opioid receptors inhibits morphine tolerance%μ阿片受体的内吞抑制吗啡耐受的形成

    Institute of Scientific and Technical Information of China (English)

    吕庆琴; 陈霆隽; 洪炎国

    2012-01-01

    Opioids are the most effective analgesics. However, prolonged administration of morphine, the representative of opioids, results in tolerance, limiting the therapeutic utility of o-piate drugs. Studies have recently suggested that endocytosis of μ opioid receptors attenuates opioid tolerance. The ability of inducing endocytosis of opioid receptor is agonist-dependent. It has been shown that the endocytotic efficacy of opioids are negatively correlated with opioid tolerance. Receptor internalization reduced adaptive changes in signaling pathways that are involved in the development of opioid tolerance. Moreover, endocytosised μ-opioid receptors are rapidly recycled back to the cell membrane surface resuming their normal function. Therefore, tolerance does not occur. Thus, the study of receptor endocytosis and trafficking following the activation of the receptors can help the therapy for chronic pain.%阿片类药物是至今最有效的镇痛药,但是长期应用会产生药物耐受,大大限制了其临床应用.μ阿片受体和特定的激动剂结合后会出现内吞.研究发现,μ阿片受体是否内吞与耐受的发生有密切关系;加强μ阿片受体的内吞能够抑制受体耐受.不同的激动剂导致μ阿片受体内吞的能力是不同的;其导致耐受的能力和导致内吞的能力呈负相关.激动剂越容易引起μ受体内吞,就越不容易产生吗啡耐受.内吞的作用在于能抑制过度刺激μ受体而导致的环腺苷酸( cyclic adenosine monophosphate,cAMP)等兴奋性信号通路的激活,而内吞的μ受体也会很快回到细胞膜上,恢复和阿片类药物结合后激活抑制性GTP 结合蛋白的能力.因此,对受体的内吞和其后迁移过程展开研究,可能为慢性疼痛的治疗找到新的路径.

  8. 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. 

  9. 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

  10. 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.

  11. 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

  12. The analgesic and anticonvulsant effects of piperine in mice.

    Science.gov (United States)

    Bukhari, I A; Pivac, N; Alhumayyd, M S; Mahesar, A L; Gilani, A H

    2013-12-01

    Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (Ppepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.

  13. EXPERIMENTAL EVALUATION FOR ANALGESIC ACTIVITY OF MAMSYADI KWATHA

    Directory of Open Access Journals (Sweden)

    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.

  14. The analgesic effect of preoperative pregabalin in radical cystectomy for cancer bladder patients

    Institute of Scientific and Technical Information of China (English)

    Ayman A. Ghoneim; Mohammed M. Hegazy

    2013-01-01

    Objective: After the pregabalin has been approved for the treatment of neuropathic pain, preliminary clinical studies suggested a possible role in the perioperative period. To our knowledge, It has never been studied the perioperative analgesic effect of pregabalin in patients with cancer bladder. In this study, we hypothesized that cancer bladder patients undergoing radical cystectomy and received oral pregabalin 75 mg twice daily for ten days preoperatively would get their postoperative pain reduced. Methods: Sixty patients scheduled for elective radical cystectomy were randomly assigned to one of 2 groups (control group or pregabalin group). Patients in the pregabalin group received 75 mg pregabalin twice daily for ten days before surgery. Standard anesthesia protocol was applied to all patients. Pain intensity, opioid consumption, level of sedation and other side effects were regularly assessed for 48 h postoperative. Results: Mean time for the first request of analgesia was statistically longer in pregabalin group. Meanwhile, mean morphine consumption, VAS scores at rest (in the first 32 h postoperatively), VAS scores during movement (in the first 20 h postoperatively) were statistically significant lower in the pregabalin group than those in the control group. Patients in the pregabalin group were statistically more sedated in the first four hours postoperative than the control group. Conclusion: Preoperative pregabalin 75 mg twice daily for ten days resulted in 60% reduction in 24 h postoperative morphine requirements in patients undergoing radical cystectomy.

  15. Electroacupuncture Reduces Postoperative Pain and Analgesic Consumption in Patients Undergoing Thoracic Surgery: A Randomized Study

    Science.gov (United States)

    Chen, Tongyu; Xu, Jianjun; Ma, Wen; Zhou, Jia

    2016-01-01

    The aim of this study was to evaluate the effect of electroacupuncture (EA) on postoperative pain management in patients undergoing thoracic surgery. A randomized study was conducted. Ninety-two thoracic surgical patients were randomly divided into an EA group and a sham group. Postoperative intravenous analgesia was applied with a half dose of the conventional drug concentration in both groups. In the EA group, EA treatment was administered for three consecutive days after the surgery with 6 sessions of 30 min each. Compared with the sham group, patients in the EA group had a lower visual analogue scale (VAS) score at 2, 24, 48, and 72 hours and consumed less analgesic after surgery. The incidence of opioid-related adverse effects of nausea was lower in the EA group. The time to first flatus and defecation was also shorter in the EA group. Furthermore, the plasma β-endorphin (β-EP) level was higher by radioimmunoassay and the plasma 5-hydroxytryptamine (5-HT) level was lower in the EA group by enzyme-linked immunosorbent assay during the first 72 hr after thoracic surgery. Therefore, EA is suitable as an adjunct treatment for postoperative pain management after thoracic surgery. PMID:27073400

  16. Utilization of a Preemptive, Multimodal Analgesic Regimen in Adult Ambulatory Septoplasty Patients: A Quality Improvement Project.

    Science.gov (United States)

    Morgan, Brett; Stanik-Hutt, Julie

    2015-01-01

    This paper describes a quality improvement project designed to decrease postoperative pain, decrease post-operative nausea and vomiting (PONV), decrease time in the recovery room, and increase patient satisfaction in adult ambulatory septoplasty patients using a multimodal, preemptive analgesic regimen. The project was conducted in a community hospital setting with nine operating rooms, and a twenty one bed recovery room. Project participants included certified registered nurse anesthetists, anesthesiologists, operating room nurses, recovery room nurses, and otolaryngology surgeons. Following a period of departmental education, adult patients scheduled for outpatient septoplasty surgery received a preoperative regimen of medications that included gabapentin, celecoxib, and acetaminophen. Using a pre-post test design, (intervention group n = 17, non-intervention group n = 17) data was collected from patient and analyzed using SPSS version 18.0. The change in practice resulted in a significant decrease in pain scores in the recovery room and on discharge from the recovery room. In addition, patients who received the preemptive regimen also required significantly fewer opioid medications and were ready to be discharged from the recovery room in less time. PMID:26753247

  17. 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...

  18. The contribution of activated peripheral kappa opioid receptors (kORs) in the inflamed knee joint to anti-nociception.

    Science.gov (United States)

    Moon, Sun Wook; Park, Eui Ho; Suh, Hye Rim; Ko, Duk Hwan; Kim, Yang In; Han, Hee Chul

    2016-10-01

    The systemic administration of opioids can be used for their strong analgesic effect. However, extensive activation of opioid receptors (ORs) beyond the targeted tissue can cause dysphoria, pruritus, and constipation. Therefore, selective activation of peripheral ORs present in the afferent fibers of the targeted tissue can be considered a superior strategy in opioid analgesia to avoid potential adverse effects. The purpose of this study was to clarify the role of peripheral kappa opioid receptors (kORs) in arthritic pain for the possible use of peripheral ORs as a target in anti-nociceptive therapy. We administered U50488 or nor-BNI/DIPPA, a selective agonist or antagonist of kOR, respectively into arthritic rat knee joints induced using 1% carrageenan. After the injection of U50488 or U50488 with nor-BNI or DIPPA into the inflamed knee joint, we evaluated nociceptive behavior as indicated by reduced weight-bearing on the ipsilateral limbs of the rat and recorded the activity of mechanosensitive afferents (MSA). In the inflamed knee joint, the intra-articular application of 1μM, 10nM, or 0.1nM U50488 resulted in a significant reduction in nociceptive behavior. In addition, 1μM and 10nM U50488 decreased MSA activity. However, in a non-inflamed knee joint, 1μM U50488 had no effect on MSA activity. Additionally, intra-articular pretreatment with 20μM nor-BNI or 10μM DIPPA significantly blocked the inhibitory effects of 1μM U50488 on nociceptive behavior and MSA activity in the inflamed knee joint. These results implicate that peripheral kORs can contribute to anti-nociceptive processing in an inflamed knee joint. PMID:27378583

  19. 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

  20. 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

  1. Who Benefits from Chronic Opioid Therapy? Rethinking the Question of Opioid Misuse Risk

    Directory of Open Access Journals (Sweden)

    Elizabeth Huber

    2016-05-01

    Full Text Available 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.

  2. 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

  3. 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.

  4. Study on Analgesic Effect of Traditional Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    YU Shan; XU Ling; WEI Pin-kang; QIN Zhi-feng; LI Jun; PENG Hai-dong

    2008-01-01

    Chinese medicine has been used in treating pain for a long time.Much progress has been made in studies on the mechanism of the analgesic effect of Chinese medicine in animal experiments.It is found that the analgesic action may be related to the following actions:(1)Reducing the secretion of peripheral algogenic substances and inducing the secretion of pain-sensitive substances;(2)Alleviating the accumulation of local algogenic substances;(3)Increasing the release of endogenous analgesic substances;(4)Regulating c-fos gene and increasing the secretion of such substances in the central newous system,etc.In this paper,the experimental methods and analgesic effect of Chinese medicines are reviewed.

  5. 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

  6. 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.

  7. Prediction of withdrawal symptoms during opioid detoxification

    NARCIS (Netherlands)

    Dijkstra, Boukje A G; Krabbe, Paul F M; De Jong, Cor A J; van der Staak, Cees P F

    2008-01-01

    OBJECTIVE: The severity of self-reported withdrawal symptoms varies during detoxification of opioid-dependent patients. The aim of this study is to identify subgroups of withdrawal symptoms within the detoxification trajectory and to predict the severity of withdrawal symptoms on the basis of drug-r

  8. 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.

  9. Opioid-induced redistribution of 6TM and 7TM μ opioid receptors: A hypothesized mechanistic facilitator model of opioid-induced hyperalgesia.

    Science.gov (United States)

    Wang, Wei; Wang, Yan; Zhang, Wei; Jin, Xiaoju; Liu, Yusheng; Xu, Shiqin; Lei, Liming; Shen, Xiaofeng; Guo, Xirong; Xia, Xiaoqiong; Wang, Fuzhou

    2016-08-01

    Opioids are still the most popular form of pain treatment, but many unavoidable side effects make opioids a big challenge in effective pain management. Opioid-induced hyperalgesia (OIH), a paradoxical phenomenon, portrays an increased sensitivity to harmful stimuli caused by opioid exposure. Changes in the neural modulation are considered a major contributor to the development of OIH. Activation of opioid receptors (ORs) and corresponding downstream molecules are the vital composition of functional performance of opioids. Increasing interests were proposed of the interaction between ORs and other neural transmitter systems such as glutamatergic, GABAergic and adrenergic ones to the genesis of OIH. G protein coupled μ-opioid receptor (MOR) was studied comprehensively on its role in the development of OIH. In addition to the relationship between MOR and other neurotransmitter receptors, a new intracellular MOR that has six transmembrane (6TM) domains was identified, and found to perform a pro-nociceptive task in contrast to the counterpart 7TM isoform. A mechanistic model of OIH in which both 6TM and 7TM MORs undergoing membrane redistribution upon opioid exposure is proposed which eventually facilitates the neurons more sensitive to nociceptive stimulation than that of the preceding opioid exposure.

  10. 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.

  11. 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

  12. Catastrophizing delays the analgesic effect of distraction.

    Science.gov (United States)

    Campbell, Claudia M; Witmer, Kenny; Simango, Mpepera; Carteret, Alene; Loggia, Marco L; Campbell, James N; Haythornthwaite, Jennifer A; Edwards, Robert R

    2010-05-01

    Behavioral analgesic techniques such as distraction reduce pain in both clinical and experimental settings. Individuals differ in the magnitude of distraction-induced analgesia, and additional study is needed to identify the factors that influence the pain relieving effects of distraction. Catastrophizing, a set of negative emotional and cognitive processes, is widely recognized to be associated with increased reports of pain. We sought to evaluate the relationship between catastrophizing and distraction analgesia. Healthy participants completed three sessions in a randomized order. In one session (Pain Alone), pain was induced by topical application of a 10% capsaicin cream and simultaneous administration of a tonic heat stimulus. In another session (Pain+Distraction), identical capsaicin+heat application procedures were followed, but subjects played video games that required a high level of attention. During both sessions, verbal ratings of pain were obtained and participants rated their degree of catastrophizing. During the other session (Distraction Alone) subjects played the video games in the absence of any pain stimulus. Pain was rated significantly lower during the distraction session compared to the "Pain Alone" session. In addition, high catastrophizers rated pain significantly higher regardless of whether the subjects were distracted. Catastrophizing did not influence the overall degree of distraction analgesia; however, early in the session high catastrophizers had little distraction analgesia, though later in the session low and high catastrophizers rated pain similarly. These results suggest that both distraction and catastrophizing have substantial effects on experimental pain in normal subjects and these variables interact as a function of time.

  13. 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...

  14. 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.)

  15. 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.

  16. Intraoperative Use of Remifentanil and Opioid Induced Hyperalgesia/Acute Opioid Tolerance - Systematic review

    Directory of Open Access Journals (Sweden)

    Sang Hun eKim

    2014-05-01

    Full Text Available IntroductionThe use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT and opioid-induced hyperalgesia (OIH in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset. ObjectivesSearch of the available literature to assess remifentanil AOT and OIH based on available published data.MethodsWe reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey. ResultsOur results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research.Discussions and ConclusionsAOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold, should be suspected with any unexplained pain report unassociated with the disease progression.The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug’s effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion.Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.

  17. Topical and peripheral ketamine as an analgesic.

    Science.gov (United States)

    Sawynok, Jana

    2014-07-01

    Ketamine, in subanesthetic doses, produces systemic analgesia in chronic pain settings, an action largely attributed to block of N-methyl-D-aspartate receptors in the spinal cord and inhibition of central sensitization processes. N-methyl-D-aspartate receptors also are located peripherally on sensory afferent nerve endings, and this provided the initial impetus for exploring peripheral applications of ketamine. Ketamine also produces several other pharmacological actions (block of ion channels and receptors, modulation of transporters, anti-inflammatory effects), and while these may require higher concentrations, after topical (e.g., as gels, creams) and peripheral application (e.g., localized injections), local tissue concentrations are higher than those after systemic administration and can engage lower affinity mechanisms. Peripheral administration of ketamine by localized injection produced some alterations in sensory thresholds in experimental trials in volunteers and in complex regional pain syndrome subjects in experimental settings, but many variables were unaltered. There are several case reports of analgesia after topical application of ketamine given alone in neuropathic pain, but controlled trials have not confirmed such effects. A combination of topical ketamine with several other agents produced pain relief in case, and case series, reports with response rates of 40% to 75% in retrospective analyses. In controlled trials of neuropathic pain with topical ketamine combinations, there were improvements in some outcomes, but optimal dosing and drug combinations were not clear. Given orally (as a gargle, throat swab, localized peritonsillar injections), ketamine produced significant oral/throat analgesia in controlled trials in postoperative settings. Topical analgesics are likely more effective in particular conditions (patient factors, disease factors), and future trials of topical ketamine should include a consideration of factors that could predispose

  18. 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

  19. 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...

  20. Relationship of opioid analgesic protocols to assessed pain and length of stay in the pediatric postanesthesia unit following tonsillectomy.

    Science.gov (United States)

    Smith, Jana; Newcomb, Patricia; Sundberg, Erin; Shaffer, Paul

    2009-04-01

    After tonsillectomy and adenoidectomy in children, postoperative pain management is an essential, yet often challenging, task. In addition to discomfort, lack of pain management can lead to delays in oral intake of patients, resulting in extended stays and increased costs. At one North Texas pediatric facility, postoperative coblation tonsillectomy and adenoidectomy pain management orders include the as-needed use of both intravenous fentanyl and intravenous morphine. Both drugs are effective and both have potential side effects that might prolong the recovery period. Nurses in the postanesthesia care unit retrospectively compared a fentanyl and morphine regimen with a morphine-only regimen to determine whether either protocol made a difference in length-of-stay or pain relief. Analysis of available data revealed no statistically significant differences in length of stay between the groups and trivial differences thought to be clinically irrelevant on other variables.

  1. 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

  2. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment : a randomized controlled trial

    NARCIS (Netherlands)

    De Jong, Cor A J; Laheij, Robert J F; Krabbe, Paul F M

    2005-01-01

    AIM: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without an

  3. 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.

  4. Addiction to opioids in chronic pain patients: a literature review

    DEFF Research Database (Denmark)

    Højsted, Jette; Sjøgren, Per

    2007-01-01

    Opioids have proven very useful for treatment of acute pain and cancer pain, and in the developed countries opioids are increasingly used for treatment of chronic non-malignant pain patients as well. This literature review aims at giving an overview of definitions, mechanisms, diagnostic criteria......, 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...

  5. Opioid-induced hyperalgesia: when pain killers make pain worse.

    Science.gov (United States)

    Kaneria, Anshuni

    2014-06-04

    A 44-year-old woman had a temporal glioma and was admitted to the hospice with pain that was not controlled despite escalating opioids. Her pain levels rose after every dose increase resulting now in continuous pain, making her very low in mood. Her short-term memory had also declined in a stepwise fashion with each increase in opioids. Additionally, her poor health had had a detrimental effect on family life. Physical examination was difficult due to allodynia but no major abnormality was found. The team suspected opioid-induced hyperalgesia and decided to cut the patient's opioids by one-third initially. This immediately improved the overall pain. The opioids continued to be decreased incrementally every 1-2 days until the pain had disappeared completely. She was stabilised on a dose almost one-seventh of her original regime. Mood and memory also improved as opioids decreased and she was discharged home after 8 days.

  6. Anesthesia for opioid addict: Challenges for perioperative physician

    Directory of Open Access Journals (Sweden)

    Rohit Goyal

    2013-01-01

    Full Text Available Opioid addiction is on a rise globally. Such a patient presents to an anesthesiologist as well as to the surgeon with an array of challenges. We present the case of an opioid addict (pentazocine who presented for debridement and grafting of eschars and old healed scars. Initially he was medically managed for opioid addiction followed by a planned anesthesia. We hereby discuss the challenges faced during perioperative period.

  7. 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...

  8. 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...

  9. 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)

  10. EVALUATION OF ANALGESIC ACTIVITY OF LEPIDAGATHIS CRISTATA WILLD LEAF EXTRACTS

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    Purma Aravinda Reddy

    2013-04-01

    Full Text Available Aim of the study is to screen the Lepidagathis cristata Willd, leaf extracts for analgesic activity, because the plant was screened only for immunosuppressive, antipyretic activities only, now in the present study the analgesic activity of leaf extracts were performed. The ethanolic, ethyl acetate, chloroform extracts were prepared and are used for analgesic activity in two dose level that is 200 and 400 mg/kg body weight per oral in two screening methods, one is Hot Plate (n=5, another is Tail Immersion method (n=5, and the leaf extracts are showed significant analgesic activity. The plant extracts did not exhibit any mortality up to the dose level 4000 mg/kg. The methanol, Chloroform and Ethyl acetate extracts of leaf was evaluated for analgesic activity. . The 400mg/kg dose of leaf chloroform extract has highest activity in both the experimental models with 62.5% protection after 30min and 47.3% after 60 min with the significance of p< 0.001 when compared with 0 time interval and after 90 min it was shown 50% of protection and all the extracts has graded dose response.

  11. Antiplasmodial and analgesic activities ofClausena anisata

    Institute of Scientific and Technical Information of China (English)

    Jude E Okokon; Ette O Etebong; John A Udobang; Grace E Essien

    2012-01-01

    Objective:Antiplasmodial and analgesic activities of the leaf extract and fractions ofClausena anisata (C. anisata) were evaluated for antimalarial and analgesic activities.Methods:The crude leaf extract (39 - 117 mg/kg) and fractions (chloroform and acqeous; 78 mg/kg) ofC. anisata were investigated for antiplasmodial activity against chloroquine-sensitivePlasmodium berghei (P. berghei ) infections in mice using suppressive, prophylactic and curative models and analgesic activity against acetic acid, formalin and heat-induced pains. Artesunate,5 mg/kg and pyrimethamine,1.2 mg/kg were used as positive controls. Thin films made from tail blood of each mouse were used to assess the level of parasitaemia of the mice.Results: The extract and its fractions dose-dependently reduced parasitaemia induced by chloroquine-sensitive P. berghei in prophylactic, suppressive and curative models in mice. These reductions were statistically significant (P<0.001). They also improved the mean survival time (MST) from17 to21 days relative to control (P<0.01 - 0.001). On chemically and thermally- induced pains, the extract inhibited acetic acid and formalin-induced inflammation as well as hot plate-induced pain in mice. These inhibitions were statistically significant (P<0.001) and in a dose-dependent fashion. Conclusions: The antiplasmodial and analgesic effects of this plant may in part be mediated through its chemical constituents and it can be concluded that the C. anisata possess significant antimalarial and analgesic properties.

  12. Computer Modeling of Human Delta Opioid Receptor

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    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.

  13. 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...

  14. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H;

    2015-01-01

    Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double......TMS. In the remaining 14 conditioning modulation studies either absence of effects or ambiguous effects by MOR-antagonists, were observed. In the STP-studies, no effect of the opioid-blockade could be demonstrated in 5 out of 6 secondary hyperalgesia studies. The direction of MOR-antagonist dependent effects upon pain...

  15. [Opioid-induced hyperalgesia. Pathophysiology and clinical relevance].

    Science.gov (United States)

    Koppert, W

    2004-05-01

    Opioids are the drugs of choice for the treatment of moderate to severe acute and chronic pain. However, clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that administration of opioids can activate both pain inhibitory and pain facilitatory systems. Acute receptor desensitization via uncoupling of the receptor from G-proteins, up-regulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA) receptor system, as well as descending facilitation, have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. Numerous reports exist demonstrating that opioid-induced hyperalgesia is observed both in animal and human experimental models. Brief exposures to micro-receptor agonists induce long-lasting hyperalgesic effects for days, which might by reflected by clinical observations that large doses of intraoperative micro-receptor agonists increased postoperative pain and morphine consumption. Furthermore, the prolonged use of opioids in patients often requires increasing doses and may be accompanied by the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs like NMDA-antagonists, alpha(2)-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor selectivity.

  16. Effect of Opioid on Adult Hippocampal Neurogenesis

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    Yue Zhang

    2016-01-01

    Full Text Available 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.

  17. [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

  18. Analgesic Effect of Gabapentin on Post-Operative Pain After Arthroscopic Anterior Cruciate Ligament Reconstruction

    Directory of Open Access Journals (Sweden)

    Mario I. Ortiz

    2014-03-01

    Full Text Available To the Editor Mardani-Kivi et al presented results about a triple blinded randomized controlled trial with gabapentin in patients that underwent anterior cruciate ligament (ACL reconstruction (1. In their manuscript, the introduction section is very illustrative about the subject. With respect to methodology, it is well known that the physical diagnosis of ACL injury is particularly difficult in several patients, and partial ACL tears are also difficult to diagnose on physical examination. In this particular case, how did the authors obtain the diagnosis of ACL in the patients? Likewise, ACL reconstruction can be delayed several weeks or months until the swelling has decreased and there is an appropriate range of motion. For this reason, I want to ask: was the cause of the ACL injury homogeneous in all patients?; was the time delay of the surgery the same for everyone; and was the type of damage the same for all participants? Meperidine is an opioid with analgesic effects. The American Pain Society and the Institute for Safe Medication Practice (ISMP do not recommend meperidine use as pain relieving medication or they recommend it only in very special cases and with many precautions during its administration (2, 3. What was the rationale of the authors choosing meperidine as analgesic drug? In this same sense, authors did not indicate in their manuscript whether meperidine was administered by oral, intramuscular or intravenous pathways or patient-controlled analgesia. The time schedule of meperidine administration was not indicate in the manuscript; was meperidine administered q4h or q6h? How many doses were received by patients? I think it was a mistake to publish the demographic data of all patients (n=114. You had to eliminate the patients deleted in the presentation of the demographic characteristics of the patients (n=108, that is more correct. Table 2 and 3 were poorly prepared. Table 2 has missing data about the results at 24 hours in the

  19. 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.

  20. Effect of antipyretic analgesics on immune responses to vaccination.

    Science.gov (United States)

    Saleh, Ezzeldin; Moody, M Anthony; Walter, Emmanuel B

    2016-09-01

    While antipyretic analgesics are widely used to ameliorate vaccine adverse reactions, their use has been associated with blunted vaccine immune responses. Our objective was to review literature evaluating the effect of antipyretic analgesics on vaccine immune responses and to highlight potential underlying mechanisms. Observational studies reporting on antipyretic use around the time of immunization concluded that their use did not affect antibody responses. Only few randomized clinical trials demonstrated blunted antibody response of unknown clinical significance. This effect has only been noted following primary vaccination with novel antigens and disappears following booster immunization. The mechanism by which antipyretic analgesics reduce antibody response remains unclear and not fully explained by COX enzyme inhibition. Recent work has focused on the involvement of nuclear and subcellular signaling pathways. More detailed immunological investigations and a systems biology approach are needed to precisely define the impact and mechanism of antipyretic effects on vaccine immune responses. PMID:27246296

  1. 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

  2. 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.

  3. 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.

  4. 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.)

  5. 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

  6. Effect of opioid prescribing guidelines in primary care.

    Science.gov (United States)

    Chen, Jonathan H; Hom, Jason; Richman, Ilana; Asch, Steven M; Podchiyska, Tanya; Johansen, Nawal Atwan

    2016-08-01

    Long-term opioid use for noncancer pain is increasingly prevalent yet controversial given the risks of addiction, diversion, and overdose. Prior literature has identified the problem and proposed management guidelines, but limited evidence exists on the actual effectiveness of implementing such guidelines in a primary care setting.A multidisciplinary working group of institutional experts assembled comprehensive guidelines for chronic opioid prescribing, including monitoring and referral recommendations. The guidelines were disseminated in September 2013 to our medical center's primary care clinics via in person and electronic education.We extracted electronic medical records for patients with noncancer pain receiving opioid prescriptions (Rxs) in seasonally matched preintervention (11/1/2012-6/1/2013) and postintervention (11/1/2013-6/1/2014) periods. For patients receiving chronic (3 or more) opioid Rxs, we assessed the rates of drug screening, specialty referrals, clinic visits, emergency room visits, and quantity of opioids prescribed.After disseminating guidelines, the percentage of noncancer clinic patients receiving any opioid Rxs dropped from 3.9% to 3.4% (P = 0.02). The percentage of noncancer patients receiving chronic opioid Rxs decreased from 2.0% to 1.6% (P = 0.03). The rate of urine drug screening increased from 9.2% to 17.3% (P = 0.005) amongst noncancer chronic opioid patients. No significant differences were detected for other metrics or demographics assessed.An educational intervention for primary care opioid prescribing is feasible and was temporally associated with a modest reduction in overall opioid Rx rates. Provider use of routine drug screening increased, but overall rates of screening and specialty referral remained low despite the intervention. Despite national pressures to introduce opioid prescribing guidelines for chronic pain, doing so alone does not necessarily yield substantial changes in clinical practice.

  7. 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

  8. 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...

  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. 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.

  12. Managing cancer pain at the end of life with multiple strong opioids: a population-based retrospective cohort study in primary care.

    Directory of Open Access Journals (Sweden)

    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

  13. 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

  14. Superpotent [Dmt¹] dermorphin tetrapeptides containing the 4-aminotetrahydro-2-benzazepin-3-one scaffold with mixed μ/δ opioid receptor agonistic properties.

    Science.gov (United States)

    Vandormael, Bart; Fourla, Danai-Dionysia; Gramowski-Voss, Alexandra; Kosson, Piotr; Weiss, Dieter G; Schröder, Olaf H-U; Lipkowski, Andrzej; Georgoussi, Zafiroula; Tourwé, Dirk

    2011-11-24

    Novel dermorphin tetrapeptides are described in which Tyr(1) is replaced by Dmt(1), where d-Ala(2) and Gly(4) are N-methylated, and where Phe(3)-Gly(4) residue is substituted by the constrained Aba(3)-Gly(4) peptidomimetic. Most of these peptidic ligands displayed binding affinities in the nanomolar range for both μ- and δ-opioid receptors but no detectable affinity for the κ-opioid receptor. Measurements of cAMP accumulation, phosphorylation of extracellular signal-regulated kinase (ERK1/2) in HEK293 cells stably expressing each of these receptors individually, and functional screening in primary neuronal cultures confirmed the potent agonistic properties of these peptides. The most potent ligand H-Dmt-NMe-d-Ala-Aba-Gly-NH(2) (BVD03) displayed mixed μ/δ opioid agonist properties with picomolar functional potencies. Functional electrophysiological in vitro assays using primary cortical and spinal cord networks showed that this analogue possessed electrophysiological similarity toward gabapentin and sufentanil, which makes it an interesting candidate for further study as an analgesic for neuropathic pain.

  15. Determination of structure-activity relationships between fentanyl analogs and human μ-opioid receptors based on active binding site models

    Institute of Scientific and Technical Information of China (English)

    Ming Liu; Xiaoli Liu; Ping Wan; Qiangsan Wu; Wenxiang Hu

    2011-01-01

    Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective μ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SiteID showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains (TM) among TM3, TM5, TM6, and TM7. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.

  16. A randomized, phase 2 study investigating TRV130, a biased ligand of the μ-opioid receptor, for the intravenous treatment of acute pain.

    Science.gov (United States)

    Viscusi, Eugene R; Webster, Lynn; Kuss, Michael; Daniels, Stephen; Bolognese, James A; Zuckerman, Seth; Soergel, David G; Subach, Ruth Ann; Cook, Emily; Skobieranda, Franck

    2016-01-01

    Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 is a structurally novel biased ligand of the μ-opioid receptor that activates G protein signaling with little β-arrestin recruitment. In this phase 2, randomized, placebo- and active-controlled study, we investigated the efficacy and tolerability of TRV130 in acute pain after bunionectomy. We used an adaptive study design in which 144 patients experiencing moderate-to-severe acute pain after bunionectomy were randomized to receive double-blind TRV130, placebo, or morphine in a pilot phase. After pilot phase analysis, 195 patients were randomized to receive double-dummy TRV130 0.5, 1, 2, or 3 mg every 3 hours (q3h); placebo; or morphine 4 mg q4h intravenously. The primary end point was the time-weighted average change in numeric rating scale pain intensity over the 48-hour treatment period. Secondary end points included stopwatch and categorical assessments of pain relief. Safety and tolerability were also assessed. TRV130 2 and 3 mg q3h, and morphine 4 mg q4h produced statistically greater mean reductions in pain intensity than placebo over 48 hours (P opioid receptor activation is a promising target for development of novel analgesics.

  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.

  18. Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.

    Science.gov (United States)

    Cui, Yijun; Ostlund, Sean B; James, Alex S; Park, Chang Sin; Ge, Weihong; Roberts, Kristofer W; Mittal, Nitish; Murphy, Niall P; Cepeda, Carlos; Kieffer, Brigitte L; Levine, Michael S; Jentsch, James David; Walwyn, Wendy M; Sun, Yi E; Evans, Christopher J; Maidment, Nigel T; Yang, X William

    2014-02-01

    μ-opioid receptors (MORs) are necessary for the analgesic and addictive effects of opioids such as morphine, but the MOR-expressing neuronal populations that mediate the distinct opiate effects remain elusive. Here we devised a new conditional bacterial artificial chromosome rescue strategy to show, in mice, that targeted MOR expression in a subpopulation of striatal direct-pathway neurons enriched in the striosome and nucleus accumbens, in an otherwise MOR-null background, restores opiate reward and opiate-induced striatal dopamine release and partially restores motivation to self administer an opiate. However, these mice lack opiate analgesia or withdrawal. We used Cre-mediated deletion of the rescued MOR transgene to establish that expression of the MOR transgene in the striatum, rather than in extrastriatal sites, is needed for the restoration of opiate reward. Our study demonstrates that a subpopulation of striatal direct-pathway neurons is sufficient to support opiate reward-driven behaviors and provides a new intersectional genetic approach to dissecting neurocircuit-specific gene function in vivo.

  19. Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain.

    Science.gov (United States)

    Jhaveri, Maulik D; Richardson, Denise; Kendall, David A; Barrett, David A; Chapman, Victoria

    2006-12-20

    Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states. The aim of this study was to determine whether local inhibition of FAAH alters nociceptive responses of spinal neurons in the spinal nerve ligation model of neuropathic pain. Electrophysiological studies were performed 14-18 d after spinal nerve ligation or sham surgery, and the effects of the FAAH inhibitor cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597) on mechanically evoked responses of spinal neurons and levels of endocannabinoids were determined. Intraplantar URB597 (25 microg in 50 microl) significantly (p < 0.01) attenuated mechanically evoked responses of spinal neurons in sham-operated rats. Effects of URB597 were blocked by the cannabinoid 1 receptor (CB1) antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] (30 microg in 50 microl) and the opioid receptor antagonist naloxone. URB597 treatment increased levels of anandamide, 2-arachidonyl glycerol, and oleoyl ethanolamide in the ipsilateral hindpaw of sham-operated rats. Intraplantar URB597 (25 microg in 50 microl) did not, however, alter mechanically evoked responses of spinal neurons in spinal nerve ligated (SNL) rats or hindpaw levels of endocannabinoids. Intraplantar injection of a higher dose of URB597 (100 microg in 50 microl) significantly (p < 0.05) attenuated evoked responses of spinal neurons in SNL rats but did not alter hindpaw levels of endocannabinoids. Spinal administration of URB597 attenuated evoked responses of spinal neurons and elevated levels of endocannabinoids in sham-operated and SNL rats. These data suggest that peripheral FAAH activity may be altered or that alternative pathways of metabolism have greater importance in SNL rats.

  20. 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.

  1. Pharmacological characterization of the dermorphin analog [Dmt(1)]DALDA, a highly potent and selective mu-opioid peptide.

    Science.gov (United States)

    Neilan, C L; Nguyen, T M; Schiller, P W; Pasternak, G W

    2001-05-01

    The dermorphin-derived peptide [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)), labels mu-opioid receptors with high affinity and selectivity in receptor binding assays. In mouse, radiant heat tail-flick assay [Dmt(1)]DALDA produced profound spinal and supraspinal analgesia, being approximately 5000- and 100-fold more potent than morphine on a molar basis, respectively. When administered systemically, [Dmt(1)]DALDA was over 200-fold more potent than morphine. Pharmacologically, [Dmt(1)]DALDA was distinct from morphine. [Dmt(1)]DALDA displayed no cross-tolerance to morphine in the model used and it retained supraspinal analgesic activity in morphine-insensitive CXBK mice. Supraspinally, it also differed from morphine in its lack of sensitivity towards naloxonazine. Finally, in antisense mapping studies, [Dmt(1)]DALDA was insensitive to MOR-1 exon probes that reduced morphine analgesia, implying a distinct receptor mechanism of action. Thus, [Dmt(1)]DALDA is an interesting and extraordinarily potent, systemically active peptide analgesic, raising the possibility of novel approaches in the design of clinically useful drugs.

  2. 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

  3. Evaluation of analgesic activity of Aegle marmelos steam bark in experimental animals

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    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

  4. The mu opioid receptor A118G gene polymorphism moderates effects of trait anger-out on acute pain sensitivity.

    Science.gov (United States)

    Bruehl, Stephen; Chung, Ok Y; Burns, John W

    2008-10-15

    Both trait anger-in (managing anger through suppression) and anger-out (managing anger through direct expression) are related to pain responsiveness, but only anger-out effects involve opioid mechanisms. Preliminary work suggested that the effects of anger-out on postoperative analgesic requirements were moderated by the A118G single nucleotide polymorphism of the mu opioid receptor gene. This study further explored these potential genotypexphenotype interactions as they impact acute pain sensitivity. Genetic samples and measures of anger-in and anger-out were obtained in 87 subjects (from three studies) who participated in controlled laboratory acute pain tasks (ischemic, finger pressure, thermal). McGill Pain Questionnaire (MPQ) Sensory and Affective ratings for each pain task were standardized within studies, aggregated across pain tasks, and combined for analyses. Significant anger-outxA118G interactions were observed (p'seffects tests for both pain measures revealed that whereas anger-out was nonsignificantly hyperalgesic in subjects homozygous for the wild-type allele, anger-out was significantly hypoalgesic in those with the variant G allele (p'spain sensitivity in high anger-out subjects with the G allele and heightened pain sensitivity in low anger-out subjects with the G allele relative to responses in homozygous wild-type subjects. No genetic moderation was observed for anger-in, although significant main effects on MPQ-Affective ratings were noted (peffects were due to overlap with negative affect, but anger-outxA118G interactions were not, suggesting unique effects of expressive anger regulation. Results support opioid-related genotypexphenotype interactions involving trait anger-out.

  5. 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

  6. Cognitive function in patients with chronic pain treated with opioids

    DEFF Research Database (Denmark)

    Kurita, G P; de Mattos Pimenta, C A; Braga, P E;

    2012-01-01

    The paucity of studies regarding cognitive function in patients with chronic pain, and growing evidence regarding the cognitive effects of pain and opioids on cognitive function prompted us to assess cognition via neuropsychological measurement in patients with chronic non-cancer pain treated...... with opioids....

  7. δ-OPIOID RECEPTOR ADAPTATION IN NEUROBLASTOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    D-M,Chuang; M.Belchers; J.Barg; J.Rowinski; G.Clark; C.A.Gloeckner; A.Ho; X-M.Gao; C.J.Coscia

    1993-01-01

    The mechanisms underlying tolerance and dependence arising from chronic opioid exposure are poorly understood. However, the development of neuroblastoma and neurohybrid cell culturea, has provided a simplified model for the atudy of opioid receptor adaptation. Using neuroblastoma NG108-15 cells,

  8. Evidenced-based treatment of opioid-dependent patients

    NARCIS (Netherlands)

    W. van den Brink; C. Haasen

    2006-01-01

    Objective: To provide an overview of treatment options for opioid-dependent patients. Method: We screened all published studies on the treatment of opioid dependence, with a special focus on systematic literature reviews, formal metaanalyses, and recent trials. Results: Both clinical experience and

  9. Treating opioid dependence. Growing implications for primary care.

    Science.gov (United States)

    Krantz, Mori J; Mehler, Philip S

    2004-02-01

    Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

  10. Opioid-induced hyperalgesia: clinically relevant or extraneous research phenomenon?

    Science.gov (United States)

    Tompkins, D Andrew; Campbell, Claudia M

    2011-04-01

    Opioids have become the unequivocal therapy of choice in treating many varieties of chronic pain. With the increased prescription of opioids, some unintended consequences have occurred. After prolonged opioid exposure, opioid-induced hyperalgesia (OIH), the paradoxical effect that opioid therapy may in fact enhance or aggravate preexisting pain, may occur. Over the past several decades, an increasing number of laboratory and clinical reports have suggested lowered pain thresholds and heightened atypical pain unrelated to the original perceived pain sensations as hallmarks of OIH. However, not all evidence supports the clinical importance of OIH, and some question whether the phenomenon exists at all. Here, we present a nonexhaustive, brief review of the recent literature. OIH will be reviewed in terms of preclinical and clinical evidence for and against its existence; recommendations for clinical evaluation and intervention also will be discussed.

  11. 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...

  12. Disruption of gut homeostasis by opioids accelerates HIV disease progression

    Directory of Open Access Journals (Sweden)

    Jingjing eMeng

    2015-06-01

    Full Text Available Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population.

  13. 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.

  14. 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

  15. Quaternary ammonium salt derivatives of allylphenols with peripheral analgesic effect

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    A. B de Oliveira

    1991-01-01

    Full Text Available Ammonium salt derivatives of natural allylphenols were synthesized with the purpose of obtaining potential peripheral analgesics. These drugs, by virtue of their physicochemical properties, would not be able to cross the blood brain barrier. Their inability to enter into the central nervous system (CNS should prevent several adverse effects observed with classical opiate analgesics (Ferreira et al., 1984. Eugenol (1 O-methyleugenol (5 and safrole (9 were submitted to nitration, reduction and permethylation, leading to the ammonium salts 4, 8 and 12. Another strategy applied to eugenol (1, consisting in its conversion to a glycidic ether (13, opening the epoxide ring with secondary amines and methylation, led to the ammonium salts 16 and 17. All these ammonium salts showed significant peripheral analgesic action, in modified version of the Randall-Sellito test (Ferreira et al. 1978, at non-lethal doses. The ammonium salt 8 showed an activity comparable to that of methylnalorphinium, the prototype of an ideal peripheral analgesic (Ferreira et al., 1984.

  16. 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.

  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

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    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. [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

  19. In vivo delta opioid receptor internalization controls behavioral effects of agonists.

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    Amynah A A Pradhan

    Full Text Available BACKGROUND: GPCRs regulate a remarkable diversity of biological functions, and are thus often targeted for drug therapies. Stimulation of a GPCR by an extracellular ligand triggers receptor signaling via G proteins, and this process is highly regulated. Receptor activation is typically accompanied by desensitization of receptor signaling, a complex feedback regulatory process of which receptor internalization is postulated as a key event. The in vivo significance of GPCR internalization is poorly understood. In fact, the majority of studies have been performed in transfected cell systems, which do not adequately model physiological environments and the complexity of integrated responses observed in the whole animal. METHODS AND FINDINGS: In this study, we used knock-in mice expressing functional fluorescent delta opioid receptors (DOR-eGFP in place of the native receptor to correlate receptor localization in neurons with behavioral responses. We analyzed the pain-relieving effects of two delta receptor agonists with similar signaling potencies and efficacies, but distinct internalizing properties. An initial treatment with the high (SNC80 or low (AR-M100390 internalizing agonist equally reduced CFA-induced inflammatory pain. However, subsequent drug treatment produced highly distinct responses. Animals initially treated with SNC80 showed no analgesic response to a second dose of either delta receptor agonist. Concomitant receptor internalization and G-protein uncoupling were observed throughout the nervous system. This loss of function was temporary, since full DOR-eGFP receptor responses were restored 24 hours after SNC80 administration. In contrast, treatment with AR-M100390 resulted in retained analgesic response to a subsequent agonist injection, and ex vivo analysis showed that DOR-eGFP receptor remained G protein-coupled on the cell surface. Finally SNC80 but not AR-M100390 produced DOR-eGFP phosphorylation, suggesting that the two

  20. From the potent and selective mu opioid receptor agonist H-Dmt-d-Arg-Phe-Lys-NH(2) to the potent delta antagonist H-Dmt-Tic-Phe-Lys(Z)-OH.

    Science.gov (United States)

    Balboni, Gianfranco; Cocco, Maria Teresa; Salvadori, Severo; Romagnoli, Romeo; Sasaki, Yusuke; Okada, Yoshio; Bryant, Sharon D; Jinsmaa, Yunden; Lazarus, Lawrence H

    2005-08-25

    H-Dmt-d-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA) binds with high affinity and selectivity to the mu opioid receptor and is a potent and long-acting analgesic. Substitution of d-Arg in position 2 with Tic and masking of the lysine amine side chain by Z protection and of the C-terminal carboxylic function instead of the amide function transform a potent and selective mu agonist into a potent and selective delta antagonist H-Dmt-Tic-Phe-Lys(Z)-OH. Such a delta antagonist could be used as a pharmacological tool.

  1. 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

  2. Patrones de uso de los opioides mayores en el dolor de origen neuropático

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    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. 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

  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. 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.

  7. 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

  8. Post-operative pain and analgesic requirements after paravertebral block for mastectomy: A randomized controlled trial of different concentrations of bupivacaine and fentanyl

    Directory of Open Access Journals (Sweden)

    V Bhuvaneswari

    2012-01-01

    Full Text Available Background: Paravertebral block (PVB is useful for post-operative analgesia after breast surgery. Bupivacaine is used for PVB at higher concentrations (0.5%, which may lead to systemic toxicity after absorption. Therefore, we proposed to evaluate the efficacy of lower concentrations of bupivacaine with and without fentanyl for thoracic PVB in patients undergoing surgery for carcinoma breast. Methods: Forty-eight patients scheduled for surgery for breast cancer were enrolled in this prospective, randomized, double-blinded, placebo-controlled trial and were allocated to one of four groups: 0.25% bupivacaine with epinephrine 5 mcg/ ml, 0.25% bupivacaine + epinephrine 5 mcg/ ml with 2 mcg/ml fentanyl, 0.5% bupivacaine + epinephrine 5 mcg/ml or isotonic saline. PVB was performed and 0.3 ml/kg of the test drug was administered before induction of general anaesthesia. The primary outcome assessed was post-operative analgesic requirement for a period of 24 h. Secondary outcome measures were post-operative pain scores at rest and on movement of the arm, latency to first opioid, post-operative nausea and vomiting, quality of sleep, ability to move arm and patient satisfaction. Results: The patient characteristics and anaesthetic technique were comparable among the groups. The rescue analgesic consumption as well as cumulative pain scores at rest and on movement were significantly less in 0.25% bupivacaine+epinephrine with fentanyl and 0.5% bupivacaine+epinephrine groups (P<0.05. The average duration of analgesia was found to be 18 h after either 0.25% bupivacaine with epinephrine+fentanyl or 0.5% bupivacaine with epinephrine. Conclusions: Lower concentrations of bupivacaine can be combined with fentanyl to achieve analgesic efficacy similar to bupivacaine at higher concentrations, decreasing the risk of toxicity in PVB.

  9. The role of peroxynitrite in opioid tolerance or opioid induced hyperalgesia%过氧亚硝酸阴离子引起阿片耐受或痛觉过敏的研究进展

    Institute of Scientific and Technical Information of China (English)

    王春艳; 王国林

    2014-01-01

    背景 吗啡等阿片类药物是临床疼痛治疗的代表性药物,主要用于急、慢性疼痛和癌痛的治疗,但长期应用可产生诸多副作用,如吗啡耐受和痛觉过敏等,从而大大限制了阿片类药物在临床上的使用. 目的 通过对近年过氧亚硝基阴离子在吗啡耐受和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 就过氧亚硝基阴离子的生成途径、消除方式和过氧亚硝基阴离子在阿片耐受或痛觉过敏中的作用方式进行综述.得出如下结论,过氧亚硝基阴离子主要通过硝基化体内蛋白质酪氨酸残基、激活神经炎症和促进细胞凋亡3个方面,引起阿片耐受或痛觉过敏. 趋向 随着越来越多的学者对过氧亚硝基阴离子在吗啡耐受和痛觉过敏中发挥的重要作用达成共识,过氧亚硝基阴离子有望成为临床疼痛治疗的新靶点.%Background Opioids are the most powerful analgesics for the treatment of acute pain,chronic pain and cancer pain.Although opioids have analgesic effect,long term opioids exposure can induce many side effects including morphine tolerance and hyperalgesia.The use of opioids,therefore,is largely limited in clinical settings.Objective The relevant literatures in recent years involved in the role of peroxynitrite in morphine tolerance and hyperalgesia were summarized,which helps readership to update the latest information about this topic.Content The generation of peroxynitrite,eliminating methods and the role of peroxynitrite in opioids tolerance or hyperalgesia were reviewed in this article.Those researches suggest that peroxynitrite plays an important role in morphine tolerance and hyperalgesia mainly through nitrating protein tyrosine residues,activating the neuroinflammation and promoting neuron apoptosis.Trend Since the effect of peroxynitrite is widely acknowledged,peroxynitrite may become a new target to relieve pain in

  10. 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,...

  11. 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.

  12. Opioid regulation of Pavlovian overshadowing in fear conditioning.

    Science.gov (United States)

    Zelikowsky, Moriel; Fanselow, Michael S

    2010-08-01

    In Pavlovian overshadowing, a stimulus that predicts a biologically important event reduces conditioning to another, equally predictive stimulus. We tested the effects of an opioid antagonist and dopamine agonist on the ability of a salient white noise to overshadow a less salient light. Rats were conditioned to fear a light or a noise-light compound using a mild footshock. Compound-conditioned rats trained under the saline vehicle revealed significant overshadowing of the light by the noise. This overshadowing effect was significantly attenuated in rats trained under the opioid antagonist naltrexone, consistent with an opioid-mediated negative feedback model of conditioning. In line with predictions made by negative feedback-type models, we failed to obtain overshadowing with few trials, suggesting that the processes underlying conditioning during initial trials do not contribute to the opioid-dependent Pavlovian overshadowing obtained in our preparation. Lastly, we compared the involvement of dopamine-mediated and opioid-mediated processes in overshadowing by conditioning rats under the partial dopamine D1 receptor agonist SKF 38393 or the opioid antagonist naltrexone. Both naltrexone and SKF 38393 were found to attenuate overshadowing; however, the behavioral profiles produced by each pharmacological manipulation were distinct. Collectively, these studies demonstrate an important role for both opioid- and dopamine-mediated processes in multiple-trial overshadowing.

  13. 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

  14. Analgesic effect of parecoxib and flurbiprofen axetil for patients undergoing laparoscopic cholecystectomy and their influences on platelet aggregation

    Institute of Scientific and Technical Information of China (English)

    JI Fu-hai; JIN Xin; YANG Jian-ping; ZAN Li-li

    2010-01-01

    It is known that opioids produce postoperative analgesia,while it can also cause, especially in large doses, side effects like nausea, vomiting, constipation, syncope, skin itching, urinary retention and even respiratory inhibition.These factors have all greatly limited its clinical use for treating postoperative pain. Meanwhile, non-steroidal anti-inflammatory drags (NSAIDs) play an increasingly important role in postoperative analgesia. Some studies suggest that NSAIDS may be neural protective in cerebral ischemic conditions.1 Flurbiprofen axetil, which utilizes a lipid microsphere drag delivery system, may promote accumulation of flurbiprofen granular at inflammatory lesion sites and absorption by inflammatory cells,2 both factors which help to effectively target therapy. Parecoxib is the first selective cyclooxygenase-2 (COX-2) inhibitor available for intravenous injection, which is beneficial to patients susceptible to NSAIDs3 and those prone to gastrointestinal disturbances like perforation, ulcers, and bleeding.4 This investigation assesses the analgesic effect of parecoxib and flurbiprofen axetil for patients undergoing laparoscopic cholecystectomy and their influence on platelet aggregation in order to offer some guidance for clinic practice.

  15. 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

  16. PRE-CLINICAL SCREENING OF INDIGENOUS MEDICINAL PLANT PHYLLANTHUS AMARUS FOR ITS ANALGESIC ACTIVITY

    Directory of Open Access Journals (Sweden)

    Sundeep Hegde K

    2014-11-01

    Full Text Available Background: Phyllanthus amarus aqueous extract was investigated for its central and peripheral analgesic activities. Objectives: To evaluate the central and peripheral analgesic activities of aqueous extract of Phyllanthus amarus. Materials and Methods: The aqueous extract of Phyllanthus amarus was prepared using soxhlet apparatus. An in vivo study using Swiss albino mice was done to screen the central and peripheral analgesic activity of P.amarus extract. The extract was administered at a dose of 100 mg/kg body weight I.P. The peripheral analgesic activity was assessed using acetic acid induced writhing test.The central analgesic activity was assessed using Eddy’s hot plate apparatus. Results: The aqueous extract of P.amarus showed significant (p<0.05 peripheral and central analgesic activity.Conclusion: This study demonstrated that P.amarus aqueous extract exhibited significant analgesic activities.

  17. 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

  18. The cognitive effects of opioids in cancer: a systematic review

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Lundorff, Lena; Pimenta, Cibele Andrucioli de Mattos;

    2008-01-01

    OBJECTIVE AND METHODS: In order to better understand the effects of opioids on the cognitive function in cancer pain patients, a literature search was performed in PubMed, EMBASE, PsycInfo, CINAHL and Lilacs databases. Ten controlled trials were selected and classified according to the study design......, the level of evidence, and opioid regimen. RESULT: Six studies reported association between poor cognitive performance (reaction time, attention, balance, and memory) and opioid use. CONCLUSION: These cognitive deficits were captured with neuropsychological tests; however, their clinical relevance is still...

  19. 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...

  20. Opioid antinociception and positive reinforcement are mediated by different types of opioid receptors.

    Science.gov (United States)

    Pollerberg, G E; Costa, T; Shearman, G T; Herz, A; Reid, L D

    1983-10-17

    Fentanyl (FEN) and diprenorphine's (DIPR) potentials for analgesia and reinforcement were assayed using rats. Analgesia was measured by the classic tail-flick test. The test germane to opioid reinforcement involved measuring pressing rates for direct electrical stimulation of the lateral hypothalamus and ventral tegmental area. FEN, as does morphine and heroin, produced strong analgesia and enhanced pressing rates for brain stimulation. DIPR produced no analgesia and antagonized FEN's analgesia. DIPR, at doses antagonizing FEN's analgesia, enhanced pressing for brain stimulation. DIPR's enhancement of pressing was antagonized by naloxone (100 micrograms/kg). When FEN and DIPR were given concurrently, pressing for brain stimulation was not reduced and was greater than after FEN alone was given. These data support a conclusion that different types of receptors are associated with opioid analgesia and reinforcement.

  1. 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...

  2. 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.

  3. Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic.

    Science.gov (United States)

    Balboni, Gianfranco; Salvadori, Severo; Marczak, Ewa D; Knapp, Brian I; Bidlack, Jean M; Lazarus, Lawrence H; Peng, Xuemei; Si, Yu Gui; Neumeyer, John L

    2011-02-01

    Bifunctional ligands containing an ester linkage between morphine and the δ-selective pharmacophore Dmt-Tic were synthesized, and their binding affinity and functional bioactivity at the μ, δ and κ opioid receptors determined. Bifunctional ligands containing or not a spacer of β-alanine between the two pharmacophores lose the μ agonism deriving from morphine becoming partial μ agonists 4 or μ antagonists 5. Partial κ agonism is evidenced only for compound 4. Finally, both compounds showed potent δ antagonism.

  4. Progress of mechanisms and treatment regimens of neuraxial opioid-induced pruritus%椎管内注射阿片类药物所致瘙痒的发生机制及治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    张静; 刘秀兰; 上官王宁

    2013-01-01

    morphine-induced itching,which offers the possibility to develop a novel therapeutic strategy to specifically attenuate itch without affecting the analgesic efficacy of opioids.

  5. Identification and characterization of seven new exon 11-associated splice variants of the rat mu opioid receptor gene, OPRM1

    Directory of Open Access Journals (Sweden)

    Pasternak Gavril W

    2011-01-01

    Full Text Available Abstract Background The mouse mu opioid receptor (OPRM1 gene undergoes extensive alternative splicing at both the 3'- and 5'-ends of the gene. Previously, several C-terminal variants generated through 3' splicing have been identified in the rat OPRM1 gene. In both mice and humans 5' splicing generates a number of exon 11-containing variants. Studies in an exon 11 knockout mouse suggest the functional importance of these exon 11-associated variants in mediating the analgesic actions of a subset of mu opioids, including morphine-6β-glucuronide (M6G and heroin, but not others such as morphine and methadone. We now have examined 5' splicing in the rat. Results The current studies identified in the rat a homologous exon 11 and seven exon 11-associated variants, suggesting conservation of exon 11 and its associated variants among mouse, rat and human. RT-PCR revealed marked differences in the expression of these variants across several brain regions, implying region-specific mRNA processing of the exon 11-associated variants. Of the seven rat exon 11-associated variants, four encoded the identical protein as found in rMOR-1, two predicted 6 TM variants, and one, rMOR-1H2, generated a novel N-terminal variant in which a stretch of an additional 50 amino acids was present at the N-terminus of the previously established rMOR-1 sequence. When expressed in CHO cells, the presence of the additional 50 amino acids in rMOR-1H2 significantly altered agonist-induced G protein activation with little effect on opioid binding. Conclusion The identification of the rat exon 11 and its associated variants further demonstrated conservation of 5' splicing in OPRM1 genes among rodents and humans. The functional relevance of these exon 11 associated variants was suggested by the region-specific expression of their mRNAs and the influence of the N-terminal sequence on agonist-induced G protein coupling in the novel N-terminal variant, rMOR-1H2. The importance of the exon

  6. Using analgesics as tools: young women's treatment for headache

    DEFF Research Database (Denmark)

    Hansen, Dana Lee; Hansen, Ebba Holme; Holstein, Bjørn E

    2008-01-01

    the context of their everyday lives. The central elements in the participants' accounts emerged via a phenomenological approach. Analysis revealed that participants attributed headache to stressful conditions in their everyday lives. Analgesic use in treating headache was found to serve highly valued......'s findings demonstrate a need for health education programs aimed at empowering young women to better manage headaches as well as everyday stress.......In this study, the authors explore the context surrounding young women's use of analgesics to deal with headache. In-depth interviews were conducted with 20 young women between the ages of 16 and 20 in Copenhagen, Denmark. Interviews focused on the young women's experiences with medications within...

  7. 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

  8. Peripheral analgesic effects of ketamine in acute inflammatory pain

    DEFF Research Database (Denmark)

    Pedersen, J L; Galle, T S; Kehlet, H

    1998-01-01

    BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers.......02). Secondary hyperalgesia and suprathreshold pain responses to heat and mechanical stimuli were not significantly affected by local ketamine. No difference between local ketamine and placebo could be detected 1 h and 2 h after the burn. CONCLUSIONS: Ketamine infiltration had brief local analgesic effects......, but several measures of pain and hyperalgesia were unaffected. Therefore, a clinically relevant effect of peripheral ketamine in acute pain seems unlikely....

  9. 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 ...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. [Has ketamine preemptive analgesic effect in patients undergoing abdominal hysterectomy?].

    Science.gov (United States)

    Karaman, Semra; Kocabaş, Seden; Zincircioğlu, Ciler; Firat, Vicdan

    2006-07-01

    The aim of this study was to determine if preemptive use of the NMDA receptor antogonist ketamine decreases postoperative pain in patients undergoing abdominal hystrectomy. A total of 60 patients admitted for total abdominal hysterectomy were included in this study after the approval of the ethic committee, and the patients were randomly classified into three groups. After standart general anaesthesia, before or after incision patients received bolus saline or ketamine. Group S received only saline while Group Kpre received ketamine 0.4 mg/kg before incision and saline after incision, and Group Kpost received saline before incision and 0.4 mg/kg ketamine after incision. Postoperatif analgesia was maintained with i.v. PCA morphine. Pain scores were assessed with Vizüal Analog Scale (VAS), Verbal Rating Scale (VRS) at 1., 2, 3., 4., 8., 12. ve 24. hours postoperatively. First analgesic requirement time, morphine consumption and side effects were recorded. There were no significant differences between groups with respect to VAS / VRS scores, the time for first analgesic dose, and morphine consumption ( p>0.05). Patients in Group S had significantly lower sedation scores than either of the ketamine treated groups ( pketamin had no preemptive analgesic effect in patients undergoing abdominal hysterectomy, but further investigation is needed for different operation types and dose regimens.

  17. 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.

  18. [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

  19. 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.

  20. ANALGESIC ACTIVITY OF ROOT EXTRACT OF SOLANUM MELONGENA LINN ROOT

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    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.