Per-capita consumption of analgesics: a nine-country survey over 20 years.

PubMed

Diener, H-C; Schneider, R; Aicher, B

2008-08-01

There are no reliable data at present on use of analgesics in various countries. We compared per-capita consumption in nine different countries during the period 1986-2005. The per-capita consumption was calculated on the basis of the sales figures of distributors to pharmacies and direct purchases by pharmaceutical companies in a sample of 1,000 pharmacies. The countries studied were: Australia, Austria, Belgium, Canada, France, Germany, Sweden, Switzerland, and the USA. In international comparison Austria, Switzerland, and Germany showed the lowest per-capita consumption of analgesics (approx. 40-50 Standard Units (SU) per capita per year), while in Sweden and France consumption was three times as high. The correlation analysis over the various countries and time points confirmed a significant correlation between use of single analgesics and overall use of analgesics. In Germany, where an allegedly particularly high and constantly rising analgesic use has been discussed controversially (Meiner, Pharm Ind 49:1247-1251, 1987), per-capita consumption of analgesics from 1980 to 2005 remained practically unchanged at approx. 50 SU per capita per year. The prevalence of conditions inducing analgesic use shows appropriate analgesics use on an overall population level.

Design and Synthesis of Mannich bases as Benzimidazole Derivatives as Analgesic Agents.

PubMed

Datar, Prasanna A; Limaye, Saleel A

2015-01-01

Mannich bases were selected for 2D QSAR study to derive meaningful relationship between the structural features and analgesic activity. Using the knowledge of important features a novel series was designed to obtain improved analgesic activity. A series of novel Mannich bases 1-(N-substituted amino)methyl]-2-substituted benzimidazole derivatives were synthesized and were screened for analgesic activity. Some of these compounds showed promising analgesic activity when compared with the standard drug diclofenac sodium.

Analgesic Activity.

PubMed

2016-01-01

Analgesics are agents which selectively relieve pain by acting in the CNS and peripheral pain mediators without changing consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical, and technical problems. Both peripheral and central pain models are included to make the test more evident for the analgesic property of the plant. This chapter highlights methods such as hot plate and formalin and acetic acid-induced pain models to check the analgesic activity of medicinal plants.

Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design.

PubMed

Keppel Hesselink, Jan M; Kopsky, David J; Stahl, Stephen M

2017-01-01

Topical analgesics can be defined as topical formulations containing analgesics or co-analgesics. Since 2000, interest in such formulations has been on the rise. There are, however, four critical issues in the research and development phases of topical analgesics: 1) The selection of the active pharmaceutical ingredient. Analgesics and co-analgesics differ greatly in their mechanism of action, and it is required to find the most optimal fit between such mechanisms of action and the pathogenesis of the targeted (neuropathic) pain. 2) Issues concerning the optimized formulation. For relevant clinical efficacy, specific characteristics for the selected vehicle (eg, cream base or gel base) are required, depending on the physicochemical characteristics of the active pharmaceutical ingredient(s) to be delivered. 3) Well-designed phase II dose-finding studies are required, and, unfortunately, such trials are missing. In fact, we will demonstrate that underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. 4) Selection of clinical end points and innovatively designed phase III trials. End point selection can make or break a trial. For instance, to include numbness together with tingling as a composite end point for neuropathic pain seems stretching the therapeutic impact of an analgesic too far. Given the fast onset of action of topical analgesics (usually within 30 minutes), enrichment designs might enhance the chances for success, as the placebo response might decrease. Topical analgesics may become promising inroads for the treatment of neuropathic pain, once sufficient attention is given to these four key aspects.

Some patients don't need analgesics after surgery.

PubMed Central

McQuay, H J; Bullingham, R E; Moore, R A; Evans, P J; Lloyd, J W

1982-01-01

Postoperative analgesic requirements of 410 patients undergoing elective orthopaedic limb surgery were studied. Premedication and anaesthetic were standardized with no narcotic. Twenty-three patients required no analgesic at all during their hospital stay. The importance of acknowledging the existence of this group of patients is discussed. The distribution of time to first analgesic requirement for the other patients was obtained. The importance of knowing the distribution for particular operative procedures and the effect of analgesic interventions such as premedication is discussed. PMID:7120254

Role of Dentists in Prescribing Opioid Analgesics and Antibiotics: An Overview.

PubMed

Dana, Ralph; Azarpazhooh, Amir; Laghapour, Nima; Suda, Katie J; Okunseri, Christopher

2018-04-01

Opioid analgesics and antibiotics prescribed by dentists is a useful and cost-effective measure when prescribed appropriately. Common dental conditions are best managed by extracting the offending tooth, restoring the tooth with an appropriate filling material, performing root canal therapy, and/or fabricating a prosthesis for the edentulous space. Unnecessary prescription of opioid analgesics and antibiotics to treat dental pain and bacterial infection is a growing public health concern. This article highlights the state of the literature on opioid analgesic and antibiotic prescribing practices in dentistry, the impact of opioid analgesic overdose, and prevention strategies to reduce opioid analgesics and antibiotic overprescription. Copyright © 2017 Elsevier Inc. All rights reserved.

Study of analgesic effect of earthworm extract

PubMed Central

Luo, Wei; Deng, Zhen-han; Li, Rui; Cheng, Guo; Kotian, Ronak Naveenchandra

2017-01-01

Pain represents a major clinical problem and one which has exercised generations of healthcare professionals. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, the analgesic effects of earthworm extract (EE) are seldom studied. Hence, we evaluated the analgesic effects of EE in mice. The obtained data showed that EE increased pain threshold and exhibited peripheral but not central analgesic effects in mice; evidenced by increased inhibition ratio in acetic acid writhing test and formalin test, whereas only slight increase in inhibition ratio in hot plate test and tail immersion test. In addition, EE decreased serum norepinephrine (NE), 5-hydroxytryptamine (5-HT), and nitric oxide (NO) synthase (NOS) concentration, similar to other analgesic drugs like morphine and aspirin. In a nutshell, the obtained data have demonstrated that EE has peripheral analgesic properties and could be used as a promising analgesic drug. PMID:29273677

Efficacy of Common Analgesics for Postsurgical Pain in Rats

PubMed Central

Waite, Megan E; Tomkovich, Ashleigh; Quinn, Tammie L; Schumann, Alan P; Dewberry, L Savannah; Totsch, Stacie K; Sorge, Robert E

2015-01-01

Each year, millions of rats undergo surgery for research purposes and receive analgesics to alleviate pain. We sought to evaluate the efficacy of common analgesics in tests of hot-plate nociception and postsurgical pain by using the Rat Grimace Scale. Rats received a single dose of one of several drug–dose combinations and were tested by using the hot-plate test (acute pain) or after laparotomy (with either prophylactic or intraoperative analgesic). The efficacy of analgesics for hot-plate pain was generally not predictive of efficacy for surgical pain. Carprofen and ketoprofen were rarely effective in any of the conditions tested. With the exception of the opioid buprenorphine, several of the drugs we tested required higher-than-recommended doses to alleviate pain. Taken together, our data suggest that current analgesic use frequently is insufficient, and many rats may experience significant postsurgical pain even when analgesics are used in commonly recommended doses. PMID:26224443

Purification and function of two analgesic and anti-inflammatory peptides from coelomic fluid of the earthworm, Eisenia foetida.

PubMed

Li, Chunlong; Chen, Mengrou; Li, Xiaojie; Yang, Meifeng; Wang, Ying; Yang, Xinwang

2017-03-01

The potential application of anti-inflammatory and analgesic compounds in medication and therapeutic care have become of increasing interest. We purified and characterized two novel analgesic and anti-inflammatory peptides, VQ-5 and AQ-5, from the coelomic fluid of the earthworm (Eisenia foetida). Their primary structures were determined as VSSVQ and AMADQ, respectively. Both peptides, especially AQ-5, exhibited analgesic activity in mouse models of persistent neuropathic pain and inflammation. AQ-5 also inhibited tumor necrosis factor alpha and cyclooxygenase-2 production. The mitogen-activated protein kinase signaling pathway, which is involved in analgesic and anti-inflammatory functions, was inhibited by AQ-5. Thus, the analgesic and anti-inflammatory effects of these peptides, especially AQ-5, demonstrated their potential as candidates for the development of novel analgesic medicines. Copyright © 2017 Elsevier Inc. All rights reserved.

What do we (not) know about how paracetamol (acetaminophen) works?

PubMed

Toussaint, K; Yang, X C; Zielinski, M A; Reigle, K L; Sacavage, S D; Nagar, S; Raffa, R B

2010-12-01

Although paracetamol (acetaminophen), N-(4-Hydroxyphenyl)acetamide, is one of the world's most widely used analgesics, the mechanism by which it produces its analgesic effect is largely unknown. This lack is relevant because: (i) optimal pain treatment matches the analgesic mechanism to the (patho)physiology of the pain and (ii) modern drug discovery relies on an appropriate screening assay. To review the clinical profile and preclinical studies of paracetamol as means of gaining insight into its mechanism of analgesic action. A literature search was conducted of clinical and preclinical literature and the information obtained was organized and reviewed from the perspective of its contribution to an understanding of the mechanism of analgesic action of paracetamol. Paracetamol's broad spectrum of analgesic and other pharmacological actions is presented, along with its multiple postulated mechanism(s) of action. No one mechanism has been definitively shown to account for its analgesic activity. Further research is needed to uncover the mechanism of analgesic action of paracetamol. The lack of this knowledge affects optimal clinical use and impedes drug discovery efforts. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Analysis of factors related to the use of opioid analgesics in regional cancer centers in Japan.

PubMed

Sugiura, Munetoshi; Miyashita, Mitsunori; Sato, Kazuki; Tsuneto, Satoru; Matoba, Motohiro; Sano, Motohiko; Shima, Yasuo

2010-07-01

The use of opioid analgesics and nonopioid medicines for the treatment of various symptoms in regional cancer centers is considered to be an index of the effectiveness of the structural plan for palliative care in such institutions. The present study aimed to establish an accurate representation of the actual use of opioid analgesics for palliative care in regional cancer centers. In November 2007, a questionnaire regarding the use of medications for palliative care was conducted in 288 regional cancer centers in Japan. Valid responses were received from 264 institutions (response rate, 91.4%). All regional cancer centers reported using both opioid analgesics and nonopioid medicines. However, regarding opioid analgesics, the use of each standard strength ranged from 7% to 100%. The total amount of opioid analgesics used was 1739.6 +/- 1216.5 g (mean +/- SD). Factors found to be significantly related to the total amount of opioid analgesics used in an institution were the number of opioid analgesic medicines in use (p = 0.008), the number of inpatients with cancer (p < 0.001), the number of deaths among patients with cancer (p < 0.001), and the number of beds (p < 0.001). Increase in the amount of opioid analgesics might improve the quality of palliative care at regional cancer centers.

Analgesic Activity of Some 1,2,4-Triazole Heterocycles Clubbed with Pyrazole, Tetrazole, Isoxazole and Pyrimidine

PubMed Central

Gajanan Khanage, Shantaram; Raju, Appala; Baban Mohite, Popat; Bhanudas Pandhare, Ramdas

2013-01-01

Purpose: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. Methods: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. Results: Thirty six different derivatives containing 1,2,4-triazole ring were subjected to study their in vivo analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted derivatives showed excellent analgesic activity and dimethylamino, furan and phenyl substituted derivatives showed moderate analgesic activity in both of the methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj IV3a and IIj were found to be superior analgesic agents after screening by Acetic acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb, IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after screening of Hot plate method. Conclusion: All tested compounds containing 1,2,4-triazole were found to be promising analgesic agents, for this activity pyrazole, tetrazole, isoxazole and pyrimidine leads might be supported. PMID:24312806

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

PubMed

Chen, Li Hui; Hedegaard, Holly; Warner, Margaret

2014-09-01

Data from the National Vital Statistics System, Mortality File. The age-adjusted rate for opioid-analgesic poisoning deaths nearly quadrupled from 1.4 per 100,000 in 1999 to 5.4 per 100,000 in 2011. Although the opioid-analgesic poisoning death rates increased each year from 1999 through 2011, the rate of increase has slowed since 2006. Natural and semisynthetic opioid analgesics, such as hydrocodone, morphine, and oxycodone, were involved in 11,693 drug-poisoning deaths in 2011, up from 2,749 deaths in 1999. Benzodiazepines were involved in 31% of the opioid-analgesic poisoning deaths in 2011, up from 13% of the opioid-analgesic poisoning deaths in 1999. During the past decade, adults aged 55-64 and non-Hispanic white persons experienced the greatest increase in the rates of opioid-analgesic poisoning deaths. Poisoning is the leading cause of injury death in the United States (1). Drugs-both illicit and pharmaceutical-are the major cause of poisoning deaths, accounting for 90% of poisoning deaths in 2011. Misuse or abuse of prescription drugs, including opioid-analgesic pain relievers, is responsible for much of the recent increase in drug-poisoning deaths (2). This report highlights trends in drug-poisoning deaths involving opioid analgesics (referred to as opioid-analgesic poisoning deaths) and updates previous Data Briefs on this topic. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

Impact of Internet Pharmacy Regulation on Opioid Analgesic Availability*

PubMed Central

Boyer, Edward W.; Wines, James D.

2008-01-01

Objective: Access to prescription opioid analgesics has made Internet pharmacies the object of increased regulatory scrutiny, but the effectiveness of regulatory changes in curtailing availability of opioid analgesics from online sources has been not assessed. As part of an ongoing investigation into the relationship between the Internet and substance abuse, we examined the availability of prescription opioid analgesics from online pharmacies. Method: From a pharmacy watch Web site, we constructed a data set of postings entered every 3 months beginning November 1, 2005, that were related to the purchase of prescription opioid analgesics. Trained examiners assessed whether the final post described accessibility of pain medications that was increasing or decreasing. Results: We identified 45 threads related to the availability of opioid analgesics from Internet pharmacies. Of the 41 (91%) threads describing the declining availability of opioid analgesic agents from Internet pharmacies, 34 (82%) received posts on November 1, 2007. Despite the subjective nature of the research question, there was high interobserver agreement between coders (κ = .845) that availability of opioid analgesics from online pharmacies had decreased. This finding was supported by a dramatic rise in the number of pageviews (an accepted measure of Web site visitor interest in a page's content) of Web pages describing decreased availability of opioid analgesics. Conclusions: These data suggest striking decreases in the availability of prescription opioid analgesic pharmaceuticals. This self-reported change in drug availability may be related to increased regulation of and law enforcement operations directed against Internet pharmacies. PMID:18781245

Impact of Internet pharmacy regulation on opioid analgesic availability.

PubMed

Boyer, Edward W; Wines, James D

2008-09-01

Access to prescription opioid analgesics has made Internet pharmacies the object of increased regulatory scrutiny, but the effectiveness of regulatory changes in curtailing availability of opioid analgesics from online sources has been not assessed. As part of an ongoing investigation into the relationship between the Internet and substance abuse, we examined the availability of prescription opioid analgesics from online pharmacies. From a pharmacy watch Web site, we constructed a data set of postings entered every 3 months beginning November 1, 2005, that were related to the purchase of prescription opioid analgesics. Trained examiners assessed whether the final post described accessibility of pain medications that was increasing or decreasing. We identified 45 threads related to the availability of opioid analgesics from Internet pharmacies. Of the 41 (91%) threads describing the declining availability of opioid analgesic agents from Internet pharmacies, 34 (82%) received posts on November 1, 2007. Despite the subjective nature of the research question, there was high interobserver agreement between coders (kappa= .845) that availability of opioid analgesics from online pharmacies had decreased. This finding was supported by a dramatic rise in the number of pageviews (an accepted measure of Web site visitor interest in a page's content) of Web pages describing decreased availability of opioid analgesics. These data suggest striking decreases in the availability of prescription opioid analgesic pharmaceuticals. This self-reported change in drug availability may be related to increased regulation of and law enforcement operations directed against Internet pharmacies.

Use of analgesics in young adults as a predictor of health care utilization and pain prevalence: Israel defense forces experience.

PubMed

Dorfman, Karina; Komargodski, Olga; Magnezi, Racheli; Lifshitz, Stanislav; Tzur, Dorit; Yavnai, Nirit; Ifergane, Gal

2017-06-01

Pain evaluation in large community studies is difficult. Analgesics can be a useful tool in estimating pain-related conditions in which analgesic use is highly regulated. In this study, we evaluated analgesics consumption patterns of regular Israel Defense Force soldiers. We have performed a historical cohort study of 665,137 young adults during active duty in 2002 to 2012. Analgesics were prescribed to 518,242 (78%) soldiers, mostly for musculoskeletal pain (69.3%), abdominal pain (12.7%), and headache (12.1%). Acute (1-14 days), subacute (15-90), and chronic (>90 days) analgesic use episodes were experienced by 396,987 (59.7%), 74,591 (11.2%), and 46,664 (7%) of the population. In a multivariate model, predictors for chronic analgesics use were as follows: low intelligence, service in a combat supporting unit, previous pain diagnosis, male sex, Israeli nativity, low socioeconomic status, and high body mass index. Low intelligence had the highest odds ratio for chronic analgesic consumption (2.1) compared with other predictors. Chronic analgesic use was associated with a significant increase in health care utilization cost per year (911$ per soldier vs 199$ for nonusers), increased sick leave days per year (7.09 vs 0.67 for nonusers), and higher dropout rate from combat units (25% vs 9.2% for nonusers). Chronic use of analgesics is common among young adults, and it is an important predictor for unsuccessful military service and high health care utilization costs. Further studies in other setups are indicated.

Use of medications and resources for treatment of nausea, vomiting, or constipation in hospitalized patients treated with analgesics.

PubMed

Suh, Dong-Churl; Kim, Myoung S; Chow, Wing; Jang, Eun-Jin

2011-01-01

Hospitalized patients often experience adverse events of the gastrointestinal tract due to analgesic treatment. The objectives of this study were to estimate use of medications for treatment of nausea, vomiting, or constipation (NVC medications) after initiation of analgesic treatment, and to compare differences in length of stay and treatment costs between patients who received NVC medications and those who did not. This retrospective cohort study used the Premier Perspective data from January 1, 2005 to December 31, 2007 and stratified inpatients into 4 groups based on the first analgesic agent they were given. Patients were observed for 14 days after the first analgesic use until a regimen change, first use of NVC medication, or hospital discharge, whichever occurred first. Data were analyzed using a Cox proportional hazards model and a generalized linear model. This study found that 239,183 (55.1%) of 434,304 patients received NVC medications after analgesic administration. Compared with oral nonopioid analgesics, the risk of using NVC medication was 4.8 times higher for injectable opioid analgesics after controlling for confounders. Patients who received NVC medications were hospitalized 0.26 days longer (P < 0.0001) at an additional cost of $756 per patient compared with patients who did not receive NVC medications (P < 0.0001). Use of an analgesic with improved gastrointestinal tolerability may potentially reduce use of NVC medications and hospital resources.

An evaluation of analgesic regimens for abdominal surgery in mice.

PubMed

Hayes, K E; Raucci, J A; Gades, N M; Toth, L A

2000-11-01

This study was designed to evaluate the efficacy of several analgesic regimens for use after intraperitoneal implantation of telemetry transmitters in mice. The lengths of time required for postoperative recovery of food and water intake, locomotor activity, and core temperature of mice that did not receive postsurgical analgesic medication were compared to those of mice that were given either an analgesic in the drinking water or buprenorphine injections. Many measured variables were not substantially altered by analgesic medications. However, ibuprofen-treated mice demonstrated significantly greater locomotor activity on days 2 through 5 after surgery and a more rapid return to stable postsurgical levels of activity and water intake as compared to those in untreated mice. These changes are consistent with potential analgesic efficacy of the ibuprofen treatment regimen. Buprenorphine injections elicited hyperactivity, hyperthermia, and reduced food and water intake during both the immediate postsurgical recovery period and after apparent recuperation from surgery, as compared to effects observed in saline-treated mice. Evaluating the effect of analgesic regimens on postsurgical changes in physiologic and behavioral variables can be useful in assessing the efficacy of analgesic treatments, but some changes may indicate pharmacologic effects that do not reflect pain relief.

Safety of lornoxicam in the treatment of postoperative pain: a post-marketing study of analgesic regimens containing lornoxicam compared with standard analgesic treatment in 3752 day-case surgery patients.

PubMed

Rawal, Narinder; Krøner, Karsten; Simin-Geertsen, Marija; Hejl, Charlotte; Likar, Rudolf

2010-01-01

Post-marketing surveillance studies can provide supplemental data on the safety of medications in the general population. This study aimed to evaluate the safety of analgesic regimens including the NSAID lornoxicam in the short-term treatment of postoperative pain in a clinically relevant population. Randomized, open-label, multicentre, multinational, observational cohort study of 4 days' duration. In-hospital postoperative setting, with discharge to home treatment within 24 hours of surgery. Adults aged > or =18 years expected to be in need of analgesic treatment after day-case surgery. Analgesic regimens containing lornoxicam were compared with a standard analgesic treatment, which was defined as the treatment that the patient would normally receive at the centre. Following day-case surgery, patients were provided with appropriate analgesic medication, and adverse events (AEs; defined as all recorded events with symptoms) were recorded by the investigator during the in-hospital stay and by the patient for the next 3 days using entries recorded morning and evening in a patient diary. Statistical analyses tested for between-treatment differences in AEs, adverse drug reactions (ADRs; defined as events probably, possibly or unlikely to be related to treatment) and gastrointestinal AEs (GI-AEs). A total of 4152 patients were randomized to treatment. Since 400 patients did not take any analgesic, the safety population consisted of 1838 patients for lornoxicam and 1914 patients for standard analgesic treatment. Demographic and disease characteristics were similar between the two treatment groups, as were the type of surgery and the anaesthesia used in surgery. In the safety population, 16.9% of patients received no analgesic in hospital, and when analgesics were provided they were often administered in combination. Similarly, approximately 17% of patients did not take any analgesics at home. AEs were reported in 27.1% and 29.4% of patients in the lornoxicam and standard analgesic treatment groups, respectively, and ADRs constituted the majority of these events. No significant differences were demonstrated with regard to the incidence of AEs between the two groups. Most events were of mild or moderate intensity. Consistent with what may be expected for an NSAID, most AEs with lornoxicam were related to the GI system. GI-AEs were reported in 19.5% and 21.3% of patients in the lornoxicam and standard analgesic treatment groups, respectively, and most of these were considered ADRs. Most patients were satisfied with their pain treatment both in hospital and at home. Lornoxicam-containing regimens are as well tolerated as other analgesic regimens over 4 days in the treatment of postoperative pain.

Mechanisms of topical analgesics in relieving pain in an animal model of muscular inflammation.

PubMed

Duan, Wan-Ru; Lu, Jie; Xie, Yi-Kuan

2013-09-01

To investigate the possible mechanisms of topical analgesics in relieving pain in an animal model of muscular inflammation. Adult Sprague-Dawley rats of both sexes were injected with complete Freund's adjuvant to induce inflammation in the anterior tibialis muscle of left hindlimb. One of two types of topical analgesics: Xiaotong Tiegao (XTT), a Tibetan herb compound, or Capzasin (CAP), a cream containing 0.1% capsaicin, was applied to the skin over the inflamed anterior tibialis muscle. The following experiments were performed: pain behavioral tests, evaluation of plasma extravasation in the affected limb, and electrophysiological recordings of afferent nerve fibers. The behavioral experiments demonstrated that applications of either type of topical analgesic to the skin over the inflamed muscle significantly reduced muscular inflammatory pain, as indicated by the increased weight bearing capacity on the affected hindlimb (with latencies of 10 minutes for XTT and 1-2 hours for CAP). Meanwhile, both analgesics caused plasma extravasation in the affected skin. Electrophysiological recordings from the afferent fibers in the related cutaneous nerve indicated that topical analgesics selectively activated C-fibers, but not A-fibers innervating the same region of receptive field. The latency and duration of C-fiber activation was similar to those of the reduction of muscular inflammatory pain. On the contrary, topical analgesics substantially decreased C-fiber afferent spontaneous firing in the nerve innervating the inflamed muscle. Moreover, denervation of the affected skin blocked the analgesic effects of both topical analgesics in muscular inflammatory pain. This study suggests that topical analgesics may reduce the nociceptive input from inflamed muscles via a reflex mechanism by activating the cutaneous nociceptive afferents. Wiley Periodicals, Inc.

Personalized Medicine and Opioid Analgesic Prescribing for Chronic Pain: Opportunities and Challenges

PubMed Central

Bruehl, Stephen; Apkarian, A. Vania; Ballantyne, Jane C.; Berger, Ann; Borsook, David; Chen, Wen G.; Farrar, John T.; Haythornthwaite, Jennifer A.; Horn, Susan D.; Iadarola, Michael J.; Inturrisi, Charles E.; Lao, Lixing; Mackey, Sean; Mao, Jianren; Sawczuk, Andrea; Uhl, George R.; Witter, James; Woolf, Clifford J.; Zubieta, Jon-Kar; Lin, Yu

2013-01-01

Use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. There is currently no well-validated objective means of accurately identifying patients likely to experience good analgesia with low side effects and abuse risk prior to initiating opioid therapy. This paper discusses the concept of data-based personalized prescribing of opioid analgesics as a means to achieve this goal. Strengths, weaknesses, and potential synergism of traditional randomized placebo-controlled trial (RCT) and practice-based evidence (PBE) methodologies as means to acquire the clinical data necessary to develop validated personalized analgesic prescribing algorithms are overviewed. Several predictive factors that might be incorporated into such algorithms are briefly discussed, including genetic factors, differences in brain structure and function, differences in neurotransmitter pathways, and patient phenotypic variables such as negative affect, sex, and pain sensitivity. Currently available research is insufficient to inform development of quantitative analgesic prescribing algorithms. However, responder subtype analyses made practical by the large numbers of chronic pain patients in proposed collaborative PBE pain registries, in conjunction with follow-up validation RCTs, may eventually permit development of clinically useful analgesic prescribing algorithms. Perspective Current research is insufficient to base opioid analgesic prescribing on patient characteristics. Collaborative PBE studies in large, diverse pain patient samples in conjunction with follow-up RCTs may permit development of quantitative analgesic prescribing algorithms which could optimize opioid analgesic effectiveness, and mitigate risks of opioid-related abuse and mortality. PMID:23374939

[Use and potential risks of over-the-counter analgesics].

PubMed

Freytag, A; Quinzler, R; Freitag, M; Bickel, H; Fuchs, A; Hansen, H; Hoefels, S; König, H-H; Mergenthal, K; Riedel-Heller, S G; Schön, G; Weyerer, S; Wegscheider, K; Scherer, M; van den Bussche, H; Haefeli, W E; Gensichen, J

2014-04-01

We investigated the use of prescription and non-prescription (over-the-counter, OTC) analgesics and the associated risks in elderly patients with multiple morbidities. Pain medication use was evaluated from the baseline data (2008/2009) of the MultiCare cohort enrolling elderly patients with multiple morbidities who were treated by primary care physicians (trial registration: ISRCTN89818205). We considered opioids (N02A), other analgesics, and antipyretics (N02B) as well as nonsteroidal anti-inflammatory drugs (NSAIDs; M01A). OTC use, duplicate prescription, dosages, and interactions were examined for acetylsalicylic acid, diclofenac, (dex)ibuprofen, naproxen, and acetaminophen. Of 3,189 patients with multiple morbidities aged 65-85 years, 1,170 patients reported to have taken at least one prescription or non-prescription analgesic within the last 3 months (36.7 %). Of these, 289 patients (24.7 % of 1,170) took at least one OTC analgesic. Duplicate prescription was observed in 86 cases; 15 of these cases took the analgesics regularly. In two cases, the maximum daily dose of diclofenac was exceeded due to duplicate prescription. In 235 cases, patients concurrently took a drug with a potentially clinically relevant interaction. In 43 cases (18.3 % of 235) an OTC analgesic, usually ibuprofen, was involved. About one third of the elderly patients took analgesics regularly or as needed. Despite the relatively high use of OTC analgesics, the proportions of duplicate prescription, medication overdoses, and adverse interactions due to OTC products was low.

Do caffeine-containing analgesics promote dependence? A review and evaluation.

PubMed

Feinstein, A R; Heinemann, L A; Dalessio, D; Fox, J M; Goldstein, J; Haag, G; Ladewig, D; O'Brien, C P

2000-11-01

Debates about the suspected association between kidney disease and use of analgesics have led to concern about whether caffeine could stimulate an undesirable overuse of phenacetin-free combined analgesics. A committee was asked to critically review the pertinent literature and to suggest guides for clinical practice and for consideration of international regulatory authorities. A group of international scientists, jointly selected by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry. All invited experts evaluated relevant literature and reports and added further information and comments. Caffeine has a synergistic effectiveness with analgesics. Although caffeine has a dependence potential, the potential is low. Experimental data regarding dependence potential for caffeine alone may not correspond to the conditions in patients with pain. Withdrawal is not likely to cause stimulation or sustainment of analgesic intake. For drug-induced headache, no single or combined analgesic was consistently identified as causative, and no evidence exists for a special role of caffeine. Strong dependence behavior was observed only in patients using phenacetin-containing preparations, coformulated with antipyretics/analgesics and caffeine. This finding may have led to the impression that caffeine stimulates overuse of analgesics. Although more experimental and long-term data would be desirable to show possible mechanisms of dependence and to offer unequivocal proof of safety, the committee concluded that the available evidence does not support the claim that analgesics coformulated with caffeine, in the absence of phenacetin, stimulate or sustain overuse.

Rational use of analgesic combinations.

PubMed

Phero, James C; Becker, Daniel

2002-10-01

Careful selection of an effective analgesic regimen based on the amount and type of pain the patient is expected to have can prevent the stress and anxiety associated with breakthrough pain. When analgesics fail, it is not unusual for patients to go to desperate lengths to seek relief. The clinician can and should develop a variety of effective, safe analgesic regimens based on estimates of anticipated pain intensity that apply sound pharmacologic principles.

Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus)

PubMed Central

Taylor, Bryan F; Ramirez, Harvey E; Battles, August H; Andrutis, Karl A; Neubert, John K

2016-01-01

Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose–response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period. PMID:26817983

Opioid Receptors: Toward Separation of Analgesic from Undesirable Effects

PubMed Central

Law, P.Y.; Reggio, Patricia H.; Loh, H.H.

2013-01-01

The use of opioid analgesics for pain has always been hampered by their many side effects; in particular, the addictive liability associated with chronic use. Recently, attempts to develop analgesic agents with reduced side effects have targeted either the putative opioid receptor splice variants or the receptor heterooligomers. This review discusses the potential for receptor splice variant- and the hetero-oligomer-based discovery of new opioid analgesics. We also examine an alternative approach of using receptor mutants for pain management. Finally, we discuss the role of the biased agonism observed and the recently reported opioid receptor crystal structures in guiding the future development of opioid analgesics PMID:23598157

[Management of opioid maintenance treatments when analgesic treatments are required].

PubMed

Laprevote, Vincent; Geoffroy, Pierre A; Rolland, Benjamin; Leheup, Benoît F; Di Patrizio, Paolo; Cottencin, Olivier; Schwan, Raymund

2013-01-01

Opioid maintenance treatments (OMT) reduce illicit opiate use and its associated risks. They are often prescribed on a long-term basis. Physiological changes induced by long-term OMT may cause hyperalgesia and cross-tolerance to opioid agonists, which suggests that the dosage of analgesic treatment should be modified in cases of acute pain, especially when an opioid-based analgesia is required. When treatment with analgesics is necessary, OMT must be maintained, except in exceptional cases. If a split-dosing schedule is temporarily employed during OMT, the daily dosage should not be increased for analgesic purposes. Analgesic treatment must be managed differently in case of treatment with buprenorphine or methadone. With buprenorphine, non-opioid analgesics should be introduced first, if possible. If this strategy is inefficient or contraindicated, a temporary or definitive switch to methadone should be considered. In the case of methadone-based OMT, opioid analgesics should be added directly and the dosage should be adapted according to the level of pain reported by the patient. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The association between adolescent and parental use of non-prescription analgesics for headache and other somatic pain - A cross-sectional study.

PubMed

Hasseleid, Synva Nesheim; Clench-Aas, Jocelyne; Raanaas, Ruth Kjærsti; Lundqvist, Christofer

2017-07-01

Over the last years, concern has been expressed about adolescents' possible liberal attitude towards - and use of - non-prescription analgesics. A high consumption of analgesics is unfortunate as it may lead to various harmful effects and worsening of headache. In order to address this challenge, it is necessary to achieve a more extensive knowledge about adolescent consumption. The main aim of this study was to examine the association between adolescent and parental use of non-prescription analgesics, taking into account headache as well as other somatic pain. The effects of parental prescription analgesics use was a secondary aim. The study is based on data from two cross-sectional health studies conducted in 2005 and 2012 in Norway, including 646 adolescents and an accompanying parent. By using sample weights, the final weighted sample used in the analysis was 1326. Data was collected through postal questionnaires to parents and adolescents as well as parental telephone interviews. Questionnaires included questions on different pain locations and the pain for each location was graded according to how troubling the pain was. Medication data on prescription and non-prescription analgesics was from telephone interviews and was quantified based on the pattern over the past 4 weeks. Multivariate logistic regression models and complex samples analyses were used. 20% of adolescents were reported as using non-prescription analgesics during the previous 4 weeks. Girls were more often reported to use non-prescription analgesics than boys. Headache and all other somatic pain locations except back pain were reported more frequently among girls while boys more frequently reported back pain. There was a clear association between the use of non-prescription analgesics and headache with 34% of adolescents with headache using non-prescription analgesics versus 19% of adolescents with other somatic pain and 14% of adolescents not reporting pain. Among adolescents reporting headache, 9% were reported to use non-prescription analgesics daily or almost daily versus 3% and 2% among those reporting other somatic pain and reporting no pain respectively. In addition, parental use of non-prescription analgesics was a strong independent predictor of adolescent use (adjusted OR 1.69 for boys, 1.54 for girls). This relationship increased when the adolescents were less bothered by headache themselves. Headache is the dominant medication-driving pain for non-prescription analgesics among adolescents but parental medication use of non-prescription analgesics also strongly influences adolescent use. There is a need for health services to improve information to parents and adolescents about risks associated with use of analgesics and also to work on prophylactic strategies focusing on adolescents. Parents should be made aware that their medicine use strongly influences that of their children. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Analgesic activity of Nelsonia canescens (Lam.) Spreng.root in albino rats

PubMed Central

Mohaddesi, Behzad; Dwivedi, Ravindra; Ashok, B. K.; Aghera, Hetal; Acharya, Rabinarayan; Shukla, V. J.

2013-01-01

Present study was undertaken to evaluate analgesic activity of root of Nelsonia canescens (Lam.) Spreng, a folklore medicinal plant used as the one of the source plant of Rasna. Study was carried out at two dose levels (270 mg/kg and 540 mg/kg) in albino rats. Analgesic activity was evaluated in formalin induced paw licking, and tail flick methods whereas indomethacin and pentazocine were used as standard analgesic drugs, respectively. At both the dose levels, test drug non-significantly decreased paw licking response at both time intervals. In tail flick model, the administration of the test drug increased pain threshold response in a dose dependent manner. In therapeutically equivalent dose level, analgesic activity was observed only after 180 min while in TED ×2 treated group analgesia was observed at 30 min and lasted even up to 240 min. The results suggested that N.canescens root possess moderate analgesic activity. PMID:24250136

Are Prescription Opioids Driving the Opioid Crisis? Assumptions vs Facts.

PubMed

Rose, Mark Edmund

2018-04-01

Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics. Medical literature discussions of opioid analgesics began emphasizing patient and public health hazards. Repetitive exposure to this information may influence physician assumptions. While highly consequential to patients with pain whose function and quality of life may benefit from opioid analgesics, current assumptions about prescription opioid analgesics, including their role in the ongoing opioid overdose epidemic, have not been scrutinized. Information was obtained by searching PubMed, governmental agency websites, and conference proceedings. Opioid analgesic prescribing and associated overdose deaths both peaked around 2011 and are in long-term decline; the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co-ingested benzodiazepines, alcohol, or other central nervous system/respiratory depressants, are infrequent. Within five years of initial prescription opioid misuse, 3.6% initiate heroin use. The United States consumes 80% of the world opioid supply, but opioid access is nonexistent for 80% and severely restricted for 4.1% of the global population. Many current assumptions about opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid prescribing, now fuel the current opioid overdose epidemic. National discussion has often neglected the potentially devastating effects of uncontrolled chronic pain. Opioid analgesic prescribing and related overdoses are in decline, at great cost to patients with pain who have benefited or may benefit from, but cannot access, opioid analgesic therapy.

Meperidine utilization and compliance with Agency for Health Care Policy and Research guidelines in a tertiary care hospital.

PubMed

Pellegrini, J E; Paice, J; Faut-Callahan, M

1999-11-01

The Agency for Health Care Policy and Research (AHCPR) established guidelines for the use of meperidine (demerol), a common inpatient analgesic. These guidelines define standards of care for acute and chronic cancer pain management and address many of the problems with meperidine and its metabolite, normeperidine. The purpose of this study was to determine whether meperidine was prescribed in compliance with AHCPR guidelines, whether patients exhibited any adverse reactions to meperidine, and to determine the analgesic efficacy of meperidine. Three hundred inpatient charts were reviewed and identified meperidine as the primary analgesic in 157 nonobstetric inpatients. Age, sex, weight, dosing interval, route of administration, duration of meperidine use, serum chemistry values, primary diagnosis, associated medical conditions, and medications concurrently being taken with meperidine were the parameters analyzed. An interview was conducted to ascertain medical and drug history, chronicity of pain syndromes, analgesic drug history, and analgesic efficacy. A visual analog scale for pain (range = 0 to 10) and an analgesic satisfaction survey (range = 1 to 5) were used. Of 157 patients, 124 (79.8%) were in conflict with AHCPR guidelines. The most frequent conflict was found to be suboptimal dosing regimen and treatment of chronic pain. Often concurrent analgesics were given with the meperidine to achieve adequate analgesia. Higher analgesic satisfaction scores were noted when meperidine was given with concurrent analgesics. Meperidine also was administered to patients in renal failure or with medications contraindicated with meperidine use. No significant adverse effects were noted with meperidine use in this sample population other than an increased incidence of confusion in the elderly population.

Clinical Analysis of Analgesics and Steroids Use for Extraction of Teeth in Patients with Intellectual Disability Under General Anesthesia.

PubMed

Maeda, Shigeru; Honda, Yuka; Tanimura, Hiroshi; Tomoyasu, Yumiko; Higuchi, Hitoshi; Murata, Naomichi; Egusa, Masahiko; Miyawaki, Takuya

2017-01-01

The extraction of lower wisdom teeth is often performed under general anesthesia in patients with intellectual disabilities. However, the choice of analgesics has not yet been investigated. To analyze the use of analgesics during general anesthesia for extraction including lower wisdom teeth in patients with intellectual disabilities. This research is a retrospective observational study. The study population was composed of all patients presenting for extraction of lower wisdom teeth under ambulatory general anesthesia in the clinic of Special Needs Dentistry in Okayama University Hospital from April 2011 to March 2016. The distribution of the combination of analgesics and the relationship between the use of analgesics and the type of extraction were investigated. One hundred and twelve cases were enrolled in this study. Intravenous injections of flurbiprofen, acetaminophen and betamethasone were used in 96 (85.7%), 12 (10.7%) and 26 cases (23.2%), respectively. Flurbiprofen is a non-steroid anti-inflammatory drugs (NSAIDs). Acetaminophen is an old analgesic, but an injection of acetaminophen is new, which was released in 2013 in Japan. And betamethasone is not an analgesic, but a steroid. Betamethasone was used in combination with other analgesics, and was used at a higher dose in a case in which four wisdom teeth were extracted. Flurbiprofen was the main analgesic used for extraction of wisdom teeth under general anesthesia in patients with intellectual disabilities. Betamethasone was used to support flurbiprofen or acetaminophen for extractions of multiple wisdom teeth, with the aim of controlling swelling rather than relieving pain.

Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use Among HIV-Infected Individuals with Chronic Pain.

PubMed

Sohler, Nancy L; Starrels, Joanna L; Khalid, Laila; Bachhuber, Marcus A; Arnsten, Julia H; Nahvi, Shadi; Jost, John; Cunningham, Chinazo O

2018-01-17

Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades, possibly accounting for the current opioid addiction epidemic. Co-morbid drug use in those prescribed opioid analgesics is common, but there are few data on polysubstance use patterns. We explored patterns of use of cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics. We conducted a secondary data analysis of screening interviews conducted as part of a parent randomized trial of financial incentives to improve HIV outcomes among drug users. In a convenience sample of people with HIV and chronic pain, we collected self-report data on demographic characteristics; pain; patterns of opioid analgesic use (both prescribed and illicit); cigarette, alcohol, and illicit drug use (including cannabis, heroin, and cocaine) within the past 30 days; and current treatment for drug use and HIV. Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use (N = 372, 47.1%). Illicit drug use was common (N = 505, 63.9%), and cannabis was the most commonly used illicit substance (N = 311, 39.4%). In multivariate analyses, only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use (adjusted odds ratio = 0.57; 95% confidence interval: 0.38-0.87). Conclusions/Importance: Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management, which could help to address adverse events associated with opioid analgesic use.

Clinical pharmacology of analgesics assessed with human experimental pain models: bridging basic and clinical research

PubMed Central

Oertel, Bruno Georg; Lötsch, Jörn

2013-01-01

The medical impact of pain is such that much effort is being applied to develop novel analgesic drugs directed towards new targets and to investigate the analgesic efficacy of known drugs. Ongoing research requires cost-saving tools to translate basic science knowledge into clinically effective analgesic compounds. In this review we have re-examined the prediction of clinical analgesia by human experimental pain models as a basis for model selection in phase I studies. The overall prediction of analgesic efficacy or failure of a drug correlated well between experimental and clinical settings. However, correct model selection requires more detailed information about which model predicts a particular clinical pain condition. We hypothesized that if an analgesic drug was effective in an experimental pain model and also a specific clinical pain condition, then that model might be predictive for that particular condition and should be selected for development as an analgesic for that condition. The validity of the prediction increases with an increase in the numbers of analgesic drug classes for which this agreement was shown. From available evidence, only five clinical pain conditions were correctly predicted by seven different pain models for at least three different drugs. Most of these models combine a sensitization method. The analysis also identified several models with low impact with respect to their clinical translation. Thus, the presently identified agreements and non-agreements between analgesic effects on experimental and on clinical pain may serve as a solid basis to identify complex sets of human pain models that bridge basic science with clinical pain research. PMID:23082949

High use of over-the-counter analgesic; possible warnings of reduced quality of life in adolescents - a qualitative study.

PubMed

Skarstein, Siv; Lagerløv, Per; Kvarme, Lisbeth Gravdal; Helseth, Sølvi

2016-01-01

Use of over-the-counter analgesics among adolescents has increased markedly. High consumption of over-the-counter analgesics among adolescents is associated with frequent pain, lower self-esteem, reduced sleep, lower educational ambition, binge drinking, higher caffeine consumption, and part-time employment. Knowledge about life experiences of adolescents who frequently use over-the-counter analgesics may be useful to prevent health problems. The purpose of the study was to increase knowledge about adolescents who suffer from frequent pain and have a high consumption of over-the-counter analgesics. A qualitative study, employing one-on-one, in-depth interviews using a thematic interview guide. Data were collected in Norway in 2013-2014. Three boys and sixteen girls; aged 14-16 years, who continuously consumed over-the-counter analgesics were recruited from ten high schools in urban and suburban districts. Candidate participants were excluded if they were medically diagnosed with an acute or chronic illness, requiring extended use of over-the-counter analgesics within the last year. The interviews were taped, transcribed and analysed as text according to Kvale's three contexts of interpretation: self-understanding, common sense and theory. All participants disclosed unresolved physical and psychosocial distress characterized as pain. Frequent pain from various body parts made everyday life challenging. Methods of pain self-appraisal and over-the-counter analgesics use often mimicked maternal patterns. Participants reported being raised under unpredictable circumstances that contributed to long lasting family conflicts and peer-group problems. Participants wanted to feel appreciated and to be socially and academically successful. However, pain reduced their ability to manage everyday life, hampered experienced possibilities for success, and made social settings difficult. Childhood experiences influence how adolescents experience pain and use over-the-counter analgesics. Coping with difficult situations or attempting to mask symptoms with over-the-counter analgesics can perpetuate and amplify underlying problems. High consumption of over-the-counter analgesics and frequent pain may be warning signs of adolescents with possible health threatening conditions and reduced quality of life. These adolescent might be in need of support from school nurses and General Practitioners. This study identifies new perspectives that may lead to novel approaches to identify, guide, and support adolescents with frequent pain and high consumption of over-the-counter analgesics.

Prehospital and En Route Analgesic Use in the Combat Setting: A Prospectively Designed, Multicenter, Observational Study

DTIC Science & Technology

2015-03-01

combat medic has access to both opioid and nonopioid analgesics.3 Morphine and fentanyl are effective opioid analgesics and are commonly used...transmucosal (TM) fentanyl8,9 or parenteral ketamine. YM fentanyl has been shown to be a safe, effective, and easy method of administer- ing analgesics in a...a subsequent different drug, or the same drug via an alternative route). Ketamine was most frequently administered, followed by fentanyl , mor- phine

Preventability of adverse effects of analgesics: analysis of spontaneous reports.

PubMed

Cazacu, Irina; Miremont-Salamé, Ghada; Mogosan, Cristina; Fourrier-Réglat, Annie; Loghin, Felicia; Haramburu, Françoise

2015-05-01

The aims of this study were to determine the patterns of analgesic adverse drug reactions (ADRs) and to assess their preventability and contributing factors. This is a retrospective, descriptive study conducted on ADRs of analgesics and other drugs indicated as analgesics, spontaneously reported to the Bordeaux pharmacovigilance center from January 2011 to June 2012. The 141 cases selected for the analysis included 16 cases of medication errors (11.3%) and 15 addiction cases (10.6%). In total, 214 ADRs were registered, for which 173 analgesic medicines were suspected. The most frequent ADRs reported were nervous system disorders (26.6%), psychiatric disorders (15.0%), and skin and subcutaneous tissue disorders (12.1%). Tramadol alone or in combination (17.3%), followed by morphine (15%), fentanyl (9.8%), and paracetamol (8.7%) were the most frequently involved analgesics. More than half of the cases (54.6%) were serious and led to hospitalization or prolonged hospitalization. Preventability was determined for 134 cases (95%): 51.5% were considered as preventable, 26.1% not preventable, and 22.4% not assessable. The main contributing factors for the preventable cases included negligence of recommendations for analgesic use and failure to consider patients' risk factors when prescribing. A significant number of analgesic ADRs could be prevented, and being aware of their contributing factors promotes efficient analgesia with minimum risks to the patients.

Clinical and demographic covariates of chronic opioid and non-opioid analgesic use in rural-dwelling older adults: the MoVIES project.

PubMed

Karp, Jordan F; Lee, Ching-Wen; McGovern, Jonathan; Stoehr, Gary; Chang, Chung-Chou H; Ganguli, Mary

2013-11-01

To describe covariates and patterns of late-life analgesic use in the rural, population-based MoVIES cohort from 1989 to 2002. Secondary analysis of epidemiologic survey of elderly people conducted over six biennial assessment waves. Potential covariates of analgesic use included age, gender, depression, sleep, arthritis, smoking, alcohol, and general health status. Of the original cohort of 1,681, this sample comprised 1,109 individuals with complete data on all assessments. Using trajectory analysis, participants were characterized as chronic or non-chronic users of opioid and non-opioid analgesics. Multivariable regression was used to model predictors of chronic analgesic use. The cohort was followed for mean (SD) 7.3 (2.7) years. Chronic use of opioid analgesics was reported by 7.2%, while non-opioid use was reported by 46.1%. In the multivariable model, predictors of chronic use of both opioid and non-opioid analgesics included female sex, taking ≥2 prescription medications, and "arthritis" diagnoses. Chronic opioid use was also associated with age 75-84 years; chronic non-opioid use was also associated with sleep continuity disturbance. These epidemiological data confirm clinical observations and generate hypotheses for further testing. Future studies should investigate whether addressing sleep problems might lead to decreased use of non-opioid analgesics and possibly enhanced pain management.

Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users.

PubMed

Sites, Brian D; Beach, Michael L; Davis, Matthew A

2014-01-01

In the United States, use of oral opioid analgesics has been associated with increasing rates of addiction, abuse, and diversion. However, little is known about the recent national use of non-illicit prescription opioid analgesics (those prescribed in a physician-patient relationship), the primary source of these drugs for the general US population. Our primary objective was to examine trends in the use of prescription opioid analgesics in the United States and to identify defining characteristics of patient users of prescribed opioids from 2000 to 2010. We used the nationally representative Medical Expenditure Panel Survey to examine trends in prescription oral opioid analgesic use from 2000 to 2010. We used survey design methods to make national estimates of adults (18 years and older) who reported receiving an opioid analgesic prescription (referred to as opioid users) and used logistic regression to examine predictors of opioid analgesic use. Our primary outcome measures were national estimates of total users of prescription opioid analgesics and total number of prescriptions. Our secondary outcome was that of observing changes in the disability and health of the users. The estimated total number of opioid analgesic prescriptions in the United States increased by 104%, from 43.8 million in 2000 to 89.2 million in 2010. In 2000, an estimated 7.4% (95% confidence interval, 6.9-7.9) of adult Americans were prescription opioid users compared with 11.8% (95% confidence interval, 11.2-12.4) in 2010. On the basis of estimates adjusted for changes in the general population, each year was associated with a 6% increase in the likelihood of receiving an opioid prescription from 2000 to 2010. Despite the apparent increase in use, there were no demonstrable improvements in the age- or sex-adjusted disability and health status measures of opioid users. The use of prescription opioid analgesics among adult Americans has increased in recent years, and this increase does not seem to be associated with improvements in disability and health status among users. On a public health level, these data suggest that there may be an opportunity to reduce the prescribing of opioid analgesics without worsening of population health metrics.

Nursing knowledge and beliefs regarding patient-controlled oral analgesia (PCOA).

PubMed

Sawhney, Monakshi; Maeda, Eri

2013-12-01

Patient-controlled oral analgesia (PCOA) allows patients to self-administer oral opioids for pain management. Advantages of PCOA include improved pain control with lower doses of opioids, decreased length of stay, increased patient satisfaction, and better functional outcomes than conventional nurse-administered oral analgesia. Sucessful PCOA programs are well described in the literature. However, nurses have concerns about allowing patients to self-administer opioids. The purpose of this study was to identify nurses' knowledge and beliefs regarding PCOA. Nurses who work at the Holland Orthopaedic and Arthritic Centre were asked to complete a survey exploring their beliefs regarding PCOA. The nurses were asked to complete the same survey twice: before an education program in February 2010, and 3 months after implementation of PCOA in June 2010. In February 2010, 74 nurses and in June 2010, 32 nurses participated in the survey. Some nurses (18%) had previous experience with PCOA. At both the pre-education and the postimplementation times, nurses thought that the PCOA program reduced wait times for analgesics and improved patient satisfaction with pain management. Before program implementation, negative beliefs included that patients on the PCOA program would lose their analgesics, would give their analgesics to visitors or other patients, and were at risk for having their analgesics stolen and that the nurse was liable if the patient's analgesics were lost or stolen. After program implementation, no nurse believed that patients would lose their analgesics or give their analgesics to visitors or other patients or that they were liable for lost or stolen analgesics. However, nurses continued to think that patients were at risk for having their analgesics stolen. We found that nurses were concerned that analgesics could be lost, misused, or stolen and that they would be liable for lost analgesics. These findings were consistent with literature discussing patients' outcomes regarding PCOA. However, after education and experience these concerns decreased or resolved. It is important to address these concerns before PCOA program implementation. Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Pattern of Self Prescribed Analgesic Use in a Rural Area of Delhi: Exploring the Potential Role of Internet.

PubMed

Kochhar, Anjali; Gupta, Tanya

2017-07-01

Analgesics are the most common self prescribed drugs. Although considered to be relatively safe, side effects are often seen when these drugs are used for prolonged period, in high doses or used where contraindicated. Majority of the consumers are not aware of the side effects. These days ample amount of information is available on web, it is important to explore its role in educating the population regarding the safe use of self prescribed analgesics. To explore pattern of analgesic use, to identify population at risk of developing side effects related to analgesic use, awareness of side effects and potential role of internet to bring awareness about safe use of self prescribed analgesic drugs in a rural area of Delhi. A cross-sectional survey based study was done on 500 adults in the age group of 18-65 years of Madanpur Khadar area of South Delhi, India. Data collection was done by conducting visits to pharmacy shops from the people who were buying drugs without prescription and taking face to face interviews using a semi-structured questionnaire. Statistical analysis was performed using descriptive tests with Microsoft office excel 2007. Results of our study showed that among all the self prescribed analgesics paracetamol (57%) was used most frequently followed by aspirin and other NSAIDs. It was found that 9.6% of the consumers were having associated co-morbid illness, 11.4% were simultaneously taking other drugs and 15.2% were alcoholics. Majority (65.4%) of the buyers were not aware about any kind of side effects of the analgesics. Internet friendly consumers were found to be 44%. Ability to use internet and education level were found to be directly related (r=0.802). The pattern of analgesic consumption in the rural population of Delhi shows that a large number of consumers may be at risk of developing side effects of self prescribed analgesics. The awareness about the side effects is limited. A significant number of consumers are internet friendly. Hence, we recommend use of website/mobile apps as potential source of information in educating the population regarding the use of self prescribed analgesics.

Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian national authority from 2007 to 2014.

PubMed

Sunara, Petra; Krnic, Darko; Puljak, Livia

2017-11-01

Adverse drug reactions (ADRs) are commonly observed in the health services because of system weaknesses and individual errors. Analgesics are widely used and it can be expected that with the increased use one can expect increased number of ADRs of analgesics. The aim of this study was to analyze ADRs of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) from 2007 to 2014. HALMED provided data on generic drug name, year of the ADR report, type of report, institution, reporting person, patient's age, sex and ADR type. In the analyzed period 796 ADRs of analgesics were reported, of which 367 (46%) were serious ADRs. Number of ADR reports was continuously increasing during the analyzed period. There were 20 analgesics that had ≥5 reports, making 597 (75%) of all ADR reports for analgesics. The most common adverse reaction reports of those 20 analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side effects (n=572; 96%) were reported spontaneously through appropriate forms by patients or health professionals. ADRs were most commonly reported in women (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most common ADRs of opioid and non-opioid analgesics have been reported on the skin and mucous membranes. Most serious ADRs were result of action of opioid analgesics. Number of ADR reports in Croatia is continuously increasing and a considerable number of them refers to serious ADRs. To keep better track of medications and ADRs it is necessary to educate and encourage health professionals and patients in reporting side effects. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Patterns and predictors of analgesic use in pregnancy: a longitudinal drug utilization study with special focus on women with migraine.

PubMed

Harris, Gerd-Marie Eskerud; Wood, Mollie; Eberhard-Gran, Malin; Lundqvist, Christofer; Nordeng, Hedvig

2017-07-14

Few studies have investigated the drug utilization patterns and factors predicting drug use in pregnant women with migraine. This longitudinal drug utilization study aimed to describe patterns of analgesic use in a sample of Norwegian pregnant women according to their migraine history, and to identify predictors for analgesic use among these women. Pregnant women giving birth at Akershus University Hospital between 2008 and 2010 were recruited at ultrasound examination in gestational week 17. Data were collected by questionnaires in gestational weeks 17 and 32, and at 8 weeks postpartum, and linked to birth records. Women were grouped into four categories according to migraine history: no migraine history, previous migraine history, recent migraine history (within 1 year prior to pregnancy) and migraine in pregnancy. Patterns of use of analgesics were analyzed descriptively. Multivariable logistic regression was used to identify factors predicting analgesic use. Out of 1981 women, 5.0% reported having migraine in pregnancy, 13.2% had a recent history of migraine, 11.5% had a previous history of migraine, and 68.8% reported no history of migraine. Analgesic use declined during pregnancy. Many women switched from triptans and non-steroidal anti-inflammatory drugs to paracetamol, which constituted most of the analgesic use. Factors associated with analgesic use included recent migraine history (OR 1.6, 95% CI 1.2-2.2), more severe headache intensity (OR 1.3, 95% CI 1.3-1.4), smoking (OR 1.9, 95% CI 1.1-3.3) and multiparity (OR 1.4, 95% CI 1.1-1.7). Women with migraine stop or switch medications during pregnancy. Analgesic use in pregnancy is affected by migraine characteristics and intensity, and also by socio-demographic factors. Clinicians should bear this in mind when giving advice on adequate management of migraine in pregnancy and safe analgesic use.

The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis

PubMed Central

Au, Alvin Ho Yeung; Choi, Siu Wai; Cheung, Chi Wai; Leung, Yiu Yan

2015-01-01

Objectives To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?”. Materials and Methods A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review. Results Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 – 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects. Conclusion This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study. PMID:26053953

[Caffeine as adjuvant analgeticum for treating acute pain].

PubMed

Nikolajsen, Lone; Haroutiunian, Simon

2013-10-14

Based on 19 studies (7,238 participants) a Cochrane review concludes that the addition of caffeine to an analgesic drug provides superior analgesia compared with the analgesic drug alone. The benefit is small, with a number needed to treat of approx. 16. The use of analgesics containing caffeine is associated with an increased risk of the development of physical dependence, overuse headache, and withdrawal symptoms upon abrupt discontinuation. Combination analgesics with caffeine should only be used temporarily and exclusively for the treatment of acute pain conditions.

Prevalence of Analgesic Prescriptions among Patients with Cancer in Japan: An Analysis of Health Insurance Claims Data

PubMed Central

Higashi, Takahiro; Yoshimoto, Tetsusuke; Matoba, Motohiro

2012-01-01

Objectives: To promote effective management of cancer pain as a nationwide health policy, it is necessary to monitor the performance of health care providers in managing pain in their patients. To plan a system that monitors the performance of pain management, the exact methods of measurement, including the range of target patients, and estimate the resources must be defined. Performance in pain management can be evaluated either in all patients with cancer or restricted to patients with cancer who are already taking analgesics. Restricting the target patient group to patients on analgesics may be more efficient but the extent of that efficiency remains uncertain. Methods: Using insurance claims from eight employer-sponsored insurance companies, we analyzed data from patients (N = 2858) who had received anti-cancer treatment (ie, surgery, chemotherapy, and radiation therapy) for the five major cancers in Japan (ie, breast, colorectal, liver, lung, and stomach cancers). Results: Overall, 22.9% of patients received some kind of analgesic prescription in the course of a month. Lung cancer patients were more likely to be prescribed analgesic prescriptions (any analgesics 34.8%; opioids 18.2%) than patients with the other four cancers. The observed percentage of patients who received analgesic prescriptions over the study period (ie, January 2005 to November 2009) decreased. Conclusion: If we limit the target patient group to patients with cancer already on analgesics, we can reduce the number of persons to be contacted by about three-fourths, compared to assessing pain in all patients with cancer. Although we do not wish to ignore the problem of undetected pain among patients with cancer, beginning our systematic evaluation with patients with cancer already on analgesics may be a realistic option. PMID:23121757

Inequality in analgesic prescription in Spain. A gender development issue.

PubMed

Chilet-Rosell, Elisa; Ruiz-Cantero, M Teresa; Sáez, José Fernández; Alvarez-Dardet, Carlos

2013-01-01

It is well known that sex differences in analgesic prescription are not merely the logical result of greater prevalence of pain in women, since this therapeutic variability is related to factors such as educational level or social class. This study aims to analyse the relationship between analgesic prescription and gender development in different regions of Spain. Cross-sectional study of sex-differences in analgesic prescription according to the gender development of the regions studied. Analgesic prescription, pain and demographic variables were obtained from the Spanish Health Interview Survey in 2006. Gender development was measured with the Gender Development Index (GDI). A logistic regression analysis was conducted to compare analgesic prescription by sex in regions with a GDI above or below the Spanish average. Once adjusted by pain, age and social class, women were more likely to be prescribed analgesics than men, odds ratio (OR) = 1.74 (1.59-1.91), as residents in regions with a lower GDI compared with those in region with a higher GDI: ORWomen = 1.26 (1.12-1.42), ORMen = 1.30 (1.13-1.50). Women experiencing pain in regions with a lower GDI were more likely than men to be treated by a general practitioner rather than by a specialist, OR = 1.32 (1.04-1.67), irrespective of age and social class. Gender bias may be one of the pathways by which inequalities in analgesic treatment adversely affect women's health. Moreover, research into the adequacy of analgesic treatment and the possible medicalisation of women should consider contextual factors, such as gender development. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

Analgesics in postoperative care in hip fracture patients with dementia - reported by nurses.

PubMed

Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi

2014-11-01

To describe the analgesic use in hip fracture patients with dementia during the first two postoperative days as reported by nurses. Nurses play a pivotal role in treating postoperative pain in patients with dementia and monitoring the effects of administered analgesics. Cross-sectional descriptive questionnaire study in seven university hospitals and 10 central hospitals in Finland. The study was conducted from March until May in 2011 in Finland. For this analysis, the focus was on the sample of nurses (n = 269) who were working in orthopaedic units. Analgesics were classified according to the Anatomical Therapeutic Chemical Classification System. Nonparametric tests were applied to find out the significant differences between analgesic use and different hospitals. Paracetamol and strong opioids administered orally or parenterally seemed to be the most typical of postoperatively used types of analgesics in patients with dementia. Nonsteroidal anti-inflammatory analgesics and weak opioids were also commonly reported to be in use. There were no statistically significant differences between hospitals in typical daily doses. The majority of the nurses reported that the primary aim of postoperative pain management in hip fracture patients with dementia was 'slight pain, which does not prevent normal functioning' (72%). The pharmacological postoperative pain treatment in acute care was commonly based on the use of strong opioids and paracetamol in hip fracture patients with dementia. The reported use of transdermal opioids and codeine combination warrants further examination. Further studies are also needed to find out whether the pain is appropriately and adequately treated. Transdermal opioids and codeine combination may not be relevant analgesics for acute pain management in older adults. It is important to create a balance between sufficient pain relief and adverse effects of analgesics to allow early mobilisation and functional recovery. © 2014 John Wiley & Sons Ltd.

Adherence to Analgesics in Oncology Outpatients: Focus on Taking Analgesics on Time.

PubMed

Oldenmenger, Wendy H; Sillevis Smitt, Peter A E; de Raaf, Pleun J; van der Rijt, Carin C D

2017-06-01

Inadequate adherence to prescribed analgesics may be one of the reasons why patients with cancer experience unrelieved pain. Adherence is directly influenced by patients' barriers about pain management. Patient pain education programs (PEPs) have been developed to reduce patients' barriers and increase patients' adherence to their analgesics. The purpose of this article was to evaluate patients' adherence in patients receiving a pain consult and patient pain education in comparison with patients receiving standard pain treatment (standard care [SC]), to better explore the difficulties in medication adherence in cancer-related pain and the effects of PEP. In 54 adult outpatients with cancer-related pain, patients' adherence to the prescribed around-the-clock analgesics was measured with a Medication Event Monitoring System, in the following time intervals: weeks 1 and 2, weeks 3 and 4, and weeks 7 and 8 after randomization. Adherence was differentiated into taking adherence, taking the correct dose, and taking analgesics at the right time intervals. Taking adherence increased in the intervention group compared to baseline (from 91% to 93%) and decreased in the SC group (from 85% to 78%; P < 0.05). At the end of the study, more patients in the intervention group took their analgesics at the right intervals (78%) than did patients in the SC group (64%, P < 0.05). During the study, patients were more adherent to opioids than to World Health Organization step 1 analgesics. The combined intervention can increase adherence. The true problem in pain management is that patients do not take their prescribed analgesics at the right time intervals. With the detailed adherence information from this study, it is possible to further tailor patient education to the individual patient. © 2016 World Institute of Pain.

Vocal local versus pharmacological treatments for pain management in tubal ligation procedures in rural Kenya: a non-inferiority trial.

PubMed

Keogh, Sarah C; Fry, Kenzo; Mbugua, Edwin; Ayallo, Mark; Quinn, Heidi; Otieno, George; Ngo, Thoai D

2014-02-04

Vocal local (VL) is a non-pharmacological pain management technique for gynecological procedures. In Africa, it is usually used in combination with pharmacological analgesics. However, analgesics are associated with side-effects, and can be costly and subject to frequent stock-outs, particularly in remote rural settings. We compared the effectiveness of VL + local anesthesia + analgesics (the standard approach), versus VL + local anesthesia without analgesics, on pain and satisfaction levels for women undergoing tubal ligations in rural Kenya. We conducted a site-randomised non-inferiority trial of 884 women receiving TLs from 40 Marie Stopes mobile outreach sites in Kisii and Machakos Districts. Twenty sites provided VL + local anesthesia + analgesics (control), while 20 offered VL + local anesthesia without additional analgesics (intervention). Pain was measured using a validated 11-point Numeric Rating Scale; satisfaction was measured using 11-point scales. A total of 461 women underwent tubal ligations with VL + local anesthesia, while 423 received tubal ligations with VL + local anesthesia + analgesics. The majority were aged ≥30 years (78%), and had >3 children (99%). In a multivariate analysis, pain during the procedure was not significantly different between the two groups. The pain score after the procedure was significantly lower in the intervention group versus the control group (by 0.40 points; p = 0.041). Satisfaction scores were equally high in both groups; 96% would recommend the procedure to a friend. VL + local anesthesia is as effective as VL + local anesthesia + analgesics for pain management during tubal ligation in rural Kenya. Avoiding analgesics is associated with numerous benefits including cost savings and fewer issues related to the maintenance, procurement and monitoring of restricted opioid drugs, particularly in remote low-resource settings where these systems are weak. Pan-African Clinical Trials Registry PACTR201304000495942.

Analgesic properties of Capraria biflora leaves aqueous extract.

PubMed

Acosta, S L; Muro, L V; Sacerio, A L; Peña, A R; Okwei, S N

2003-12-01

The analgesic properties of dried leaves of Capraria biflora were investigated. The aqueous extract (50-200 mg kg(-1)) produced moderate inhibition of acetic acid-induced writhing in mice. At the same doses, a better analgesic effect was observed on the hot plate test.

Role of preemptive tapentadol in reduction of postoperative analgesic requirements after laparoscopic cholecystectomy

PubMed Central

Yadav, Ghanshyam; Jain, Gaurav; Samprathi, Abhishek; Baghel, Annavi; Singh, Dinesh Kumar

2016-01-01

Background and Aims: Poorly managed acute postoperative pain may result in prolonged morbidity. Various pharmacotherapies have targeted this, but research on an ideal preemptive analgesic continues, taking into account drug-related side effects. Considering the better tolerability profile of tapentadol, we assessed its role as a preemptive analgesic in the reduction of postoperative analgesic requirements, after laparoscopic cholecystectomy. Material and Methods: In a prospective-double-blinded fashion, sixty patients posted for above surgery, were randomized to receive tablet tapentadol 75 mg (Group A) or starch tablets (Group B) orally, an hour before induction of general anesthesia. Perioperative analgesic requirement, time to first analgesia, pain, and sedation score were compared for first 24 h during the postoperative period and analyzed by one-way analysis of variance test. A P < 0.05 was considered significant. Results: Sixty patients were analyzed. The perioperative analgesic requirement was significantly lower in Group A. Verbal numerical score was significantly lower in Group A at the time point, immediately after shifting the patient to the postanesthesia care unit. Ramsay sedation scores were similar between the groups. No major side effects were observed except for nausea and vomiting in 26 cases (10 in Group A, 16 in Group B). Conclusion: Single preemptive oral dose of tapentadol (75 mg) is effective in reducing perioperative analgesic requirements and acute postoperative pain, without added side effects. It could be an appropriate preemptive analgesic, subjected to future trials concentrating upon its dose-response effects. PMID:28096581

Can quantitative sensory testing predict responses to analgesic treatment?

PubMed

Grosen, K; Fischer, I W D; Olesen, A E; Drewes, A M

2013-10-01

The role of quantitative sensory testing (QST) in prediction of analgesic effect in humans is scarcely investigated. This updated review assesses the effectiveness in predicting analgesic effects in healthy volunteers, surgical patients and patients with chronic pain. A systematic review of English written, peer-reviewed articles was conducted using PubMed and Embase (1980-2013). Additional studies were identified by chain searching. Search terms included 'quantitative sensory testing', 'sensory testing' and 'analgesics'. Studies on the relationship between QST and response to analgesic treatment in human adults were included. Appraisal of the methodological quality of the included studies was based on evaluative criteria for prognostic studies. Fourteen studies (including 720 individuals) met the inclusion criteria. Significant correlations were observed between responses to analgesics and several QST parameters including (1) heat pain threshold in experimental human pain, (2) electrical and heat pain thresholds, pressure pain tolerance and suprathreshold heat pain in surgical patients, and (3) electrical and heat pain threshold and conditioned pain modulation in patients with chronic pain. Heterogeneity among studies was observed especially with regard to application of QST and type and use of analgesics. Although promising, the current evidence is not sufficiently robust to recommend the use of any specific QST parameter in predicting analgesic response. Future studies should focus on a range of different experimental pain modalities rather than a single static pain stimulation paradigm. © 2013 European Federation of International Association for the Study of Pain Chapters.

Temporal Trends in Analgesic Use in Long-Term Care Facilities: A Systematic Review of International Prescribing.

PubMed

La Frenais, Francesca L; Bedder, Rachel; Vickerstaff, Victoria; Stone, Patrick; Sampson, Elizabeth L

2018-02-01

To explore global changes in the prescription of analgesic drugs over time in the international long-term care (LTC) population. Systematic review. We included original research articles in English, published and unpublished, that included number of participants, country and year(s) of data collection, and prescription of analgesics (analgesics not otherwise specified, opioids, acetaminophen; scheduled only, or scheduled plus as needed (PRN)). LTC residents. We searched PubMed, EMBASE, CINAHL, International Pharmaceutical Abstracts, PsycINFO, Cochrane, Web of Science, Google Scholar, using keywords for LTC facilities and analgesic medication; hand-searched references of eligible papers; correspondence. Studies were quality rated using an adapted Newcastle-Ottawa scale. Pearson correlation coefficients were generated between percentage of residents prescribed an analgesic and year of data collection. If available, we investigated changes in acetaminophen and opioid prescriptions. Forty studies met inclusion criteria. A moderate correlation (0.59) suggested that scheduled prescription rates for analgesics have increased over time. Similar findings were reflected in scheduled prescriptions for acetaminophen and opioids. No increase was seen when analyzing scheduled plus PRN analgesics. Use of opioids (scheduled plus PRN) appears to have increased over time. Worldwide, use of opioids and acetaminophen has increased in LTC residents. Research is needed to explore whether this reflects appropriate pain management for LTC residents and if PRN medication is used effectively. © 2017 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

Electroencephalography and analgesics.

PubMed

Malver, Lasse Paludan; Brokjaer, Anne; Staahl, Camilla; Graversen, Carina; Andresen, Trine; Drewes, Asbjørn Mohr

2014-01-01

To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms 'analgesics', 'electroencephalography' and 'evoked potentials' for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients. © 2013 The British Pharmacological Society.

Analgesic Prodrugs for Combating their Side-Effects: Rational Approach.

PubMed

Ruchita; Sucheta; Nanda, Sanju; Pathak, Dharampal

2017-01-01

Analgesics are the drugs which bring insensibility to pain without loosing consciousness. Treatment strategy is generally based on the type of pain. Most of the analgesics are associated with serious side effects, such as NSAIDS can cause severe GI disturbance and opioids can cause addiction. There are various ways to reduce their side effects The analgesic prodrug approach is one of the several strategies used to attain the required pharmacological response with a considerable decrease in side effects. The aim of this paper is to introduce in depth the rational behind the use of the analgesic prodrug approach from past to present. Data is collected from online as well as from extensive literature survey which have appeared on this subject during the last decades. This review will map the origins and development of the most important of the analgesic prodrugs to date. This review indicates that, designing analgesic prodrugs represent successful strategy to gain the required pharmacological activity with a considerable decrease in side effects. However thorough knowledge of diverse biological phenomena is needed which enables scientists to invent and design superior, nontoxic and better-targeted prodrugs. The newly synthesized chemical entity or prodrugs may or may not have intrinsic pharmacological activity and also synthesizing novel molecules consume a lot of time and money than developing prodrugs of existing clinically used analgesic drugs which is surely an attractive and promising area of research now a days. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Canadian veterinarians’ use of analgesics in cattle, pigs, and horses in 2004 and 2005

PubMed Central

Hewson, Caroline J.; Dohoo, Ian R.; Lemke, Kip A.; Barkema, Herman W.

2007-01-01

Anecdotal evidence suggests that many veterinarians may not use analgesics in livestock for routine surgical procedures or painful disease states. To investigate this, we conducted a national mail survey of a random sample of 1431 Canadian veterinarians (response rate, 50.1%). Questions primarily concerned veterinarians’ analgesic usage for common surgeries and medical conditions in beef and dairy cattle, pigs, and horses, and attitudes toward pain management. More than 90% of veterinarians used analgesic drugs for equine surgeries, for cesarean section in sows and cows, and for bovine claw amputation and omentopexy. However, in these and other categories, the analgesics used were often inadequate, and many veterinarians did not give analgesics to young animals. When castrated, < 0.001% of piglets received analgesia, compared with 6.9% of beef calves and 18.7% of dairy calves ≤ 6 mo of age, 19.9% of beef calves and 33.2% of dairy calves > 6 mo of age, and 95.8% of horses. Respondents largely agreed that there are no long-acting, cost-effective analgesics available for use in livestock (median rating 8/10; interquartile range 4–9), and that the long or unknown withdrawal periods of some drugs outweighed the benefits of using them (median rating 7/10; interquartile range 4–9). The results indicate an urgent need for veterinarians to manage pain in livestock better. Continuing education would help, as would an increase in the number of approved, cost-effective analgesic drugs with known withdrawal periods. PMID:17334029

21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The active...

21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Analgesic, anesthetic, and antipruritic active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the...

21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The active...

21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Analgesic, anesthetic, and antipruritic active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the...

21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The active...

21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Analgesic, anesthetic, and antipruritic active... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the...

Use and abuse of opioid analgesics in chronic pain.

PubMed Central

Goldman, B.

1993-01-01

Primary care physicians are frequently required to treat patients with chronic debilitating pain. Opioid analgesics can successfully manage chronic pain. To prescribe opioid analgesics effectively, physicians must identify appropriate patients. Several methods can be used to identify and distinguish appropriate patients, addicted patients, and for-profit drug seekers. PMID:8097128

78 FR 29142 - Anesthetic and Analgesic Drug Products Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Anesthetic and Analgesic Drug Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Anesthetic and Analgesic Drug Products Advisory Committee. General Function of the Committee: To provide...

21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The active...

21 CFR 348.10 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 348.10 Section 348.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Active Ingredients § 348.10 Analgesic, anesthetic, and antipruritic active ingredients. The active...

77 FR 67380 - Anesthetic and Analgesic Drug Products Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Anesthetic and Analgesic Drug Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Anesthetic and Analgesic Drug Products Advisory Committee. General Function of the Committee: To provide...

76 FR 78283 - Anesthetic and Analgesic Drug Products Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Anesthetic and Analgesic Drug Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Anesthetic and Analgesic Drug Products Advisory Committee. General Function of the Committee: To provide...

78 FR 37551 - Request for Nominations for Voting and/or Nonvoting Consumer Representatives on Public Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-21

..., Center for Drug Anesthetic and Analgesic Evaluation and Research, Food and Drug Drugs. Administration... vacancies Approximate date needed Anesthetic and Analgesic Drugs-- 1--Voting Immediately. Knowledgeable in.... Anesthetic and Analgesic Drug Products The committee reviews and evaluates available data concerning the...

77 FR 39710 - Draft Guidance for Industry on Organ-Specific Warnings: Internal Analgesic, Antipyretic, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

...] Draft Guidance for Industry on Organ-Specific Warnings: Internal Analgesic, Antipyretic, and... Warnings: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use... enforcement discretion with regard to the liver warning required in the labeling. DATES: Although you can...

Analgesic-Like Activity of Essential Oil Constituents: An Update

PubMed Central

de Cássia da Silveira e Sá, Rita; Lima, Tamires Cardoso; da Nóbrega, Flávio Rogério; de Brito, Anna Emmanuela Medeiros

2017-01-01

The constituents of essential oils are widely found in foods and aromatic plants giving characteristic odor and flavor. However, pharmacological studies evidence its therapeutic potential for the treatment of several diseases and promising use as compounds with analgesic-like action. Considering that pain affects a significant part of the world population and the need for the development of new analgesics, this review reports on the current studies of essential oils’ chemical constituents with analgesic-like activity, including a description of their mechanisms of action and chemical aspects. PMID:29232831

''As-Needed'' Range Orders for Opioid Analgesics in the Management of Pain: A Consensus Statement of the American Society for Pain Management Nursing and the American Pain Society.

PubMed

Drew, Debra J; Gordon, Debra B; Morgan, Bonnie; Manworren, Renee C B

2018-06-01

Effective pain management requires careful titration of analgesics and evaluation of individual patient's responses to treatment using valid and reliable pain and pain relief assessment tools, and evidence-based patient monitoring for adverse treatment effects. A registered nurse, competent in pain assessment and analgesic administration, can safely interpret and implement properly written ''as-needed'' or ''PRN'' range orders for analgesic medications. The American Society for Pain Management Nursing (ASPMN) and the American Pain Society (APS) support safe medication practices and the appropriate use of PRN range orders for opioid analgesics in the management of pain. Copyright © 2018 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Benzodiazepines: a major component in unintentional prescription drug overdoses with opioid analgesics.

PubMed

Jann, Michael; Kennedy, William Klugh; Lopez, Gaylord

2014-02-01

The misuse and abuse of prescription medications in the United States continues to increase despite interventions by health care professionals, regulatory, and law enforcement agencies. Opioid analgesics are the leading class of prescription drugs that have caused unintentional overdose deaths. Benzodiazepines when taken alone are relatively safe agents in overdose. However, a 5-fold increase in deaths attributed to benzodiazepines occurred from 1999 to 2009. Emergency department visits related to opioid analgesics increased by 111% followed by benzodiazepines 89%. During 2003 to 2009, the 2 prescriptions drugs with the highest increase in death rates were oxycodone 264.6% and alprazolam 233.8%. Therefore, benzodiazepines have a significant impact on prescription drug unintentional overdoses second only to the opioid analgesics. The combination prescribing of benzodiazepines and opioid analgesics commonly takes place. The pharmacokinetic drug interactions between benzodiazepines and opioid analgesics are complex. The pharmacodynamic actions of these agents differ as their combined effects produce significant respiratory depression. Physician and pharmacy shopping by patients occurs, and prescription drug-monitoring programs can provide important information on benzodiazepine and opioid analgesic prescribing patterns and patient usage. Health care professionals need to inform patients and work closely with regulatory agencies and legislatures to stem the increasing fatalities from prescription drug unintentional overdoses.

Post-marketing withdrawal of analgesic medications because of adverse drug reactions: a systematic review.

PubMed

Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

2018-01-01

Many analgesics have been withdrawn from the market because of adverse drug reactions. Controversy still surrounds the use of some approved analgesics for pain management. However, the trends and reasons for withdrawal of analgesics when harms are attributed to their use have not been systematically assessed. Areas covered: We conducted searches in PubMed; Embase; Google Scholar; clinicaltrials.gov; WHO databases of withdrawn products; websites of the European Medicines Agency, the US Food and Drug Administration, the UK Medicines and Healthcare products Regulatory Agency; Meyler's Side Effects of Drugs; Stephens' Detection of New Adverse Drug Reactions; the Pharmaceutical Manufacturing Encyclopedia; and the Merck Index. We included licensed analgesics that were withdrawn after marketing because of adverse reactions between 1950 and March 2017. We excluded herbal products, non-human medicines, and non-prescription medicines. We used the Oxford Centre for Evidence Based Medicine criteria to document the levels of evidence, and chi-squared tests to compare withdrawal patterns across geographical regions. Expert opinion: Pharmacovigilance systems in low-resource settings should be strengthened. Greater co-ordination across regulatory authorities in assessing and interpreting the benefit-harm balance of new analgesics should be encouraged. Future reporting of harms in clinical trials of analgesics should follow standardized guidelines.

[The Analgesic Sparing Effect of Ketamine for Postoperative Pain Management after Pediatric Surgery on the Body Surface].

PubMed

Urabe, Tomoaki; Nakanuno, Ryuichi; Hayase, Kazuma; Sasada, Shogo; Iwamitsu, Reimi; Senami, Masaki

2016-04-01

It is reported that ketamine, a N-methyl-D-aspertate (NMDA) receptor antagonist, can provide analgesic effect improving postoperative pain management and decrease the supplementary analgesic requirement. We investigated the analgesic sparing effect of ketamine for postoperative pain in children undergoing surgery of body surface. Fifty eight patients (0-9 yrs) who had surgery of body surface were divided into two groups (ketamine : n = 27, Group K or control : n = 31, Group N). Postoperative analgesia extracted from charts was retrospectively evaluated by the times patients used analgesics until discharge after the operations. Chi-square and Mann-Whitney U tests were used for statistical analysis. Results : The ketamine group received an intrave- nous bolus of ketamine (1 mg - kg-1) before surgical skin incision. However, there were no significant differ- ences of usage (Group K vs Group N : 4/27 vs 7/31, P=0.45) and frequency of supplementary analgesic us- ages (P=0.85) among groups. In addition, there were also no significant demographic differences between the two groups. Conclusions : Our investigation suggests that the intravenous bolus of ketamine (1 mg - kg-1) before surgical skin incision does not decrease the supple- mentary analgesic requirements on postoperative pain management in pediatric surgery of the body surface.

Screening of analgesic activity of Tunisian Urtica dioica and analysis of its major bioactive compounds by GCMS.

PubMed

Dhouibi, Raouia; Moalla, Dorsaf; Ksouda, Kamilia; Ben Salem, Maryem; Hammami, Serria; Sahnoun, Zouheir; Zeghal, Khaled Mounir; Affes, Hanen

2017-11-20

The present study was aimed to evaluate the analgesic properties of Urtica dioica (UD) and to profile phytochemicals by gas chromatography-mass spectrometry (GC-MS). The ethanolic extracts were prepared by maceration method and extraction using rotary evaporator. The analgesic activity was analysed by hot plate method, formalin test, acetic acid-induced writhing test and the tail-flick test with different doses of the ethanolic extract. In all tests, the leaf's ethanolic extract exhibited significant analgesic activity (p < .001) at a dose of 400 mg/kg. Even with a low dose, we noticed an analgesic activity with many tests. The GC-MS analysis of the ethanol extract of leaf revealed many compounds; 2-methyltetradecane dodecane, 2,6,11-trimethyl-; 2,6,11-trimethyldodecane, and trimethylhexane which are pharmaceutically the most important. These findings justify that UD can be a valuable natural analgesic source which seemed to provide potential phototherapeutics against various ailments. The analysis of ethanolic extract of UD by GCMS revealed the presence of several compounds including polyphenols, flavonoids, triterpenes which can explain the analgesic effect of UD and its mechanism of action. Hence, UD could be another therapeutic alternative for relieving pain and for minimising the use of drugs that have long-term secondary effects.

Increases in the Use of Prescription Opioid Analgesics and the Lack of Improvement in Disability Metrics Among Users

PubMed Central

Sites, Brian D.; Beach, Michael L.; Davis, Matthew

2014-01-01

Background and Objectives In the United States, use of oral opioid analgesics has been associated with increasing rates of addiction, abuse, and diversion. However, little is known about recent national use of non-illicit prescription opioid analgesics (those prescribed in a doctor-patient relationship), the primary source of these drugs for the general US population. Our primary objective was to examine trends in the use of prescription opioid analgesics in the United States and to identify defining characteristics of patient users of prescribed opioids from 2000 to 2010. Methods We used the nationally representative Medical Expenditure Panel Survey to examine trends in prescription oral opioid analgesic use from 2000 to 2010. We used survey design methods to make national estimates of adults (18 years and older) who reported receiving an opioid analgesic prescription (referred to as opioid users) and used logistic regression to examine predictors of opioid analgesic use. Our primary outcome measures were national estimates of total users of prescription opioid analgesics and total number of prescriptions. Our secondary outcome was that of observing changes in the disability and health of the users. Results The estimated total number of opioid analgesic prescriptions in the United States increased by 104%, from 43.8 million in 2000 to 89.2 million in 2010. In 2000, an estimated 7.4% (95% CI, 6.9–7.9) of adult Americans were prescription opioid users compared with 11.8% (95% CI, 11.2–12.4) in 2010. Based on estimates adjusted for changes in the general population, each year was associated with a 6% increase in the likelihood of receiving an opioid prescription from 2000 to 2010. Despite the apparent increase in use, there were no demonstrable improvements in the age- or sex-adjusted disability and health status measures of opioid users. Conclusions The use of prescription opioid analgesics among adult Americans has increased in recent years, and this increase does not appear to be associated with improvements in disability and health status among users. On a public health level, these data suggest that there may be an opportunity to reduce the prescribing of opioid analgesics without worsening of population health metrics. PMID:24310049

Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality.

PubMed

Dasgupta, Nabarun; Funk, Michele Jonsson; Proescholdbell, Scott; Hirsch, Annie; Ribisl, Kurt M; Marshall, Steve

2016-01-01

Previous studies examining opioid dose and overdose risk provide limited granularity by milligram strength and instead rely on thresholds. We quantify dose-dependent overdose mortality over a large spectrum of clinically common doses. We also examine the contributions of benzodiazepines and extended release opioid formulations to mortality. Prospective observational cohort with one year follow-up. One year in one state (NC) using a controlled substances prescription monitoring program, with name-linked mortality data. Residential population of North Carolina (n = 9,560,234), with 2,182,374 opioid analgesic patients. Exposure was dispensed prescriptions of solid oral and transdermal opioid analgesics; person-years calculated using intent-to-treat principles. Outcome was overdose deaths involving opioid analgesics in a primary or additive role. Poisson models were created, implemented using generalized estimating equations. Opioid analgesics were dispensed to 22.8% of residents. Among licensed clinicians, 89.6% prescribed opioid analgesics, and 40.0% prescribed ER formulations. There were 629 overdose deaths, half of which had an opioid analgesic prescription active on the day of death. Of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year). Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9). Dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold. There is urgent need for guidance about combined classes of medicines to facilitate a better balance between pain relief and overdose risk. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government employees and is in the public domain in the US.

Reducing the default dispense quantity for new opioid analgesic prescriptions: study protocol for a cluster randomised controlled trial.

PubMed

Bachhuber, Marcus A; Nash, Denis; Southern, William N; Heo, Moonseong; Berger, Matthew; Schepis, Mark; Cunningham, Chinazo O

2018-04-20

As opioid analgesic consumption has grown, so have opioid use disorder and opioid-related overdoses. Reducing the quantity of opioid analgesics prescribed for acute non-cancer pain can potentially reduce risks to the individual receiving the prescription and to others who might unintentionally or intentionally consume any leftover tablets. Reducing the default dispense quantity for new opioid analgesic prescriptions in the electronic health record (EHR) is a promising intervention to reduce prescribing. This study is a prospective cluster randomised controlled trial with two parallel arms. Primary care sites (n=32) and emergency departments (n=4) will be randomised in matched pairs to either a modification of the EHR so that new opioid analgesic prescriptions default to a dispense quantity of 10 tablets (intervention) or to no EHR change (control). The dispense quantity will remain fully modifiable by providers in both arms. From 6 months preintervention to 18 months postintervention, patient-level data will be analysed (ie, the patient is the unit of inference). Patient eligibility criteria are: (A) received a new opioid analgesic prescription, defined as no other opioid analgesic prescription in the prior 6 months; (B) age ≥18 years; and (C) no cancer diagnosis within 1 year prior to the new opioid analgesic prescription. The primary outcome will be the quantity of opioid analgesics prescribed in the initial prescription. Secondary outcomes will include opioid analgesic reorders and health service utilisation within 30 days after the initial prescription. Outcomes will be compared between study arms using a difference-in-differences analysis. This study has been approved by the Montefiore Medical Center/Albert Einstein College of Medicine Institutional Review Board with a waiver of informed consent (2016-6036) and is registered on ClinicalTrials.gov (NCT03003832, 6 December 2016). Findings will be disseminated through publication, conferences and meetings with health system leaders. NCT03003832; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evolving Role of Local Anesthetics in Managing Postsurgical Analgesia.

PubMed

Golembiewski, Julie; Dasta, Joseph

2015-06-01

Opioid analgesics, the cornerstone of effective postsurgical pain management, may be associated with risk of opioid-related adverse drug events (ADEs) that may complicate the postsurgical experience. Perioperative multimodal analgesic regimens have the potential to improve postsurgical pain control and may permit use of lower analgesic doses and reduce the incidence of opioid-related ADEs. Utility of traditional local anesthetic formulations to provide analgesia over the entire postsurgical period is limited by their short duration of action. Liposome bupivacaine, a liposomal formulation of bupivacaine indicated for single-dose administration into the surgical site to produce postsurgical analgesia, was evaluated in multiple surgical models as part of multimodal analgesic regimens and was found in clinical trials to provide postsurgical analgesia for up to 72 hours. Here, we provide an overview of the available multimodal analgesic options and recent recommendations for optimal postsurgical pain management. A review of the literature was conducted, and results from recent clinical trials are included. The use of a multimodal analgesic regimen, including liposome bupivacaine, can extend the time to first postsurgical opioid use, may reduce postsurgical opioid consumption, and reduce hospital length of stay and costs compared with an opioid-only analgesic regimen. Use of multimodal analgesic regimens is a practical way to achieve good postsurgical analgesia while minimizing reliance on opioids and associated adverse events. Taken as a whole, evidence from the clinical studies of liposome bupivacaine suggests this local anesthetic formulation may be a useful component of multimodal analgesic regimens for managing postsurgical pain in select patients, with the potential to reduce opioid use and opioid-related ADEs in the postsurgical setting. As with bupivacaine, appropriate use of liposome bupivacaine to optimize clinical effects, economic implications, and patient tolerability will depend on appropriate patient selection, practitioner training, and institutional protocols. As a component of a multimodal analgesic regimen, liposome bupivacaine represents a new approach to extending the duration of postsurgical analgesia. Further studies across a range of surgical settings should help clarify the most appropriate roles for this prolonged-release formulation of bupivacaine. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Relative Efficacy of Ultrasound-guided Ilioinguinal-iliohypogastric Nerve Block versus Transverse Abdominis Plane Block for Postoperative Analgesia following Lower Segment Cesarean Section: A Prospective, Randomized Observer-blinded Trial.

PubMed

Kiran, L Vamsee; Sivashanmugam, T; Kumar, V R Hemanth; Krishnaveni, N; Parthasarathy, S

2017-01-01

Quality of postoperative analgesia after cesarean section makes difference to mother in child bonding, early ambulation, and discharge. Ilioinguinal iliohypogastric (ILIH) and transverse abdominis plane (TAP) block had been tried to reduce the opioid analgesics, but the relative efficacy is unknown. Hence, this study was designed to compare the efficacy of these two regional analgesic techniques in sparing postoperative rescue analgesic requirement following lower segment cesarean section (LSCS). Sixty patients who underwent LSCS were randomly allocated into two groups to receive either US-guided TAP block or ILIH nerve block using sealed envelope technique at the end of the surgery. In the postoperative ward, whenever patient complained of pain, pain nurse in-charge administered the rescue analgesics as per the study protocol. A blinded observer visited the patient at 0, 2, 4, 6, 8, 10, 12, and 24 h postoperative intervals and recorded the quality of pain relief and the amount of rescue analgesic consumed. All patients in both the study groups required one dose of rescue analgesics in the form of injection diclofenac sodium 50 mg intravenously but subsequently 57% of patients did not require any further analgesics till 24 h in the TAP block group whereas in ILIH group, only 13% did not require further analgesics ( P = 0.00), correspondingly the cumulative tramadol dose was significantly higher at all the time interval in the ILIH group when compared to the TAP group. Quality of postoperative analgesia provided by TAP block was superior to ILIH block following LSCS.

Analgesia (mis)usage on a dental emergency service: a patient survey.

PubMed

Hommez, Geert; Ongena, B; Cauwels, R G E C; De Paepe, P; Christiaens, V; Jacquet, W

2018-04-01

Analgesics are one of the most frequently used medicines. Self-medication and misuse have been described in the literature. The purpose of this study was to document analgesic (mis)use in a population seeking emergency dental treatment. Patients consulting a dental emergency service were randomly asked to complete a questionnaire on analgesic use, knowledge and information on the analgesics and on their pain history. A photobook was used as an aid to identify products used. Descriptive statistics were combined with chi-square and Mann-Whitney U testing. Ninety-eight patients were included. Acetaminophen (69.4%) and ibuprofen (65.3%) were the most frequently used products. Nearly half of the subjects (43.9%) combined at least two analgesics. Although 42.9% of subjects were aware of the maximum daily dose, 62.2% of the subjects exceeded this limit, specifically 76.6% of subjects using ibuprofen and 32.4% of subjects using acetaminophen overdosing. Females overdosed significantly more than males. Ingestion on medical advice did not affect the overdose rates significantly. No significant relation was found between the absence of knowledge on the maximum daily dose and actual overdosing. No higher pain reduction was found in patients overdosing analgesics. The average number of days patients experienced pain before consulting the emergency unit was 12. A significant relation was found between the lag time and overdosing. A large portion of the patients overdosed analgesics. Even prior medical advice did not reduce significantly overdose rates. Dentists treating emergency cases clearly need to be aware of the high risk and high rates of overdosing analgesics in their patients.

The evidence of neuraxial administration of analgesics for cancer-related pain: a systematic review.

PubMed

Kurita, G P; Benthien, K S; Nordly, M; Mercadante, S; Klepstad, P; Sjøgren, P

2015-10-01

The present systematic review analysed the existing evidence of analgesic efficacy and side effects of opioids without and with adjuvant analgesics delivered by neuraxial route (epidural and subarachnoid) in adult patients with cancer. Search strategy was elaborated with words related to cancer, pain, neuraxial route, analgesic and side effects. The search was performed in PubMed, EMBASE, and Cochrane for the period until February 2014. Studies were analysed according to methods, results, quality of evidence, and strength of recommendation. The number of abstracts retrieved was 2147, and 84 articles were selected for full reading. The final selection comprised nine articles regarding randomised controlled trials (RCTs) divided in four groups: neuraxial combinations of opioid and adjuvant analgesic compared with neuraxial administration of opioid alone (n = 4); single neuraxial drug in bolus compared with continuous administration (n = 2); single neuraxial drug compared with neuraxial placebo (n = 1); and neuraxial opioid combined with or without adjuvant analgesic compared with other comprehensive medical management than neuraxial analgesics (n = 2). The RCTs presented clinical and methodological diversity that precluded a meta-analysis. They also presented several limitations, which reduced study internal validity. However, they demonstrated better pain control for all interventions analysed. Side effects were described, but there were few significant differences in favour of the tested interventions. Heterogeneous characteristics and several methodological limitations of the studies resulted in evidence of low quality and a weak recommendation for neuraxial administration of opioids with or without adjuvant analgesics in adult patients with cancer. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

21 CFR 341.85 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... “pain reliever” or “analgesic (pain reliever).” If the product is also labeled to relieve fever, then the analgesic-antipyretic component is identified as a “pain reliever-fever reducer” or “analgesic (pain reliever)-antipyretic (fever reducer).” (2) [Reserved] (b) Indications. The labeling of the...

21 CFR 341.85 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... “pain reliever” or “analgesic (pain reliever).” If the product is also labeled to relieve fever, then the analgesic-antipyretic component is identified as a “pain reliever-fever reducer” or “analgesic (pain reliever)-antipyretic (fever reducer).” (2) [Reserved] (b) Indications. The labeling of the...

21 CFR 341.85 - Labeling of permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... “pain reliever” or “analgesic (pain reliever).” If the product is also labeled to relieve fever, then the analgesic-antipyretic component is identified as a “pain reliever-fever reducer” or “analgesic (pain reliever)-antipyretic (fever reducer).” (2) [Reserved] (b) Indications. The labeling of the...

21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 346.16 Section 346.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the...

21 CFR 346.16 - Analgesic, anesthetic, and antipruritic active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Analgesic, anesthetic, and antipruritic active ingredients. 346.16 Section 346.16 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Ingredients § 346.16 Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the...

Synthetic substances with morphine-like effect

PubMed Central

Braenden, Olav J.; Eddy, Nathan B.; Halbach, H.

1955-01-01

For morphine-, morphinan-, pethidine-, methadone-, and dithienyl-butenylamine groups of analgesic compounds a systematic survey is given of how analgesic activity is quantitatively affected by alteration of the chemical constitution. Features common to the structural formulae of substances with morphine-like analgesic effect are pointed out. ImagesFIG. 1FIG. 1(Contd.) PMID:13284565

S-adenosyl methionine (SAM) attenuates the development of tolerance to analgesic activity of morphine in rats.

PubMed

Katyal, Jatinder; Kumar, Hemant; Joshi, Dinesh; Gupta, Yogendra Kumar

2017-04-03

Development of tolerance to analgesic effect, on chronic administration of morphine, limits its clinical usefulness in pain management. S-adenosyl methionine (SAM) used for arthritis and approved as a supplement in many countries including United States was evaluated for reducing morphine tolerance. Male 'Wistar' rats were used. The analgesic activity was determined using tail flick analgesiometer (Columbus Instruments, USA). Rats given morphine (7mg/kg), intraperitoneally (i.p.), once daily for 5days developed tolerance to analgesic effect. To evaluate the effect of SAM on morphine tolerance, SAM 800mg/kg was administered orally (p.o.), 45min prior to each dose of morphine. The analgesic activity of SAM and opioidergic component in its activity was also evaluated. Co-administration of morphine and SAM reversed morphine tolerance. SAM exhibited analgesic effect after repeated administration which was reversed by naloxone administration. Since safety of SAM on chronic use is documented it can be a good option in morphine tolerance. Role in drug addiction and withdrawal should also be evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Guaifenesin enhances the analgesic potency of paracetamol in mice.

PubMed

Dolezal, T; Krsiak, M

2002-12-01

Guaifenesin is used as an expectorant and it has been reported to possess muscle relaxant and sedative activity. Guaifenesin has been used as a component of composite OTC analgesics containing paracetamol for many years. The aim of our study was to ascertain effects of guaifenesin on paracetamol analgesic activity and locomotor performance. Antinociceptive efficacy was tested in mice using an acetic acid (0.7%) writhing test. Locomotor performance was tested in rota-rod test and activity cage. All drugs were given orally and tested in mice. In combination with a subeffective dose of guaifenesin (200 mg/kg), the ED(50) for paracetamol in the writhing test was significantly lower (82.2 mg/kg) than that of paracetamol administered alone (233.7 mg/kg). Guaifenesin alone did not show an analgesic effect. Guaifenesin did not produce statistically significant locomotor impairment in the rota-rod test at doses enhancing analgesic activity of paracetamol, although there was a trend for decreased locomotor activity in activity cage. The present results indicate that guaifenesin may enhance analgesic activity of paracetamol.

Peripheral analgesic sites of action of anti-inflammatory drugs.

PubMed

Ferreira, S H

2002-07-01

Inflammatory signs and symptoms of redness, swelling, heat and pain are due to the effects of inflammatory mediators released during the inflammatory response. Depending on the type of injurious stimuli and the tissue involved, the array of mediators may differ but eicosanoids are involved in the genesis of inflammatory pain. They are responsible for the hypersensitisation of the nociceptors (allodynialhyperalgesia). The basic mechanism of analgesic action of nonsteroidal anti-inflammatory drugs results from the inhibition of prostaglandin synthesis (prostacyclin or PGE2), thus preventing nociceptor threshold lowering. Because there is a temporal hierarchy in the release of inflammatory mediators, there are several targets for the action of peripheral acting analgesics before and after the inhibition of prostaglandin synthesis. Blockade of the release and inhibition of inducible cyclooxygenase explain the analgesic action of glucocorticoids. Nimesulide also has an inhibitory action on the cascade of hypersensitising cytokines. Some analgesics, such as dipyrone, flurbiprofen or diclofenac, act directly upon ongoing inflammatory hypersensitisation. Those analgesics restore the nociceptor by stimulating the arginine/NO/cGMP/K(ATP) channel pathway.

Options for treating postherpetic neuralgia in the medically complicated patient

PubMed Central

Bruckenthal, Patricia; Barkin, Robert L

2013-01-01

Patients with postherpetic neuralgia (PHN) are often of advanced age or immunocompromised and likely to have ≥1 comorbid medical condition for which they receive ≥1 medication (polypharmacy). Comorbidities affecting renal or hepatic function can alter pharmacokinetics, thereby impacting the efficacy or tolerability of PHN analgesic therapies. Cardiovascular, cerebrovascular, or psychiatric comorbidities may increase patient vulnerability to potential adverse events associated with some PHN analgesic therapies. Because PHN is a localized condition, localized therapy with a topical analgesic (lidocaine patch 5% and capsaicin 8% patch or cream) may provide adequate efficacy while mitigating the risk of systemic adverse events compared with oral analgesics (eg, tricyclic antidepressants, anticonvulsants, opioids). However, combined therapy with a topical and an oral analgesic or with >1 oral analgesic may be needed for optimal pain management in some patients. This review summarizes how comorbidities and concomitant medications should be taken into account when selecting among available pharmacotherapies for PHN and provides recommendations for the selection of therapies that will provide analgesia while minimizing the risk of adverse events. PMID:23990726

Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance.

PubMed

Mercer, Susan L; Coop, Andrew

2011-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationships to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.

Methoxyflurane and Nitrous Oxide as Obstetric Analgesics. II.—A Comparison by Self-administered Intermittent Inhalation

PubMed Central

Jones, Peter L.; Rosen, M.; Mushin, W. W.; Jones, E. V.

1969-01-01

Methoxyflurane (0·35%) in air and nitrous oxide/oxygen (50%/50%) self-administered intermittently in the usual way have been compared as analgesics for labour. There were 25 patients in each group. Objective assessment by an anaesthetist showed that methoxyflurane is the more effective analgesic, and this was supported by the opinion of the multiparae. Nausea and vomiting were significantly less with methoxyflurane. Fifty per cent. nitrous oxide in oxygen given intermittently does not appear to be the best analgesic concentration. Nevertheless, since a considerable variation in sensitivity exists, it would probably be unwise to consider the introduction of higher concentrations for use by unsupervised midwives. This trial confirms the predictions made by us using a method for screening inhalational analgesics, in which methoxyflurane and nitrous oxide were given continuously. PMID:4895339

Methoxyflurane and nitrous oxide as obstetric analgesics. II. A comparison by self-administered intermittent inhalation.

PubMed

Jones, P L; Rosen, M; Mushin, W W; Jones, E V

1969-08-02

Methoxyflurane (0.35%) in air and nitrous oxide/oxygen (50%/50%) self-administered intermittently in the usual way have been compared as analgesics for labour. There were 25 patients in each group. Objective assessment by an anaesthetist showed that methoxyflurane is the more effective analgesic, and this was supported by the opinion of the multiparae. Nausea and vomiting were significantly less with methoxyflurane. Fifty per cent. nitrous oxide in oxygen given intermittently does not appear to be the best analgesic concentration. Nevertheless, since a considerable variation in sensitivity exists, it would probably be unwise to consider the introduction of higher concentrations for use by unsupervised midwives.This trial confirms the predictions made by us using a method for screening inhalational analgesics, in which methoxyflurane and nitrous oxide were given continuously.

Usage of paracetamol-containing combination analgesics remains high in primary care

PubMed Central

Usher, Cara; Teeling, Mary; Bennett, Kathleen; McGowan, Bernie; Feely, John

2005-01-01

Aims Paracetamol-containing combination analgesics are widely prescribed but the use of paracetamol/dextropropoxyphene (co-proxamol) is particularly controversial. We aim to examine the prescribing patterns of the paracetamol-containing analgesics in Ireland. Methods A national primary care prescribing database was used to investigate patterns of usage. Twenty-six thousand three hundred and eighteen patients who were new to therapy with paracetamol and paracetamol-containing analgesics between January and June 2002 were identified as follows: no previous analgesic medication in the 6 months prior to enrolment into the study, and followed up for at least 12 months from the time of enrolment. Duration of therapy and the number of prescriptions received post enrolment were analyzed according to age. Odds ratios for receiving long-term (>1 month) compared with short-term (1 month) prescriptions for co-proxamol, paracetamol only or a paracetamol combination-type analgesic were calculated for women vs. men, and in those aged over 65 vs. those aged under 65 years. Results Co-proxamol was the most commonly prescribed analgesic, accounting for 42% of all prescriptions dispensed during 2003. Long-term use of paracetamol-containing analgesic preparations was uncommon, with 56.7% receiving only 1 month's prescription during the study period. However, women (OR = 1.18, 95% CI 1.07, 1.28, P < 0.0001) and those over 65 years (OR = 1.71, 95% CI 1.57, 1.86, P < 0.0001) were more likely to receive a follow-up prescription for co-proxamol, but also for paracetamol (women, OR = 1.28, 95% CI 1.16, 1.39; over 65 year olds, OR = 2.67, 95%CI 2.44, 2.93) and the paracetamol combinations (women, OR = 1.33, 95% CI 1.20, 1.47; over 65 year olds, OR = 1.69, 95% CI 1.53, 1.87). Conclusions Co-proxamol was the most commonly prescribed paracetamol-containing analgesic preparation in Ireland. The results may indicate inappropriate use in primary care. PMID:16305590

Levetiracetam interacts synergistically with nonsteroidal analgesics and caffeine to produce antihyperalgesia in rats.

PubMed

Tomić, Maja A; Micov, Ana M; Stepanović-Petrović, Radica M

2013-11-01

Levetiracetam is a novel anticonvulsant with antihyperalgesic efficacy in inflammatory pain. Nonsteroidal analgesics and caffeine, as analgesic adjuvant, are widely used against inflammatory pain. This study characterized the manner in which levetiracetam interacts with analgesics (ibuprofen, celecoxib, and paracetamol) and caffeine to suppress hyperalgesia in a model of localized inflammation. Rat paw inflammation was induced by intraplantar carrageenan (.1 mL, 1%). Hyperalgesia and antihyperalgesic effects of levetiracetam (orally), analgesics (orally), and caffeine (intraperitoneally) alone and 2-drug combinations of levetiracetam with analgesics or caffeine were examined by a modified paw pressure test. The type of interaction between components was determined by isobolographic analysis or by analysis of the log dose-response curves for drug combination and drugs alone. Levetiracetam (10-200 mg/kg), ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200 mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with analgesics/caffeine produced a significant, dose-dependent reduction of inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and 11-fold reduction of doses of both drugs in combination of levetiracetam with paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose-response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10 mg/kg) and levetiracetam applied alone also revealed a synergistic interaction. Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11-fold. The presented data suggest that 2-drug combinations of levetiracetam and nonsteroidal analgesics or caffeine could be useful in treatment of inflammatory pain. The efficacy and the adverse effects of those mixtures should be explored further in clinical settings. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Effects of analgesics on olfactory function and the perception of intranasal trigeminal stimuli.

PubMed

Mizera, L; Gossrau, G; Hummel, T; Haehner, A

2017-01-01

There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls. For this purpose, a psychophysical approach was chosen to measure these sensory functions in 100 chronic pain patients and 95 controls. Olfactory testing was performed using the 'Sniffin' Sticks' test kit, which involves tests for odour threshold, odour discrimination and odour identification. Further, participants were asked to rate the intensity of trigeminal stimuli by using a visual analogue scale. We observed that the chronic use of pain medication was associated with significantly reduced perception of intranasal trigeminal stimuli and olfactory function compared to age-matched controls without intake of analgesics. Results indicate that non-opioid and opioid drugs, or a combination of both did not differ in their effects on chemosensory function. Further, after eliminating the effect of a co-existing depression and the use of co-analgesics, the negative influence of analgesics on olfactory function and trigeminal perception was still evident. The observed effect might be mediated due to interaction with opioid receptors in trigeminal ganglia and nuclei or due to trigeminal/olfactory interaction. As a practical consequence, patients should be made aware of a possible impairment of their olfactory and trigeminal function under long-term analgesic treatment. WHAT DOES THIS STUDY ADD?: We observed that the chronic use of pain medication was associated with significantly reduced olfactory function and perception of intranasal trigeminal stimuli compared to age-matched controls without intake of analgesics. Non-opioid and opioid drugs did not differ in their effects on chemosensory function. © 2016 European Pain Federation - EFIC®.

Pharmacologic management of non-cancer pain among nursing home residents.

PubMed

Lapane, Kate L; Quilliam, Brian J; Chow, Wing; Kim, Myoung S

2013-01-01

Pain is common in nursing home settings. To describe scheduled analgesic use among nursing home (NH) residents experiencing non-cancer pain and evaluate factors associated with scheduled analgesic use. We identified 2508 residents living in one of 185 NHs predominantly from one for-profit chain, with pain recorded on two consecutive Minimum Data Set assessments. Pharmacy transaction files provided detailed medication information. Logistic regression models adjusted for clustering of residents in NHs identified factors related to scheduled prescription analgesics. Twenty-three percent had no scheduled analgesics prescribed. Those with scheduled analgesics were more likely to have excruciating pain (5.5% vs. 1.2%) and moderate pain documented (64.7% vs. 47.5%) than residents without scheduled analgesics. Hydrocodone (41.7%), short-acting oxycodone (16.6%), and long-acting fentanyl (9.4%) were common, and 13.8% reported any nonsteroidal anti-inflammatory agent use. Factors associated with decreased odds of scheduled analgesics included severe cognitive impairment (adjusted odds ratio [AOR] 0.56; 95% confidence interval [CI] 0.36 to 0.88), age more than 85 years (AOR 0.57; 95% CI 0.41 to 0.80), and Parkinson's disease (AOR 0.55; 95% CI 0.30 to 0.99). Factors associated with increased odds of scheduled analgesic use included history of fracture (AOR 1.79; 95% CI 1.16 to 2.76), diabetes (AOR 1.30; 95% CI 1.02 to 1.66), and higher Minimum Data Set mood scores (AOR 1.11; 95% CI 1.04 to 1.19). Some improvements in pharmacologic management of pain in NHs have been realized. Yet, presence of pain without scheduled analgesics prescribed was still common. Evidence-based procedures to assure adherence to clinical practice guidelines for pain management in this setting are warranted. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Pattern of self-medication with analgesics among Iranian University students in central Iran

PubMed Central

Sarahroodi, Shadi; Maleki-Jamshid, Ali; Sawalha, Ansam F.; Mikaili, Peyman; Safaeian, Leila

2012-01-01

Background: Self-medication is defined as the use of drugs for the treatment of self-diagnosed disorders. It is influenced by factors such as education, family, society, law, availability of drugs and exposure to advertisements. This study was performed to evaluate self-medication with analgesics and its pattern among different groups of Iranian University Students. Materials and Methods: A randomized, cross-sectional, multicenter study was conducted from December 2009 to February 2010. The target population of this study was 564 students out of 10,000 students attending four medical and non-medical science universities in Qom state. Data was analyzed using SPSS version 16, and analysis was conducted with descriptive analysis procedures. Results: 76.6% of the students had used analgesics in self-medication in the previous 3 months. The frequency of analgesic use in the study period was once in 19.2% of the participants, twice in 22.2%, three times in 16.3% and more than three times in 35.5% of the participants, although 6.8% of them were not sure when they were used. Of all the respondents, 49.8% reported headache as the problem. This was the most common problem, after which came Dysmenorrhea,headache and stomach ache. Bone and joint pains were other problems that led to the use of analgesics. The most commonly used source of information for self-medication with analgesics was advice from friends and family (54.7%), previously prescribed medications (30.1%), their medical knowledge (13.3%) and recommendation of a pharmacist (1.9%). Conclusion: Self-medication with analgesics is very high among Iranian students in Qom city. This could be an index for other parts of the Iranian community. Because the source of information about analgesics is inappropriate, we would recommend education courses about analgesics and self-medication on the radio and television for the entire population. PMID:22870417

Pattern of self-medication with analgesics among Iranian University students in central Iran.

PubMed

Sarahroodi, Shadi; Maleki-Jamshid, Ali; Sawalha, Ansam F; Mikaili, Peyman; Safaeian, Leila

2012-05-01

Self-medication is defined as the use of drugs for the treatment of self-diagnosed disorders. It is influenced by factors such as education, family, society, law, availability of drugs and exposure to advertisements. This study was performed to evaluate self-medication with analgesics and its pattern among different groups of Iranian University Students. A randomized, cross-sectional, multicenter study was conducted from December 2009 to February 2010. The target population of this study was 564 students out of 10,000 students attending four medical and non-medical science universities in Qom state. Data was analyzed using SPSS version 16, and analysis was conducted with descriptive analysis procedures. 76.6% of the students had used analgesics in self-medication in the previous 3 months. The frequency of analgesic use in the study period was once in 19.2% of the participants, twice in 22.2%, three times in 16.3% and more than three times in 35.5% of the participants, although 6.8% of them were not sure when they were used. Of all the respondents, 49.8% reported headache as the problem. This was the most common problem, after which came Dysmenorrhea,headache and stomach ache. Bone and joint pains were other problems that led to the use of analgesics. The most commonly used source of information for self-medication with analgesics was advice from friends and family (54.7%), previously prescribed medications (30.1%), their medical knowledge (13.3%) and recommendation of a pharmacist (1.9%). Self-medication with analgesics is very high among Iranian students in Qom city. This could be an index for other parts of the Iranian community. Because the source of information about analgesics is inappropriate, we would recommend education courses about analgesics and self-medication on the radio and television for the entire population.

Use of opioid analgesics or sleeping medication and survival of cancer patients.

PubMed

Chang, Wen-Pei; Lin, Chia-Chin

2015-06-01

Pain and sleep disturbance have been shown to have a profound influence on the outcomes of cancer treatment. This study sought to determine whether administering opioid analgesics or sleeping medication to cancer patients during their first admission to a hospital is associated with poor prognoses. We conducted a population-based retrospective cohort study by analyzing data obtained from the National Health Insurance Research Database in Taiwan. The study population comprised cancer patients whose first admission to a hospital for initial cancer treatment was in 2004. We collected data on 2302 cancer patients. To analyze the effect of opioid analgesic and sleeping medication usage on cancer patient survival, we compared the 3-year survival rates among 4 groups of patients (no use, sleeping medications-only, opioid analgesics-only, both used). The 3-year Kaplan-Meier plots for these 4 groups show that the difference was statistically significant (log rank 48.244, p < 0.001). The longevity of cancer patients was the greatest among the no-use group, followed by the sleeping medications-only group, then the opioid analgesics-only group, and finally, the group in which both sleeping medications and opioid analgesics were used. The use of opioid analgesics or sleeping medication was shown to be negatively correlated with the survival rate of cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

A systematic review and meta-analysis of the ability of analgesic drugs to reduce metastasis in experimental cancer models

PubMed Central

Hooijmans, Carlijn R.; Geessink, Florentine J.; Ritskes-Hoitinga, Merel; Scheffer, Gert-Jan

2015-01-01

Abstract Analgesics are commonly used to manage pain in cancer patients. It has been suggested that there might be a relation between analgesics and the outgrowth of metastases. Opioids might increase and non-steroidal anti-inflammatory drugs decrease the risk of metastasis. Robust analysis of all preclinical evidence, however, has so far been lacking. Therefore, we conducted a systematic review and meta-analysis on the effect of treatment with analgesics on metastasis in experimental animal models. One hundred forty-seven studies met the inclusion criteria. Study characteristics, outcome data on the number, and incidence of metastases were extracted, and methodological quality was assessed. In the meta-analysis, we included 215 (±4000 animals) and 137 (±3000 animals) comparisons between analgesic vs control treatment, respectively, on the number and incidence of metastases. Overall, treatment with analgesics significantly decreases the number and risk of metastasis. This effect appears mainly to be the consequence of the efficacy of NSAIDs. Other factors that modify the efficacy are species, type of NSAIDs administered, timing, and duration of treatment. There is no evidence indicating that treatment with any analgesics increases the occurrence of metastases. Our findings appear robust for the various animal models and designs included in this review, which increases our confidence in the result and translatability to the clinical situation. PMID:26181303

The availability of prescription-only analgesics purchased from the internet in the UK.

PubMed

Raine, Connie; Webb, David J; Maxwell, Simon R J

2009-02-01

Increasing numbers of people are accessing medicines from the internet. This online market is poorly regulated and represents a potential threat to the health of patients and members of the public. Prescription-only analgesics, including controlled opioids, are readily available to the UK public through internet pharmacies that are easily identified by popular search engines. The majority of websites do not require the customer to possess a valid prescription for the drug. Less than half provide an online health screen to assess suitability for supply. The majority have no registered geographical location. Analgesic medicines are usually purchased at prices significantly above British National Formulary prices and are often supplied in large quantities. These findings are of particular relevance to pain-management specialists who are trying to improve the rational use of analgesic drugs. To explore the availability to the UK population of prescription-only analgesics from the internet. Websites were identified by using several keywords in the most popular internet search engines. From 2000 websites, details of 96 were entered into a database. Forty-six (48%) websites sold prescription analgesics, including seven opioids, two non-opioids and 18 nonsteroidal anti-inflammatory drugs. Thirty-five (76%) of these did not require the customer to possess a valid prescription. Prescription-only analgesics, including controlled opioids, are readily available from internet websites, often without a valid prescription.

Pain in children--are we accomplishing the optimal pain treatment?

PubMed

Lundeberg, Stefan

2015-01-01

Morphine, paracetamol and local anesthetics have for a long time been the foremost used analgesics in the pediatric patient by tradition but not always enough effective and associated with side effects. The purpose with this article is to propose alternative approaches in pain management, not always supported up by substantial scientific work but from a combination of science and clinical experience in the field. The scientific literature has been reviewed in parts regarding different aspects of pain assessment and analgesics used for treatment of diverse pain conditions with focus on procedural and acute pain. Clinical experience has been added to form the suggested improvements in accomplishing an improved pain management in pediatric patients. The aim with pain management in children should be a tailored analgesic medication with an individual acceptable pain level and optimal degree of mobilization with as little side effects as possible. Simple techniques of pain control are as effective as and complex techniques in pediatrics but the technique used is not of the highest importance in achieving a good pain management. Increased interest and improved education of the doctors prescribing analgesics is important in accomplishing a better pain management. The optimal treatment with analgesics is depending on the analysis of pain origin and analgesics used should be adjusted thereafter. A multimodal treatment regime is advocated for optimal analgesic effect. © 2014 John Wiley & Sons Ltd.

Comparison of Electroacupuncture and Morphine-Mediated Analgesic Patterns in a Plantar Incision-Induced Pain Model

PubMed Central

Tsai, Shih-Ying; Chen, Kuen-Bao; Hsu, Sheng-Feng; Chen, Julia Yi-Ru

2014-01-01

Electroacupuncture (EA) is a complementary therapy to improve morphine analgesia for postoperative pain, but underlying mechanism is not well-known. Herein, we investigated EA-induced analgesic effect in a plantar incision (PI) model in male Sprague-Dawley rats. PI was performed at the left hind paw. EA of 4 Hz and high intensity or sham needling was conducted at right ST36 prior to PI and repeated for another 2 days. Behavioral responses to mechanical and thermal stimuli, spinal phospho-ERK, and Fos expression were all analyzed. In additional groups, naloxone and morphine were administered to elucidate involvement of opioid receptors and for comparison with EA. EA pretreatment significantly reduced post-PI tactile allodynia for over 1 day; repeated treatments maintained analgesic effect. Intraperitoneal naloxone could reverse EA analgesia. Low-dose subcutaneous morphine (1 mg/kg) had stronger inhibitory effect on PI-induced allodynia than EA for 1 h. However, analgesic tolerance appeared after repeated morphine injections. Both EA and morphine could equally inhibit PI-induced p-ERK and Fos inductions. We conclude that though EA and morphine attenuate postincision pain through opioid receptor activations, daily EA treatments result in analgesic accumulation whereas daily morphine injections develop analgesic tolerance. Discrepant pathways and mechanisms underlying two analgesic means may account for the results. PMID:25530786

21 CFR 358.760 - Labeling of permitted combinations of active ingredients for the control of dandruff.

Code of Federal Regulations, 2013 CFR

2013-04-01

... control of dandruff and external analgesic active ingredients in § 358.720(b). The label states “dandruff...) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b). The labeling.... (1) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b...

21 CFR 358.760 - Labeling of permitted combinations of active ingredients for the control of dandruff.

Code of Federal Regulations, 2014 CFR

2014-04-01

... control of dandruff and external analgesic active ingredients in § 358.720(b). The label states “dandruff...) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b). The labeling.... (1) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b...

21 CFR 358.760 - Labeling of permitted combinations of active ingredients for the control of dandruff.

Code of Federal Regulations, 2012 CFR

2012-04-01

... control of dandruff and external analgesic active ingredients in § 358.720(b). The label states “dandruff...) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b). The labeling.... (1) Combinations of control of dandruff and external analgesic active ingredients in § 358.720(b...

Comparison Between the Use of Ropivacaine Alone and Ropivacaine With Sufentanil in Epidural Labor Analgesia

PubMed Central

Wang, Xian; Xu, Shiqin; Qin, Xiang; Li, Xiaohong; Feng, Shan-Wu; Liu, Yusheng; Wang, Wei; Guo, Xirong; Shen, Rong; Shen, Xiaofeng; Wang, Fuzhou

2015-01-01

Abstract To compare the analgesic efficacy and safety of the sole local anesthetic ropivacaine with the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil given epidurally on the labor pain control. After institutional review board approval and patient consent, a total of 500 nulliparas requesting epidural labor analgesia were enrolled and 481 eventually were randomized into 2 groups: a sole local anesthetic group (ropivacaine 0.125%) and a combination of local anesthetic and opioidergic analgesic group (0.125% ropivacaine + 0.3 μg/mL sufentanil). After the test dose, a 10-mL epidural analgesic solution was given in a single bolus, followed by intermittent bolus injection of 10 to 15 mL of the solution. The primary outcome was the analgesic efficacy measured using Numerical Rating Scale (NRS) of pain. Other maternal and infant variables were evaluated as secondary outcomes. A total of 346 participants completed the study. The median NRS pain score during the 1st stage of labor was significantly lower in the combination group 2.2 (interquartile range [IQR]: 1.8–2.7) comparing to the sole local analgesic group 2.4 (IQR: 2.0–2.8) (P < 0.0001). No significant difference was observed in NRS pain score prior epidural analgesia and during the 2nd stage of labor. Patients in both groups rated same satisfaction of analgesia. Patients in the sole local analgesic group experienced fewer side effects than those in the combination group (37.7% vs 47.2%, P = 0.082). The individual analgesia-related cost in the sole local analgesic group was less ($5.7 ± 2.06) than that in the combination group ($9.76 ± 3.54) (P < 0.0001). The incidence of 1-minute Apgar ≤ 7 was lower in the sole local analgesic group 2 (1.2%) than the combination group 10 (5.5%) (P = 0.038). No difference was found between other secondary outcomes. The sole local anesthetic ropivacaine produces a comparable labor analgesic effect as the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil at different stages of labor (ΔNRS = 0.2) but the former has less side effects, lower cost, and less incidence of lower 1-minute Apgar scoring. These results imply the necessity of a systematic reevaluation of epidural labor analgesia with sole local anesthetics against combination regimens of local anesthetics and other opioids. PMID:26512604

Comparison Between the Use of Ropivacaine Alone and Ropivacaine With Sufentanil in Epidural Labor Analgesia.

PubMed

Wang, Xian; Xu, Shiqin; Qin, Xiang; Li, Xiaohong; Feng, Shan-Wu; Liu, Yusheng; Wang, Wei; Guo, Xirong; Shen, Rong; Shen, Xiaofeng; Wang, Fuzhou

2015-10-01

To compare the analgesic efficacy and safety of the sole local anesthetic ropivacaine with the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil given epidurally on the labor pain control.After institutional review board approval and patient consent, a total of 500 nulliparas requesting epidural labor analgesia were enrolled and 481 eventually were randomized into 2 groups: a sole local anesthetic group (ropivacaine 0.125%) and a combination of local anesthetic and opioidergic analgesic group (0.125% ropivacaine + 0.3 μg/mL sufentanil). After the test dose, a 10-mL epidural analgesic solution was given in a single bolus, followed by intermittent bolus injection of 10 to 15 mL of the solution. The primary outcome was the analgesic efficacy measured using Numerical Rating Scale (NRS) of pain. Other maternal and infant variables were evaluated as secondary outcomes.A total of 346 participants completed the study. The median NRS pain score during the 1st stage of labor was significantly lower in the combination group 2.2 (interquartile range [IQR]: 1.8-2.7) comparing to the sole local analgesic group 2.4 (IQR: 2.0-2.8) (P < 0.0001). No significant difference was observed in NRS pain score prior epidural analgesia and during the 2nd stage of labor. Patients in both groups rated same satisfaction of analgesia. Patients in the sole local analgesic group experienced fewer side effects than those in the combination group (37.7% vs 47.2%, P = 0.082). The individual analgesia-related cost in the sole local analgesic group was less ($5.7 ± 2.06) than that in the combination group ($9.76 ± 3.54) (P < 0.0001). The incidence of 1-minute Apgar ≤ 7 was lower in the sole local analgesic group 2 (1.2%) than the combination group 10 (5.5%) (P = 0.038). No difference was found between other secondary outcomes.The sole local anesthetic ropivacaine produces a comparable labor analgesic effect as the combination of both local anesthetic ropivacaine and opioidergic analgesic sufentanil at different stages of labor (ΔNRS = 0.2) but the former has less side effects, lower cost, and less incidence of lower 1-minute Apgar scoring. These results imply the necessity of a systematic reevaluation of epidural labor analgesia with sole local anesthetics against combination regimens of local anesthetics and other opioids.

Prescription of opioid analgesics for nontraumatic dental conditions in emergency departments.

PubMed

Okunseri, Christopher; Dionne, Raymond A; Gordon, Sharon M; Okunseri, Elaye; Szabo, Aniko

2015-11-01

Opioid analgesics prescribed for nontraumatic dental conditions (NTDCs) by emergency physicians continue to receive attention because of the associated potential for misuse, abuse and addiction. This study examined rates of prescription of opioid analgesics and types of opioid analgesics prescribed for NTDC visits in U.S. emergency departments. Data from the National Hospital Ambulatory Medical Care Survey from 2007 to 2010 were analyzed. Descriptive statistics and logistic regression analysis were performed and adjusted for the survey design. NTDCs made up 1.7% of all ED visits from 2007 to 2010. The prescription of opioid analgesics was 50.3% for NTDC and 14.8% for non-NTDC visits. The overall rate of opioid analgesics prescribed for NTDCs remained fairly stable from 2007 through 2010. Prescription of opioids was highest among patients aged 19-33 years (56.8%), self-paying (57.1%), and non-Hispanic Whites (53.2%). The probability of being prescribed hydrocodone was highest among uninsured patients (68.7%) and for oxycodone, it was highest among private insurance patients (33.6%). Compared to 34-52 year olds, children 0-4 years were significantly more likely to be prescribed codeine and less likely to be prescribed oxycodone. Compared to non-Hispanic Whites, non-Hispanic Blacks had significantly higher odds of been prescribed codeine and somewhat lower odds of been prescribed oxycodone, but it was not statistically significant. There was no significant change in the rates of opioid analgesics prescribed over time for NTDC visits to EDs. Age, payer type and race/ethnicity were significant predictors for the prescription of different opioid analgesics by emergency physicians for NTDC visits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

New Opioid Analgesic Approvals and Outpatient Utilization of Opioid Analgesics in the United States, 1997 through 2015.

PubMed

Chai, Grace; Xu, Jing; Osterhout, James; Liberatore, Mark A; Miller, Kathleen L; Wolff, Carolyn; Cruz, Marisa; Lurie, Peter; Dal Pan, Gerald

2018-05-01

The opioid epidemic, driven in part by increased prescribing, is a public health emergency. This study examines dispensed prescription patterns and approvals of new opioid analgesic products to investigate whether the introduction of these new drugs increases prescribing. Prescribing patterns based on dispensed prescription claims from the U.S. retail setting were assessed with new brand and generic opioid analgesic products approved in the United States from 1997 through 2015. From 1997 through 2015, the U.S. Food and Drug Administration (Silver Spring, Maryland) approved 263 opioid analgesic products, including 33 brand products. Dispensed prescriptions initially increased 80% from 145 million prescriptions in 1997 to a peak of 260 million prescriptions in 2012 before decreasing by 12% to 228 million prescriptions in 2015. Morphine milligram equivalents dispensed per prescription increased from 486 in 1997 to a peak of 950 in 2010, before decreasing to 905 in 2015. In 2015, generic products accounted for 96% (218/228 million prescriptions) of all opioid analgesic prescriptions dispensed. The remaining prescriptions were dispensed for brand products, of which nearly half were dispensed for one brand product (OxyContin, Purdue, USA). There has been a dramatic increase in prescriptions dispensed for opioid analgesics since 1997 and an increasing number of opioid analgesic approvals; however, the number of prescriptions dispensed has declined since 2012 despite an increasing number of approvals. Examination of dispensed prescriptions shows a shifting and complex market where multiple factors likely influence prescribing; the approval of new products alone may not be sufficient to be a primary driver of increased prescribing. An online visual overview is available for this article at http://links.lww.com/ALN/B705.

Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

PubMed

Larochelle, Marc R; Cocoros, Noelle M; Popovic, Jennifer; Dee, Elizabeth C; Kornegay, Cynthia; Ju, Jing; Racoosin, Judith A

A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. Retrospective cohort study. Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

PubMed

Whittaker, Alexandra L; Lymn, Kerry A; Wallace, Georgia L; Howarth, Gordon S

2016-01-01

Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

Pharmacogenetics of new analgesics

PubMed Central

Lötsch, Jörn; Geisslinger, Gerd

2011-01-01

Patient phenotypes in pharmacological pain treatment varies between individuals, which could be partly assigned to their genotypes regarding the targets of classical analgesics (OPRM1, PTGS2) or associated signalling pathways (KCNJ6). Translational and genetic research have identified new targets, for which new analgesics are being developed. This addresses voltage-gated sodium, calcium and potassium channels, for which SCN9A, CACNA1B, KCNQ2 and KCNQ3, respectively, are primary gene candidates because they code for the subunits of the respective channels targeted by analgesics currently in clinical development. Mutations in voltage gated transient receptor potential (TRPV) channels are known from genetic pain research and may modulate the effects of analgesics under development targeting TRPV1 or TRPV3. To this add ligand-gated ion channels including nicotinic acetylcholine receptors, ionotropic glutamate-gated receptors and ATP-gated purinergic P2X receptors with most important subunits coded by CHRNA4, GRIN2B and P2RX7. Among G protein coupled receptors, δ-opioid receptors (coded by OPRD1), cannabinoid receptors (CNR1 and CNR2), metabotropic glutamate receptors (mGluR5 coded by GRM5), bradykinin B1 (BDKRB1) and 5-HT1A (HTR1A) receptors are targeted by new analgesic substances. Finally, nerve growth factor (NGFB), its tyrosine kinase receptor (NTRK1) and the fatty acid amide hydrolase (FAAH) have become targets of interest. For most of these genes, functional variants have been associated with neuro-psychiatric disorders and not yet with analgesia. However, research on the genetic modulation of pain has already identified variants in these genes, relative to pain, which may facilitate the pharmacogenetic assessments of new analgesics. The increased number of candidate pharmacogenetic modulators of analgesic actions may open opportunities for the broader clinical implementation of genotyping information. PMID:20942817

Randomized controlled trial to compare oral analgesic requirements and patient satisfaction in using oral non-steroidal anti-inflammatory drugs versus benzydamine hydrochloride oral rinses after mandibular third molar extraction: a pilot study.

PubMed

Goswami, Devalina; Jain, Gaurav; Mohod, Mangesh; Baidya, Dalim Kumar; Bhutia, Ongkila; Roychoudhury, Ajoy

2018-02-01

Third molar extraction is associated with considerable pain and discomfort, which is mostly managed with oral analgesic medication. We assessed the analgesic effect of benzydamine hydrochloride, a topical analgesic oral rinse, for controlling postoperative pain following third molar extraction. A randomized controlled trial was conducted in 40 patients divided into two groups, for extraction of fully erupted third molar. Groups A received benzydamine hydrochloride mouthwash and group B received normal saline gargle with oral ibuprofen and paracetamol. Oral ibuprofen and paracetamol was the rescue analgesic drug in group A. Patients were evaluated on the 3 rd and 7 th post-operative days (POD) for pain using the visual analogue score (VAS), trismus, total number of analgesics consumed, and satisfaction level of patients. The VAS in groups A and B on POD3 and POD7 was 4.55 ± 2.54 and 3.95 ± 1.8, and 1.2 ± 1.64 and 0.95 ± 1.14, respectively and was statistically insignificant. The number of analgesics consumed in groups A and B on POD3 (5.25 ± 2.22 and 6.05 ± 2.43) was not statistically different from that consumed on POD7 (9.15 ± 5.93 and 10.65 ± 6.46). The p values for trismus on POD3 and POD7 were 0.609 and 0.490, respectively and those for patient satisfaction level on POD3 and POD7 were 0.283 and 0.217, respectively. Benzydamine hydrochloride oral rinses do not significantly reduce intake of oral analgesics and are inadequate for pain relief following mandibular third molar extraction.

Analgesic use and the risk of kidney cancer: a meta-analysis of epidemiologic studies.

PubMed

Choueiri, Toni K; Je, Youjin; Cho, Eunyoung

2014-01-15

Analgesics are the most commonly used over-the-counter drugs worldwide with certain analgesics having cancer prevention effect. The evidence for an increased risk of developing kidney cancer with analgesic use is mixed. Using a meta-analysis design of available observational epidemiologic studies, we investigated the association between analgesic use and kidney cancer risk. We searched the MEDLINE and EMBASE databases to identify eligible case-control or cohort studies published in English until June 2012 for three categories of analgesics: acetaminophen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Study-specific effect estimates were pooled to compute an overall relative risk (RR) and its 95% confidence interval (CI) using a random-effects model for each category of the analgesics. We identified 20 studies (14 with acetaminophen, 13 with aspirin and five with other NSAIDs) that were performed in six countries, including 8,420 cases of kidney cancer. Use of acetaminophen and non-aspirin NSAIDs were associated with an increased risk of kidney cancer (pooled RR: 1.28; 95% CI: 1.15-1.44 and 1.25; 95% CI: 1.06-1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR: 1.10; 95% CI: 0.95-1.28), except for non-US studies (five studies, pooled RR: 1.17; 95% CI: 1.04-1.33). Similar increases in risks were seen with higher analgesic intake. In this largest meta-analysis to date, we found that acetaminophen and non-aspirin NSAIDs are associated with a significant risk of developing kidney cancer. Further work is needed to elucidate biologic mechanisms behind these findings. © 2013 UICC.

Use of a new finger-mounted device to compare mechanical nociceptive thresholds in cats given pethidine or no medication after castration.

PubMed

Slingsby, L S; Jones, A; Waterman-Pearson, A E

2001-06-01

Mechanical nociceptive thresholds are regularly used to determine the efficacy of analgesic agents both experimentally and clinically in a variety of species. The 'pressure of palpation device' (PPD) was developed for use in cats and is a small battery operated device with a finger-mounted force sensing resistor (FSR, Interlink Electronics, Northumberland. UK). The PPD was used in a study assessing the analgesic efficacy of pethidine after castration in cats. Pethidine was demonstrated to prevent the development of post-operative scrotal hypersensitivity for up to 2 hours after castration, whereas cats given no analgesics showed marked hyperalgesia immediately after surgery. Visual Analogue Scale (VAS) pain scores after castration showed a similar analgesic effect of pethidine. These results suggest that the PPD could become a useful research tool to assess the effectiveness of analgesic agents in the cat.

The Analgesic Potential of Cannabinoids

PubMed Central

Elikottil, Jaseena; Gupta, Pankaj; Gupta, Kalpna

2013-01-01

Historically and anecdotally cannabinoids have been used as analgesic agents. In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as anti-emetic, appetite modulating and analgesic agents. However, the efficacy of individual products is variable and dependent upon the route of administration. Since opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain. PMID:20073408

Prediction of Patient-Controlled Analgesic Consumption: A Multimodel Regression Tree Approach.

PubMed

Hu, Yuh-Jyh; Ku, Tien-Hsiung; Yang, Yu-Hung; Shen, Jia-Ying

2018-01-01

Several factors contribute to individual variability in postoperative pain, therefore, individuals consume postoperative analgesics at different rates. Although many statistical studies have analyzed postoperative pain and analgesic consumption, most have identified only the correlation and have not subjected the statistical model to further tests in order to evaluate its predictive accuracy. In this study involving 3052 patients, a multistrategy computational approach was developed for analgesic consumption prediction. This approach uses data on patient-controlled analgesia demand behavior over time and combines clustering, classification, and regression to mitigate the limitations of current statistical models. Cross-validation results indicated that the proposed approach significantly outperforms various existing regression methods. Moreover, a comparison between the predictions by anesthesiologists and medical specialists and those of the computational approach for an independent test data set of 60 patients further evidenced the superiority of the computational approach in predicting analgesic consumption because it produced markedly lower root mean squared errors.

3-methyl-2-phenyl-1-substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents.

PubMed

Abdellatif, Khaled R A; Lamie, Phoebe F; Omar, Hany A

2016-01-01

In a new group of 3-methyl-2-phenyl-1-substituted-indole derivatives (10a-f), the indomethacin analogs were prepared via the Fisher indole synthesis reaction of propiophenone with appropriately substituted phenylhydrazine hydrochloride. This is followed by the insertion of the appropriate benzyl or benzoyl fragment. All the synthesized compounds were evaluated for their anti-inflammatory (in vitro and in vivo) and analgesic activities. The methanesulphonyl derivatives 10d, e and f showed the highest anti-inflammatory (in vitro and in vivo) and analgesic activities. In addition, molecular docking studies were performed on compounds 10a-f and the results were in agreement with that obtained from the in vitro COX inhibition assays. The significant anti-inflammatory and analgesic activities exhibited by 10d and 10e warrant continued preclinical development as potential anti-inflammatory and analgesic agents.

Analgesic activity of diterpene alkaloids from Aconitum baikalensis.

PubMed

Nesterova, Yu V; Povet'yeva, T N; Suslov, N I; Zyuz'kov, G N; Pushkarskii, S V; Aksinenko, S G; Schultz, E E; Kravtsova, S S; Krapivin, A V

2014-08-01

We compared analgesic activities of individual alkaloids extracted from Baikal aconite (Aconitum baikalensis): napelline, hypaconitine, songorine, mesaconitine, 12-epinapelline N-oxide. The detected analgesic activity was comparable to that of sodium metamizole. The mechanisms of analgesia were different in diterpene alkaloids of different structure. The antinociceptive effect of atisine alkaloids (12-epinapelline N-oxide, songorine) was naloxonedependent and realized via opioid receptor modulation.

Comparative analgesic effect of Ligusticum chuanxiong pieces and its products in mice

PubMed Central

GAO, Demin; XU, Lingchuan

2010-01-01

The present study was undertaken with the objective of finding out the comparative analgesic effect of Ligusticum chuanxiong (LC) pieces decoction, LC formula granule decoction, liquored LC pieces decoction and liquored LC formula granule decoction. The analgesic effects were analyzed using the hot plate and acetic-induced writhing test in mice, and antidysmenorrheic effect was observed with primary dysmenorrhea model. The results showed that four kinds of LC decoction had definite effect in delaying incubation period and decreasing the writhing frequency within 30 min. They also effectively relieved dysmenorrhea. Moreover, liquored LC had better analgesic effect than crude LC in four decoctions. PMID:20668580

Rodent analgesia: Assessment and therapeutics.

PubMed

Flecknell, Paul

2018-02-01

Current use of analgesics to control procedure-related pain in laboratory rodents is unacceptably low. Almost all currently available analgesics were developed in small rodents, prior to use in man, so that safety and efficacy data in laboratory assays are available. Greater use of analgesics would be encouraged by critical evaluation of the potential interactions of these compounds with the outcomes of specific research studies. As in other species, effective post-procedural analgesia requires reliable 'cage-side' methods of assessing pain. Recent advances in pain assessment should lead to both more extensive and more effective use of analgesics in these species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of analgesic and anti-inflammatory activities of Rubia cordifolia L. by spectrum-effect relationships.

PubMed

Shen, Cai-Hong; Liu, Cui-Ting; Song, Xiao-Juan; Zeng, Wei-Ya; Lu, Xiao-Ying; Zheng, Zuo-Liang; Jie-Pan; Zhan, Ruo-Ting; Ping-Yan

2018-07-15

The objective of the current work was to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and analgesic and anti-inflammatory effects of Rubia cordifolia L. extract (RCE), and to identify active components of RCE. Chemical fingerprints of ten batches of RC from various sources were obtained by HPLC, and similarity and hierarchical clustering analyses were carried out. Pharmacodynamic assays were performed in adjuvant-induced arthritis rat model to assess the analgesic and anti-inflammatory properties of RCE. The spectrum-effect relationships between chemical fingerprints and the analgesic and anti-inflammatory effects of RCE were established by gray correlation analysis. UPLC-ESI-MS was used to identify the structures of potential active components, by reference standards comparison. The results showed that a close correlation existed between chemical fingerprints with analgesic and anti-inflammatory activities, and alizarin, 6-hydroxyrubiadin, purpurin and rubiadin might be the active constituents of RCE. In addition, RCE attenuated pathological changes in adjuvant-induced arthritis. The current findings provide a strong basis for combining chemical fingerprints with analgesic and anti-inflammatory activities in assessing the spectrum-effect relationships of RCE. Copyright © 2018. Published by Elsevier B.V.

Opioid Analgesics and P-glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

PubMed Central

Mercer, Susan L.; Coop, Andrew

2012-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationship development to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation. PMID:21050174

Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial.

PubMed

Isiordia-Espinoza, M-A; Pozos-Guillen, A; Martinez-Rider, R; Perez-Urizar, J

2016-09-01

Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. According to the VAS and UAC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery.

The recent progress in research on effects of anesthetics and analgesics on G protein-coupled receptors.

PubMed

Minami, Kouichiro; Uezono, Yasuhito

2013-04-01

The exact mechanisms of action behind anesthetics and analgesics are still unclear. Much attention was focused on ion channels in the central nervous system as targets for anesthetics and analgesics in the 1980s. During the 1990s, major advances were made in our understanding of the physiology and pharmacology of G protein coupled receptor (GPCR) signaling. Thus, several lines of studies have shown that G protein coupled receptors (GPCRs) are one of the targets for anesthetics and analgesics and especially, that some of them inhibit the functions of GPCRs, i.e,, muscarinic receptors and substance P receptors. However, these studies had been focused on only G(q) coupled receptors. There has been little work on G(s)- and G(i)-coupled receptors. In the last decade, a new assay system, using chimera G(i/o)-coupled receptor fused to Gq(i5), has been established and the effects of anesthetics and analgesics on the function of G(i)-coupled receptors is now more easily studied. This review highlights the recent progress of the studies regarding the effects of anesthetics and analgesics on GPCRs.

Anti-inflammatory and analgesic activities of Tunisian Citrullus colocynthis Schrad. immature fruit and seed organic extracts.

PubMed

Marzouk, B; Marzouk, Z; Fenina, N; Bouraoui, A; Aouni, M

2011-06-01

Inflammations and immune-related diseases including rheumatoid arthritis are widespread in the entire globe. The treatment of these illnesses is mainly based on the use of synthetic and biotechnological drugs, in recent years. Tunisian traditional medicine is a potential source of new remedies namely Citrullus colocynthis Schrad. (Cucurbitaceae): endemic in southern Tunisia and used in folk medicine to treat many inflammation disorders. Our goal was to assess the in vivo analgesic and anti-inflammatory activities of Tunisian Citrullus colocynthis immature fruit and seed organic extracts (petroleum ether, chloroform, ethyl acetate, acetone and finely methanol extract). Yields of prepared organic extracts are gravimetrically determined. For the analgesic and anti-inflammatory activities, we have used respectively, the acetic acid writhing test in mice and the carrageenan-induced paw edema assay in rats. All extracts displayed an important analgesic and anti-inflammatory activities at different doses without inducing any side effects. This study has demonstrated the analgesic and anti-inflammatory activities of Citrullus colocynthis immature fruit and seed extracts. Experiment results provide scientific insight into the ancient practice of utilizing Citrullus colocynthis Schrad. as analgesic and as anti-inflammatory agents.

Parents' preferences strongly influence their decisions to withhold prescribed opioids when faced with analgesic trade-off dilemmas for children: a prospective observational study.

PubMed

Voepel-Lewis, Terri; Zikmund-Fisher, Brian J; Smith, Ellen Lavoie; Zyzanski, Sarah; Tait, Alan R

2015-08-01

Despite parents' stated desire to treat pain in their children, recent studies have critiqued their underuse of prescribed analgesics to treat pain in their children after painful procedures. Parents' analgesic preferences, including their perceived importance of providing pain relief or avoiding adverse drug effects may have important implications for their analgesic decisions, yet no studies have evaluated the influence of preferences on decisions to withhold prescribed opioids for children. We prospectively explored how parents' preferences influenced decisions to withhold prescribed opioids when faced with hypothetical dilemmas and after hospital discharge. Prospective Observational Study Design: Phase 1 included hypothetical analgesic decisions and Phase 2, real analgesic decisions after hospital discharge. Large tertiary care pediatric hospital in the Midwest of the United States. Five-hundred seven parents whose children underwent a painful surgical procedure requiring an opioid prescription were included. At baseline, parents completed surveys assessing their pain relief preference (i.e., their rated importance of pain relief relative to adverse drug event avoidance), preferred treatment thresholds (i.e., pain level at which they would give an opioid), adverse drug event understanding, and hypothetical trade-off decisions (i.e., scenarios presenting variable pain and adverse drug event symptoms in a child). After discharge, parents recorded all analgesics they gave their child as well as pain scores at the time of administration. Higher preference to provide pain relief (over avoid analgesic risk) lessened the likelihood that parents would withhold the prescribed opioid when adverse drug event symptoms were present together with high pain scores in the hypothetical scenarios. Additionally, higher preferred treatment thresholds increased the likelihood of parents withholding opioids during their hypothetical decision-making as well as at home. The strong influence of these preferences weakened the effect of opioid ADE understanding on decisions to withhold opioids when ADEs (i.e., nausea/vomiting or oversedation) were present together with high pain. Findings from this study suggest that preferences strongly influence and may interfere with parents' effective and safe analgesic decision-making when conflicting symptoms (i.e., high pain and an ADE) are present. To improve effective analgesic use, there is a need to shape parents' preferences and improve their understanding of safe actions that will treat pain when ADE symptoms are present. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sedative and Analgesic Drugs Online: A Content Analysis of the Supply and Demand Information Available in Thailand.

PubMed

Pinyopornpanish, Kanokporn; Jiraporncharoen, Wichuda; Thaikla, Kanittha; Yoonut, Kulyapa; Angkurawaranon, Chaisiri

2018-03-21

Evidence from other countries has suggested that many controlled drugs are also offered online, even though it is illegal to sell these drugs without a license. To evaluate the current contents related to the supply and demand of sedatives and analgesic drugs available online in Thailand, with a particular focus on Facebook. A team of reviewers manually searched for data by entering keywords related to analgesic drugs and sedatives. The contents of the website were screened for supply and demand-related information. A total of 5,352 websites were found publicly available. The number of websites and Facebook pages containing the information potentially related to the supply and demand of analgesic drugs and sedatives was limited. Nine websites sold sedatives, and six websites sold analgesics directly. Fourteen Facebook pages were found, including 7 sedative pages and 7 analgesic pages. Within one year, the three remaining active pages multiplied in the number of followers by three- to nine-fold. The most popular Facebook page had over 2,900 followers. Both the internet and social media contain sites and pages where sedatives and analgesics are illegally advertised. These websites are searchable through common search engines. Although the number of websites is limited, the number of followers on these Facebook pages does suggest a growing number of people who are interested in such pages. Our study emphasized the importance of monitoring and developing potential plans relative to the online marketing of prescription drugs in Thailand.

Analgesic efficacy of preoperative dexketoprofen trometamol: A systematic review and meta-analysis.

PubMed

Esparza-Villalpando, Vicente; Pozos-Guillén, Amaury; Masuoka-Ito, David; Gaitán-Fonseca, César; Chavarría-Bolaños, Daniel

2018-03-01

Post-Market Research Clinical evidence supports the use of dexketoprofen trometamol (DEX) to manage acute postoperative pain. However, controversies surround the impact of the use of this drug in preoperative analgesic protocols. The aim of the present meta-analysis was to evaluate the effectiveness of the preoperative administration of DEX under postoperative pain conditions. Electronic and manual searches were conducted through diverse electronic databases. A systematic review and meta-analysis to evaluate the analgesic efficacy of the preoperative administration of DEX was performed including Randomized Clinical Trials (RCTs) published between 2002 and 2017. Suitable individual studies were evaluated through a quality system, and the data were extracted and analyzed. Fourteen RTCs were included (12 parallel trials and 2 cross-over trials), published in the English and Turkish languages. Follow-up periods ranged from 4, 6, 8, 24, and 48 hr. All trials measured the outcome result as Acute Pain Level (APL) (VAS, NRS, VRS), time to requiring a second dose of DEX or analgesic emergency and consumption of opioids via patient-controlled analgesia. When the comparators were other drugs - paracetamol, Lornoxicam or placebo during the preoperative time, preoperative administration of DEX was superior. When the comparison comprised preoperative and postoperative DEX, both alternatives exhibited comparable analgesic effects. The analgesic efficacy of the preoperative administration of DEX when compared to placebo, lornoxicam, and paracetamol on postoperative pain was evident. Preoperative administration of DEX compared to its immediate postoperative administration showed a similar analgesic effect. © 2017 Wiley Periodicals, Inc.

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity

PubMed Central

Madaan, Reecha; Kumar, S.

2012-01-01

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1st h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum. PMID:23716876

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity.

PubMed

Madaan, Reecha; Kumar, S

2012-09-01

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1(st) h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum.

Changes Over Time of Prescription and Nonprescription Analgesics for Headache With or Without Other Somatic Pain: Effects of Prescription Regulatory Changes.

PubMed

Halvorsen, Marianne Moe; Clench-Aas, Jocelyne; Patil, Grete; Lundqvist, Christofer

2016-07-01

The aim of this study was to examine the association and changes over time between headaches with or without somatic pain and the self-reported use of pain medication. The study further examined whether the law amendment in 2003 in Norway releasing the sale of nonprescription drugs to shops has changed these relationships. The study is on the basis of repeated self-report cross-sectional studies from 1998 to 2012 in Norway. A total of 27,247 adults were included. As expected, there was a strong association between headache, especially headache with comorbid somatic pain and consumption of prescription versus nonprescription analgesics, although the overall consumption decreased slightly after 2003. We conclude that the strong association between especially headache, whether complicated by somatic pain or not, and the consumption of prescription-free analgesics did not seem to be negatively affected by the prescription regulatory changes. The very high use of nonprescription medication among headache patients suggests the need for continued observation and information regarding the risk of medication-overuse headache. In Norway, headache was strongly associated with use of over-the-counter analgesics, for other somatic pain prescription analgesics were equally common. Between 1998 and 2012 headache and related analgesic consumption was reduced and other somatic pain increased. Making over-the-counter analgesics available outside pharmacies in 2003 did not increase the self-reported intake. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

A Prospective, Observational Study to Evaluate the Role of Gabapentin as Preventive Analgesic in Thyroidectomy under General Anesthesia.

PubMed

Hema, Vadakkoot Raghavan; Ramadas, Konnanath Thekkethil; Biji, Kannammadathy Poulose; Indu, Suseela; Arun, Aravind

2017-01-01

Effective management of postoperative pain is a part of well-organized perioperative care, which helps in reduced morbidity and improved patient satisfaction. Preventive analgesia can reduce acute and chronic pain by blocking the noxious inputs to pain pathways, preventing sensitization. Studies have reported efficacy of gabapentin as a preventive analgesic in perioperative pain. In this study, we aimed to determine whether preoperative gabapentin reduced postoperative pain and tramadol consumption after thyroidectomy under general anesthesia. Sixty patients scheduled for thyroidectomy were allocated to two groups of thirty each for this prospective, observational study. Patients in Group A and Group B received oral gabapentin 600 mg (6 × 10 -4 kg) and diazepam 10 mg (1 × 10 -5 kg), respectively, 2 h prior to surgery. Tramadol was given as rescue analgesic for postoperative pain with a verbal rating score of two. The analgesic efficacy of preoperative gabapentin was assessed in terms of postoperative pain scores at rest or swallowing, time to first rescue analgesic, and total tramadol consumption for 24 h. Ramsay sedation score and side effects of drug were also looked into. Postoperative pain scores and total tramadol consumption were significantly lower in Group A during 24 h ( P = 0.00). Time to first rescue analgesic was significantly prolonged in Group A ( P = 0.001). Side effects were comparable. Oral gabapentin is effective as a preventive analgesic in reducing postoperative pain and tramadol consumption after thyroidectomy under general anesthesia.

Electroencephalography and analgesics

PubMed Central

Malver, Lasse Paludan; Brokjær, Anne; Staahl, Camilla; Graversen, Carina; Andresen, Trine; Drewes, Asbjørn Mohr

2014-01-01

To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms ‘analgesics’, ‘electroencephalography’ and ‘evoked potentials’ for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients. PMID:23593934

Analgesics use and ESRD in younger age: a case-control study

PubMed Central

van der Woude, Fokke J; Heinemann, Lothar AJ; Graf, Helmut; Lewis, Michael; Moehner, Sabine; Assmann, Anita; Kühl-Habich, Doerthe

2007-01-01

Background An ad hoc peer-review committee was jointly appointed by Drug Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to review the evidence for a causal relation between phenacetin-free analgesics and nephropathy. The committee found the evidence as inconclusive and requested a new case-control study of adequate design. Methods We performed a population-based case-control study with incident cases of end-stage renal disease (ESRD) under the age of 50 years and four age and sex-matched neighborhood controls in 170 dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to December 31, 2004. Data on lifetime medical history, risk factors, treatment, job exposure and intake of analgesics were obtained in a standardized face-to-face interview using memory aids to enhance accuracy. Study design, study performance, analysis plan, and study report were approved by an independent international advisory committee and by the Drug Authorities involved. Unconditional logistic regression analyses were performed. Results The analysis included 907 cases and 3,622 controls who had never used phenacetin-containing analgesics in their lifetime. The use of high cumulative lifetime dose (3rd tertile) of analgesics in the period up to five years before dialysis was not associated with later ESRD. Adjusted odds ratios with 95% confidence intervals were 0.8 (0.7 – 1.0) and 1.0 (0.8 – 1.3) for ever- compared with no or low use and high use compared with low use, respectively. The same results were found for all analgesics and for mono-, and combination preparations with and without caffeine. No increased risk was shown in analyses stratifying for dose and duration. Dose-response analyses showed that analgesic use was not associated with an increased risk for ESRD up to 3.5 kg cumulative lifetime dose (98 % of the cases with ESRD). While the large subgroup of users with a lifetime dose up to 0.5 kg (278 cases and 1365 controls) showed a significantly decreased risk, a tiny subgroup of extreme users with over 3.5 kg lifetime use (19 cases and 11 controls) showed a significant risk increase. The detailed evaluation of 22 cases and 19 controls with over 2.5 kg lifetime use recommended by the regulatory advisors showed an impressive excess of other conditions than analgesics triggering the evolution of ESRD in cases compared with controls. Conclusion We found no clinically meaningful evidence for an increased risk of ESRD associated with use of phenacetin-free analgesics in single or combined formulation. The apparent risk increase shown in a small subgroup with extreme lifetime dose of analgesics is most likely an indirect, non-causal association. This hypothesis, however, cannot be confirmed or refuted within our case-control study. Overall, our results lend support to the mounting evidence that phenacetin-free analgesics do not induce ESRD and that the notion of "analgesic nephropathy" needs to be re-evaluated. PMID:18053232

Efficacy of Magnesium Sulphate as an Adjunct to Ropivacaine in Local Infiltration for Postoperative Pain Following Lower Segment Caesarean Section.

PubMed

Kundra, Sandeep; Singh, Rupinder M; Singh, Gaganpreet; Singh, Tania; Jarewal, Vikrant; Katyal, Sunil

2016-04-01

Intravenous and peri-articular magnesium has been shown to reduce perioperative analgesic consumption. With this background, subcutaneous infiltration was hypothesized to potentiate the subcutaneous infiltration of local anaesthetic agent. To comparatively evaluate the efficacy of magnesium sulphate as an adjunct to ropivacaine in local infiltration for postoperative pain following lower segment cesarean section. Sixty parturients undergoing cesarean delivery were randomized to either group A or B in a double blinded manner. After uterine and muscle closure but before skin closure, Group A was administered local subcutaneous wound infiltration of Injection (Inj) ropivacaine 0.75% 150 milligram (mg) or 20 millilitres(ml) whereas, group B patients were given a local subcutaneous wound infiltration of Inj magnesium sulphate 750 mg (1.5 ml of Inj 50% Magnesium sulphate) added to Inj ropivacaine 0.75% (18.5 ml) making a total volume of 20 ml. In postoperative period, Heart rate (HR), Mean Arterial Pressure (MAP), Visual Analogue Score (VAS), supplemental analgesic consumption and timing of each subsequent analgesic was noted for the initial 24 hours. There was no difference in the timings for the requirement of first Intravenous (IV) rescue analgesic among both the groups (p=0.279). However, the need for 2(nd) and 3(rd) doses of rescue analgesics was significantly later in group B and the difference was statistically significant with p-value of 0.034 and 0.031 respectively. The number of patients who were administered 2(nd), 3(rd) and 4(th) doses of rescue analgesics was significantly greater in group A as compared to group B. None of the patients in group B needed more than 4 doses of rescue analgesia while in group A, 5 patients were administered a rescue analgesic for 5(th) time. The cumulative analgesic requirement in the initial 24 hours was also greater in group A as compared to group B and the difference was statistically significant (p =0.01). The incidence of adverse effects was similar in both the groups. Subcutaneous infiltration of magnesium along with local anaesthetic prolongs the analgesic efficacy of local anaesthetic and is not associated with any significant adverse effects.

Adamantyl Analogues of Paracetamol as Potent Analgesic Drugs via Inhibition of TRPA1

PubMed Central

Fresno, Nieves; Pérez-Fernández, Ruth; Goicoechea, Carlos; Alkorta, Ibon; Fernández-Carvajal, Asia; de la Torre-Martínez, Roberto; Quirce, Susana; Ferrer-Montiel, Antonio; Martín, M. Isabel; Goya, Pilar; Elguero, José

2014-01-01

Paracetamol also known as acetaminophen, is a widely used analgesic and antipyretic agent. We report the synthesis and biological evaluation of adamantyl analogues of paracetamol with important analgesic properties. The mechanism of nociception of compound 6a/b, an analog of paracetamol, is not exerted through direct interaction with cannabinoid receptors, nor by inhibiting COX. It behaves as an interesting selective TRPA1 channel antagonist, which may be responsible for its analgesic properties, whereas it has no effect on the TRPM8 nor TRPV1 channels. The possibility of replacing a phenyl ring by an adamantyl ring opens new avenues in other fields of medicinal chemistry. PMID:25438056

Designing Safer Analgesics via μ-Opioid Receptor Pathways.

PubMed

Chan, H C Stephen; McCarthy, Dillon; Li, Jianing; Palczewski, Krzysztof; Yuan, Shuguang

2017-11-01

Pain is both a major clinical and economic problem, affecting more people than diabetes, heart disease, and cancer combined. While a variety of prescribed or over-the-counter (OTC) medications are available for pain management, opioid medications, especially those acting on the μ-opioid receptor (μOR) and related pathways, have proven to be the most effective, despite some serious side effects including respiration depression, pruritus, dependence, and constipation. It is therefore imperative that both academia and industry develop novel μOR analgesics which retain their opioid analgesic properties but with fewer or no adverse effects. In this review we outline recent progress towards the discovery of safer opioid analgesics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Designing Safer Analgesics via μ-Opioid Receptor Pathways

PubMed Central

Chan, H.C. Stephen; McCarthy, Dillon; Li, Jianing; Palczewski, Krzysztof; Yuan, Shuguang

2017-01-01

Pain is both a major clinical and economic problem, affecting more people than diabetes, heart disease, and cancer combined. While a variety of prescribed or over-the-counter (OTC) medications are available for pain management, opioid medications, especially those acting on the μ-opioid receptor (μOR) and related pathways, have proven to be the most effective, despite some serious side effects including respiration depression, pruritus, dependence, and constipation. It is therefore imperative that both academia and industry develop novel μOR analgesics which retain their opioid analgesic properties but with fewer or no adverse effects. In this review we outline recent progress towards the discovery of safer opioid analgesics. PMID:28935293

The toxic effect of opioid analgesics on human sperm motility in vitro.

PubMed

Xu, Bo; Wang, Zhi-Ping; Wang, Yan-Juan; Lu, Pei-Hua; Wang, Li-Jun; Wang, Xiao-Hai

2013-04-01

Opioid analgesics are the most common therapeutic analgesic for acute pain. In this study, the toxicological and pharmacological features of a group of opioid analgesics were characterized by the motility of human sperm. Aliquots of sperm were incubated with various concentrations of opioid analgesics in vitro. Computer-assisted sperm analysis was used to assess sperm motility at 15 minutes, 2 hours, and 4 hours after drug addition to the medium. Butorphanol and dezocine showed marked reduction of motility after incubation with sperm for 15 minutes. Butorphanol was more effective than dezocine in immobilizing sperm. Other opioids studied, such as fentanyl, alfentanil, and sufentanil, showed only partial inhibitory activity. Based on the data reported herein, we have found that butorphanol and dezocine exert a sperm-immobilizing effect. However, fentanyl, alfentanil, and sufentanil exhibit only partial inhibition of sperm motility. Given the increasing use of opioids and their potential effect on sperm motility, these findings are greatly relevant to male reproductive health.

Evaluation of analgesic activity of various extracts of Sida tiagii Bhandari.

PubMed

Kumawat, Ram Kumar; Kumar, Suresh; Sharma, Sunil

2012-01-01

Sida tiagii Bhandari mostly found in India and Pakistan which belongs to family Malvaceae, is traditionally used as analgesic, anti-inflammatory, sedative, anxiolytic, anti-seizure and anti-platelet. The present study was done to explore the analgesic activity of various extracts of fruits of the plant Sida tiagii Bhandari. The grinded fruits were extracted with 90% ethanol and partitioned with n-hexane (n-hexane extract; HS) and ethyl acetate (ethyl acetate extract; EAS), successively. The residual ethanol fraction (residual ethanol extract; RES) was also prepared by drying on water bath separately. All three extracts were administered orally at a dose of 200 mg/kg and 500 mg/kg of body weight. The analgesic activity of above extracts was evaluated by using acetic acid induced writhing, tail immersion and tail flick tests in Swiss albino mice. The EAS extract was found to reduce pain and RES extract of Sida tiagii B. was found to have good analgesic activity in comparison to other extracts.

Management of pain in advanced disease.

PubMed

Harris, Dylan G

2014-06-01

Pain is common in advanced malignancy but also prevalent in other non-malignant life-limiting diseases such as advanced heart disease; end stage renal failure and multiple sclerosis. Patients with renal or liver impairment need specific consideration, as most analgesics rely on either or both for their metabolism and excretion. Recent evidence-based guidelines and the systematic reviews that have informed their recommendations. The principles of the WHO (World Health Organisation) analgesic ladder are commonly endorsed as a structured approach to the management of pain. For neuropathic pain, the efficacy of different agents is similar and choice of drug more guided by side effects, drug interactions and cost. Evidence supporting the WHO analgesic ladder is disputed and alternatives suggested, but no overwhelming evidence for an alternative approach exists to date. Alternative approaches to the WHO analgesic ladder, new analgesic agents, e.g. rapid onset oral/intranasal fentanyl. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects.

PubMed

Vardigan, Joshua D; Houghton, Andrea K; Lange, Henry S; Adarayan, Emily D; Pall, Parul S; Ballard, Jeanine E; Henze, Darrell A; Uslaner, Jason M

2018-01-01

The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates. In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting. Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect. We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics.

Synthesis, analgesic, anti-inflammatory and anti-ulcerogenic activities of certain novel Schiff's bases as fenamate isosteres.

PubMed

Alafeefy, Ahmed M; Bakht, Mohammed A; Ganaie, Majid A; Ansarie, Mohd N; El-Sayed, Nahed N; Awaad, Amani S

2015-01-15

A series of certain novel Schiff bases as fenamate isosteres (VI:a-k) were synthesized to locate analgesic, anti-inflammatory agent with minimal ulcerogenic potential. The structures of the newly synthesized compounds were elucidated on the basis of their elemental analysis as well as IR, and NMR and mass spectroscopic data. All the compounds were evaluated for their anti-inflammatory activity by carrageenan induced paw oedema method. The compounds possessing good anti-inflammatory activity were further tested for analgesic, ulcerogenic, lipid peroxidation potentials and liver toxicity. Compounds (VI-c), (VI-f), (VI-h) and (VI-i) showed the best anti-inflammatory and significant analgesic activities at doses comparable to that of the standard drug Indomethacin. However, compounds (VI-c) and (VI-f) could be considered the most potent anti-inflammatory and analgesic molecules with maximum reduction in gastro-intestinal ulceration with no hepatocyte necrosis or liver degeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of 12-monoketocholic acid on modulation of analgesic action of morphine and tramadol.

PubMed

Kuhajda, Ivan; Posa, Mihalj; Jakovljević, Vida; Ivetić, Vesna; Mikov, Momir

2009-01-01

This work is concerned with the potential promotive action of 12-monoketocholic acid (12-MKC) on the analgesic effect of morphine and tramadol. The investigation was carried out on laboratory Wistar rats divided into five test groups, each treated with either morphine (2 mg/kg), tramadol (9.6 mg/kg), 12-MKC (2 mg/kg), morphine + 12-MKC, or tramadol + 12-MKC, the control group receiving physiological solution (2 mg/kg). The effect of 12-MKC on the analgesic action of morphine and tramadol was determined by radiation heat method. Morphine and tramadol, given in equimolar doses, did not show significant difference in the degree of analgesia. In combination with morphine, 12-MKC increased significantly the analgesic effect compared with the group treated with morphine alone. However, 12-MKC caused no change in the action of tramadol. The 5-day intravenous application of 12-MKC in combination with the two analgesics caused no changes in the biochemical parameters nor pathohistological changes in the liver parenchyma of tested animals.

Pharmacological validation of a novel nonhuman primate measure of thermal responsivity with utility for predicting analgesic effects

PubMed Central

Vardigan, Joshua D; Houghton, Andrea K; Lange, Henry S; Adarayan, Emily D; Pall, Parul S; Ballard, Jeanine E; Henze, Darrell A; Uslaner, Jason M

2018-01-01

Introduction The development of novel analgesics to treat acute or chronic pain has been a challenge due to a lack of translatable measurements. Preclinical end points with improved translatability are necessary to more accurately inform clinical testing paradigms, which may help guide selection of viable drug candidates. Methods In this study, a nonhuman primate biomarker which is sensitive to standard analgesics at clinically relevant plasma concentrations, can differentiate analgesia from sedation and utilizes a protocol very similar to that which can be employed in human clinical studies is described. Specifically, acute heat stimuli were delivered to the volar forearm using a contact heat thermode in the same manner as the clinical setting. Results Clinically efficacious exposures of morphine, fentanyl, and tramadol produced robust analgesic effects, whereas doses of diazepam that produce sedation had no effect. Conclusion We propose that this assay has predictive utility that can help improve the probability of success for developing novel analgesics. PMID:29692626

Papillary Necrosis in Experimental Analgesic Nephropathy

PubMed Central

Saker, B. M.; Kincaid-Smith, Priscilla

1969-01-01

A proprietary aspirin, phenacetin, and caffeine preparation given to rats in a dose equivalent to that taken by patients with analgesic nephropathy produced papillary necrosis in 55%. There was a higher incidence in rats deprived of fluids overnight. Papillary necrosis was not noted in rats receiving twice as much phenacetin. These findings support the argument that phenacetin should not be singled out as the substance responsible for analgesic nephropathy in man. PMID:5762278

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.

PubMed

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J; Lesport, Pierre; Bourinet, Emmanuel; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-07-18

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT₂R, with this action being not affected by known ligands of AT₂R. This result points towards novel AT₂R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.

Synthetic Neurotensin Analogues Are Nontoxic Analgesics for the Rabbit Cornea

PubMed Central

Kim, Charles; Barbut, Denise; Heinemann, Murk H.; Pasternak, Gavril; Rosenblatt, Mark I.

2014-01-01

Purpose. To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion. Methods. Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology. Results. NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers. Conclusions. Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion. PMID:24825106

Oral Feeding Outcome after Analgesic and Sedative Exposure in VLBW Preterm Infant.

PubMed

Astoria, Mark T; Thacker, Leroy; Hendricks-Muñoz, Karen D

2018-06-08

 The objective of this study was to assess the association of analgesics and sedatives on oral feeding function and need for feeding tube at discharge in the very low birth weight (VLBW) (<1,500 g) preterm infant.  A retrospective review of surviving inborn infants < 1,500 g and < 32 weeks' gestation ( n  = 209), discharged between January 1, 2012, and December 31, 2014, from the neonatal intensive care unit identified exposure to analgesic and sedative medications, demographics, medical course, and nasogastric or gastrostomy tube (GT) feeding at discharge. Predictive modeling with logistic regression to identify independent factors associated with discharge on tube feedings.  Out of 209, 45 (21.5%) infants received an analgesic/sedative with 23 out of 45 (51.1%) discharged with tube feedings. Infants discharged with tube feedings were born smaller, of younger gestation, with greater SNAPPE-II scores, periventricular leukomalacia, chronic lung disease, postnatal glucocorticoids, lansoprazole, and longer time intubated. After adjusting for covariates, exposure to analgesic/sedatives (fentanyl, midazolam, or morphine) was independently predictive of discharge on tube feedings.  Analgesic and sedative exposure in VLBW infants is highly associated with poor oral feeding and need for tube feedings at discharge. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluation of Analgesic Activity of Papaver libanoticum Extract in Mice: Involvement of Opioids Receptors

PubMed Central

El-Mallah, Ahmed; Aboul-Ela, Maha; Ellakany, Abdalla

2017-01-01

Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae) that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE) using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome. PMID:28280516

Evaluation of Analgesic Activity of Papaver libanoticum Extract in Mice: Involvement of Opioids Receptors.

PubMed

Hijazi, Mohamad Ali; El-Mallah, Ahmed; Aboul-Ela, Maha; Ellakany, Abdalla

2017-01-01

Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae) that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE) using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome.

Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract of Polyalthia suberosa Leaves

PubMed Central

Yasmen, Nelufar; Tajmim, Afsana; Akter, Mst. Irin; Hazra, Amit Kumar; Rahman, S. M. Mushiur

2018-01-01

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti-inflammatory activities of diethyl ether and n-hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin-induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene-induced ear edema test was used to evaluate anti-inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti-inflammatory activities in mice. In formalin-induced paw licking test, acetic acid induced writhing test, and xylene-induced ear edema test, the extracts exhibited significant inhibition (⁎P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant (⁎P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents which support its use in traditional medicine. PMID:29599807

Revisiting the Role of the Urban Environment in Substance Use: The Case of Analgesic Overdose Fatalities

PubMed Central

Ransome, Yusuf; Keyes, Katherine M.; Koenen, Karestan C.; Tardiff, Kenneth; Vlahov, David; Galea, Sandro

2013-01-01

Objectives. We examined whether neighborhood social characteristics (income distribution and family fragmentation) and physical characteristics (clean sidewalks and dilapidated housing) were associated with the risk of fatalities caused by analgesic overdose. Methods. In a case-control study, we compared 447 unintentional analgesic opioid overdose fatalities (cases) with 3436 unintentional nonoverdose fatalities and 2530 heroin overdose fatalities (controls) occurring in 59 New York City neighborhoods between 2000 and 2006. Results. Analgesic overdose fatalities were less likely than nonoverdose unintentional fatalities to have occurred in higher-income neighborhoods (odds ratio [OR] = 0.82; 95% confidence interval [CI] = 0.70, 0.96) and more likely to have occurred in fragmented neighborhoods (OR = 1.35; 95% CI = 1.05, 1.72). They were more likely than heroin overdose fatalities to have occurred in higher-income (OR = 1.31; 95% CI = 1.12, 1.54) and less fragmented (OR = 0.71; 95% CI = 0.55, 0.92) neighborhoods. Conclusions. Analgesic overdose fatalities exhibit spatial patterns that are distinct from those of heroin and nonoverdose unintentional fatalities. Whereas analgesic fatalities typically occur in lower-income, more fragmented neighborhoods than nonoverdose fatalities, they tend to occur in higher-income, less unequal, and less fragmented neighborhoods than heroin fatalities. PMID:24134362

Analgesic activity of piracetam: effect on cytokine production and oxidative stress.

PubMed

Navarro, Suelen A; Serafim, Karla G G; Mizokami, Sandra S; Hohmann, Miriam S N; Casagrande, Rubia; Verri, Waldiceu A

2013-04-01

Piracetam is a prototype of nootropic drugs used to improve cognitive impairment. However, recent studies suggest that piracetam can have analgesic and anti-inflammatory effects. Inflammatory pain is the result of a process that depends on neutrophil migration, cytokines and prostanoids release and oxidative stress. We analyze whether piracetam has anti-nociceptive effects and its mechanisms. Per oral pretreatment with piracetam reduced in a dose-dependent manner the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, formalin and complete Freund's adjuvant. Piracetam also diminished carrageenin-induced mechanical and thermal hyperalgesia, myeloperoxidase activity, and TNF-α-induced mechanical hyperalgesia. Piracetam presented analgesic effects as post-treatment and local paw treatment. The analgesic mechanisms of piracetam were related to inhibition of carrageenin- and TNF-α-induced production of IL-1β as well as prevention of carrageenin-induced decrease of reduced glutathione, ferric reducing ability and free radical scavenging ability in the paw. These results demonstrate that piracetam presents analgesic activity upon a variety of inflammatory stimuli by a mechanism dependent on inhibition of cytokine production and oxidative stress. Considering its safety and clinical use for cognitive function, it is possible that piracetam represents a novel perspective of analgesic. Copyright © 2013 Elsevier Inc. All rights reserved.

Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract of Polyalthia suberosa Leaves.

PubMed

Yasmen, Nelufar; Aziz, Md Abdullah; Tajmim, Afsana; Akter, Mst Irin; Hazra, Amit Kumar; Rahman, S M Mushiur

2018-01-01

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti-inflammatory activities of diethyl ether and n-hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin-induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene-induced ear edema test was used to evaluate anti-inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti-inflammatory activities in mice. In formalin-induced paw licking test, acetic acid induced writhing test, and xylene-induced ear edema test, the extracts exhibited significant inhibition ( ⁎ P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant ( ⁎ P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents which support its use in traditional medicine.

Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial

PubMed Central

Isiordia-Espinoza, Mario-Alberto; Martinez-Rider, Ricardo; Perez-Urizar, Jose

2016-01-01

Background Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. Material and Methods A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Results Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. Conclusions According to the VAS and AUC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery. Key words:Ketorolac, tramadol, third molar surgery, pain, preemptive analgesia. PMID:27475688

Screening of Bauhinia purpurea Linn. for analgesic and anti-inflammatory activities

PubMed Central

Shreedhara, C.S.; Vaidya, V.P.; Vagdevi, H.M.; Latha, K.P.; Muralikrishna, K.S.; Krupanidhi, A.M.

2009-01-01

Objectives: Ethanol extract of the stem of Bauhinia purpurea Linn. was subjected to analgesic and anti-inflammatory activities in animal models. Materials and Methods: Albino Wistar rats and mice were the experimental animals respectively. Different CNS depressant paradigms like analgesic activity (determined by Eddy's hot plate method and acetic acid writhing method) and anti-inflammatory activity determined by carrageenan induced paw edema using plethysmometer in albino rats) were carried out, following the intra-peritoneal administration of ethanol extract of Bauhinia purpurea Linn. (BP) at the dose level of 50 mg/kg and 100 mg/kg. Results: The analgesic and anti-inflammatory activities of ethanol extracts of BP were significant (P < 0.001). The maximum analgesic effect was observed at 120 min at the dose of 100 mg/kg (i.p.) and was comparable to that of standard analgin (150 mg/kg) and the percentage of edema inhibition effect was 46.4% and 77% for 50 mg/kg and 100 mg/kg (i.p) respectively. Anti-inflammatory activity was compared with standard Diclofenac sodium (5 mg/kg). Conclusion: Ethanol extract of Bauhinia purpurea has shown significant analgesic and anti-inflammatory activities at the dose of 100 mg/kg and was comparable with corresponding standard drugs. The activity was attributed to the presence of phytoconstituents in the tested extract. PMID:20336222

Access to Strong Opioid Analgesics in the Context of Legal and Regulatory Barriers in Eleven Central and Eastern European Countries.

PubMed

Vranken, Marjolein J M; Mantel-Teeuwisse, Aukje K; Schutjens, Marie-Hélène D B; Scholten, Willem K; Jünger, Saskia; Medic, Dr Rer; Leufkens, Hubert G M

2018-04-06

In 2011-2013, >95% of the global opioid analgesics consumption occurred in three regions, accounting for 15% of the world population. Despite abundant literature on barriers to access, little is known on the correlation between actual access to opioid analgesics and barriers to access, including legal and regulatory barriers. This study aimed to evaluate the correlation between access to strong opioid analgesics and barriers to access in national legislation and regulations in 11 central and eastern European countries that participated in the Access to Opioid Medication in Europe (ATOME) project. Two variables were contrasted to assess their correlation: the country level of access to strong opioid analgesics indicated by the Adequacy of Consumption Measure (ACM) and the number of potential legal and regulatory barriers identified by an external review of legislation and regulations. A linear correlation was evaluated using a squared linear correlation coefficient. Evaluation of the correlation between the ACM and the number of potential barriers produces an R 2 value of 0.023 and a correlation plot trend line gradient of -0.075, indicating no correlation between access to strong opioid analgesics and the number of potential barriers in national legislation and regulations in the countries studied. No correlation was found, which indicates that other factors besides potential legal and regulatory barriers play a critical role in withholding prescribers and patients essential pain medication in the studied countries. More research is needed toward better understanding of the complex interplay of factors that determine access to strong opioid analgesics.

Pharmacist's impact on acute pain management during trauma resuscitation.

PubMed

Montgomery, Kayla; Hall, A Brad; Keriazes, Georgia

2015-01-01

The timely administration of analgesics is crucial to the comprehensive management of trauma patients. When an emergency department (ED) pharmacist participates in trauma resuscitation, the pharmacist acts as a medication resource for trauma team members and facilitates the timely administration of analgesics. This study measured the impact of a pharmacist on time to first analgesic dose administered during trauma resuscitation. All adult (>18 years) patients who presented to this level II trauma center via activation of the trauma response system between January 1, 2009, and May 31, 2013, were screened for eligibility. For inclusion, patients must have received intravenous fentanyl, morphine, or hydromorphone in the trauma bay. The time to medication administration was defined as the elapsed time from ED arrival to administration of first analgesic. There were 1328 trauma response system activations during the study period; of which 340 patients were included. The most common analgesic administered was fentanyl (62% in both groups). When a pharmacist was participating, the mean time to first analgesic administered was decreased (17 vs 21 minutes; P = .03). Among the 78% of patients with documented pain scores, the overall mean reduction in pain scores from ED arrival to ED discharge was similar between the 2 groups. There was a 2.4 point reduction with a pharmacist versus 2.7 without a pharmacist, using a 0 to 10 numeric pain rating scale. The participation of a clinical pharmacist during trauma resuscitation significantly decreased the time to first analgesic administration in trauma patients. The results of this study supplement the literature supporting the integration of clinical ED pharmacists on trauma teams.

Heterogenic control groups in randomized, controlled, analgesic trials of total hip and knee arthroplasty.

PubMed

Karlsen, Anders P; Mathiesen, Ole; Dahl, Jørgen B

2018-03-01

Postoperative analgesic interventions are often tested adjunct to basic non-opioid analgesics in randomized controlled trials (RCTs). Consequently, treatment in control groups, and possible assay sensitivity, differs between trials. We hypothesized that postoperative opioid requirements and pain intensities vary between different control groups in analgesic trials. Control groups from RCTs investigating analgesic interventions after total hip and knee arthroplasty were categorized based on standardized basic analgesic treatment. Morphine consumption 0 to 24 hours postoperatively, and resting pain scores at 6 and 24 hours for subgroups of basic treatments, were compared with ANOVA. In an additional analysis, we compared pain and opioid requirements in trials where a non-steroidal anti-inflammatory drug (NSAID) was administered as an intervention with trial where NSAID was administered in a control group. We included 171 RCTs employing 28 different control groups with large variability in pain scores and opioid requirements. Four types of control groups (comprising 78 trials) were eligible for subgroup comparisons. These subgroups received "opioid" alone, "NSAID + opioid", "acetaminophen + opioid", or "NSAID + acetaminophen + opioid", respectively. Morphine consumption and pain scores varied substantially between these groups, with no consistent superior efficacy in any subgroup. Additionally, trials administering NSAID as an intervention demonstrated lower pain scores and opioid requirements than trials where NSAID was administered in a control group. Analgesic treatment in RCT control groups varies considerably. Control groups receiving various combinations of opioid, NSAID and acetaminophen did not differ consistently in pain and opioid requirements. Pain and opioid requirements were lower in trials administering NSAID as an intervention compared with trials administering NSAID in a control group.

A comparison of the effects of two volumes of local analgesic solution in the distal interphalangeal joint of horses with lameness caused by solar toe or solar heel pain.

PubMed

Schumacher, J; Schumacher, J; de Graves, F; Steiger, R; Schramme, M; Smith, R; Coker, M

2001-05-01

The response of horses, with solar pain in the dorsal or palmar aspect of the foot, to 6 or 10 ml local analgesic solution administered into the distal interphalangeal (DIP) joint was examined. Lameness was induced in 7 horses by creating solar pain in the dorsal aspect of one forefoot and, at another time, the palmar aspect of the other forefoot with set-screws inserted into a custom-made shoe. Horses were videotaped trotting before and after application of set-screws and, in separate trials, after 6 or 10 ml local analgesic solution was administered into the DIP joint. Lameness scores were assigned by examining videotaped gaits. Scores were significantly lower (P < 0.05) for horses with set-screws applied to the angles of the sole and receiving 10 ml, but not 6 ml, local analgesic solution into the DIP joint. Scores were significantly lower (P < 0.05) for all horses with set-screws in the dorsal margin of the sole receiving either volume of local analgesic solution. Analgesia of the DIP joint was less effective in desensitising the angles of the sole than in desensitising the dorsal margin of the sole, and 10 ml local analgesic solution was more effective than 6 ml in desensitising these regions. The response of horses with solar pain to local analgesic solution in the DIP joint was influenced by the volume administered and the region of sole affected.

Enhanced analgesic effects of tramadol and common trace element coadministration in mice.

PubMed

Alexa, Teodora; Marza, Aurelia; Voloseniuc, Tudor; Tamba, Bogdan

2015-10-01

Chronic pain is managed mostly by the daily administration of analgesics. Tramadol is one of the most commonly used drugs, marketed in combination with coanalgesics for enhanced effect. Trace elements are frequent ingredients in dietary supplements and may enhance tramadol's analgesic effect either through synergic mechanisms or through analgesic effects of their own. Swiss Weber male mice were divided into nine groups and were treated with a combination of the trace elements Mg, Mn, and Zn in three different doses and a fixed dose of tramadol. Two groups served as positive (tramadol alone) and negative (saline) controls. Nociceptive assessment by tail-flick (TF) and hot-plate (HP) tests was performed at baseline and at 15, 30, 45, and 60 min after intraperitoneal administration. Response latencies were recorded and compared with the aid of ANOVA testing. All three trace elements enhanced tramadol's analgesic effect, as assessed by TF and HP test latencies. Coadministration of these trace elements led to an increase of approximately 30% in the average pain inhibition compared with the tramadol-alone group. The most effective doses were 0.6 mg/kg b.w. for Zn, 75 mg/kg b.w. for Mg, and 7.2 mg/kg b.w. for Mn. Associating trace elements such as Zn, Mg, and Mn with the standard administration of tramadol increases the drug's analgesic effect, most likely a consequence of their synergic action. These findings impact current analgesic treatment because the addition of these trace elements may reduce the tramadol dose required to obtain analgesia. © 2015 Wiley Periodicals, Inc.

A Prospective, Observational Study to Evaluate the Role of Gabapentin as Preventive Analgesic in Thyroidectomy under General Anesthesia

PubMed Central

Hema, Vadakkoot Raghavan; Ramadas, Konnanath Thekkethil; Biji, Kannammadathy Poulose; Indu, Suseela; Arun, Aravind

2017-01-01

Background: Effective management of postoperative pain is a part of well-organized perioperative care, which helps in reduced morbidity and improved patient satisfaction. Preventive analgesia can reduce acute and chronic pain by blocking the noxious inputs to pain pathways, preventing sensitization. Studies have reported efficacy of gabapentin as a preventive analgesic in perioperative pain. In this study, we aimed to determine whether preoperative gabapentin reduced postoperative pain and tramadol consumption after thyroidectomy under general anesthesia. Materials and Methods: Sixty patients scheduled for thyroidectomy were allocated to two groups of thirty each for this prospective, observational study. Patients in Group A and Group B received oral gabapentin 600 mg (6 × 10−4 kg) and diazepam 10 mg (1 × 10−5 kg), respectively, 2 h prior to surgery. Tramadol was given as rescue analgesic for postoperative pain with a verbal rating score of two. The analgesic efficacy of preoperative gabapentin was assessed in terms of postoperative pain scores at rest or swallowing, time to first rescue analgesic, and total tramadol consumption for 24 h. Ramsay sedation score and side effects of drug were also looked into. Results: Postoperative pain scores and total tramadol consumption were significantly lower in Group A during 24 h (P = 0.00). Time to first rescue analgesic was significantly prolonged in Group A (P = 0.001). Side effects were comparable. Conclusion: Oral gabapentin is effective as a preventive analgesic in reducing postoperative pain and tramadol consumption after thyroidectomy under general anesthesia. PMID:28928577

Sedatives and Analgesics Given to Infants in Neonatal Intensive Care Units at the End of Life

PubMed Central

Zimmerman, Kanecia O.; Hornik, Christoph P.; Ku, Lawrence; Watt, Kevin; Laughon, Matthew M.; Bidegain, Margarita; Clark, Reese H.; Smith, P. Brian

2015-01-01

Objective To describe the administration of sedatives and analgesics at the end of life in a large cohort of infants in North American neonatal intensive care units (NICUs). Study design Data on mortality and sedative and analgesic administration were obtained from infants who died from 1997–2012 in 348 NICUs managed by the Pediatrix Medical Group. Sedatives and analgesics of interest included opioids (fentanyl, methadone, morphine), benzodiazepines (clonazepam, diazepam, lorazepam, midazolam), central alpha-2 agonists (clonidine, dexmedetomidine), ketamine, and pentobarbital. We used multivariable logistic regression to evaluate the association between administration of these drugs on the day of death and infant demographics and illness severity. Results We identified 19,726 infants who died. Of these, 6188 (31%) received a sedative or analgesic on the day of death; opioids were most frequently administered, 5366/19,726 (27%). Administration of opioids and benzodiazepines increased during the study period, from 16/283 (6%) for both in 1997 to 523/1465 (36%) and 295/1465 (20%) in 2012, respectively. Increasing gestational age, increasing postnatal age, invasive procedure within 2 days of death, more recent year of death, mechanical ventilation, inotropic support, and antibiotics on the day of death were associated with exposure to sedatives or analgesics. Conclusions Administration of sedatives and analgesics increased over time. Infants of older gestational age and those more critically ill were more likely to receive these drugs on the day of death. These findings suggest that drug administration may be driven by severity of illness. PMID:26012893

Criminal Activity or Treatable Health Condition? News Media Framing of Opioid Analgesic Abuse in the United States, 1998-2012.

PubMed

McGinty, Emma E; Kennedy-Hendricks, Alene; Baller, Julia; Niederdeppe, Jeff; Gollust, Sarah; Barry, Colleen L

2016-04-01

Opioid analgesic abuse is a complex and relatively new public health problem, and to date little is known about how the news media frame the issue. To better understand how this issue has been framed in public discourse, an analysis was conducted of the volume and content of news media coverage of opioid analgesic abuse over a 15-year period from 1998 to 2012 (N=673 news stories). A 70-item structured coding instrument was used to measure items in four domains that prior research suggests can influence public attitudes about health and social issues: causes, solutions, and consequences of the problem and individual depictions of persons who abuse opioid analgesics. Although experts have deemed opioid analgesic abuse a public health crisis, results of our study suggest that the news media more often frame the problem as a criminal justice issue. The most frequently mentioned cause of the problem was illegal drug dealing, and the most frequently mentioned solutions were law enforcement solutions designed to arrest and prosecute the individuals responsible for diverting opioid analgesics onto the illegal market. Prevention-oriented approaches, such as prescription drug-monitoring programs, were mentioned more frequently in the latter years of the study period, but less than 5% of news stories overall mentioned expanding substance abuse treatment, and even fewer mentioned expanding access to evidence-based medication-assisted treatments, such as buprenorphine. Findings underscore the need for a concerted effort to reframe opioid analgesic abuse as a treatable condition addressable via well-established public and behavioral health approaches.

Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation.

PubMed

Kumar, Priyank; Sunkaraneni, Soujanya; Sirohi, Sunil; Dighe, Shveta V; Walker, Ellen A; Yoburn, Byron C

2008-11-12

This study examined the antinociceptive (analgesic) efficacy of hydromorphone and hydromorphone-induced tolerance and regulation of mu-opioid receptor density. Initially s.c. hydromorphone's time of peak analgesic (tail-flick) effect (45 min) and ED50 using standard and cumulative dosing protocols (0.22 mg/kg, 0.37 mg/kg, respectively) were determined. The apparent analgesic efficacy (tau) of hydromorphone was then estimated using the operational model of agonism and the irreversible mu-opioid receptor antagonist clocinnamox. Mice were injected with clocinnamox (0.32-25.6 mg/kg, i.p.) and 24 h later, the analgesic potency of hydromorphone was determined. The tau value for hydromorphone was 35, which suggested that hydromorphone is a lower analgesic efficacy opioid agonist. To examine hydromorphone-induced tolerance, mice were continuously infused s.c. with hydromorphone (2.1-31.5 mg/kg/day) for 7 days and then morphine cumulative dose response studies were performed. Other groups of mice were injected with hydromorphone (2.2-22 mg/kg/day) once, or intermittently every 24 h for 7 days. Twenty-four hours after the last injection, mice were tested using morphine cumulative dosing studies. There was more tolerance with infusion treatments compared to intermittent treatment. When compared to higher analgesic efficacy opioids, hydromorphone infusions induced substantially more tolerance. Finally, the effect of chronic infusion (31.5 mg/kg/day) and 7 day intermittent (22 mg/kg/day) hydromorphone treatment on spinal cord mu-opioid receptor density was determined. Hydromorphone did not produce any change in mu-opioid receptor density following either treatment. These results support suggestions that analgesic efficacy is correlated with tolerance magnitude and regulation of mu-opioid receptors when opioid agonists are continuously administered. Taken together, these studies indicate that analgesic efficacy and treatment protocol are important in determining tolerance and regulation of mu-opioid receptors.

Analgesic use and patterns of estrogen metabolism in premenopausal women.

PubMed

Fortner, Renée T; Oh, Hannah; Daugherty, Sarah E; Xu, Xia; Hankinson, Susan E; Ziegler, Regina G; Eliassen, A Heather

2014-04-01

Analgesic use has been hypothesized to reduce the risk of some cancers, with inverse associations between analgesics and colon cancer, and suggestive inverse associations for breast cancer. Estrogen metabolites (EM) have genotoxic and estrogenic potential; genotoxicity may differ by hydroxylation pathway. Analgesic use may impact patterns of estrogen metabolism; effects of analgesics on disease risk could be mediated through these patterns. We conducted a cross-sectional study among 603 premenopausal women in the Nurses' Health Study II. Frequency of aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen use was reported via questionnaire; average frequency in 1997 and 1999 was calculated. Women provided urine samples between 1996 and 1999, collected during the mid-luteal phase of the menstrual cycle. Urinary EM were quantified using high-performance liquid chromatography-tandem mass spectrometry. We observed no association between analgesic use and estradiol, estrone, or specific pathways of estrogen metabolism. Women reporting more frequent aspirin use had lower methylated 2-catechols (e.g., 2-hydroxyestrone-3-methyl ether, 2+ days/week vs. non-use: 0.95 vs. 1.21 pmol/mg creatinine; p difference = 0.01, p trend = 0.07). Non-aspirin NSAID use was positively associated with 17-epiestriol (4+ days/week vs. non-use: 2.48 vs. 1.52 pmol/mg creatinine; p difference = 0.01, p trend = 0.11). Acetaminophen use was positively associated with total EM (2+ days/week vs. non-use: 236 vs. 198 pmol/mg creatinine; p difference = 0.02, p trend = 0.11), 2-hydroxyestrone-3-methyl ether (1.6 vs. 1.1 pmol/mg creatinine; p difference < 0.01, p trend = 0.02), and 16α-hydroxyestrone (17 vs. 12 pmol/mg creatinine; p difference = 0.01, p trend = 0.05). This study provides the first assessment of analgesic use and patterns of estrogen metabolism in women. While we observed some associations between analgesics and individual EM, no clear patterns emerged.

THE EFFECTS OF INTRATHECAL NEOSTIGMINE ADDED TO BUPIVACAINE ON POSTOPERATIVE ANALGESIC REQUIREMENT IN PATIENTS UNDERGOING LOWER LIMB ORTHOPEDIC SURGERY.

PubMed

Kayalha, Hamid; Mousavi, Zinat; Sadat Barikani, Ameneh; Yaghoobi, Siamak; Khezri, Marzieh Beigom

2015-06-01

Several additives have been suggested to enhance analgesic effect of local anesthetic agents to decrease the adverse effects of them and increase the degree of satisfaction. We designed this randomized double-blind controlled study to evaluate the analgesic efficacy of the neostigmine added to bupivacaine using spinal anesthesia in patients undergoing lower limb orthopedic surgery. Sixty patients 18-80 yr old American Society of Anesthesiologists (ASA) physical status I or II, scheduled for femur surgery under spinal anesthesia, were recruited in a prospective, double-blinded, randomized way. The patients were randomly allocated to one of two groups of 30 each. The neostigmine group (group N) received bupivacaine 20 mg combined with 25 µg neostigmine, and the placebo group (group C) received bupivacaine 20 mg combined with 0.5ml distilled water (intrathecally) 5 minutes prior to surgery. The time to the first analgesic request, analgesic requirement in the first 12 hours after surgery, the duration of sensory and motor blockade, the incidence of adverse effects such as nausea,vomiting,hypotension, ephedrine requirements, bradycardia, and hypoxemia were recorded. Patients receiving neostigmine had a significantly prolonged duration of motor block (C95% CI 30.27 to 87.65; P < 0.001) and sensory block (C95% CI 101.04 to 224.64; P < 0.001) compared to the control group. The difference of the mean time to the first analgesic request was also significantly longer in neostigmine group (C95% CI 83.139 to 208.526; P < 0.001). The total analgesic consumption during the first 12 hours after surgery was devoid of any significant difference between groups N and C (p = 0.41).The two groups were not significantly different in terms of intraoperative and postoperative side effects. Intrathecal neostigmine 25 µg with bupivacaine caused a prolonged time to the first analgesic request and its use was not associated with any side effects.

Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

PubMed Central

Pergolizzi, Joseph V; van de Laar, Mart; Langford, Richard; Mellinghoff, Hans-Ulrich; Merchante, Ignacio Morón; Nalamachu, Srinivas; O’Brien, Joanne; Perrot, Serge; Raffa, Robert B

2012-01-01

Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a “do ask, do tell” approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with minimal toxicity. PMID:23055775

Effects of intra-articular levobupivacaine, fentanyl-levobupivacaine and tramadol-levobupivacaine for postoperative pain in arthroscopic knee surgery.

PubMed

Sayın, Pınar; Dobrucalı, Hale; Türk, Hacer Şebnem; Totoz, Tolga; Işıl, Canan Tülay; Hancı, Ayşe

2015-01-01

The aim of this study was to compare the postoperative analgesic efficacy of intra-articularly injected levobupivacaine, levobupivacaine-fentanyl, and levobupivacaine-tramadol combinations. Eighty patients scheduled for elective knee arthroscopy were divided randomly into 4 groups of 20 patients each. Group 1 (the control group) received intra-articular saline, Group 2 received levobupivacaine 2.5 mg/ml, Group 3 received levobupivacaine 2.5 mg/ml + tramadol 50 mg, and Group 4 received levobupivacaine 2.5 mg/ml + fentanyl l50 mcg. All patients were operated on under general anesthesia, and a total of 20 ml study solution was injected: 7 ml subcutaneously before surgery and 13 ml intra-articularly upon completion of surgery. For postoperative, pain visual analogue scale (VAS) was assessed at the 1st, 2nd, 4th, 8th, 12th, and 24th hours postoperatively. Patients with a VAS score over 5 received diclofenac sodium, and the need for rescue analgesics was recorded. At the 1st, 2nd, 4th, 8th, 12th, and 24th postoperative hours, Group 3 and Group 4 had statistically significant lower VAS scores of pain (p<0.01). Postoperative rescue analgesic requirements were different among the groups. The postoperative 1st hour analgesic requirement was statistically significantly lower in Group 3 and Group 4 when compared to the other groups (p<0.01). At the postoperative 2nd and 4th hours, analgesic requirements were statistically significantly lower in Group 3 than in the other groups (p<0.01). Analgesic requirements were statistically significantly lower in Group 3 and Group 4 than in the other groups (p<0.01). Analgesic requirements at the 12th and 24th postoperative hours did not show any statistically significant difference (p>0.05). The results indicated that levobupivacaine combined with either fentanyl or tramadol decreased rescue analgesic requirements when compared to levobupivacaine alone.

Current analgesic use predicts low emotional quality of life in youth: a cross-sectional survey among university students in Sikkim, North East India.

PubMed

Ahongshangbam, Shurmala; Chakrabarti, Amit

2013-06-01

Occurrence of chronic physical pain is increasingly identified among youth, and medically unsupervised analgesic use is a possible risk factor for opioid dependence and other mental diseases in later life. Therefore, the present study was carried out in young student population in Sikkim, India, to explore predictors (including current chronic pain and current analgesic use) of low QoL in youth to identify a subset of population vulnerable to substance use and mental diseases in later life. The study was conducted in a health university setting in Sikkim, North East India. In this cross-sectional study, 156 participants were enrolled with almost equal number of males and females. Generic instruments for demographics and current analgesic use and SF - 36, for assessment of quality of life (QoL), were used. QoL was measured in general, physical and emotional domains. Presence of chronic physical pain during past four weeks was captured using SF - 36. Almost two-third participants reported presence of current physical pain (69%, n=108); and (14%, n=22) reported current analgesic use for pain. In logistic regression model controlled for age, ethnicity, gender and residence, higher body mass index (BMI) (β=-0.16, P=0.02) and current analgesic use (β=1.6, P=0.006) predicted low QoL in emotional domain (less accomplishment due to emotional problem). Current analgesic use also predicted low QoL in another measure of emotional domain (depressed β=2.0, P=0.001). This study identified a subset of participants in their youth with low QoL in emotional domain predicted by current analgesic use and possible overweight problem. Low QoL in more than one emotional domain also identifies possibility of later psychiatric impairment. However, chronic pain did not emerge as a significant predictor of low QoL in emotional domain.

Accounting for the sedative and analgesic effects of medication changes during patient participation in clinical research studies: measurement development and application to a sample of institutionalized geriatric patients.

PubMed

Sloane, Philip; Ivey, Jena; Roth, Mary; Roederer, Mary; Williams, Christianna S

2008-03-01

To date, no system has been published that allows investigators to adjust for the overall sedative and/or analgesic effects of medications, or changes in medications, in clinical trial participants for whom medication use cannot be controlled. This is common in clinical trials of behavioral and complementary/alternative therapies, and in research involving elderly or chronically ill patients for whom ongoing medical care continues during the trial. This paper describes the development, and illustrates the use, of a method we developed to address this issue, in which we generate single continuous variables to represent the daily sedative and analgesic loads of multiple medications. Medications for 90 study participants in a clinical trial of a nonpharmacological intervention were abstracted from medication administration records across multiple treatment periods. An expert panel of three academic clinical pharmacists and a geriatrician met to develop a system by which each study medication could be assigned a sedative and analgesic effect rating. The two measures, when applied to data on 90 institutionalized persons with Alzheimer's disease, resulted in variables with moderately skewed distributions that are consistent with the clinical profile of analgesia and sedation use in long-term care populations. The average study participant received 1.89 analgesic medications per day and had a daily analgesic load of 2.96; the corresponding figures for sedation were 2.07 daily medications and an average daily load of 11.41. A system of classifying the sedative and analgesic effects of non-study medications was created that divides drugs into categories based on the strength of their effects and assigns a rating to express overall sedative and analgesic effects. These variables may be useful in comparing patients and populations, and to control for drug effects in future studies.

Does the use of a brief cryotherapy intervention with analgesic administration improve pain management after total knee arthroplasty?

PubMed

Wittig-Wells, Deborah; Johnson, Ifeya; Samms-McPherson, Jacqueline; Thankachan, Soosan; Titus, Bobina; Jacob, Ani; Higgins, Melinda

2015-01-01

Prior studies have evaluated only the prolonged use of cryotherapy as a nonpharmacologic pain intervention. The purpose of this study was to determine whether a 30-minute application of cryotherapy at the time pain medication was given after a total knee arthroplasty (TKA) provided better pain relief than analgesic drugs alone. A pretest, posttest, randomized controlled trial study design with crossover was used to evaluate the effects of cryotherapy on postoperative pain and satisfaction with pain management. A convenience sample of postoperative knee replacement patients constituted participants in the study. Two sequential episodes of pain requiring analgesic administration were studied in each patient, one with a 30-minute cryotherapy application and the other without cryotherapy. Dependent variables were changes in pain (posttest minus pretest) and level of satisfaction with pain management. Data were analyzed with repeated-measures analysis of variance, with p < .05 considered significant. During two sequential treatments for postoperative pain, a total of 29 TKA patients received analgesic medication administration alone for one pain episode and analgesic medication administration with a brief cryotherapy administration for the other pain episode. No significant difference between the two treatments was found for changes in pain scores after the treatments or patient satisfaction with pain management (p > .05). The order in which the treatments were provided was found to be significant (p = .02) for scores on patient satisfaction with pain management, with cryotherapy as the treatment for the second pain episode having higher scores than when delivered for the first pain episode. Sixty minutes after analgesic administration with or without cryotherapy, average pain scores remained greater than 7. In TKA patients, the short-term application of cryotherapy with analgesic medication administration did not significantly decrease pain or improve patient satisfaction with pain management compared with analgesic medication administration only. Further study is necessary to determine whether short-term cryotherapy shortly after TKA is of benefit to pain relief and patient satisfaction.

A mutant of the Buthus martensii Karsch antitumor-analgesic peptide exhibits reduced inhibition to hNav1.4 and hNav1.5 channels while retaining analgesic activity.

PubMed

Xu, Yijia; Meng, Xiangxue; Hou, Xue; Sun, Jianfang; Kong, Xiaohua; Sun, Yuqi; Liu, Zeyu; Ma, Yuanyuan; Niu, Ye; Song, Yongbo; Cui, Yong; Zhao, Mingyi; Zhang, Jinghai

2017-11-03

Scorpion toxins can kill other animals by inducing paralysis and arrhythmia, which limits the potential applications of these agents in the clinical management of diseases. Antitumor-analgesic peptide (AGAP), purified from Buthus martensii Karsch, has been proved to possess analgesic and antitumor activities. Trp 38 , a conserved aromatic residue of AGAP, might play an important role in mediating AGAP activities according to the sequence and homology-modeling analyses. Therefore, an AGAP mutant, W38G, was generated, and effects of both AGAP and the mutant W38G were examined by whole-cell patch clamp techniques on the sodium channels hNa v 1.4 and hNa v 1.5, which were closely associated with the biotoxicity of skeletal and cardiac muscles, respectively. The data showed that both W38G and AGAP inhibited the peak currents of hNa v 1.4 and hNa v 1.5; however, W38G induced a much weaker inhibition of both channels than AGAP. Accordingly, W38G exhibited much less toxic effect on both skeletal and cardiac muscles than AGAP in vivo The analgesic activity of W38G and AGAP were verified in vivo as well, and W38G retained analgesic activity similar to AGAP. Inhibition to both Na v 1.7 and Na v 1.8 was involved in the analgesic mechanism of AGAP and W38G. These findings indicated that Trp 38 was a key amino acid involved in the biotoxicity of AGAP, and the AGAP mutant W38G might be a safer alternative for clinical application because it retains the analgesic efficacy with less toxicity to skeletal and cardiac muscles. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Radiotherapy of Painful Vertebral Hemangiomas: The Single Center Retrospective Analysis of 137 Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miszczyk, Leszek, E-mail: leszek@io.gliwice.pl; Tukiendorf, Andrzej

2012-02-01

Purpose: An evaluation of dose-response relationship and an attempt to define predictive factors. Methods and Materials: A total of 137 cases of painful vertebral hemangioma irradiations (101 patients). Fraction dose (fd) varied from 2 to 15 Gy (123 fractionated and 14 radiosurgical treatments), and total dose (TD) from 8 to 30 Gy (111 cases irradiated with fd of 2 GY to TD of 24 Gy). We evaluated pain relief, changes in analgesic requirements, and reossification. Results: Means of pain relief 1, 6, 12, and 18 months after radiotherapy (defined as a decrease of primary pain level expressed in percent) weremore » 60.5%, 65.4%, 68.3%, and 78.4%, respectively. Proportion of patients with no need for analgesics and patients using tramadol were 39%, 40%, 44%, 57%, and 20%, 17%, 22%, and 11% in these times. The proportion of patients experiencing complete/partial pain relief changed from 36/48% 1 month, to 64/22% 1.5 years after radiotherapy. No impact of radiotherapy on reossification was found. The positive impact of fd and TD increase for analgesics uptake reduction and pain relief was found. An increase of the fd by 1 Gy results in 27% chance of analgesics uptake reduction and 3.8% reduction of pain, whereas 14% analgesics uptake reduction and 2.2% of pain reduction in case of the TD. The predictive factors improving results were found: female gender, older age, better performance states (the chance of the lower analgesic treatment decreases over 2.5 times in comparison to the higher Zubrod degree), bigger Hb concentration, shorter symptoms duration and lower analgesics uptake before radiotherapy. Conclusions: The obtained data support the efficacy of radiotherapy in improving pain secondary to vertebral hemangioma, with the degree of pain amelioration being related to increasing fd and TD. The positive predictive factors were defined: female gender, older age, better performance status, increased Hb concentration, shorter symptoms duration, and lower analgesics uptake before radiotherapy.« less

High-frequency use of over-the-counter analgesics among adolescents: reflections of an emerging difficult life, a cross-sectional study.

PubMed

Skarstein, Siv; Rosvold, Elin O; Helseth, Sølvi; Kvarme, Lisbeth G; Holager, Tanja; Småstuen, Milada C; Lagerløv, Per

2014-03-01

To examine characteristics of 15- to 16-year-old adolescents who used over-the-counter analgesics daily to weekly (high-frequency users) as compared to those who used less or no analgesics (low-frequency users). Further to analyse the differences in pain experience, lifestyle, self-esteem, school attendance and educational ambition. An anonymous cross-sectional questionnaire-based study. The questionnaire covered the use of over-the-counter analgesics, pain experience, sociodemographics, lifestyle factors, self-esteem, school absence and future educational plans. The study took place in the 10th grade in six junior high schools in a medium-sized town in Norway. The local sales data for analgesics and antipyretics were close to the national average. We invited 626 adolescents to participate. Of the 367 adolescents (59%) who responded, 51% were girls. Associations between the frequency of use of over-the-counter analgesic and the mentioned variables were analysed using multiple logistic regression. In total, 26% (42 boys and 48 girls) used over-the-counter analgesics daily to weekly. These high-frequency users experienced more widespread pain, slept less, had more paid spare-time work, drank more caffeinated drinks, participated more often in binge drinking, had lower self-esteem, less ambitious educational plans and more frequent school absence than did the low-frequency users. These associations remained significant when controlling for gender, cultural background and self-evaluated economic status. Adolescent, who are high-frequency users of over-the-counter analgesics, suffer more pain and have identifiable characteristics indicative of complex problems. Their ability to handle stress appears to be discordant with the kind of situations to which they are exposed. The wear and tear associated with allostatic mechanisms counteracting stress may heighten their pain experience. © 2013 Nordic College of Caring Science. Published by Blackwell Publishing Ltd.

Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil.

PubMed

Intahphuak, S; Khonsung, P; Panthong, A

2010-02-01

This study investigated some pharmacological properties of virgin coconut oil (VCO), the natural pure oil from coconut [Cocos nucifera Linn (Palmae)] milk, which was prepared without using chemical or high-heat treatment. The anti-inflammatory, analgesic, and antipyretic effects of VCO were assessed. In acute inflammatory models, VCO showed moderate anti-inflammatory effects on ethyl phenylpropiolate-induced ear edema in rats, and carrageenin- and arachidonic acid-induced paw edema. VCO exhibited an inhibitory effect on chronic inflammation by reducing the transudative weight, granuloma formation, and serum alkaline phosphatase activity. VCO also showed a moderate analgesic effect on the acetic acid-induced writhing response as well as an antipyretic effect in yeast-induced hyperthermia. The results obtained suggest anti-inflammatory, analgesic, and antipyretic properties of VCO.

[Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids versus nonopioid analgesics of at least four week's duration].

PubMed

Welsch, P; Sommer, C; Schiltenwolf, M; Häuser, W

2015-02-01

Some leading German pain medicine experts postulate that there is a type of chronic non-cancer pain (CNCP) with an opioid requirement. We tested whether opioids are superior to nonopioid analgesics in the management of CNCP in studies of at least 4 week's duration. We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomised controlled trials (RCTs) of opioids in CNCP. We included double-blind RTCs comparing opioids to nonopioid analgesics of at least 4 week's duration. Relative risks differences (RD) of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. We included 10 RCTs with 3046 participants. Median study duration was 6 weeks (range 4-12 weeks). Five studies compared tramadol with nonsteroidal anti-inflammatory drugs (NSAIDs) in osteoarthritis pain and one trial compared tramadol to flupirtine in low back pain. Morphine was compared to antidepressants (two studies), an anticonvulsant (one study) and an antiarrhythmic (one study) in different neuropathic pain syndromes. There was no significant difference between opioids and nonopioid analgesics in pain reduction (SMD 0.03 [95 % confidence interval, CI - 0.18, 0.24]; p = 0.76). Nonopioid analgesics were superior to opioids in improving physical function (SMD 0.17 [95 % CI 0.02, 0.32]; p = 0.03). Patients dropped out due to adverse events more frequently with opioids than with nonopioid analgesics (RD 0.09 [95 % CI 0.06, 0.13]; p < 0.0001). There was no significant difference between opioids and nonopioid analgesics in terms of serious adverse events or dropout rates due to lack of efficacy. Nonopioid analgesics are superior to opioids in terms of improvement of physical function and tolerability in short-term (4-12 weeks) therapy of neuropathic, low back and osteoarthritis pain. Our results do not support the concept of an"opioid-requiring" CNCP. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").

Polysubstance use and misuse or abuse of prescription opioid analgesics: a multi-level analysis of international data.

PubMed

Morley, Katherine I; Ferris, Jason A; Winstock, Adam R; Lynskey, Michael T

2017-06-01

Increasing mortality and morbidity associated with opioid analgesics has led to concerns about their misuse and abuse, even when obtained through a prescription. These concerns have been most pronounced in the United States, but limited data make it difficult to determine whether it is a problem in other countries. We investigated opioid analgesic misuse and abuse in participants from the Global Drug Survey 2015 resident in the United States (N = 1334), United Kingdom (N = 1199), France (N = 1258), Germany (N = 866), and Australia (N = 1013) who had used at least 1 prescription opioid analgesic medication in the past year. We also investigated the relationship with polysubstance use, one of the most consistent predictors of problematic opioid analgesic use. Data included misuse and abuse of codeine, hydrocodone, oxycodone, and tramadol; ability to obtain a prescription; different sources for obtaining drugs; and past-year use of benzodiazepines and illicit drugs. In multilevel models, country of residence accounted for less than 3% of the variance in opioid analgesic misuse or abuse. Adjusting for country of residence and sociodemographic factors, use of illicit drugs and benzodiazepines was associated with 4-fold greater odds of misuse (odds ratio 4.36, 95% confidence interval 3.29-5.93) and 6-fold greater odds of abuse compared with not using either drug (odds ratio 6.49, 95% confidence interval 4.0-10.48), although the strength of the association with abuse varied by country. Misuse and abuse by those prescribed opioid analgesics seem to be a problem that is not limited to the United States and warrant attention on an international scale.

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

PubMed

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.

Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study.

PubMed

Park, Tae Woo; Saitz, Richard; Ganoczy, Dara; Ilgen, Mark A; Bohnert, Amy S B

2015-06-10

To study the association between benzodiazepine prescribing patterns including dose, type, and dosing schedule and the risk of death from drug overdose among US veterans receiving opioid analgesics. Case-cohort study. Veterans Health Administration (VHA), 2004-09. US veterans, primarily male, who received opioid analgesics in 2004-09. All veterans who died from a drug overdose (n=2400) while receiving opioid analgesics and a random sample of veterans (n=420,386) who received VHA medical services and opioid analgesics. Death from drug overdose, defined as any intentional, unintentional, or indeterminate death from poisoning caused by any drug, determined by information on cause of death from the National Death Index. During the study period 27% (n=112,069) of veterans who received opioid analgesics also received benzodiazepines. About half of the deaths from drug overdose (n=1185) occurred when veterans were concurrently prescribed benzodiazepines and opioids. Risk of death from drug overdose increased with history of benzodiazepine prescription: adjusted hazard ratios were 2.33 (95% confidence interval 2.05 to 2.64) for former prescriptions versus no prescription and 3.86 (3.49 to 4.26) for current prescriptions versus no prescription. Risk of death from drug overdose increased as daily benzodiazepine dose increased. Compared with clonazepam, temazepam was associated with a decreased risk of death from drug overdose (0.63, 0.48 to 0.82). Benzodiazepine dosing schedule was not associated with risk of death from drug overdose. Among veterans receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of death from drug overdose in a dose-response fashion. © Park et al 2015.

On subclasses of opioid analgesics.

PubMed

Raffa, Robert B

2014-12-01

The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids. A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given. By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids. An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical use and regulatory control of the current drugs, and provide direction/strategy for the discovery of new drugs.

Analgesic use, parents' clan, and coffee intake are three independent risk factors of chronic kidney disease in middle and elderly-aged population: a community-based study.

PubMed

Hsu, Yung-Chien; Lee, Pei-Hsien; Lei, Chen-Chou; Shih, Ya-Hsueh; Lin, Chun-Liang

2014-04-01

Chronic kidney disease (CKD) is a world-wide public health problem. The purpose of this study was to identify the role of some controversial potential risk factors in development of CKD. "Community Complex Health Screening" is a large-scale, free, health program for individuals ≥40 years of age that has been available since January 2002 in Chiayi County, Taiwan. A questionnaire was administered to study participants, collecting information on ethnicity, use of analgesics, and life habits. Age, sex, and blood biochemical analyses were considered as potential confounders. A high prevalence and low awareness of CKD were noted in this population. Females with CKD had a lower awareness of their illness than males. Analgesic users had a significantly lower estimated glomerular filtration rate (eGFR). Age (OR = 1.095), females (OR = 0.348), fasting plasma glucose (OR = 1.005), level of uric acid (UA) (OR = 1.517), and analgesic usage (OR = 1.512) remained independent predictors of CKD. Multivariate linear regression found that use of analgesics, father' clan from Fujian, mother' clan from Fujian, and coffee intake were independent determinants of renal outcome with coefficient of regression (β) of -0.102, -0.192, 0.210 and 0.88, respectively. The prevalence of CKD decreased with advanced education. Further, there was no significant difference between education background and analgesics use. In conclusion, analgesic use, parents' clan, and coffee intake were independent risk factors for CKD in middle-aged and elderly Taiwanese. Thus, an effective educational program that increases the awareness of such individuals residing in rural counties is warranted.

Dose-dependency of dexamethasone on the analgesic effect of interscalene block for arthroscopic shoulder surgery using ropivacaine 0.5%: A randomised controlled trial.

PubMed

Woo, Jae Hee; Kim, Youn Jin; Kim, Dong Yeon; Cho, Sooyoung

2015-09-01

Dexamethasone prolongs the duration of single-shot interscalene brachial plexus block (SISB). However, dose-dependency of dexamethasone as an adjuvant for SISB remains insufficiently understood. The objective of this study is to evaluate the effect of different doses of dexamethasone on the duration of SISB using ropivacaine 0.5%. A randomised, double-blind controlled trial. Single university tertiary care centre. One hundred and forty-four patients scheduled for elective arthroscopic shoulder surgery were allocated randomly to one of four groups. Patients received 12 ml of ropivacaine 0.5% in 0.9% saline (control group), or containing dexamethasone 2.5, 5.0 or 7.5 mg for SISB. The primary endpoint was the time to the first analgesic request. Pain scores and adverse effects were also assessed up to 48 h postoperatively. Inclusion of dexamethasone 2.5, 5.0 and 7.5 mg resulted in significant (P < 0.001) increases in time to the first analgesic request by factors of 1.6, 2.2 and 1.8, respectively. The percentages of patients not requiring analgesics in the first 48 h postoperatively with dexamethasone 0.0, 2.5, 5.0 and 7.5 mg were 3, 22, 39 and 33%, respectively (P < 0.001). There were no significant effects on pain scores or incidences of adverse effects. Dexamethasone demonstrated significant beneficial dose-dependent effects on duration to the first analgesic request, the number of patients not requiring analgesics and analgesic use in the first 48 h after SISB for arthroscopic shoulder surgery. There were no significant effects on pain scores or incidences of adverse effects. the trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001078.

Pain level after ACL reconstruction: A comparative study between free quadriceps tendon and hamstring tendons autografts.

PubMed

Buescu, Cristian Tudor; Onutu, Adela Hilda; Lucaciu, Dan Osvald; Todor, Adrian

2017-03-01

The objective of this study was to compare the pain levels and analgesic consumption after single bundle ACL reconstruction with free quadriceps tendon autograft versus hamstring tendon autograft. A total of 48 patients scheduled for anatomic single-bundle ACL reconstruction were randomized into two groups: the free quadriceps tendon autograft group (24 patients) and the hamstring tendons autograft group (24 patients). A basic multimodal analgesic postoperative program was used for all patients and rescue analgesia was provided with tramadol, at pain scores over 30 on the Visual Analog Scale. The time to the first rescue analgesic, the number of doses of tramadol and pain scores were recorded. The results within the same group were compared with the Wilcoxon signed test. Supplementary analgesic drug administration proved significantly higher in the group of subjects with hamstring grafts, with a median (interquartile range) of 1 (1.3) dose, compared to the group of subjects treated with a quadriceps graft, median = 0.5 (0.1.25) (p = 0.009). A significantly higher number of subjects with a quadriceps graft did not require any supplementary analgesic drug (50%) as compared with subjects with hamstring graft (13%; Z-statistics = 3.01, p = 0.002). The percentage of subjects who required a supplementary analgesic drug was 38% higher in the HT group compared with the FQT group. The use of the free quadriceps tendon autograft for ACL reconstruction leads to less pain and analgesic consumption in the immediate postoperative period compared with the use of hamstrings autograft. Level I Therapeutic study. Copyright © 2017 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

General anesthesia and postoperative pain management in analgesic intolerant patients with/without asthma: is it safe?

PubMed

Celiker, V; Basgül, E; Karakaya, G; Oguzalp, H; Bozkurt, B; Kalyoncu, A F

2004-01-01

Analgesic intolerance (AI) appears in approximately 1 % of the general population. The triad of bronchial asthma, nasal polyposis, and analgesic intolerance is called analgesic-induced asthma (AIA). These patients are frequently referred to adult allergy clinics for preoperative evaluation for possible analgesic cross reactivity and intolerance to anesthetic agents. To determine allergic problems related to anesthesia and postoperative pain management in AI patients with and without asthma. The medical records of 45 patients who had been diagnosed with AI between January 1991 and December 2002 in the adult allergy unit and who underwent surgery in the same hospital in the last 4 years were retrospectively analyzed. The mean age of the patients was 44.4 13.4 years and 30 (66.6 %) were female. Thirty-six (80 %) had AIA, 34 (75.6 %) had persistent allergic rhinitis and 21 (46.7 %) had nasal polyps. Fifty-one surgical procedures were performed in 45 patients, in whom ear, nose and throat surgery was the main procedure (64.7 %). Anesthesia was induced with propofol, fentanyl, and vecuronium and was maintained by sevoflurane or isoflurane. Fentanyl was used for early postoperative pain relief. No complications appeared in relation to anesthesia or early pain management except in a 44-year-old AIA woman who had a reaction in the postoperative period after receiving an inappropriate analgesic. None of the patients had anesthesia-related allergic problems. Atropine and diazepam in the premedication, propofol and fentanyl during induction, muscle relaxation facilitation by vecuronium, and sevoflurane or isoflurane for maintenance seem to be a safe general anesthetic choice for analgesic intolerant patients with and without asthma.

A Subanalgesic Dose of Morphine Eliminates Nalbuphine Anti-analgesia in Postoperative Pain

PubMed Central

Gear, Robert W.; Gordon, Newton C.; Hossaini-Zadeh, Mehran; Lee, Janice S.; Miaskowski, Christine; Paul, Steven M.; Levine, Jon D.

2008-01-01

The agonist-antagonist kappa-opioid nalbuphine administered for postoperative pain produces greater analgesia in females than in males. In fact, males administered nalbuphine (5 mg) experience pain greater than those receiving placebo, suggesting the existence of an anti-analgesic effect. These sexually dimorphic effects on postoperative pain can be eliminated by co-administration of a fixed ratio of the prototypical opioid receptor antagonist naloxone with nalbuphine, implying a role for opioid receptors in the anti-analgesic as well as analgesic effects of nalbuphine. In the present study, we further evaluated the role of opioid receptors in the sex-specific effects on pain produced by nalbuphine by co-administering a dose of morphine low enough that it does not produce analgesia. Following extraction of bony impacted third molar teeth, nalbuphine (5 mg) was administered alone or in combination with either of two low doses of morphine (2 mg or 4 mg). Both doses of morphine reversed nalbuphine-induced anti-analgesia in males, but only the lower dose (2 mg) reached statistical significance. Neither dose affected nalbuphine-induced analgesia in females, and when administered alone in either males or females, morphine (2 mg) had no analgesic effect. Though not observed in females, the effect of morphine in males argues that, like naloxone, low dose morphine may act as an anti-analgesia opioid receptor antagonist. Perspective Previously we reported that the nalbuphine produces both analgesic and anti-analgesic effects, and that the opioid antagonist naloxone can enhance nalbuphine analgesia by selectively antagonizing the anti-analgesic effect. Here we show that morphine, given in a subanalgesic dose, reverses nalbuphine-induced anti-analgesia in males, perhaps by a similar mechanism. PMID:18201935

Internet-Based Survey Evaluating Use of Pain Medications and Attitudes of Radiation Oncology Patients Toward Pain Intervention

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simone, Charles B.; Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; Vapiwala, Neha

Purpose: Pain is a common symptom among cancer patients, yet many patients do not receive adequate pain management. Few data exist quantifying analgesic use by radiation oncology patients. This study evaluated the causes of pain in cancer patients and investigated the reasons patients fail to receive optimal analgesic therapy. Methods and Materials: An institutional review board-approved, Internet-based questionnaire assessing analgesic use and pain control was posted on the OncoLink (available at (www.oncolink.org)) Website. Between November 2005 and April 2006, 243 patients responded. They were predominantly women (73%), white (71%), and educated beyond high school (67%) and had breast (38%), lungmore » (6%), or ovarian (6%) cancer. This analysis evaluated the 106 patients (44%) who underwent radiotherapy. Results: Of the 106 patients, 58% reported pain from their cancer treatment, and 46% reported pain directly from their cancer. The pain was chronic in 51% and intermittent in 33%. Most (80%) did not use medication to manage their pain. Analgesic use was significantly less in patients with greater education levels (11% vs. 36%, p = 0.002), with a trend toward lower use by whites (16% vs. 32%, p 0.082) and women (17% vs. 29%, p = 0.178). The reasons for not taking analgesics included healthcare provider not recommending medication (87%), fear of addiction or dependence (79%), and inability to pay (79%). Participants experiencing pain, but not taking analgesics, pursued alternative therapies for relief. Conclusions: Many radiation oncology patients experience pain from their disease and cancer treatment. Most study participants did not use analgesics because of concerns of addiction, cost, or failure of the radiation oncologist to recommend medication. Healthcare providers should have open discussions with their patients regarding pain symptoms and treatment.« less

[Analgesic efficacy of magnetoledotherapy in patients with low back pain syndromes].

PubMed

Krukowska, Jolanta; Woldańska-Okońska, Marta; Jankowska, Katarzyna; Kwiecień-Czerwieniec, Ilona; Czernicki, Jan

2010-01-01

Low back pain syndromes most often occur due to overloading of the musculoskeletal system. The cause is a frequent, improper lifting of heavy objects, most commonly by those working physically, with repetitive movements of bending and straightening of the trunk (turning and bending with load). This problem affects not only adults but also children and adolescents. There is a growing interest in new forms of analgesic therapy nowadays, especially in those that exhibit synergistic therapeutic effects. The aim of this work is to evaluate the analgesic efficacy of magnetoledotherapy in patients with lumbar--sacrum spinal pain syndromes caused by joints degenerative changes. The examination was carried out in 66 patients of both sexes aged 30 to 76 (average 54.7 +/- 13.8) with low back pain syndrome caused by spinal degenerative changes. The patients were divided into three groups according to the applied analgesic therapy (magnetoledotherapy, magnetostimulation, TENS currents). Level of pain has been evaluated four times in all patients--before the start of therapy and after 5, 10 and 15 applications with the use of the modified Laitinen Questionnaire and Visual-Analoque Scale (VAS). Post therapy levels of pain in the studied patients decreased significantly. According to Laitinen questionnaire, the greatest improvement was observed in the group treated with magnetoledotherapy and TENS currents and the smallest improvement was observed in the group treated with magnetostimulation. 1. Magnetoledotherapy shows significant analgesic efficacy in patients with low back pain syndrome and shows no side effects. 2. Concurrent application of both the infrared radiation generated by LED's and magnetostimulation synergistically reinforces analgesic effect in patients with low back pain syndrome, especially in level of pain and frequency of its occurrence, which results in the increase of movement activity and decrease in administration of analgesics.

Involvement of peripheral TRPV1 channels in the analgesic effects of thalidomide.

PubMed

Song, Tieying; Wang, Liwen; Gu, Kunfeng; Yang, Yunliang; Yang, Lijun; Ma, Pengyu; Ma, Xiaojing; Zhao, Jianhui; Yan, Ruyv; Guan, Jiao; Wang, Chunping; Qi, Yan; Ya, Jian

2015-01-01

Thalidomide was introduced to the market in 1957 as a sedative and antiemetic agent, and returned to the market for the treatment of myelodysplastic syndrome and multiple myeloma. There are reports and studies of thalidomide as an analgesic or analgesic adjuvant in clinic. However, the underlying mechanism is quite elusive. Many studies suggest that the analgesic effect of thalidomide may be due to its immunomodulatory and anti-inflammatory properties as it suppresses the production of tumor necrosis factor α (TNF-α) selectively. However, it is not clear whether any other mechanisms are implicated in the pain relief. In this study, we demonstrated that the peripheral vanilloid receptor 1 (TRPV1) channel was also involved in the analgesic effect of thalidomide in different cell and animal models. During the activation by its agonist capsaicin, the cation inward influx through TRPV1 channels and the whole-cell current significantly decreased after TRPV1-overexpressed HEK293 cells or dorsal root ganglion (DRG) neurons were pre-treated with thalidomide for 20 minutes. And such attenuation in the TRPV1 activity was in a dose-dependent manner of thalidomide. In an acetic acid writhing test, pre-treatment of thalidomide decreased the writhing number in the wild type mice, while it did not happen in TRPV1 knockout mice, suggesting that the TRPV1 channel was involved in the pain relief by thalidomide. Taken together, the study showed that TRPV1 channels were involved in the analgesic effects of thalidomide. Such alteration in the action of TRPV1 channels by thalidomide may help understand how thalidomide takes analgesic effect in the body in addition to its selective inhibition of TNF-α production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analgesic and anti-inflammatory activities of Piper nigrum L.

PubMed

Tasleem, Farhana; Azhar, Iqbal; Ali, Syed Nawazish; Perveen, Shaista; Mahmood, Zafar Alam

2014-09-01

To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. The analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. Piperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min. It is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Over-the-counter analgesics: a toxicology perspective.

PubMed

Jones, Alison

2002-01-01

The decision to use any analgesic is a balance of benefit and risk. In the case of analgesics, it is important to balance the therapeutic benefit against both the risk in therapeutic use and the risk (and ease of treatment) in overdose. Paracetamol in therapeutic dose carries little risk of adverse events. Less than 0.1% of the estimated 30 million paracetamol users in the United Kingdom attend hospital with a paracetamol overdose each year, and approximately 200 people die, most of whom presented late or did not receive antidote, N-acetylcysteine, within 12 hours. Nonsteriodal anti-inflammatory drugs (NSAIDs) have greater adverse effects in therapeutic use than paracetamol but also have a lower incidence of severe features or death in overdose. There is no antidote available for NSAID poisoning. Aspirin carries both significant adverse effects in therapeutic dose and a substantial risk in overdose, for which there is no antidote. Its risk-benefit profile is probably the poorest of all analgesics currently available over-the-counter (OTC); this is reflected in current trends both in analgesic use and overdose figures. Although a number of options to reduce deaths from poisoning by OTC analgesics have been considered, few are practical, and all must take account of the public health benefits provided by these drugs. A perspective should be retained that the vast majority of the population in Australia, the United States, the United Kingdom, and Denmark derive therapeutic benefit from OTC analgesics and do not take them in overdose. The majority of those who do take overdoses come to little or no harm. Management of serious poisoning by paracetamol, aspirin, or NSAIDs remains a medical challenge.

Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study

PubMed Central

Saitz, Richard; Ganoczy, Dara; Ilgen, Mark A; Bohnert, Amy S B

2015-01-01

Objective To study the association between benzodiazepine prescribing patterns including dose, type, and dosing schedule and the risk of death from drug overdose among US veterans receiving opioid analgesics. Design Case-cohort study. Setting Veterans Health Administration (VHA), 2004-09. Participants US veterans, primarily male, who received opioid analgesics in 2004-09. All veterans who died from a drug overdose (n=2400) while receiving opioid analgesics and a random sample of veterans (n=420 386) who received VHA medical services and opioid analgesics. Main outcome measure Death from drug overdose, defined as any intentional, unintentional, or indeterminate death from poisoning caused by any drug, determined by information on cause of death from the National Death Index. Results During the study period 27% (n=112 069) of veterans who received opioid analgesics also received benzodiazepines. About half of the deaths from drug overdose (n=1185) occurred when veterans were concurrently prescribed benzodiazepines and opioids. Risk of death from drug overdose increased with history of benzodiazepine prescription: adjusted hazard ratios were 2.33 (95% confidence interval 2.05 to 2.64) for former prescriptions versus no prescription and 3.86 (3.49 to 4.26) for current prescriptions versus no prescription. Risk of death from drug overdose increased as daily benzodiazepine dose increased. Compared with clonazepam, temazepam was associated with a decreased risk of death from drug overdose (0.63, 0.48 to 0.82). Benzodiazepine dosing schedule was not associated with risk of death from drug overdose. Conclusions Among veterans receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of death from drug overdose in a dose-response fashion. PMID:26063215

Differences in prescription opioid analgesic availability: comparing minority and white pharmacies across Michigan.

PubMed

Green, Carmen R; Ndao-Brumblay, S Khady; West, Brady; Washington, Tamika

2005-10-01

Little is known about physical barriers to adequate pain treatment for minorities. This investigation explored sociodemographic determinants of pain medication availability in Michigan pharmacies. A cross-sectional survey-based study with census data and data provided by Michigan community retail pharmacists was designed. Sufficient opioid analgesic supplies was defined as stocking at least one long-acting, short-acting, and combination opioid analgesic. Pharmacies located in minority (or=70% white residents) zip code areas were randomly selected by using a 2-stage sampling selection process (response rate, 80%). For the 190 pharmacies surveyed, most were located in white areas (51.6%) and had sufficient supplies (84.1%). After accounting for zip code median age and stratifying by income, pharmacies in white areas (odds ratio, 13.36 high income vs 54.42 low income) and noncorporate pharmacies (odds ratio, 24.92 high income vs 3.61 low income) were more likely to have sufficient opioid analgesic supplies (P < .005). Racial differences in the odds of having a sufficient supply were significantly higher in low income areas when compared with high income areas. Having a pharmacy located near a hospital did not change the availability for opioid analgesics. Persons living in predominantly minority areas experienced significant barriers to accessing pain medication, with greater disparities in low income areas regardless of ethnic composition. Differences were also found on the basis of pharmacy type, suggesting variability in pharmacist's decision making. Michigan pharmacies in minority zip codes were 52 times less likely to carry sufficient opioid analgesics than pharmacies in white zip codes regardless of income. Lower income areas and corporate pharmacies were less likely to carry sufficient opioid analgesics. This study illustrates barriers to pain care and has public health implications.

Adherence to Analgesics for Cancer Pain: A Comparative Study of African Americans and Whites Using an Electronic Monitoring Device.

PubMed

Meghani, Salimah H; Thompson, Aleda M L; Chittams, Jesse; Bruner, Deborah W; Riegel, Barbara

2015-09-01

Despite well-documented disparities in cancer pain outcomes among African Americans, surprisingly little research exists on adherence to analgesia for cancer pain in this group. We compared analgesic adherence for cancer-related pain over a 3-month period between African Americans and whites using the Medication Event Monitoring System (MEMS). Patients (N = 207) were recruited from outpatient medical oncology clinics of an academic medical center in Philadelphia (≥18 years of age, diagnosed with solid tumors or multiple myeloma, with cancer-related pain, and at least 1 prescription of oral around-the-clock analgesic). African Americans reported significantly greater cancer pain (P < .001), were less likely than whites to have a prescription of long-acting opioids (P < .001), and were more likely to have a negative Pain Management Index (P < .001). There were considerable differences between African Americans and whites in the overall MEMS dose adherence, ie, percentage of the total number of prescribed doses that were taken (53% vs 74%, P < .001). On subanalysis, analgesic adherence rates for African Americans ranged from 34% (for weak opioids) to 63% (for long-acting opioids). Unique predictors of analgesic adherence varied by race; income levels, analgesic side effects, and fear of distracting providers predicted analgesic adherence for African Americans but not for whites. Perspective: Despite evidence of disparities in cancer pain outcomes among African Americans, surprisingly little research exists on African Americans' adherence to analgesia for cancer pain. This prospective study uses objective measures to compare adherence to prescribed pain medications between African American and white patients with cancer pain. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Review article: chronobiology: influence of circadian rhythms on the therapy of severe pain.

PubMed

Junker, Uwe; Wirz, Stefan

2010-06-01

Modern pain therapy widely follows the WHO (World Health Organization) guidelines using a three-step 'ladder' for pain relief. This escalating step scheme includes the administration in the order nonopioids, mild opioids and strong opioids, and adjuvants at any step. Analgesics should be given 'by the clock' rather than 'on demand'. However, the chronobiological parameters circadian pain rhythm, circadian efficacy of analgesics, and individual circadian need for analgesics are to be considered. The results of a multitude of studies in chronobiology are not consistent. Therefore, further studies with standardized protocols are needed that allow to assign more consistent rhythms to diseases, pain causes, and analgesic efficacy of opioids. In many cases, each patient perceives pain and its intensity individually during the time of day. By administration of analgesics over a constant or continuous dosage time fluctuations in pain perception and the outcomes of many studies in chronobiology are ignored that prove the influence of biological rhythms on the pharmacokinetic and pharmacodynamic aspects of analgesics. As different types of pain show different rhythms (highest pain intensities arising at different times of the day) analgesics should be dosed flexibly. It is also very important that drug therapy can be adjusted individually to the pain rhythm of the patient as well as to the type and cause of pain. In severe pain, therapy should be particularly careful. A flexible dosage depending on pain intensity and rapid dose adjustment are essentials of a modern pain therapy. Therefore, opioids that are flexible to use are better suited to treat the individual pain of the patient than rigid modified release oral or transdermal systems.

Expression of anaesthetic and analgesic drug target genes in excised breast tumour tissue: Association with clinical disease recurrence or metastasis.

PubMed

Connolly, C; Madden, S F; Buggy, D J; Gallagher, H C

2017-01-01

Retrospective analyses suggest anaesthetic-analgesics technique during cancer surgery may affect recurrence/metastasis. This could involve direct effects of anaesthetic-analgesic drugs on cancer cells. While μ-opioid receptor over-expression in lung tumours is associated with greater metastasis, other anaesthetic-analgesic receptor targets in cancer recurrence/metastasis remain unexplored. Therefore, we evaluated the association between genetic expression of anaesthetic-analgesic receptor targets and recurrence/metastasis, using a repository of breast cancer gene expression and matching clinical data. A list of 23 genes encoding for the most prominent anaesthetic-analgesic receptor targets was compiled. This was processed through BreastMark- an algorithm integrating gene expression data from ~17,000 samples and clinical data from >4,500 breast cancer samples. Gene expression data was dichotomized using disease-free survival (survival without recurrence) and distant disease-free survival (survival without metastasis) as end points. Hazard ratios were calculated by Cox-regression analysis. Enrichment for prognostic markers was determined by randomly choosing 23-member gene lists from all available genes, calculating how often >5 significant markers were observed and adjusting p-values for multiple testing. This was repeated 10,000 times and an empirical p-value calculated. Of 23 selected genes, 9 were significantly associated with altered rates of metastasis and 4 with recurrence on univariate analysis. Adjusting for multiple testing, 5 of these 9 genes remained significantly associated with metastasis, non with recurrence. This ratio of genes (5/23) was not significantly enriched for markers of metastasis (p = 0.07). Several anaesthetic-analgesic receptor genes were associated with metastatic spread in breast cancer. Overall there was no significant enrichment in prognostic markers of metastasis, although a trend was observed.

Local infiltration analgesia adds no clinical benefit in pain control to peripheral nerve blocks after total knee arthroplasty.

PubMed

Hinarejos, Pedro; Capurro, Bruno; Santiveri, Xavier; Ortiz, Pere; Leal, Joan; Pelfort, Xavier; Torres-Claramunt, Raul; Sánchez-Soler, Juan; Monllau, Joan C

2016-10-01

To evaluate the effect of the local infiltration of analgesics for pain after total knee arthroplasty in patients treated with femoral and sciatic peripheral nerve blocks. The secondary objective was to detect differences in analgesic consumption as well as blood loss after local infiltration of analgesics. Prospective randomized double-blinded study in patients who underwent a TKA for knee osteoarthritis under spinal anesthesia and treated with femoral and sciatic nerve blocks. This study compared 50 patients treated with local infiltration with ropivacaine, epinephrine, ketorolac and clonidine and 50 patients treated with a placebo with the same technique. The visual analogic score was registered postoperatively at 2, 6, 12, 24, 36, 48 and 72 h after surgery. Analgesic consumption was also registered. Both groups of patients were treated with the same surgical and rehabilitation protocols. A significant difference of one point was found in the visual analogic pain scores 12 h after surgery (0.6 ± 1.5 vs. 1.7 ± 2.3). There were no significant differences in the visual analogic pain scores evaluated at any other time between 2 and 72 h after surgery. No significant differences were found in the required doses of tramadol or morphine in the postoperative period. Postoperative hemoglobin and blood loss were also similar in both groups. Adding local infiltration of analgesics to peripheral nerve blocks after TKA surgery only provides minimal benefit for pain control. This benefit may be considered as non-clinically relevant. Moreover, the need for additional analgesics was the same in both groups. Therefore, the use of local infiltration of analgesics treatment in TKA surgery cannot be recommended if peripheral nerve blocks are used. I.

Increasing Use of Nonmedical Analgesics Among Younger Cohorts in the United States: A Birth Cohort Effect

PubMed Central

Miech, Richard; Bohnert, Amy; Heard, Kennon; Boardman, Jason

2017-01-01

Purpose Nonmedical use of prescription pain drugs (hereafter ‘analgesics’) has increased substantially in recent years. It is not known whether today’s youth are disproportionately driving this increase or, instead, the trend is a general one that has affected cohorts of all ages similarly. To address this question we present the first age-period-cohort analysis of nonmedical use of analgesics. Methods Data come from the National Survey on Drug Use and Health, a series of annual, nationally-representative, cross-sectional surveys of the U.S. civilian, non-institutionalized population. The analysis focuses on the years 1985 to 2009 and uses the recently developed ‘intrinsic estimator’ algorithm to disentangle age-period-cohort effects. Results Substantial increases in the prevalence of nonmedical analgesics use have occurred across all cohorts and ages in recent years, but this increase is significantly amplified among today’s adolescents. The odds of past-year, nonmedical analgesics use for today’s youngest cohort (born 1980–1994) are higher than would be expected on the basis of their age and broad, historical period influences that have increased use across people of all ages and cohorts. The independent influence of cohort on past-year, nonmedical analgesics use is about 40% higher for today’s youth cohort than any of the cohorts that came before them. This finding is present among men, women, non-Hispanic whites, non-Hispanic blacks, and Hispanics. Conclusions Although nonmedical use of analgesics is evident among all ages, cohorts, and periods, today’s younger cohorts warrant special attention for substance abuse policies and interventions targeted at reversing the increase in nonmedical analgesics use. PMID:23260832

Prescription patterns of analgesics in the last 3 months of life: a retrospective analysis of 10202 lung cancer patients

PubMed Central

Gao, W; Gulliford, M; Higginson, I J

2011-01-01

Background: To describe the prescription patterns of analgesics during the last 3 months of life in lung cancer and to determine the associated factors. Methods: Data on lung cancer patients (N=10 202) who died during 2000–2008 were extracted from the General Practice Research Database (GPRD). This database records prescriptions of patients received from UK general practices (GP), but not those from non-GP routes. Prescription prevalences were estimated. The associated factors were investigated using log-binomial regression. Results: The overall prescription prevalences were 50.4% (95% confidence interval (CI): 49.4–51.4%) for level 1 (e.g., paracetamol), 34.1% (95% CI: 33.2–35.0%) for level 2 (weak opioids), and 55.5 % (95% CI: 54.5–56.4%) for level 3 analgesics (strong opioids). Prescription prevalence of analgesics of all levels showed an increasing trend over the period 2000–2008 (annual increases range: 1.1–1.5%) but a decreasing trend with age (average decrease per group range: −5.8 to −1.8%). Patients in the older age groups were less likely to be prescribed level 3 analgesics than those in the younger age groups (PR‘90+' vs ‘<50'=0.55 (95% CI: 0.45–0.67); PR‘80−89' vs ‘<50'=0.73 (95% CI: 0.66–0.79); PR‘70−79' vs ‘<50'=0.84 (95% CI: 0.77–0.90)). Conclusion: Analgesics have been increasingly prescribed in lung cancer. However, analgesics, especially at level 3, were relatively under-prescribed to people older than 70 years, warranting further investigation. PMID:21540860

From pulses to pain relief: an update on the mechanisms of rTMS-induced analgesic effects.

PubMed

Moisset, X; de Andrade, D C; Bouhassira, D

2016-05-01

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action. Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques. Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections. rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action. © 2015 European Pain Federation - EFIC®

Synthesis and analgesic activity of some quinazoline analogs of anpirtoline.

PubMed

Rádl, S; Hezky, P; Proska, J; Krejcí, I

2000-11-01

New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, quinazoline, 7-chloroquinoline, and 7-chloroquinazoline nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 4e-4g, and 4l are at least comparable to that of clinically used drugs flupirtine and tramadol under the same conditions.

Poisoning deaths involving opioid analgesics - New York State, 2003-2012.

PubMed

Sharp, Mark J; Melnik, Thomas A

2015-04-17

Deaths involving opioid analgesics have increased dramatically in the United States. Approximately 4,000 such deaths were documented in 1999, increasing to 16,235 in 2013, reflecting a nearly quadrupled death rate from 1.4 to 5.1 deaths per 100,000. To investigate this increase in New York state, trends in poisoning deaths involving opioid analgesics from 2003 to 2012 were examined. Data sources used were New York state vital statistics multiple-cause-of-death data, consisting of data from both the New York City (NYC)* and non-NYC reporting jurisdictions, as well as statewide Medicaid enrollment data. Deaths involving opioid analgesics increased both in number and as a percentage of all drug poisoning deaths, and rates were highest among men, whites, persons aged 45-64 years, persons residing outside of NYC, and Medicaid enrollees. The analysis found that, in 2012, 70.7% of deaths involving opioid analgesics also involved at least one other drug, most frequently a benzodiazepine. These results underscore the potential to mitigate the trend of increasing opioid analgesic-related mortality through initiatives such as New York state's Internet System for Tracking Over-Prescribing (I-STOP) law,† which took effect on August 27, 2013. Provisions under I-STOP include the requirements that providers consult the Prescription Monitoring Program (PMP) Registry when writing prescriptions for controlled substances, and that they use electronic prescribing.

Retrospective case series analysis of characteristics and trends in unintentional pharmaceutical drug poisoning by methadone, opioid analgesics, antidepressants and benzodiazepines in Clark County, NV 2009-13.

PubMed

Bruno, Tamara; Pharr, Jennifer R

2017-06-01

Poisoning has become the leading cause of injury death in the USA-with opioid analgesic involved in more fatal poisonings than any other drug, including cocaine and heroin. The epidemic of prescription drug poisonings is a public health concern. This study aimed to define potential high-risk groups for unintentional prescription drug poisoning by methadone, opioid analgesics, antidepressants or benzodiazepines. A hospital-based retrospective case series analysis of admissions related to prescription drug poisonings associated with methadone, opioid analgesics, antidepressants or benzodiazepines for hospitals in Clark County, Nevada between 2009 and 2013 was employed. There were 7414 admissions with a primary diagnosis of an unintentional poisoning due to methadone, opioid analgesics, antidepressants or benzodiazepines. Women had the highest rate of admissions particularly in the 45-54 age group. Higher rates of admissions were also found among non-Hispanic whites, single and uninsured populations. There were concerning increases in admissions among 65+ and Native American/Alaskan Native subgroups in 2013. Benzodiazepines and opioid analgesics were the most prevalent drug categories for prescription drug poisoning admissions. Public health professionals can utilize hospital data to identify populations at risk and in need of targeted interventions. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antioxidant and analgesic activities of turpentine of Pinus nigra Arn. subsp. pallsiana (Lamb.) Holmboe.

PubMed

Gülçin, Ilhami; Büyükokuroglu, M Emin; Oktay, Münir; Küfrevioglu, O Irfan

2003-05-01

The aim of this study is to examine possible antioxidant and analgesic activities of turpentine exudes from Pinus nigra Arn. subsp. pallsiana (Lamb.) Holmboe (TPN). Total antioxidant activity, reducing power, superoxide anion radical scavenging, free radical scavenging, metal chelating, and hydrogen peroxide scavenging activities were studied. The total antioxidant activity increased with the increasing amount of extracts (100, 300, and 500 microg) added to linoleic acid emulsion. All of the doses of TPN showed higher antioxidant activity than alpha-tocopherol. The samples showed 49, 70, and 91% inhibition on peroxidation of linoleic acid emulsion, respectively. On the other hand, the 300 microg of alpha-tocopherol showed 40% inhibition on peroxidation of linoleic acid emulsion. There is correlation between antioxidant activity and the reducing power, superoxide anion radical scavenging, free radical scavenging, metal chelating, and hydrogen peroxide scavenging activities. Like antioxidant activity, the reducing power, superoxide anion radical scavenging, free radical scavenging, metal chelating, and hydrogen peroxide scavenging activities of TPN depending on concentration and increasing with increased concentration of TPN. These properties may be the major reasons for the inhibition of lipid peroxidation. The results obtained in the present study indicate that the TPN has a potential source of natural antioxidant. In addition, analgesic effect of TPN was investigated in present study and TPN had strong analgesic effect. The analgesic effect of TPN compared with metamizol as a standard analgesic compound.

Nonprescription analgesics and their use in solid-organ transplantation: a review.

PubMed

Gabardi, Steven; Luu, Linh

2004-09-01

To review the pharmacology, adverse events, drug interactions, and use of the nonprescription analgesics in solid-organ transplant recipients. Studies evaluating nonprescription analgesics in solid-organ transplantation were considered for evaluation. English-language studies were selected for inclusion. Nonprescription analgesics (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen, ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased over-the-counter agents in the United States. These agents, although generally considered safe, have been associated with a number of toxicities. The salicylates and nonsteroidal anti-inflammatory drugs have been associated with gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and breathing difficulties. Acetaminophen has been shown to induce hematologic changes and liver and renal dysfunction. A closer look at the nonprescription analgesics reveals their potential for harm when used by solid-organ transplant recipients. In this patient population, the salicylates and nonsteroidal anti-inflammatory drugs should generally be avoided if possible, because of their potential toxicities, especially renal dysfunction. Low-dose aspirin, for the prevention of cardiovascular and cardiocerebral events, appears to be safe, but patients must still be followed closely. Acetaminophen is generally considered the nonprescription analgesic and antipyretic of choice in transplant recipients because of its favorable toxicity profile. However, it is imperative that patients and transplant practitioners are aware that this agent is not without toxicities and proper monitoring is advised.

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

PubMed Central

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

Evaluation of Analgesic Activity of the Methanol Extract from the Galls of Quercus infectoria (Olivier) in Rats

PubMed Central

Ali, Noraisah Akbar

2014-01-01

The present study aims to investigate the analgesic activity of the methanol extract of the galls of Quercus infectoria in rats using hot plate and tail-flick methods. The extract was administered intraperitoneally at a dose of 20 mg/kg while morphine sulfate and sodium salicylate (10 mg/kg) served as standards. The methanol extract exhibited significant analgesic activity in the tail-flick model (P < 0.05) by increasing the reaction time of the rats to 8.0 sec at 30 min after treatment in comparison to control (4.4 sec). Morphine sulfate produced a reaction time of 11.9 sec in the same test. At the peak of activity (30 min), the extract produced maximum possible analgesia (MPA) of 34.2%, whilst morphine sulfate achieved a peak MPA of 70.9%. No analgesic effects have been observed using sodium salicylate in the tail-flick model. In the same model, the extract and sodium salicylate demonstrated comparable reaction times. Tail-flick is a better method to evaluate analgesic activity as no significant results were observed for all treatments using hot plate with the exception of morphine sulfate, which showed significant results only at 45 and 60 min after treatment. In conclusion, the methanol extract of the galls of Quercus infectoria displayed analgesic activity. PMID:25254062

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone

PubMed Central

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J.; Lesport, Pierre; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-01-01

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT2 receptors (angiotensin II type 2 receptors; AT2R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT2R, with this action being not affected by known ligands of AT2R. This result points towards novel AT2R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics. PMID:28718822

Analgesic, antibacterial and central nervous system depressant activities of Albizia procera leaves.

PubMed

Khatoon, Mst Mahfuza; Khatun, Mst Hajera; Islam, Md Ekramul; Parvin, Mst Shahnaj

2014-04-01

To ascertain analgesic, antibacterial and central nervous system (CNS) depressant activities of ethyl acetate, dichloromethane and carbon tetrachloride fractions of methanol extract of Albizia procera (A. procera) leaves. Leaves extracts of A. procera were tested for analgesic activity by acetic acid induced and formalin test method in mice. The in vitro antibacterial activity was performed by agar well diffusion method. CNS depressant activity was evaluated by hole cross and open field tests. All the extracts at 200 mg/kg exhibited significant (P<0.01) analgesic activity in acetic acid induced and formalin tests method in mice. Analgesic activity of the ethyl acetate fraction was almost same like as standard drug indomethacin in acetic acid induced method. The CNS depressant activity of the extracts at 500 mg/kg was comparable to the positive control diazepam as determined by hole cross and open field test method. The extracts exhibited moderate antimicrobial activity against all the tested microorganisms (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Esherichia coli, Shigella soneii, Shigella boydii) at concentration of 0.8 mg/disc. The measured diameter of zone of inhibition for the extracts was within the range of 7 to 12 mm which was less than the standard kanamycin (16-24 mm). It is concluded that all the extracts possess potential analgesic and CNS depressants activity. This study also showed that different fractions of methanol extract could be potential sources of new antimicrobial agents.

Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs

PubMed Central

Jaramillo-Juárez, Fernando

2018-01-01

Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites. Cumulative or overdoses of OTC analgesic drugs can induce acute liver failure (ALF) either directly or indirectly after their biotransformation. ALF is the result of massive death of hepatocytes induced by oxidative stress. There is an increased interest in the use of natural dietary products as nutritional supplements and/or medications to prevent or cure many diseases. The therapeutic activity of natural products may be associated with their antioxidant capacity, although additional mechanisms may also play a role (e.g., anti-inflammatory actions). Dietary antioxidants such as flavonoids, betalains and carotenoids play a preventive role against OTC analgesics-induced ALF. In this review, we will summarize the pathobiology of OTC analgesic-induced ALF and the use of natural pigments in its prevention and therapy. PMID:29364842

Analgesic effects of the COX-2 inhibitor parecoxib on surgical pain through suppression of spinal ERK signaling.

PubMed

Guo, Ya-Jing; Shi, Xu-Dan; Fu, DI; Yang, Yong; Wang, Ya-Ping; Dai, Ru-Ping

2013-07-01

Cyclooxygenase (COX)-2 inhibitors are widely used for postoperative pain control in clinical practice. However, it is unknown whether spinal sensitization is involved in the analgesic effects of COX-2 inhibitors on surgical pain. Extracellular signal-regulated kinase (ERK) in the spinal cord is implicated in various types of pain, including surgical pain. The present study investigated the role of spinal ERK signaling in the analgesic effect of the COX-2 inhibitor parecoxib on surgical pain. Surgical pain was produced in rats by surgical incision of the hind paw. Phosphorylated (p)-ERK1/2 expression was determined by immunohistochemistry. Pain hypersensitivity was evaluated by measuring the paw withdrawal threshold using the von Frey test. The selective COX-2 inhibitor parecoxib was delivered 20 min before or 20 min after the incision by intraperitoneal injection. Pretreatment with parecoxib markedly attenuated the pain hypersensitivity induced by incision. However, post-treatment with parecoxib produced minimal analgesic effects. Parecoxib inhibited the increase in spinal p-ERK expression following surgical incision. The present study thus suggests that the COX-2 inhibitor parecoxib exerts its analgesic effect on surgical pain through the inhibition of neuronal ERK activation in the spinal cord. COX-2 inhibitor delivery prior to surgery has more potent analgesic effects, suggesting the advantage of preventive analgesia for post-operative pain control.

In vivo analgesic activity, toxicity and phytochemical screening of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine.

PubMed

Alvarenga, Felipe Queiroz; Mota, Bárbara C F; Leite, Marcel N; Fonseca, Jaciara M S; Oliveira, Dario A; Royo, Vanessa de Andrade; e Silva, Márcio L A; Esperandim, Viviane; Borges, Alexandre; Laurentiz, Rosangela S

2013-10-28

Psidium cattleianum Sabine is extensively used in Brazilian traditional medicine to treat several diseases including painful disorders. Aim of the study to investigate the toxicity and the possible analgesic activities of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine (ELPCS), to support its use in folk medicine. To screen the major phytochemical constituents of this extract and evaluate their antioxidant activity. ELPCS was assessed for its antioxidant activity using the DPPH model. Its analgesic activity was examined using mouse models of acetic acid-induced writhing and hot plate paw licking models. The major phytochemical constituents of the extract were screened; their toxicity on LLC-MK2 mammalian cells was evaluated. ELPCS exhibited significant peripheral analgesic activity at doses of 60, 80, 100, 200 and 400mg/kg in mice, but it did not display central analgesic activity and not was toxic to LLC-MK2 cell (LD50>400 µg/mL). The extract exhibited free radical scavenging activity as evidenced by IC50 values (15.9 µg/mL) obtained by the DPPH method. Phytochemical screening detected flavonoids, saponins, cardiac glycosides, anthraquinones, and tannins. The results of the experimental studies proved the analgesic activity of ELPCS and supported the traditional use of this plant. © 2013 Elsevier Ireland Ltd. All rights reserved.

Synthetic neurotensin analogues are nontoxic analgesics for the rabbit cornea.

PubMed

Kim, Charles; Barbut, Denise; Heinemann, Murk H; Pasternak, Gavril; Rosenblatt, Mark I

2014-05-13

To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion. Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology. NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers. Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Analgesic use in pregnancy and male reproductive development

PubMed Central

Hurtado-Gonzalez, Pablo; Mitchell, Rod T.

2017-01-01

Purpose of review Male reproductive disorders are common and increasing in incidence in many countries. Environmental factors (including pharmaceuticals) have been implicated in the development of these disorders. This review aims to summarise the emerging epidemiological and experimental evidence for a potential role of in-utero exposure to analgesics in the development of male reproductive disorders. Recent findings A number of epidemiological studies have demonstrated an association between in-utero exposure to analgesics and the development of cryptorchidism, although these findings are not consistent across all studies. Where present, these associations primarily relate to exposure during the second trimester of pregnancy. In-vivo and in-vitro experimental studies have demonstrated variable effects of exposure to analgesics on Leydig cell function in the fetal testis of rodents, particularly in terms of testosterone production. These effects frequently involve exposures that are in excess of those to which humans are exposed. Investigation of the effects of analgesics on human fetal testis have also demonstrated effects on Leydig cell function. Variation in species, model system, dosage and timing of exposure is likely to contribute to differences in the findings between studies. Summary There is increasing evidence for analgesic effects on the developing testis that have the potential to impair reproductive function. However, the importance of these findings in relation to human-relevant exposures and the risk of male reproductive disorders remains unclear. PMID:28277341

Risks associated with borrowing and sharing of prescription analgesics among patients observed by pain management physicians in Croatia: a qualitative study.

PubMed

Markotic, Filipa; Puljak, Livia

2016-01-01

Understanding and improving patient safety is a key issue in medicine. One of the potential threats to patient safety is the sharing of medication among patients, which is a form of self-medication. This study analyzed experiences and attitudes of pain management physicians (PMPs) about sharing prescription analgesics among patients. This qualitative study was conducted by semi-structured interviews among PMPs employed in Croatian pain clinics. The study involved two researchers and 15 PMPs. Among PMPs, 80% have seen patients who share their prescription analgesics with other patients for whom prescription is not intended. Most PMPs consider prescription analgesics sharing a risky and negative behavior. Some of them, however, found certain positive aspects associated to it, such as being a benevolent behavior, helping patients to get medications when they need them, and helping them cope with pain. The majority of physicians specialized in pain management encountered patients sharing prescription analgesics. Most of them considered this as risky behavior with a number of potential consequences. It has been noted that this problem is neglected and that physicians should inquire about medication sharing. Direct-to-consumers advertising was perceived as a factor contributing to such behavior. Patient education and more involvement of physicians in identifying this behavior were cited as potential remedies for preventing sharing of prescription analgesics.

Synthesis of conolidine, a potent non-opioid analgesic for tonic and persistent pain

NASA Astrophysics Data System (ADS)

Tarselli, Michael A.; Raehal, Kirsten M.; Brasher, Alex K.; Streicher, John M.; Groer, Chad E.; Cameron, Michael D.; Bohn, Laura M.; Micalizio, Glenn C.

2011-06-01

Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (-)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain.

Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-ibuprofen in experimental animals.

PubMed

Suthakaran, Chidambarann; Kayalvizhi, Muniyagounder K; Nithya, Karnam; Raja, Thozhudalangudy Ar

2017-01-01

Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.

Descriptive study of perioperative analgesic medications associated with general anesthesia for dental rehabilitation of children.

PubMed

Carter, Laura; Wilson, Stephen; Tumer, Erwin G

2010-01-01

The purpose of this retrospective chart review was to document sedation and analgesic medications administered preoperotively, intraoperatively, and during postanesthesia care for children undergoing dental rehabilitation using general anesthesia (GA). Patient gender, age, procedure type performed, and ASA status were recorded from the medical charts of children undergoing GA for dental rehabilitation. The sedative and analgesic drugs administered pre-, intra-, and postoperatively were recorded. Statistical analysis included descriptive statistics and cross-tabulation. A sample of 115 patients with a mean age of 64 (+/-30) months was studied; 47% were females, and 71% were healthy. Over 80% of the patients were administered medications primarily during pre- and intraoperative phases, with fewer than 25% receiving medications postoperatively. Morphine and fentanyl were the most frequently administered agents intraoperatively. The procedure type, gender, and health status were not statistically associated with the number of agents administered. Younger patients, however, were statistically more likely to receive additional analgesic medications. Our study suggests that a minority of patients have postoperative discomfort in the postanesthesia care unit; mild to moderate analgesics were administered during intraoperative phases of dental rehabilitation.

Letter: The clinical course of patients with analgesic nephropathy.

PubMed Central

Gault, M. H.

1975-01-01

Thirty-four patients with analgesic nephropathy were followed at intervals of 1 to 3 months with measurements of creatinine clearance and serum concentration of acetylsalicylic acid (ASA) for a total of 105 patient-years. Diagnostic criteria included total consumption of at least 2 kg of phenacetin and 3 kg of ASA, compatible tissue abnormality on biopsy and evidence of papillary necrosis on an intravenous pyelogram. Nephropathy was induced by the same compound analgesic containing ASA, pehnacetin, caffeine and codeine (APC&C) in 30. Phenacetin was removed from this preparation in 1970 and replaced by an approximately equal amount of ASA (ACC). Creatinine clearance remained unchanged or improved in 11 of 15 patients who stopped taking analgesics containing phenacetin or ASA and in 10 of 11 of those who continued to take the ACC preparation. In contrast, renal function deteriorated in seven of eight patients who continued to abuse APC&C analgesics. The results suggest that phenacetin is necessary for the major nephrotoxic effect of this APC&C combination, but that ASA is not absolved of some nephrotoxicity. PMID:1139519

Ketoprofen is more effective than diclofenac after oral surgery when used as a preemptive analgesic: a pilot study.

PubMed

Velásquez, Grace Carolaine Esquivel; Santa Cruz, Luis A German; Espinoza, Mario Alberto Isiordia

2014-01-01

To evaluate the preemptive analgesia of ketoprofen in comparison with diclofenac after mandibular third molar surgery. This study was a double-blind, randomized clinical trial. Forty patients were randomized into two treatment groups (each with 20 patients) by using a series of random numbers: group A received ketoprofen 100 mg and group B received diclofenac 75 mg, all intramuscularly. Surgery was done 30 minutes after analgesic treatments. The durations of analgesia, pain intensity, analgesic consumption, and side effects were evaluated. The statistical analysis was done using the chi-square, Student t, Mann-Whitney U, and Log-Rank tests. The duration of analgesia was longer in the ketoprofen group when compared with the diclofenac group. The number of patients taking the first rescue analgesic at 6 hours was lower in the ketoprofen group in comparison with the diclofenac group. Patients who received ketoprofen had lower pain intensity compared with patients who received diclofenac. Intramuscular ketoprofen 100 mg is more effective than intramuscular diclofenac 75 mg after mandibular third molar extraction when used as a preemptive analgesic.

Anti-inflammatory, analgesic and antipyretic effects of Lepidagathis anobrya Nees (Acanthaceae).

PubMed

Richard, Sawadogo Wamtinga; Marius, Lompo; Noya, Somé; Innocent Pierre, Guissou; Germaine, Nacoulma-Ouedraogo Odile

2011-01-01

This study investigated the general acute, anti-inflammatory, analgesic and antipyretic effects of methanol extract of Lepidagathis anobrya Nees (Acanthaceae). Carrageenan-induced rat paw edema and croton oil-induced ear edema in rats were used for the evaluation of general acute anti-inflammatory effects. Acetic acid-induced writhing response and yeast-induced hyperpyrexia in mice were used to evaluate the analgesic and antipyretic activities respectively. The extract at doses of 10, 25, 50 and 100 mgkg(-1) for carrageenan test and doses of 0.5 mg/ear for croton oil test induced a significant reduction (p < 0.001) of paw and ear edemas in rats. In the analgesic and antipyretic tests, the extract has shown a significant inhibition of writhes and hyperpyrexia with all the doses used when compared to the untreated control group. These results clearly show the anti-inflammatory, analgesic and antipyretic effects of the methanol extract of Lepidagathis anobrya and give the scientific basis for its traditional use. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.

Use of analgesic and sedative drugs in the NICU: integrating clinical trials and laboratory data.

PubMed

Durrmeyer, Xavier; Vutskits, Laszlo; Anand, Kanwaljeet J S; Rimensberger, Peter C

2010-02-01

Recent advances in neonatal intensive care include and are partly attributable to growing attention for comfort and pain control in the term and preterm infant requiring intensive care.Limitation of painful procedures is certainly possible, but most critically ill infants require unavoidable painful or stressful procedures such as intubation, mechanical ventilation, or catheterization.Many analgesics (opioids and nonsteroidal anti-inflammatory drugs)and sedatives (benzodiazepines and other anesthetic agents) are available but their use varies considerably among units. This review summarizes current experimental knowledge on the effects of sedative and analgesic drugs on brain development and reviews clinical evidence that speaks for or against the use of common analgesic and sedative drugs in the NICU but avoids any discussion of anesthesia during surgery. Risk/benefit ratios of intermittent boluses or continuous infusions for the commonly used sedative and analgesic agents are discussed in the light of clinical and experimental studies. The limitations of extrapolating experimental results from animals to humans must be considered while making practical recommendations based on the currently available evidence.

Pain Management: Part 1: Managing Acute and Postoperative Dental Pain

PubMed Central

Becker, Daniel E.

2010-01-01

Abstract Safe and effective management of acute dental pain can be accomplished with nonopioid and opioid analgesics. To formulate regimens properly, it is essential to appreciate basic pharmacological principles and appropriate dosage strategies for each of the available analgesic classes. This article will review the basic pharmacology of analgesic drug classes, including their relative efficacy for dental pain, and will suggest appropriate regimens based on pain intensity. Management of chronic pain will be addressed in the second part of this series. PMID:20553137

[Do analgesic sweet solutions in neonates influence glycemia? A literature review].

PubMed

Walter-Nicolet, E; Chary-Tardy, A C; Tourniaire, B

2017-12-01

Sweet solutions are one of the most widely used nonpharmacologic analgesics used for newborns. They alleviate mild to moderate pain induced by painful procedures. They are used daily in neonatal intensive care units before a venepuncture or a heel stick, especially for a blood-sugar measurement. It is agreed that analgesic sweet solutions do not modify glycemia results. This nevertheless remains a recurrent question that the present review attempts to answer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Efficacy and Safety of Oral and Transdermal Opioid Analgesics for Musculoskeletal Pain in Older Adults: A Systematic Review of Randomized, Placebo-Controlled Trials.

PubMed

Megale, Rodrigo Z; Deveza, Leticia A; Blyth, Fiona M; Naganathan, Vasi; Ferreira, Paulo H; McLachlan, Andrew J; Ferreira, Manuela L

2018-05-01

This systematic review with meta-analysis was performed to evaluate the efficacy and safety of using opioid analgesics in older adults with musculoskeletal pain. We searched Cochrane Library, MEDLINE, EMBASE, Web of Science, AMED, CINAHL, and LILACS for randomized controlled trials with mean population age of 60 years or older, comparing the efficacy and safety of opioid analgesics with placebo for musculoskeletal pain conditions. Reviewers extracted data, assessed risk of bias, and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Random effects models were used to calculate standardized mean differences (when different scales were used across trials), mean differences and odds ratios with respective 95% confidence intervals (CIs). Meta-regressions were carried out to assess the influence of opioid analgesic daily dose and treatment duration on our main outcomes. We included 23 randomized placebo-controlled trials in the meta-analysis. Opioid analgesics had a small effect on decreasing pain intensity (standardized mean difference = -.27; 95% CI = -.33 to -.20) and improving function (standardized mean difference = -.27, 95% CI = -.36 to -.18), which was not associated with daily dose or treatment duration. The odds of adverse events were 3 times higher (odds ratio = 2.94; 95% CI = 2.33-3.72) and the odds of treatment discontinuation due to adverse events 4 times higher (odds ratio = 4.04; 95% CI = 3.10-5.25) in patients treated with opioid analgesics. The results show that in older adults suffering from musculoskeletal pain, using opioid analgesics had only a small effect on pain and function at the cost of a higher odds of adverse events and treatment discontinuation. For this specific population, the opioid-related risks may outweigh the benefits. The systematic review shows that, in older adults suffering from musculoskeletal conditions, opioid analgesics have only a small effect on pain and disability. Conversely, this population is at higher risk of adverse events. The results may reflect age-related physiological changes in pain processing, pharmacokinetics, and pharmacodynamics. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of once-daily, extended-release hydrocodone in individuals previously receiving hydrocodone/acetaminophen combination therapy for chronic pain.

PubMed

Bartoli, Adrian; Michna, Edward; He, Ellie; Wen, Warren

2015-01-01

Hydrocodone/acetaminophen combination analgesics are frequently prescribed for chronic pain management; however, acetaminophen presents potential hepatotoxicity to patients and thus dose limitations. These opioid medications are also widely abused. Once-daily, single-entity hydrocodone (Hysingla™ ER tablets [HYD]) is a novel formulation with abuse-deterrent properties for the management of chronic pain and represents a suitable option for those patients receiving analgesics containing the same opioid analgesic, hydrocodone. This post-hoc analysis evaluated the efficacy and safety of HYD in patients whose primary pre-study analgesic was hydrocodone/acetaminophen analgesics (23-31% of the study populations). Data were analyzed from two Phase III trials, a 12-week randomized, placebo-controlled trial (RCT) and an open-label, 52-week trial. In both trials, a dose-titration period with HYD was followed by respective periods of fixed-dose double-blind (randomized controlled trial [RCT]) or open-label, flexible-dose maintenance treatment. Pain intensity was assessed using a numerical rating scale (0-10, 0 = no pain). For the RCT, primary and sensitivity analyses of pain scores used different approaches to handle missing data. Safety data for both studies were summarized. In the RCT, the mean baseline pain score was 7.3. Pain relief was greater with HYD than placebo during double-blind treatment. In the open-label, flexible-dose trial, the majority of patients were maintained on their titrated dose. Mean baseline pain score was 6.3, about 57% of patients completed the 1-year maintenance period, and mean pain scores were between 3.6 and 4.1 during the maintenance period. Use of supplemental pain medication decreased or was maintained during the maintenance treatment with HYD. Adverse events in both trials were typical of those associated with opioid analgesics. In patients whose primary pretrial analgesic was hydrocodone/acetaminophen combination tablets, single-entity HYD was effective in reducing pain intensity and in maintaining analgesia over time without need for continued dose increase. HYD's safety and tolerability profiles were similar to other opioid analgesics.

Salient concerns in using analgesia for cancer pain among outpatients: A cluster analysis study.

PubMed

Meghani, Salimah H; Knafl, George J

2017-02-10

To identify unique clusters of patients based on their concerns in using analgesia for cancer pain and predictors of the cluster membership. This was a 3-mo prospective observational study ( n = 207). Patients were included if they were adults (≥ 18 years), diagnosed with solid tumors or multiple myelomas, and had at least one prescription of around-the-clock pain medication for cancer or cancer-treatment-related pain. Patients were recruited from two outpatient medical oncology clinics within a large health system in Philadelphia. A choice-based conjoint (CBC) analysis experiment was used to elicit analgesic treatment preferences (utilities). Patients employed trade-offs based on five analgesic attributes (percent relief from analgesics, type of analgesic, type of side-effects, severity of side-effects, out of pocket cost). Patients were clustered based on CBC utilities using novel adaptive statistical methods. Multiple logistic regression was used to identify predictors of cluster membership. The analyses found 4 unique clusters: Most patients made trade-offs based on the expectation of pain relief (cluster 1, 41%). For a subset, the main underlying concern was type of analgesic prescribed, i.e ., opioid vs non-opioid (cluster 2, 11%) and type of analgesic side effects (cluster 4, 21%), respectively. About one in four made trade-offs based on multiple concerns simultaneously including pain relief, type of side effects, and severity of side effects (cluster 3, 28%). In multivariable analysis, to identify predictors of cluster membership, clinical and socioeconomic factors (education, health literacy, income, social support) rather than analgesic attitudes and beliefs were found important; only the belief, i.e ., pain medications can mask changes in health or keep you from knowing what is going on in your body was found significant in predicting two of the four clusters [cluster 1 (-); cluster 4 (+)]. Most patients appear to be driven by a single salient concern in using analgesia for cancer pain. Addressing these concerns, perhaps through real time clinical assessments, may improve patients' analgesic adherence patterns and cancer pain outcomes.

Antiinflammatory, analgesic and hypoglycemic effects of Mangifera indica Linn. (Anacardiaceae) stem-bark aqueous extract.

PubMed

Ojewole, J A O

2005-10-01

Previous studies in our laboratories and elsewhere have shown that some members of Anacardiaceae family possess antiinflammatory, analgesic and hypoglycemic effects in man and mammalian experimental animals. The present study was, therefore, undertaken to examine the antiinflammatory, analgesic and antidiabetic properties of the stem-bark aqueous extract of Mangifera indica Linn., M. indica a member of the Anacardiaceae family, in rats and mice. The stem-bark powder of M. indica was Soxhlet extracted with distilled water and used. The analgesic effect of the plant's extract was evaluated by the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and antidiabetic effects of the stem-bark extract were investigated in rats, using fresh egg albumin-induced paw edema, and streptozotocin (STZ)-induced diabetes mellitus, respectively. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg i.p.), and chlorpropamide (250 mg/kg p.o.) were used respectively as reference analgesic, antiinflammatory, and hypoglycemic agents for comparison. M. indica stem-bark aqueous extract (MIE, 50-800 mg/kg i.p.) produced dose-dependent and significant (p<0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice. MIE (50-800 mg/kg i.p.) also significantly (p<0.05-0.001) inhibited fresh egg albumin-induced paw edema, and caused significant (p<0.05-0.001) hypoglycemic effects in rats. It is suggested that the analgesic effects of MIE (50-800 mg/kg i.p.) may be peripherally and centrally mediated. The different chemical constituents of the plant, especially the polyphenolics, flavonoids, triterpenoids, mangiferin, and other chemical compounds present in the plant may be involved in the observed antiinflammatory, analgesic, and hypoglycemic effects of the plant's extract. However, the results of this experimental animal study lend pharmacological credence to the suggested folkloric uses of the plant in the management and control of painful, arthritic and other inflammatory conditions, as well as in the management of adult-onset type 2 diabetes mellitus in some rural African communities. (c) 2005 Prous Science. All rights reserved.

(-)-Norpseudoephedrine, a metabolite of cathinone with amphetamine-like stimulus properties, enhances the analgesic and rate decreasing effects of morphine, but inhibits its discriminative properties.

PubMed

Nencini, P; Fraioli, S; Pascucci, T; Nucerito, C V

1998-04-01

Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances the analgesic effects of morphine (MOR). Thus, it is possible that full psychomotor stimulant potency is not required to increase the analgesic action of opiates. The validity of this assumption is here tested by studying the ability of (-)-norpseudoephedrine (NPE), an enantiomer of phenylpropanolamine and a metabolite of cathinone, to influence both the analgesic effects of MOR and its discriminative stimulus properties. In mice NPE (5.6-10.0-17.0 mg/kg i.p.) did not prolong the latency to lick or to remove paws from a plate warmed at 54 degrees C. However, it significantly potentiated the analgesic effect of 3.2 mg/kg of MOR. These results were replicated in rats by use of the formalin test, which measures the numbers of hind paw flinches produced by injecting 50 microl of formalin into the dorsal surface of the paw. The higher dose of NPE (17 mg/kg) increased the effect of sub-analgesic doses of MOR (0.56 and 1.0 mg/kg). In rats trained to discriminate between 0.5 mg/kg of amphetamine and solvent in a two-lever operant behavior reinforced by water access. NPE induced a dose-dependent increment of drug lever responding from 0% at 1.0 mg/kg to 100% at 32.0 mg/kg. In contrast, NPE did not generalize for the MOR cue up to the dose of 56.0 mg/kg, which produced a substantial reduction of the response rate. However, when given in combination, NPE attenuated the discriminative effects of MOR and potentiated its inhibitory action on the response rate. These results exclude a direct action of NPE on the mu opiate system. In conclusion, NPE preserves amphetamine-like properties and these properties are probably responsible for the interaction of the drug with the analgesic and discriminative effects of MOR. Therefore, this study contradicts the assumption that the analgesic effects of MOR can be enhanced by a sympathomimetic drug that lacks significant psychostimulant actions.

Adult emergency department patients with sickle cell pain crisis: a learning collaborative model to improve analgesic management.

PubMed

Tanabe, Paula; Artz, Nicole; Mark Courtney, D; Martinovich, Zoran; Weiss, Kevin B; Zvirbulis, Elena; Hafner, John W

2010-04-01

The objectives were to report the baseline (prior to quality improvement interventions) patient and visit characteristics and analgesic management practices for each site participating in an emergency department (ED) sickle cell learning collaborative. A prospective, multisite longitudinal cohort study in the context of a learning-collaborative model was performed in three midwestern EDs. Each site formed a multidisciplinary team charged with improving analgesic management for patients with sickle cell disease (SCD). Each team developed a nurse-initiated analgesic protocol for SCD patients (implemented after a baseline data collection period of 3.5 months at one site and 10 months at the other two sites). All sites prospectively enrolled adults with an acute pain crisis and SCD. All medical records for patients meeting study criteria were reviewed. Demographic, health services, and analgesic management data were abstracted, including ED visit frequency data, ED disposition, arrival and discharge pain score, and name and route of initial analgesic administered. Ten interviews per quarter per site were conducted with patients within 14 days of their ED discharge, and subjects were queried about the highest level of pain acceptable at discharge. The primary outcome variable was the time to initial analgesic administration. Variable data were described as means and standard deviations (SDs) or medians and interquartile ranges (IQR) for nonnormal data. A total of 155 patients met study criteria (median age = 32 years, IQR = 24-40 years) with a total of 701 ED visits. Eighty-six interviews were conducted. Most patients (71.6%) had between one and three visits to the ED during the study period. However, after removing Site 3 from the analysis because of the short data enrollment period (3.5 months), which influenced the mean number of visits for the entire cohort, 52% of patients had between one and three ED visits over 10 months, 21% had four to nine visits, and 27% had between 10 and 67 visits. Fifty-nine percent of patients were discharged home. The median time to initial analgesic for the cohort was 74 minutes (IQR = 48-135 minutes). Differences between choice of analgesic agent and route selected were evident between sites. For the cohort, 680 initial analgesic doses were given (morphine sulfate, 42%; hydromorphone, 46%; meperidine, 4%; morphine sulfate and ibuprofen or ketorolac, 7%) using the following routes: oral (2%), intravenous (67%), subcutaneous (3%), and intramuscular (28%). Patients reported a significantly lower targeted discharge pain score (mean +/- SD = 4.19 +/- 1.18) compared to the actual documented discharge pain score within 45 minutes of discharge (mean +/- SD = 5.77 +/- 2.45; mean difference = 1.58, 95% confidence interval = .723 to 2.44, n = 43). While half of the patients had one to three ED visits during the study period, many patients had more frequent visits. Delays to receiving an initial analgesic were common, and post-ED interviews reveal that sickle cell pain patients are discharged from the ED with higher pain scores than what they perceive as desirable.

Transmission Pathways and Mediators as the Basis for Clinical Pharmacology of Pain

PubMed Central

Kirkpatrick, Daniel R.; McEntire, Dan M.; Smith, Tyler A.; Dueck, Nicholas P.; Kerfeld, Mitchell J.; Hambsch, Zakary J.; Nelson, Taylor J.; Reisbig, Mark D.; Agrawal, Devendra K.

2016-01-01

Introduction Mediators in pain transmission are the targets of a multitude of different analgesic pharmaceuticals. This review explores the most significant mediators of pain transmission as well as the pharmaceuticals that act on them. Areas Covered The review explores many of the key mediators of pain transmission. In doing so, this review uncovers important areas for further research. It also highlights agents with potential for producing novel analgesics, probes important interactions between pain transmission pathways that could contribute to synergistic analgesia, and emphasizes transmission factors that participate in transforming acute injury into chronic pain. Expert Commentary This review examines current pain research, particularly in the context of identifying novel analgesics, highlighting interactions between analgesic transmission pathways, and discussing factors that may contribute to the development of chronic pain after an acute injury. PMID:27322358

[Pain patients in street traffic. Do analgesics impair driving safety?].

PubMed

Sohn, W

2003-06-05

Analgesics--in particular when self-prescribed or taken over the long term--may have a negative effect on safety on the road. This applies not only to vehicle drivers, but also to cyclists and pedestrians. Psychotropic effects of analgesics of all three WHO categories play a major causal role. Impairments may take the form of sleepiness, impaired vision, giddiness, loss of muscular tone or cardiovascular reactions. On the other hand, untreated severe pain has a high risk potential, since it may reduce both cognitive and psychomotoric performance. During the stabilization phase or dose adjustment of opioids, the patient must cautioned not to drive, and particular care must be taken in patients on concomitant or long-term medication or drinking excessive alcohol. In the last resort, the prescription of an analgesic is an individual decision involving both physician and patient.

Aspirin and the Kidney

PubMed Central

1974-01-01

A survey of 763 patients with rheumatoid arthritis and 145 with osteoarthritis in six clinics in New Zealand showed no association between aspirin intake and a score designed to detect analgesic nephropathy. Analgesic nephropathy was diagnosed clinically in three patients taking APC (aspirin, phenacetin, and caffeine or codeine or both) and in one who took aspirin and phenylbutazone and was suspected in one who took aspirin and paracetamol. Isolated aspirin was not implicated. The study showed that most people can take large quantities of salicylates without renal injury. The findings are, however, consistent with the view that there is a risk from APC compounds taken in large quantity, but the numbers at risk in this study were small. Aspirin may have an additive effect with other analgesics in causing renal damage. An increased frequency of urinary tract symptoms in those taking analgesics requires further investigation. PMID:4821007

Do Resting Plasma β-Endorphin Levels Predict Responses to Opioid Analgesics?

PubMed

Bruehl, Stephen; Burns, John W; Gupta, Rajnish; Buvanendran, Asokumar; Chont, Melissa; Orlowska, Daria; Schuster, Erik; France, Christopher R

2017-01-01

Clinically feasible predictors of opioid analgesic responses for use in precision pain medicine protocols are needed. This study evaluated whether resting plasma β-endorphin (BE) levels predicted responses to an opioid analgesic, and whether chronic pain status or sex moderated these effects. Participants included 73 individuals with chronic low back pain (CLBP) and 88 pain-free controls, all using no daily opioid analgesics. Participants attended 2 identical laboratory sessions during which they received either intravenous morphine (0.08 mg/kg) or saline placebo, with blood samples obtained before drug administration to assay resting plasma BE levels. Once peak drug activity was achieved in each session, participants engaged in an ischemic forearm pain task (ISC) and a heat pain task. Morphine analgesic effects were derived reflecting the difference in pain outcomes between placebo and morphine conditions. In hierarchical regressions, significant Type (CLBP vs. control)×BE interactions (Ps<0.05) were noted for morphine effects on ISC tolerance, ISC intratask pain ratings, and thermal VAS unpleasantness ratings. These interactions derived primarily from associations between higher BE levels and smaller morphine effects restricted to the CLBP subgroup. All other BE-related effects, including sex interactions, for predicting morphine analgesia failed to reach statistical significance. BE was a predictor of morphine analgesia for only 3 out of 9 outcomes examined, with these effects moderated by chronic pain status but not sex. On the whole, results do not suggest that resting plasma BE levels are likely to be a clinically useful predictor of opioid analgesic responses.

Pharmacological Treatment of Pain in Cancer Patients: The Role of Adjuvant Analgesics, a Systematic Review.

PubMed

van den Beuken-van Everdingen, Marieke H J; de Graeff, Alexander; Jongen, Joost L M; Dijkstra, Denise; Mostovaya, Irina; Vissers, Kris C

2017-03-01

In patients with cancer, pain is one of the most feared and burdensome symptoms. Adjuvant analgesics are an important cornerstone on which treatment of pain in patients with cancer is based. To update our guidelines for the treatment of pain in patients with cancer, we performed a systematic review on the use of adjuvant analgesics in pain in cancer. A systematic search of the literature was performed searching for articles that studied the effect of (1) antidepressants, (2) anti-epileptics, (3) N-methyl-d-aspartate (NMDA) receptor antagonists, and (4) other adjuvant analgesics in patients with cancer pain and described their effects on pain intensity and/or side effects. Based on the keywords and after reading the full papers, we could include 12 papers on anticonvulsants, 10 papers on antidepressants, four on NMDA receptor antagonists, and 10 papers on other adjuvant analgesics. The methodological quality of the included papers was graded as low to very low. Overall, there was a low quality of evidence that gabapentin, pregabalin, amitriptyline, and venlafaxine were effective in reducing pain intensity in patients with cancer pain. There was insufficient evidence on the effectiveness of lamotrigine, levetiracetam, NMDA antagonists, cannabinoids, corticosteroids, and local anesthetics on reducing pain intensity in patients with cancer pain. The quality of currently available evidence on the effectiveness of adjuvant analgesics in the treatment of cancer pain is low. The treatment of pain associated with cancer should be tailored to the patient's personal preferences. © 2016 World Institute of Pain.

Higher pain scores, similar opioid doses and side effects associated with antipyretic analgesics in specialised tertiary pain care.

PubMed

Lötsch, Jörn; Freynhagen, Rainer; von Hentig, Nils; Griessinger, Norbert; Zimmermann, Michael; Sittl, Reinhard; Geisslinger, Gerd

2010-11-01

To evaluate whether non-opioid antipyretic analgesics are associated with lower pain scores, opioid doses and side effects in pain patients in tertiary care. In a cross-sectional observational study, data from 519 Caucasians (197 men, 322 women; mean age 55.6 ± 15 years) who had undertaken pain therapy for various causes for 77.5 ± 90.8 months, obtained in three separate study centres, was analysed for actual 24-h pain scores, daily opioid doses and the occurrence of side effects. Of the 519 patients, 352 received opioids and 260 antipyretic analgesics, from whom 154 received both classes and 304 only either class. The administration of non-opioid antipyretic analgesics was associated with higher average pain scores (4.6 ± 2.5 vs 3.9 ± 2.6; P = 0.01), tendentially higher average oral morphine equivalent doses (121.8 ± 162.2 vs 146.7 ± 242.4 mg/d; P = 0.25) and a similar incidence of side effects (P = 0.21). These results were correspondingly seen when analysing the three study centres separately as independent cohorts. With the caution advised for cross-sectional data, the results dispute a clinical benefit of non-opioid antipyretic analgesics for most chronic pain patients in tertiary care and draw attention towards prospectively re-evaluating the utility of non-opioid antipyretic analgesics in tertiary pain care in a randomised placebo controlled trial.

Analgesic effects of breast-feeding or pacifier use with maternal holding in term infants.

PubMed

Phillips, Raylene M; Chantry, Caroline J; Gallagher, Michael P

2005-01-01

First, to compare analgesic effects of breast-feeding versus pacifier use in newborn infants undergoing blood collection via heel sticks. Second, to compare analgesic effects of pacifier use with maternal holding versus nonmaternal holding. A prospective, randomized, controlled trial. Normal newborn nursery at academic teaching hospital. Full-term breast-feeding infants scheduled for routine newborn screening blood test via heel stick (n = 96). Interventions.-Infants randomized to 3 groups for analgesia: 1) breast-feeding, 2) pacifier use while held by mothers, 3) pacifier use while held by research assistants (nonmothers). Primary outcome was crying (percent of infants who cried during the procedure and mean percent of procedure time that infants cried). Secondary outcomes were physiologic measures. Fewer breast-feeding infants cried than infants using a pacifier while held by nonmothers both during the procedure (69% vs 100%, P < .01) and after the procedure (28% vs 60%, P = .03). Those infants crying during the procedure cried for less time if held by their mothers either breast-feeding (33%, P < .01) or using a pacifier (45%, P = .03) than those using a pacifier while being held by nonmothers (66%). Breast-feeding is more analgesic than pacifier use with nonmaternal holding. Maternal holding with either breast-feeding or pacifier use is more analgesic than nonmaternal holding with pacifier use, suggesting that maternal holding itself has an analgesic effect. Breast-feeding and maternal holding should be considered as pain-control measures for the neonate during heel-stick procedures.

Analgesic, antibacterial and central nervous system depressant activities of Albizia procera leaves

PubMed Central

Khatoon, Mst. Mahfuza; Khatun, Mst. Hajera; Islam, Md. Ekramul; Parvin, Mst. Shahnaj

2014-01-01

Objective To ascertain analgesic, antibacterial and central nervous system (CNS) depressant activities of ethyl acetate, dichloromethane and carbon tetrachloride fractions of methanol extract of Albizia procera (A. procera) leaves. Methods Leaves extracts of A. procera were tested for analgesic activity by acetic acid induced and formalin test method in mice. The in vitro antibacterial activity was performed by agar well diffusion method. CNS depressant activity was evaluated by hole cross and open field tests. Results All the extracts at 200 mg/kg exhibited significant (P<0.01) analgesic activity in acetic acid induced and formalin tests method in mice. Analgesic activity of the ethyl acetate fraction was almost same like as standard drug indomethacin in acetic acid induced method. The CNS depressant activity of the extracts at 500 mg/kg was comparable to the positive control diazepam as determined by hole cross and open field test method. The extracts exhibited moderate antimicrobial activity against all the tested microorganisms (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Esherichia coli, Shigella soneii, Shigella boydii) at concentration of 0.8 mg/disc. The measured diameter of zone of inhibition for the extracts was within the range of 7 to 12 mm which was less than the standard kanamycin (16-24 mm). Conclusions It is concluded that all the extracts possess potential analgesic and CNS depressants activity. This study also showed that different fractions of methanol extract could be potential sources of new antimicrobial agents. PMID:25182551

Analgesic Effects of Toad Cake and Toad-cake-containing Herbal Drugs: Analgesic effects of toad cake.

PubMed

Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Usui, Tomomi; Sudoh, Keiichi

2014-03-01

This study was conducted to clarify the analgesic effect of toad cake and toad-cake-containing herbal drugs. We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesic effect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro- DL-phenylalanine methyl ester hydrochloride (PCPA), the catecholamine biosynthesis inhibitory drug α-methyl- DL-tyrosine methyl ester hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was also conducted. Analgesic effects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesic effect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system.

Auditing Analgesic Use in Post-operative Setting in a Teaching Hospital

PubMed Central

Bathini, Prapthi

2015-01-01

Introduction: Managing postoperative pain efficiently is one important therapeutic challenge in the hospitals. Combination use of analgesics is in vogue, where in drugs from the opioid and non-opioid group are given synergistically. The aim of this study is to audit the use of different analgesics on the first postoperative day. Effort has been made to look into the drug or drug combinations used and other factors associated with their use. Materials and Methods: Retrospective, cross sectional observational study was conducted over a period of 11 months in a tertiary care teaching hospital at Hyderabad with approval from institutional ethics committee. Medical records of 649 patients on the first postoperative day were analysed for analgesics by various indicators. Results: Average number of drugs per encounter was 4.23. Percentage of patients prescribed drugs from national essential drug list/WHO was 81.94%. Most common analgesic (monotherapy) prescribed was tramadol followed by diclofenac and the most common combination drugs prescribed were tramadol+Paracetamol. The most common route of administration was intravenous. All the drugs except piroxicam, were in the lower limit of the recommended daily dose. Conclusion: The present study gives an idea of the overall pattern of analgesic drug use in postoperative patients. The drug combinations used, the most common single use drug can be made out. The health professionals can be encouraged to prescribe by generic name and from the National List of Essential Medicines NLEMs. PMID:26023565

Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain.

PubMed

Chen, Lei; Liu, Jin-cheng; Zhang, Xiao-nan; Guo, Yan-yan; Xu, Zhao-hui; Cao, Wei; Sun, Xiao-li; Sun, Wen-ji; Zhao, Ming-Gao

2008-06-01

Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

Auraptenol attenuates vincristine-induced mechanical hyperalgesia through serotonin 5-HT1A receptors

PubMed Central

Wang, Yunfei; Cao, Shu-e; Tian, Jianmin; Liu, Guozhe; Zhang, Xiaoran; Li, Pingfa

2013-01-01

Common chemotherapeutic agents such as vincristine often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is refractory to common analgesics and represents a challenging clinical issue. Angelicae dahuricae radix is an old traditional Chinese medicine with demonstrated analgesic efficacy in humans. However, the active component(s) that attribute to the analgesic action have not been identified. This work described the anti-hyperalgesic effect of one coumarin component, auraptenol, in a mouse model of chemotherapeutic agent vincristine-induced neuropathic pain. We reported that auraptenol dose-dependently reverted the mechanical hyperalgesia in mice within the dose range of 0.05–0.8 mg/kg. In addition, the anti-hyperalgesic effect of auraptenol was significantly blocked by a selective serotonin 5-HT1A receptor antagonist WAY100635 (1 mg/kg). Within the dose range studied, auraptenol did not significantly alter the general locomotor activity in mice. Taken together, this study for the first time identified an active component from the herbal medicine angelicae dahuricae radix that possesses robust analgesic efficacy in mice. These data support further studies to assess the potential of auraptenol as a novel analgesic for the management of neuropathic pain. PMID:24287473

[Observation on the transient analgesic effect of abdominal acupuncture TENS on pain of neck, shoulder, loin and legs].

PubMed

Wang, Zhang-lian; Chen, Li-fang; Zhu, Wei-ming

2007-09-01

To observe on the transient analgesic effect of abdominal points transcutaneous electrical nerve stimulation (TENS) combined with abdominal acupuncture according to the holographic theory on pain of neck, shoulder, loin and legs. One hundred and twenty cases of pain of neck, shoulder, loin and legs were randomly divided into 4 groups: abdominal acupuncture TENS group, acupoints TENS group, electroacupuneture (EA) group, non-abdominal acupuncture TENS group, 30 cases in each group. All the cases were treated by the same stimulation parameters, but different stimulation points. The VAS scores were recorded before and after treatment. The VAS scores were significantly different before and after treatment in abdominal acupuncture TENS group (P < 0.01); the total effective rate of the transient analgesic effec t was 96.7% in the abdominal acupuncture TENS group, 93.3% in the acupoints TENS group, 96.7% in the EA group with no significant difference among the 3 groups, but with a very significant difference between the abdominal acupuncture TENS group and the non-abdominal acupunctureTENS group (10.0%), P < 0.01. Abdominal acupuncture TENS has a better transient analgesic effect and can use less stimulation points to increase the analgesic effect.

Synergetic analgesic effect of the combination of arnica and hydroxyethyl salicylate in ethanolic solution following cutaneous application by transcutaneous electrostimulation.

PubMed

Kucera, Miroslav; Horácek, Ondrej; Kálal, Jan; Kolár, Pavel; Korbelar, Peter; Polesná, Zora

2003-01-01

A combination of the active agents arnica and hydroxyethyl salicylate (HES) in ethanolic solution (Sportino Acute Spray) is cutaneously applied for the treatment of sports injuries and diseases of the locomotor apparatus. The aim was to examine the efficacy and synergism of the single substances and the combination with regard to the analgesic effect after cutaneous application as well as to validate the method of transcutaneous electronic stimulation as a method of measuring the analgesic effect. In the present article, the method of transcutaneous electrostimulation was used in a randomized, controlled, single-blind trial on healthy volunteers to provide objective evidence that the combination of active agents displays a significantly greater analgesic effect than the individual active agents. Thus there is synergy between the active agents arnica and hydroxyethyl salicylate in the combination preparation. In addition, the effect of the vehicle ethanol and the reference substance water could be determined within the framework of these comparative experiments and the difference between the combination preparation and the individual substances arnica and HES could be shown. The method of transcutaneous electrostimulation used for the objective measurement of the analgesic effect was validated.

Cyclodextrins: improving the therapeutic response of analgesic drugs: a patent review.

PubMed

de Oliveira, Makson G B; Guimarães, Adriana G; Araújo, Adriano A S; Quintans, Jullyana S S; Santos, Márcio R V; Quintans-Júnior, Lucindo J

2015-01-01

Cyclodextrins (CDs) are cyclic oligosaccharides that have recently been recognized as useful tools for optimizing the delivery of such problematic drugs. CDs can be found in at least 35 pharmaceutical products, such as anticancer agents, analgesic and anti-inflammatory drugs. Besides, several studies have demonstrated that CD-complexed drugs could provide benefits in solubility, stability and also improve pharmacological response when compared with the drug alone. The patent search was conducted in the databases WIPO, Espacenet, USPTO, Derwent and INPI, using the keywords cyclodextrin, pain and its related terms (analgesia, hyperalgesia, hypernociception, nociception, antinociception, antinociceptive). We found 442 patents. Criteria such as the complexation of analgesic agents and evidence of improvement of the therapeutic effect were indispensable for the inclusion of the patent. So, 18 patents were selected. We noticed that some patents are related to the complexation of opioids, NSAIDs, as well as natural products, in different types of CDs. The use of CDs creates the prospect of developing new therapeutic options for the most effective treatment of painful conditions, allowing a reduction of dosage of analgesic drugs and the occurrence of side effects. Thus, CDs can be an important tool to improve the efficacy and pharmacological profile of analgesic drugs.

Analgesic Efficacy and Safety of Hydromorphone in Chinchillas (Chinchilla lanigera).

PubMed

Evenson, Emily A; Mans, Christoph

2018-05-01

Limited information is available regarding the efficacy of opioid analgesics in chinchillas. Here we sought to evaluate the analgesic efficacy and safety of hydromorphone in chinchillas. In a randomized, controlled, blind, complete crossover design, hydromorphone was administered at 0.5, 1, and 2 mg/kg SC to 16 chinchillas. Analgesic efficacy was determined by measuring hindlimb withdrawal latencies after a thermal noxious stimulus (Hargreaves method) at 0, 1, 2, 4, and 8 h after drug administration. Changes in daily food intake and fecal output after hydromorphone administration were recorded. At 2 mg/kg SC, but not at lower dosages, hydromorphone increased withdrawal latencies for less than 4 h. Food intake was reduced after all 3 dosages, and fecal output decreased in the 1- and 2-mg/kg groups. The decreases in these parameters were dose-dependent, with the greatest reduction measured over the first 24 h. Our current results indicate that hydromorphone at 2 mg/kg SC is an effective, short-acting analgesic drug in chinchillas that transiently reduces food intake and fecal output. Further studies are needed to evaluate the safety of hydromorphone in animals undergoing surgical procedures and general anesthesia and to determine whether lower doses provide analgesia in different nociceptive models.

Sedative and analgesic use on night and day shifts in a pediatric cardiovascular intensive care unit.

PubMed

Staveski, Sandra L; Tesoro, Tiffany M; Cisco, Michael J; Roth, Stephen J; Shin, Andrew Y

2014-01-01

The use of sedative and analgesic medications is directly linked to patient outcomes. The practice of administering as-needed sedative or analgesic medications deserves further exploration. We hypothesized that important variations exist in the practice of administering as-needed medications in the intensive care unit (ICU). We aimed to determine the influence of time of day on the practice of administering as-needed sedative or analgesic medications to children in the ICU. Medication administration records of patients admitted to our pediatric cardiovascular ICU during a 4-month period were reviewed to determine the frequency and timing of as-needed medication usage by shift. A total of 152 ICU admissions (1854 patient days) were reviewed. A significantly greater number of as-needed doses were administered during the night shift (fentanyl, P = .005; lorazepam, P = .03; midazolam, P = .0003; diphenhydramine, P = .0003; and chloral hydrate, P = .0006). These differences remained statistically significant after excluding doses given during the first 6 hours after cardiovascular surgery. Morphine administration was similar between shifts (P = .08). We identified a pattern of increased administration of as-needed sedative or analgesic medications during nights. Further research is needed to identify the underlying causes of this practice variation.

Differential analgesic effects of a mu-opioid peptide, [Dmt(1)]DALDA, and morphine.

PubMed

Shimoyama, Megumi; Szeto, Hazel H; Schiller, Peter W; Tagaito, Yugo; Tokairin, Hideyuki; Eun, Chong moon; Shimoyama, Naohito

2009-01-01

H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA. We compared the effects of [Dmt(1)]DALDA and morphine after systemic administration in two different acute pain tests, the tail flick test and the paw withdrawal test, and examined how antagonizing the spinal opioid actions would affect their analgesic effects. [Dmt(1)]DALDA was markedly more potent in the tail flick test than in the hot plate test, while the potencies of morphine were similar in the two tests. Intrathecal naloxone completely blocked the effect of systemic [Dmt(1)]DALDA in the tail flick test, while it only partially blocked the effect of morphine. At higher doses that produced analgesia in the hot plate test, the effect of [Dmt(1)]DALDA in this test was only partially blocked by naloxone. Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.

A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain

PubMed Central

Watson, C Peter N; Gilron, Ian; Sawynok, Jana

2010-01-01

BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug. OBJECTIVE: To perform a systematic review of head-to-head RCTs of oral analgesics in NP. METHODS: A systematic review of RCTs involving NP patients was performed, of which head-to-head comparative trials were selected. Reference lists from published systematic reviews were searched. These studies were rated according to the Jadad scale for quality. RESULTS AND CONCLUSIONS: Twenty-seven such trials were identified. Seventeen were comparisons of different analgesics, and 10 were of different drugs within an analgesic class. Important information was obtained about the relative efficacy and safety of drugs in different categories and within a category. Some significant differences between active treatments were reported. Trial inadequacies were identified. More and improved head-to-head RCTs are needed to inform clinical choices. PMID:20577657

21 CFR 14.100 - List of standing advisory committees.

Code of Federal Regulations, 2012 CFR

2012-04-01

... research relevant to such communication to the public by both FDA and other entities. It also facilitates... analgesics, e.g., abuse-deterrent opioids, novel analgesics, and issues related to opioid abuse, and those...

21 CFR 14.100 - List of standing advisory committees.

Code of Federal Regulations, 2013 CFR

2013-04-01

... research relevant to such communication to the public by both FDA and other entities. It also facilitates... analgesics, e.g., abuse-deterrent opioids, novel analgesics, and issues related to opioid abuse, and those...

21 CFR 14.100 - List of standing advisory committees.

Code of Federal Regulations, 2014 CFR

2014-04-01

... research relevant to such communication to the public by both FDA and other entities. It also facilitates... analgesics, e.g., abuse-deterrent opioids, novel analgesics, and issues related to opioid abuse, and those...

Qualitative Analysis of Analgesic Tablets: An Experiment Employing High Pressure Liquid Chromatography.

ERIC Educational Resources Information Center

Beaver, Rodney W.; And Others

1983-01-01

Describes an experiment on the qualitative analysis of several over-the-counter analgesic tablets. Background information, procedures used (including high pressure liquid chromatography), and typical student results are included. (JN)

Non-opioid analgesics: Novel approaches to perioperative analgesia for major spine surgery.

PubMed

Dunn, Lauren K; Durieux, Marcel E; Nemergut, Edward C

2016-03-01

Perioperative pain management is a significant challenge following major spine surgery. Many pathways contribute to perioperative pain, including nociceptive, inflammatory, and neuropathic sources. Although opioids have long been a mainstay for perioperative analgesia, other non-opioid therapies have been increasingly used as part of a multimodal analgesic regimen to provide improved pain control while minimizing opioid-related side effects. Here we review the evidence supporting the use of novel analgesic approaches as an alternative to intravenous opioids for major spine surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment of renal colic by prostaglandin synthetase inhibitors and avafortan (analgesic antispasmodic).

PubMed

el-Sherif, A E; Foda, R; Norlen, L J; Yahia, H

1990-12-01

In a study of the pain-relieving effect of 3 drugs commonly used to treat acute renal colic in this hospital, intravenous indomethacin and intramuscular diclofenac (prostaglandin synthetase inhibitors) were compared with intravenous Avafortan (analgesic antispasmodic). As first-line analgesics, prostaglandin synthetase inhibitors, if given intravenously, offer an effective alternative to Avafortan. Of 145 patients studied, 32 required a second injection for complete relief of pain. Administering a second dose of prostaglandin synthetase inhibitors resulted in equally significant pain relief rate even though the route was intramuscular.

En Route Use of Analgesics in Nonintubated, Critically Ill Patients Transported by U.S. Air Force Critical Care Air Transport Teams.

PubMed

Mora, Alejandra G; Ganem, Victoria J; Ervin, Alicia T; Maddry, Joseph K; Bebarta, Vikhyat S

2016-05-01

U.S. Critical Care Air Transport Teams (CCATTs) evacuate critically ill patients with acute pain in the combat setting. Limited data have been reported on analgesic administration en route, and no study has reported analgesic use by CCATTs. Our objective was to describe analgesics used by CCATTs for nonintubated, critically ill patients during evacuation from a combat setting. We conducted an institutional review board-approved, retrospective review of CCATT records. We included nonintubated, critically ill patients who were administered analgesics in flight and were evacuated out of theater (2007-2012). Demographics, injury description, analgesics and anesthetics, and predefined clinical adverse events were recorded. Data were presented as mean ± standard deviation or percentage (%). Of 1,128 records, we analyzed 381 subjects with the following characteristics: age 26 ± 7.0 years; 98% male; and 97% trauma (70% blast, 17% penetrating, 11% blunt, and 3% burn). The injury severity score was 19 ± 9. Fifty-one percent received morphine, 39% hydromorphone, 15% fentanyl, and 5% ketamine. Routes of delivery were 63% patient-controlled analgesia (PCA), 32% bolus intravenous (IV) administration, 24% epidural delivery, 21% continuous IV infusions, and 9% oral opioids. Patients that were administered local anesthetics (nerve block or epidural delivery) with IV opioids received a lower total dose of opioids than those who received opioids alone. No differences were associated between analgesics and frequency of complications in flight or postflight. About half of nonintubated, critically ill subjects evacuated out of combat by CCATT received morphine and more than half had a PCA. In our study, ketamine was not frequently used and pain scores were rarely recorded. However, we detected an opioid-sparing effect associated with local anesthetics (regional nerve blocks and epidural delivery). Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Antiinflammatory and analgesic effects of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract in rats and mice.

PubMed

Ojewole, J A O

2006-09-01

In many parts of Africa, the leaf, stem-bark, and roots of Psidium guajava Linn. (Family: Myrtaceae) are used traditionally for the management, control, and/or treatment of an array of human disorders. In an effort to scientifically appraise some of the ethnomedical properties of P. guajava leaf, and probe its efficacy and safety, the present study was undertaken to examine the antiinflammatory and analgesic properties of the plant's leaf aqueous extract in some experimental animal paradigms. The antiinflammatory property of the aqueous leaf extract was investigated in rats, using fresh egg albumin-induced pedal (paw) edema, while the analgesic effect of the plant extract was evaluated by the "hot-plate" and "acetic acid" test models of pain in mice. Diclofenac (100 mg/kg, i.p.) and morphine (10 mg/kg, i.p.) were used respectively as standard, reference antiinflammatory and analgesic agents for comparison. P. guajava leaf aqueous extract (PGE, 50-800 mg/kg, i.p.) produced dose-dependent and significant (p < 0.05-0.001) inhibition of fresh egg albumin-induced acute inflammation (edema) in rats. The plant extract (PGE, 50-800 mg/kg, i.p.) also produced dose-dependent and significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain in mice. The numerous tannins, polyphenolic compounds, flavonoids, ellagic acid, triterpenoids, guiajaverin, quercetin, and other chemical compounds present in the plant are speculated to account for the observed antiinflammatory and analgesic effects of the plant's leaf extract. In summary, the findings of this experimental animal study indicate that the leaf aqueous extract of P. guajava possesses analgesic and antiinflammatory properties, and thus lend pharmacological credence to the suggested ethnomedical, folkloric uses of the plant in the management and/or control of painful, arthritic and other inflammatory conditions in some rural communities of Africa. (c) 2006 Prous Science. All rights reserved.

Should continuous rather than single-injection interscalene block be routinely offered for major shoulder surgery? A meta-analysis of the analgesic and side-effects profiles.

PubMed

Vorobeichik, L; Brull, R; Bowry, R; Laffey, J G; Abdallah, F W

2018-04-01

Major shoulder surgery is associated with moderate-to-severe pain, but consensus on the optimal analgesic approach is lacking. Continuous catheter-based interscalene block (CISB) prolongs the analgesic benefits of its single-injection counterpart (SISB), but concerns over CISB complications and difficulties in interpreting comparative evidence examining major and minor shoulder procedures simultaneously, despite their differences in postoperative pain, have limited CISB popularity. This meta-analysis evaluates the CISB analgesic role and complications compared with SISB for major shoulder surgery. We retrieved randomised controlled trials (RCTs) comparing the effects of CISB to SISB on analgesic outcomes and side-effects after major shoulder surgery. Postoperative opioid consumption at 24 h was designated as the primary outcome. Secondary outcomes included 24-48 h opioid consumption, postoperative rest and dynamic pain scores up to 72 h, time-to-first analgesic, recovery room and hospital stay durations, patient satisfaction, postoperative nausea and vomiting, respiratory function, and block-related complications. Data from 15 RCTs were pooled using random-effects modelling. Compared with SISB, CISB reduced 24- and 48-h oral morphine consumption by a weighted mean difference [95% confidence interval] of 50.9 mg [-81.6, -20.2], (P=0.001) and 44.7 mg [-80.9, -8.7], (P<0.0001), respectively. Additionally, CISB provided superior rest and dynamic pain control beyond 48 h, prolonged time-to-first analgesic, enhanced satisfaction, and reduced postoperative nausea and vomiting without complications. CISB caused an 11.0-11.7% decrease in respiratory indices. Result heterogeneity was successfully explained. High-level evidence indicates that CISB provides superior analgesia up to 48 h after major shoulder surgery, without increasing side-effects, compared with SISB. The importance of CISB-related changes in respiratory indices is questionable. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

The relationship between serum progesterone concentration and anesthetic and analgesic requirements: a prospective observational study of parturients undergoing cesarean delivery.

PubMed

Lee, Jeongwoo; Lee, Junho; Ko, Seonghoon

2014-10-01

In clinical practice, pregnant women have lower anesthetic requirements for general anesthesia than nonpregnant women. Although the hormonal changes such as progesterone associated with pregnancy may affect the minimum alveolar concentration of volatile anesthetics, the relationship between the anesthetic or analgesic requirements and progesterone level in full-term women has not been studied. In this study, we attempted to identify relationships between anesthetic or analgesic requirements and maternal serum concentrations of progesterone. We studied 100 parturients >36 weeks' gestation who were scheduled for planned cesarean delivery under general anesthesia. Venous blood was collected to measure the maternal progesterone concentration. Anesthesia was induced with 4 to 5 mg/kg thiopental and 0.8 mg/kg rocuronium. During anesthetic maintenance, sevoflurane 0.5% to 2.0% and nitrous oxide 50% in oxygen were titrated based on arterial blood pressure, heart rate, and bispectral index value. Vital signs, bispectral index, end-tidal sevoflurane concentration, and sevoflurane consumption per hour were recorded. Visual analog scale pain scores and cumulative analgesic consumption were recorded at 2, 24, and 48 hours postoperatively. The mean serum progesterone concentration was 128.2 ± 83.0 ng/mL. There was a significant negative correlation between sevoflurane consumption per hour and serum progesterone concentration (Pearson correlation r = -0.26; 95% confidence interval, -0.44 to -0.05, P = 0.01). Cumulative analgesic consumption at postoperative hours 2 (r = -0.20, P = 0.05), 24 (r = -0.25, P = 0.02), and 48 (r = -0.28, P = 0.01) were correlated inversely with serum progesterone concentration. Women with high progesterone levels (higher than the median value) had lower sevoflurane consumption per hour (P = 0.02) and 48-hour postoperative cumulative analgesic consumption (P = 0.02) than women with low (below the median value) levels. The decreased anesthetic and analgesic requirements of near full-term parturients might partially depend on serum progesterone concentration.

Adverse effects of analgesics commonly used by older adults with osteoarthritis: focus on non-opioid and opioid analgesics.

PubMed

O'Neil, Christine K; Hanlon, Joseph T; Marcum, Zachary A

2012-12-01

Osteoarthritis (OA) is the most common cause of disability in older adults, and although analgesic use can be helpful, it can also result in adverse drug events. To review the recent literature to describe potential adverse drug events associated with analgesics commonly used by older adults with OA. To identify articles for this review, a systematic search of the English-language literature from January 2001 to June 2012 was conducted using PubMed, MEDLINE, EBSCO, and the Cochrane Database of Systematic Reviews for publications related to the medical management of OA. Search terms used were "analgesics," "acetaminophen," "nonsteroidal anti-inflammatory drugs" (NSAIDs), "opioids," "pharmacokinetics," "pharmacodynamics," and "adverse drug events." The search was restricted to those articles that concerned humans aged ≥65 years. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. From these, the authors identified those studies that examined analgesic use in older adults. There are limited data to suggest that non-frail elders are more likely than their younger counterparts to develop acetaminophen-induced hepatotoxicity. However, decreased hepatic phase II metabolism in frail elders may result in increased risk of hepatotoxicity. It is now well established that older adults are at higher risk of NSAID-induced gastrointestinal toxicity and renal insufficiency. Insofar as opioids, the data that suggest an increased risk of falls, fractures, or delirium need to be tempered by the potential risk of inadequately treating severe chronic OA-related pain. Acetaminophen is the mainstay frontline analgesic for treating OA-related pain in older adults. NSAIDs should be limited to short-term use only, and for moderate to severe OA-related pain, opioids may be preferable in individuals without substance abuse or dependence issues. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Computational functional genomics-based approaches in analgesic drug discovery and repurposing.

PubMed

Lippmann, Catharina; Kringel, Dario; Ultsch, Alfred; Lötsch, Jörn

2018-06-01

Persistent pain is a major healthcare problem affecting a fifth of adults worldwide with still limited treatment options. The search for new analgesics increasingly includes the novel research area of functional genomics, which combines data derived from various processes related to DNA sequence, gene expression or protein function and uses advanced methods of data mining and knowledge discovery with the goal of understanding the relationship between the genome and the phenotype. Its use in drug discovery and repurposing for analgesic indications has so far been performed using knowledge discovery in gene function and drug target-related databases; next-generation sequencing; and functional proteomics-based approaches. Here, we discuss recent efforts in functional genomics-based approaches to analgesic drug discovery and repurposing and highlight the potential of computational functional genomics in this field including a demonstration of the workflow using a novel R library 'dbtORA'.

VIRTUAL REALITY HYPNOSIS FOR PAIN ASSOCIATED WITH RECOVERY FROM PHYSICAL TRAUMA1,2

PubMed Central

Patterson, David R.; Jensen, Mark P.; Wiechman, Shelley A.; Sharar, Sam R.

2010-01-01

Pain following traumatic injuries is common, can impair injury recovery and is often inadequately treated. In particular, the role of adjunctive nonpharmacologic analgesic techniques is unclear. The authors report a randomized, controlled study of 21 hospitalized trauma patients to assess the analgesic efficacy of virtual reality hypnosis (VRH)—hypnotic induction and analgesic suggestion delivered by customized virtual reality (VR) hardware/software. Subjective pain ratings were obtained immediately and 8 hours after VRH (used as an adjunct to standard analgesic care) and compared to both adjunctive VR without hypnosis and standard care alone. VRH patients reported less pain intensity and less pain unpleasantness compared to control groups. These preliminary findings suggest that VRH analgesia is a novel technology worthy of further study, both to improve pain management and to increase availability of hypnotic analgesia to populations without access to therapist-provided hypnosis and suggestion. PMID:20509069

Parents’ Management of Children’s Pain at Home after Surgery

PubMed Central

Vincent, Catherine; Chiappetta, Maria; Beach, Abigail; Kiolbasa, Carolyn; Latta, Kelsey; Maloney, Rebekah; Van Roeyen, Linda Sue

2012-01-01

Purpose We tested Home Pain Management for Children (HPMC) for effects on pain intensity, analgesics administered, satisfaction, and use of healthcare services over 3 post-discharge days. Design and Methods In this quasi-experimental study with 108 children and their parents, we used the numeric rating scale (NRS) or the Faces Pain Scale-Revised (FPS-R), calculated percentages of analgesics administered, and asked questions about expectations, satisfaction, and services. Between-group differences were tested with t-tests and ANOVA. Results After HPMC, children reported moderate pain and parents administered more analgesics on 2 study days. Parents and children were satisfied; parents used few services. Written instructions and a brief interactive session were not sufficient to change parents’ analgesic administration practices to relieve their children’s pain. Practice Implications Further research is needed to develop and test effective education interventions to facilitate relief of children’s post-operative pain. PMID:22463471

Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques.

PubMed

Reuben, Scott S; Buvanendran, Asokumar

2007-06-01

The prevalences of complex regional pain syndrome, phantom limb pain, chronic donor-site pain, and persistent pain following total joint arthroplasty are alarmingly high. Central nervous system plasticity that occurs in response to tissue injury may contribute to the development of persistent postoperative pain. Many researchers have focused on methods to prevent central neuroplastic changes from occurring through the utilization of preemptive or preventive multimodal analgesic techniques. Multimodal analgesia allows a reduction in the doses of individual drugs for postoperative pain and thus a lower prevalence of opioid-related adverse events. The rationale for this strategy is the achievement of sufficient analgesia due to the additive effects of, or the synergistic effects between, different analgesics. Effective multimodal analgesic techniques include the use of nonsteroidal anti-inflammatory drugs, local anesthetics, alpha-2 agonists, ketamine, alpha(2)-delta ligands, and opioids.

OTC analgesics and drug interactions: clinical implications

PubMed Central

Fendrick, A Mark; Pan, Deborah E; Johnson, Grace E

2008-01-01

The risk of drug interactions with concurrent use of multiple medications is a clinically relevant issue. Many patients are unaware that over-the-counter (OTC) analgesics can cause potentially serious adverse effects when used in combination with other common medications such as anticoagulants, corticosteroids, or antihypertensive agents. Of particular significance is the increased risk of upper abdominal gastrointestinal adverse events in patients who take traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This risk is dose dependent and further increased in patients who take more than one NSAID or use NSAIDs in combination with certain other medications. Some NSAIDs may also mitigate the antiplatelet benefits of aspirin and may increase blood pressure in patients with hypertension. Clinicians should be aware of potential drug interactions with OTC analgesics when prescribing new medications. Additionally, patients should be properly counseled on the appropriate and safe use of OTC analgesics. PMID:18257920

Analgesic, anti-inflammatory, antipyretic and haematological effects of aethiopinone, an o-naphthoquinone diterpenoid from Salvia aethiopis roots and two hemisynthetic derivatives.

PubMed

Hernández-Pérez, M; Rabanal, R M; de la Torre, M C; Rodríguez, B

1995-12-01

Aethiopinone (1), an o-naphthoquinone diterpene from Salvia aethiopis L. roots and two hemisynthetic derivatives 2 and 3 have been evaluated for toxicity, anti-inflammatory, analgesic, antipyretic, and haemostatic activities. The compounds tested showed low toxicity and a pharmacological profile similar to other NSAI substances on reducing the edema induced by carrageenan and contractions induced by phenyl-p-quinone; the most active compounds were 1 and 2. In the same way and as expected with these types of substances, the bleeding time increased. In the TPA-induced ear inflammation model, the three compounds showed a moderate reduction of edema, and 1 produced a significant increase in the reaction time against thermal painful stimuli in the tail immersion test. The results demonstrated strong anti-inflammatory, peripheral and central analgesic properties for 1, as well as antiedematose topical action and peripheral analgesic properties for 2 and 3.

Analgesic effects of branding in treatment of headaches.

PubMed

Branthwaite, A; Cooper, P

1981-05-16

The effect of branding--that is, the labelling and marketing--of a well-known proprietary analgesic used to treat headaches was studied in a sample of women given a branded or unbranded form with either an inert or an active formulation. The sample was also divided according to whether the subjects were regular users of the brand or users of other brands. The findings showed that branded tablets were overall significantly more effective than unbranded tablets in relieving headaches. Differential effects were observed: the effects of branding were more noticeable one hour after the tablets were taken compared with 30 minutes; in the women given the placebo; and in the users of the brand compared with the users of other brands. It is hypothesised that these effects are due to increased confidence in obtaining relief with a well-known brand, and that branding has an analgesic effect that interacts with the analgesic effects of placebos and active ingredients.

Effect of antipyretic analgesics on immune responses to vaccination.

PubMed

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.

Effect of antipyretic analgesics on immune responses to vaccination

PubMed Central

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

2016-01-01

ABSTRACT 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

Gender differences and pain medication.

PubMed

Richardson, Jen; Holdcroft, Anita

2009-01-01

Subtle genetic and psychological variations are increasingly recognized to contribute to pain and analgesic efficacy and safety. The influence of sex on this relationship remains poorly understood, particularly in humans. The issue is complicated by the overlay of gender onto physical sex, and its associated stereotypes and expectations. Women appear to use more pain-relieving medications than men; however, it remains unclear whether these observations represent true differences in analgesic usage patterns, or reporting bias. Differences in analgesic efficacy relating to body composition, metabolism and hormonal profiles have been demonstrated. Psychological and social elements of gender have also been associated with altered pain experiences and analgesic use profiles, albeit with significant individual variations. Intra-group differences may ultimately prove more important than sex differences. Further research may unravel the various threads linking gender and sex effects on analgesia with the aim of individualizing analgesia to optimize pain relief.

[Analgesic abuse and psychiatric comorbidity in headache patients].

PubMed

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 scrutinized in this population, but it is well documented that chronic pain patients have high rates of addiction with various types of substances. Moreover, it is well documented that these patients are at higher risk for anxious (panic disorders and phobic disorders) and depressive disorders than non abusing headache patients. Anxiety and depressive scores are related to both the chronicity of headaches, and the amount of analgesic intake. Therefore, this comorbidity is possibly related to psychoactive substance use but there is no prospective study concerning chronological link between the anxious and depressive disorders and analgesic abuse. The presence of personality disorders in these patients is poorly documented, with the exception of neuroticism, which probably reflects the anxious and depressive comorbidity. Clinical findings show that a subgroup of patients needs an hospitalisation to succeed in withdrawal. They appears likely to be dependant on several types of drugs, to present with fear of pain itself, and to present with cluster B personality disorders, whereas another subgroup is specifically dependant on one type of drug, present with fear of pain induced impairement, and present with cluster C personality disorders. Those patients, when becoming aware of dependance, succeed in withdrawal at home, without the need of an hospitalization. The analgesic medication overuse and dependance can also be considered as a maladjusted strategy to manage pain (with prevalent passive and avoidant coping strategies). More research is required focusing on psychopathological aspects of analgesic overuse and dependance, to improve withdrawal modalities and to reduce the rate of relapses.

Accessibility of opioid analgesics and barriers to optimal chronic pain treatment in Poland in 2000-2015.

PubMed

Dzierżanowski, Tomasz; Ciałkowska-Rysz, Aleksandra

2017-03-01

Based on the international reports, consumption of opioid analgesics in Poland is relatively low. There is limited information on possible impediments to optimal opioid use. This study was aimed to identify possible barriers to access to opioid analgesics and causes of failure to comply with current clinical guidelines. Consumption data per capita in 2000-2015 were analyzed in terms of oral morphine equivalents in total, per prescription type, per reimbursement status, to identify the impact of regulations specific for Poland. The consumption of opioid analgesics has been consistently growing from 36.0 in 2000 to 103.4 mg oral morphine equivalents (OME) per capita in 2015, mainly thanks to strong opioid consumption growth. Tramadol is the most commonly used opioid in Poland. Fentanyl and buprenorphine transdermal formulations are the most frequently used strong opioid analgesics in terms of OME. The vast majority (92.8 %) of opioids were distributed upon for outpatient use in 2015, with a almost fourfold growth of consumption of strong opioids and almost threefold of weak opioids between 2000 and 2015. Strong opioids were 41 % of OME used upon prescription in 2015. Acceleration of consumption growth has been observed since 2013. The prescription pattern does not abide by the current clinical guidelines for pain treatment, and the most often used opioids in Poland are tramadol, buprenorphine, and fentanyl. The use of opioids in Poland grows fast, with acceleration since 2013. The most important legal impediments of optimal opioid analgesics use have been lack of reimbursement, special prescription forms, and complicated prescribing rules.

Quality improvement activity for improving pain management in acute extremity injuries in the emergency department.

PubMed

Chang, Hyung Lan; Jung, Jin Hee; Kwak, Young Ho; Kim, Do Kyun; Lee, Jin Hee; Jung, Jae Yun; Kwon, Hyuksool; Paek, So Hyun; Park, Joong Wan; Shin, Jonghwan

2018-03-01

The aim of this study was to investigate the effectiveness of a quality improvement activity for pain management in patients with extremity injury in the emergency department (ED). This was a retrospective interventional study. The patient group consisted of those at least 19 years of age who visited the ED and were diagnosed with International Classification of Diseases codes S40-S99 (extremity injuries). The quality improvement activity consisted of three measures: a survey regarding activities, education, and the triage nurse's pain assessment, including change of pain documentation on electronic medical records. The intervention was conducted from January to April in 2014 and outcome was compared between May and August in 2013 and 2014. The primary outcome was the rate of analgesic prescription, and the secondary outcome was the time to analgesic prescription. A total of 1,739 patients were included, and 20.3% of 867 patients in the pre-intervention period, and 28.8% of 872 patients in the post-intervention period received analgesics (P< 0.001). The prescription rate of analgesics for moderate-to-severe injuries was 36.4% in 2013 and 44.5% in 2014 (P=0.026). The time to analgesics prescription was 116.6 minutes (standard deviation 225.6) in 2013 and 64 minutes (standard deviation 75.5) in 2014 for all extremity injuries. The pain scoring increased from 1.4% to 51.6%. ED-based quality improvement activities including education and change of pain score documentation can improve the rate of analgesic prescription and time to prescription for patients with extremity injury in the ED.

Efficacy of Various Analgesics on Shoulder Function and Rotator Cuff Tendon-to-Bone Healing in a Rat (Rattus norvegicus) Model

PubMed Central

Caro, Adam C; Tucker, Jennica J; Yannascoli, Sarah M; Dunkman, Andrew A; Thomas, Stephen J; Soslowsky, Louis J

2014-01-01

Although relief of postoperative pain is an imperative aspect of animal welfare, analgesics that do not interfere with the scientific goals of the study must be used. Here we compared the efficacy of different analgesic agents by using an established rat model of supraspinatus tendon healing and a novel gait-analysis system. We hypothesized that different analgesic agents would all provide pain relief in this model but would cause differences in tendon-to-bone healing and gait parameters. Buprenorphine, ibuprofen, tramadol–gabapentin, and acetaminophen were compared with a no-analgesia control group. Gait measures (stride length and vertical force) on the operative forelimb differed between the control group and both the buprenorphine (2 and 4 d postsurgery) and ibuprofen (2 d postsurgery) groups. Step length was different in the control group as compared with the tramadol–gabapentin (2 d after surgery), buprenorphine (2 and 4 d after surgery), and ibuprofen (2 d after surgery) groups. Regarding tendon-to-bone healing, the ibuprofen group showed less stiffness at the insertion site; no other differences in tendon-to-bone healing were detected. In summary, the analgesics evaluated were associated with differences in both animal gait and tendon-to-bone healing. This information will be useful for improving the management of postsurgical pain without adversely affecting tissue healing. Given its ability to improve gait without impeding healing, we recommend use of buprenorphine for postsurgical pain management in rats. In addition, our gait-analysis system can be used to evaluate new analgesics. PMID:24602546

Imaging drugs with and without clinical analgesic efficacy.

PubMed

Upadhyay, Jaymin; Anderson, Julie; Schwarz, Adam J; Coimbra, Alexandre; Baumgartner, Richard; Pendse, G; George, Edward; Nutile, Lauren; Wallin, Diana; Bishop, James; Neni, Saujanya; Maier, Gary; Iyengar, Smriti; Evelhoch, Jeffery L; Bleakman, David; Hargreaves, Richard; Becerra, Lino; Borsook, David

2011-12-01

The behavioral response to pain is driven by sensory and affective components, each of which is mediated by the CNS. Subjective pain ratings are used as readouts when appraising potential analgesics; however, pain ratings alone cannot enable a characterization of CNS pain circuitry during pain processing or how this circuitry is modulated pharmacologically. Having a more objective readout of potential analgesic effects may allow improved understanding and detection of pharmacological efficacy for pain. The pharmacological/functional magnetic resonance imaging (phMRI/fMRI) methodology can be used to objectively evaluate drug action on the CNS. In this context, we aimed to evaluate two drugs that had been developed as analgesics: one that is efficacious for pain (buprenorphine (BUP)) and one that failed as an analgesic in clinical trials aprepitant (APREP). Using phMRI, we observed that activation induced solely by BUP was present in regions with μ-opioid receptors, whereas APREP-induced activation was seen in regions expressing NK(1) receptors. However, significant pharmacological modulation of functional connectivity in pain-processing pathways was only observed following BUP administration. By implementing an evoked pain fMRI paradigm, these drugs could also be differentiated by comparing the respective fMRI signals in CNS circuits mediating sensory and affective components of pain. We report a correlation of functional connectivity and evoked pain fMRI measures with pain ratings as well as peak drug concentration. This investigation demonstrates how CNS-acting drugs can be compared, and how the phMRI/fMRI methodology may be used with conventional measures to better evaluate candidate analgesics in small subject cohorts.

Imaging Drugs with and without Clinical Analgesic Efficacy

PubMed Central

Upadhyay, Jaymin; Anderson, Julie; Schwarz, Adam J; Coimbra, Alexandre; Baumgartner, Richard; Pendse, G; George, Edward; Nutile, Lauren; Wallin, Diana; Bishop, James; Neni, Saujanya; Maier, Gary; Iyengar, Smriti; Evelhoch, Jeffery L; Bleakman, David; Hargreaves, Richard; Becerra, Lino; Borsook, David

2011-01-01

The behavioral response to pain is driven by sensory and affective components, each of which is mediated by the CNS. Subjective pain ratings are used as readouts when appraising potential analgesics; however, pain ratings alone cannot enable a characterization of CNS pain circuitry during pain processing or how this circuitry is modulated pharmacologically. Having a more objective readout of potential analgesic effects may allow improved understanding and detection of pharmacological efficacy for pain. The pharmacological/functional magnetic resonance imaging (phMRI/fMRI) methodology can be used to objectively evaluate drug action on the CNS. In this context, we aimed to evaluate two drugs that had been developed as analgesics: one that is efficacious for pain (buprenorphine (BUP)) and one that failed as an analgesic in clinical trials aprepitant (APREP). Using phMRI, we observed that activation induced solely by BUP was present in regions with μ-opioid receptors, whereas APREP-induced activation was seen in regions expressing NK1 receptors. However, significant pharmacological modulation of functional connectivity in pain-processing pathways was only observed following BUP administration. By implementing an evoked pain fMRI paradigm, these drugs could also be differentiated by comparing the respective fMRI signals in CNS circuits mediating sensory and affective components of pain. We report a correlation of functional connectivity and evoked pain fMRI measures with pain ratings as well as peak drug concentration. This investigation demonstrates how CNS-acting drugs can be compared, and how the phMRI/fMRI methodology may be used with conventional measures to better evaluate candidate analgesics in small subject cohorts. PMID:21849979

Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP.

PubMed

Liao, Zheng-Gen; Liang, Xin-Li; Zhu, Jing-Yun; Zhao, Guo-Wei; Yang, Ming; Wang, Guang-Fa; Jiang, Qie-Ying; Chen, Xu-Long

2010-05-04

Yuanhu Zhitong prescription that consists of Corydalis yanhusuo and Radix Angelicae dahuricae has been used for the treatment of gastralgia, costalgia, headache and dysmenorrhea in Traditional Chinese Medicine. Our previous studies demonstrated that Corydalis alkaloid (CA, derived from the root of Corydalis yanhusu) had potent analgesic properties, and the total coumarins of Angelica dahurica (Cou) and volatile oil (VO) that derived from the root of Radix Angelicae dahuricae all could increase the analgesic effect of CA. The major objective of this paper was to investigate the mechanism that leading the analgesia of CA increased by Cou and (or) VO. The relationship between analgesic effect of CA and the plasma concentration of Dl-tetrahydropalmatine (dl-THP, active component of CA) was assayed in mice writhing test. The CA (34, 68 and 134 mg/kg) reduced the nociception by acetic acid intraperitoneal injection in a dose-dependent manner, and there was a significant linear relationship between the analgesic effect of CA and the plasma concentration of dl-THP. Then the plasma concentration of dl-THP at different time intervals in rats after oral administration of CA, CA-Cou, CA-VO and CA-Cou-VO were examined by using HPLC. The results indicated that Cou and (or) VO raised the plasma concentration of dl-THP prominently. In conclusion, the reason that Radix Angelica dahurica extracts reinforced the analgesic effects of Corydalis alkaloid was related to the improvement of the plasma concentration of dl-THP. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Disambiguating Pharmacodynamic Efficacy from Behavior with Neuroimaging: Implications for Analgesic Drug Development.

PubMed

Wanigasekera, Vishvarani; Mezue, Melvin; Andersson, Jesper; Kong, Yazhuo; Tracey, Irene

2016-01-01

Attrition rates of new analgesics during drug development are high; poor assay sensitivity with reliance on subjective outcome measures being a crucial factor. The authors assessed the utility of functional magnetic resonance imaging with capsaicin-induced central sensitization, a mechanism relevant in neuropathic pain, for obtaining mechanism-based objective outcome measures that can differentiate an effective analgesic (gabapentin) from an ineffective analgesic (ibuprofen) and both from placebo. The authors used a double-blind, randomized phase I study design (N = 24) with single oral doses. Only gabapentin suppressed the secondary mechanical hyperalgesia-evoked neural response in a region of the brainstem's descending pain modulatory system (right nucleus cuneiformis) and left (contralateral) posterior insular cortex and secondary somatosensory cortex. Similarly, only gabapentin suppressed the resting-state functional connectivity during central sensitization between the thalamus and secondary somatosensory cortex, which was plasma gabapentin level dependent. A power analysis showed that with 12 data sets, when using neural activity from the left posterior insula and right nucleus cuneiformis, a statistically significant difference between placebo and gabapentin was detected with probability ≥ 0.8. When using subjective pain ratings, this reduced to less than or equal to 0.6. Functional imaging with central sensitization can be used as a sensitive mechanism-based assay to guide go/no-go decisions on selecting analgesics effective in neuropathic pain in early human drug development. We also show analgesic modulation of neural activity by using resting-state functional connectivity, a less challenging paradigm that is ideally suited for patient studies because it requires no task or pain provocation.

Efficacy of Opioid-free Anesthesia in Reducing Postoperative Respiratory Depression in Children Undergoing Tonsillectomy

ClinicalTrials.gov

2018-05-04

Anesthesia; General Anesthesia; Analgesics, Opioid; Postoperative Complications; Pathologic Processes; Physiologic Effects of Drugs; Narcotics; Analgesics; Sleep Disordered Breathing; Obstructive Sleep Apnea of Child; Tonsillectomy; Respiratory Depression; Dexmedetomidine; Ketamine; Lidocaine; Gabapentin; Pulse Oximetry

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

PubMed Central

Kosek, Eva; Jensen, Karin B; Lonsdorf, Tina B; Schalling, Martin; Ingvar, Martin

2009-01-01

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 < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression. 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 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions. PMID:19570226

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

PubMed

Kosek, Eva; Jensen, Karin B; Lonsdorf, Tina B; Schalling, Martin; Ingvar, Martin

2009-07-01

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 micro-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. 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 < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression. 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 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.

Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010.

PubMed

Bachhuber, Marcus A; Saloner, Brendan; Cunningham, Chinazo O; Barry, Colleen L

2014-10-01

Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them. To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality. A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included. Presence of a law establishing a medical cannabis program in the state. Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate. Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, -37.5% to -9.5%; P = .003) compared with states without medical cannabis laws. Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (-19.9%; 95% CI, -30.6% to -7.7%; P = .002), year 2 (-25.2%; 95% CI, -40.6% to -5.9%; P = .01), year 3 (-23.6%; 95% CI, -41.1% to -1.0%; P = .04), year 4 (-20.2%; 95% CI, -33.6% to -4.0%; P = .02), year 5 (-33.7%; 95% CI, -50.9% to -10.4%; P = .008), and year 6 (-33.3%; 95% CI, -44.7% to -19.6%; P < .001). In secondary analyses, the findings remained similar. Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose.

Patient-reported opioid analgesic requirements after elective inguinal hernia repair: A call for procedure-specific opioid-administration strategies.

PubMed

Mylonas, Konstantinos S; Reinhorn, Michael; Ott, Lauren R; Westfal, Maggie L; Masiakos, Peter T

2017-11-01

A better understanding of the analgesia needs of patients who undergo common operative procedures is necessary as we address the growing opioid public health crisis in the United States. The aim of this study was to evaluate patient experience with our opioid prescribing practice after elective inguinal hernia repairs. A prospective, observational study was conducted between October 1, 2015, and September 30, 2016, in a single-surgeon, high-volume, practice of inguinal hernia operation. Adult patients undergoing elective inguinal herniorrhaphy under local anesthesia with intravenous sedation were invited to participate. All patients were prescribed 10 opioid analgesic tablets postoperatively and were counseled to reserve opioids for pain not controlled by nonopioid analgesics. Their experience was captured by completing a questionnaire 2 to 3 weeks postoperatively during their postoperative visit. A total of 185 patients were surveyed. The majority of the participants were males (177, 95.7%) and ≥60 years old (96, 51.9%). Of the 185 patients, 159 (85.9%) reported using ≤4 opioid tablets; 110 patients (59.5%) reported that they used no opioid analgesics postoperatively. None of the patients was taking opioids within 7 days of their postoperative appointment. Of the 147 patients who were employed, 111 (75.5%) reported missing ≤3 work days, 57 of whom (51.4%) missed no work at all. Patients who were employed were more likely to take opioid analgesics postoperatively (P = .049). Patients who took no opioid analgesics experienced less maximum (P < .001) and persistent groin pain (P = .037). Pain interfered less with daily activities (P = .012) and leisure activities (P = .018) for patients who did not use opioids. The majority of our patients reported that they did not require any opioid analgesics, and nearly all of those who thought that they did need opioids used <5 tablets. Our data suggest that for elective inguinal hernia repair under a local anesthetic with intravenous sedation, a policy of low opioid analgesic prescribing is achievable; these findings call for further investigation of how to best prescribe opioid medications to patients after an inguinal herniorrhaphy. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical Interventions for Pain.

ERIC Educational Resources Information Center

Aronoff, Gerald M.; And Others

1986-01-01

Reviews properties and pharmacological effects of medications for pain, including peripherally acting analgesics, centrally acting narcotics, and adjuvant analgesics including antidepressants. Discusses the role of the endogenous opioid system in pain and depression. Explores clinical management issues in both inpatient and outpatient settings,…

Variability in opioid prescribing for children undergoing ambulatory surgery in the United States.

PubMed

Van Cleve, William C; Grigg, Eliot B

2017-09-01

We attempted to describe the opioid prescribing patterns for ambulatory pediatric surgery in the United States from 2007 to 2014. Retrospective database review. Operating room ambulatory encounters as determined by the Truven Health Marketscan Commercial Claims and Encounters database. A total of 929,874 ambulatory surgical encounters were identified in patients <18years of age and, of these, 439,286 encounters generated an analgesic prescription. N/A MEASUREMENTS: The analgesic prescription was described in terms of the type of opioid along with the inclusion of acetaminophen and/or NSAIDs. The probability of receiving a post-operative analgesic prescription increased with age, ranging from 18.2% of infants to 71.7% of teens. Acetaminophen with codeine (APAP/C) was the most common drug for infants (63.8%), while acetaminophen with hydrocodone (APAP/H) was the most common analgesic prescription for teens (53.6%). APAP/C and APAP/H were the predominant drugs used for all procedure types. Substantial variability in analgesic prescribing at the level of the procedure performed, both in terms of the probability of receiving a prescription and in which drugs were prescribed. We observed significant age and procedure-based variability in opioid prescribing following pediatric ambulatory surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

An ethnobotanical study of medicinal plants with narcotic, sedative and analgesic effects in west of Iran.

PubMed

Saki, K; Bahmani, M; Rafieianb-Kopaei, M D; Asadollahi, K; Emaneini, M; Taherikalani, M

2016-01-01

The first step for identification of medicinal plants and their therapeutic effects is to determine their use by local people, traditional medicine books and personal experiences. The aim of this study was to document the medicinal plants used as analgesic, sedative or narcotic agents by local residents of Dehloran, Iran. Interviews conducted with 53 informants (38 male and 15 female) revealed that a total of 32 medicinal plants belonging to 22 families are used in Dehloran as narcotic, sedative and analgesic agents. The most utilized plant families were Asteraceae, Rosaceae and Fabaceae. Approximately 74% of the utilized plants was attributed to herbs, followed by trees (13%) and shrubs (13%). Sixty-six percent of the medicinal plants used in the study area were perennial and the rest were annual or biannual. The most widely used plant parts were flowers (34%) followed by leaves (24%) and fruits (14%). Thirty-nine percent of the medicinal plants were used as sedatives, 39% as analgesics, and 24% as narcotics. Recommended plants in this study can be good candidates for further clinical and laboratory trials on diseases that are associated with pain, suffering, stress and depression. They also can be used to develop new sedative, narcotic and analgesic drugs.

Low dose ketamine use in the emergency department, a new direction in pain management.

PubMed

Pourmand, A; Mazer-Amirshahi, M; Royall, C; Alhawas, R; Shesser, R

2017-06-01

There is a need for alternative non-opioid analgesics for the treatment of acute, chronic, and refractory pain in the emergency department (ED). Ketamine is a fast acting N-methyl-d-aspartate (NMDA) receptor antagonist that provides safe and effective analgesia. The use of low dose ketamine (LDK) (<1mg/kg) provides sub-dissociative levels of analgesia and has been studied as an alternative and/or adjunct to opioid analgesics. We reviewed 11 studies using LDK either alone or in combination with opioid analgesics in the ED. Ketamine was shown to be efficacious at treating a variety of painful conditions. It has a favorable adverse effect profile when given at sub-dissociative doses. Studies have also compared LDK to opioids in the ED. Although ketamine's analgesic effects were not shown to be superior, they were comparable to opioids. LDK has the benefit of causing less respiratory depression. It likely has less wide spread potential for abuse. Nursing protocols for the administration of LDK have been studied. We believe that LDK has the potential to be a safe and effective alternative and/or adjunct to opioid analgesics in the ED. Additional studies are needed to expand upon and determine the optimal use of LDK in the ED. Copyright © 2017 Elsevier Inc. All rights reserved.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.

PubMed

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S; Wieclaw, Linda; Clifford, David B

2013-07-01

There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo. This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout. Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. Wiley Periodicals, Inc.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

PubMed Central

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

2014-01-01

Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

Factors Associated With the Use of Postoperative Analgesics in Patients Undergoing Direct Microlaryngoscopy.

PubMed

Taliercio, Salvatore; Sanders, Brian; Achlatis, Stratos; Fang, Yixin; Branski, Ryan; Amin, Milan

2017-05-01

Morbidity associated with suspension laryngoscopy has been well documented. However, standard of care with regard to postoperative analgesia has not been described, and anecdotal evidence suggests wide variability with regard to postoperative narcotic and non-narcotic recommendations. We sought to quantify the postoperative course following suspension microlaryngoscopy by relating patient-based and intraoperative measures with analgesic use. Body mass index (BMI), Friedman tongue position (FTP), and Mallampati scores as well as laryngoscope type, number of attempts required for optimal visualization, and suspension time were documented in 50 consecutive patients undergoing routine suspension microlaryngoscopy. Postoperative symptoms and analgesic use was queried on postoperative days 1, 3, and 10. In this cohort, 62.5% employed postoperative analgesia. However, only 20% required narcotics. No difference in suspension time was identified in those taking analgesics (33.0 vs 37.3 minutes, P = .44). In addition, no relationship between procedure type and the need for analgesia was noted. The majority of patients (76%) described sore throat persisting for 3 postoperative days; 36% reported sore throat persisting beyond postoperative day 3. The majority of patients undergoing microlaryngoscopy reported discomfort, but symptoms were largely ameliorated with over-the-counter analgesics. Routine prescription of narcotics following routine suspension laryngoscopy may be unnecessary.

Parental attitudes regarding analgesic use for children: differences in ethnicity and language.

PubMed

Fortier, Michelle A; Martin, Sarah R; Kain, Danielle I; Tan, Edwin T

2011-11-01

The aim of this study was to identify the impact of ethnicity and language on parental attitudes regarding analgesic use to treat children's pain. A total of 206 parents of children undergoing outpatient surgery were recruited to complete the Medication Attitudes Questionnaire, a measure of parental beliefs about using analgesic medications to treat children's pain. Parents were grouped into one of 3 categories according to ethnicity and primary language spoken: English-speaking white, English-speaking Hispanic, and Spanish-speaking Hispanic. Group differences in pain medication attitudes were examined. After controlling for socioeconomic status, English-speaking Hispanic parents endorsed higher levels of misconceptions about pain medication use, including a tendency to avoid analgesic use for children, compared with English-speaking white and Spanish-speaking Hispanic parents. This study highlights parental characteristics, including ethnicity and language, which may place children at higher risk for undertreatment of acute pain based on misconceptions about analgesic use for children. Specifically, English-speaking Hispanic parents may be most likely to undertreat children's pain at home. Future studies are needed to identify the most appropriate means of providing education to counter parental misconceptions and support optimal pain management of children's pain in the home setting. Copyright © 2011 Elsevier Inc. All rights reserved.

Analgesic and anti-inflammatory controlled-released injectable microemulsion: Pseudo-ternary phase diagrams, in vitro, ex vivo and in vivo evaluation.

PubMed

Pineros, Isabel; Slowing, Karla; Serrano, Dolores R; de Pablo, Esther; Ballesteros, Maria Paloma

2017-04-01

Development of analgesic and anti-inflammatory controlled-released injectable microemulsions utilising lysine clonixinate (LC) as model drug and generally regarded as safe (GRAS) excipients. Different microemulsions were optimised through pseudo-ternary phase diagrams and characterised measuring droplet size, viscosity, ex vivo haemolytic activity and in vitro drug release. The anti-inflammatory and analgesic activity was tested in mice (Hot plate test) and rats (Carrageenan-induced paw edema test) respectively and their activity was compared to an aqueous solution of LC salt. The aqueous solution showed a faster and shorter response whereas the optimised microemulsion increased significantly (p<0.01) the potency and duration of the analgesic and anti-inflammatory activity after deep intramuscular injection. The droplet size and the viscosity were key factors to control the drug release from the systems and enhance the effect of the formulations. The microemulsion consisting of Labrafil®/Lauroglycol®/Polysorbate 80/water with LC (56.25/18.75/15/10, w/w) could be a promising formulation after buccal surgery due to its ability to control the drug release and significantly achieve greater analgesic and anti-inflammatory effect over 24h. Copyright © 2016. Published by Elsevier B.V.

Effect of music on labor pain relief, anxiety level and postpartum analgesic requirement: a randomized controlled clinical trial.

PubMed

Simavli, Serap; Gumus, Ilknur; Kaygusuz, Ikbal; Yildirim, Melahat; Usluogullari, Betul; Kafali, Hasan

2014-01-01

The control of labor pain and the prevention of suffering are major concerns of clinicians and their patients. The aim of this study was to evaluate the effect of music on labor pain and anxiety, maternal hemodynamics, fetal-neonatal parameters and postpartum analgesic requirement in primiparous women. Overall, 156 primiparous women who expected vaginal delivery were recruited and randomly assigned to a music group (n = 77) or a control group (n = 79). Women in the music group listened to music during labor. Pain intensity and anxiety level were measured using a visual analogue scale (0-10 cm). The two groups were compared in terms of pain severity, anxiety level, maternal hemodynamics, fetal-neonatal parameters and postpartum analgesic requirement. Mothers in the music therapy group had a lower level of pain and anxiety compared with those in the control group at all stages of labor (p < 0.001). A significant difference was observed between the two groups in terms of maternal hemodynamics and fetal heart rate after intervention (p < 0.01). Postpartum analgesic requirement significantly decreased in the music therapy group (p < 0.01). Listening to music during labor has a positive impact on labor pain and anxiety, maternal-fetal parameters and analgesic requirement. © 2014 S. Karger AG, Basel.

Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

PubMed Central

Calixto-Campos, Cassia; Corrêa, Mab P.; Carvalho, Thacyana T.; Zarpelon, Ana C.; Hohmann, Miriam S. N.; Rossaneis, Ana C.; Coelho-Silva, Leticia; Pavanelli, Wander R.; Pinge-Filho, Phileno; Bernardy, Catia C. F.; Verri, Waldiceu A.

2015-01-01

Cancer pain directly affects the patient's quality of life. We have previously demonstrated that the subcutaneous administration of the mammary adenocarcinoma known as Ehrlich tumor induces pain in mice. Several studies have shown that the flavonoid quercetin presents important biological effects, including anti-inflammatory, antioxidant, analgesic, and antitumor activity. Therefore, the analgesic effect and mechanisms of quercetin were evaluated in Ehrlich tumor-induced cancer pain in mice. Intraperitoneal (i.p.) treatments with quercetin reduced Ehrlich tumor-induced mechanical and thermal hyperalgesia, but not paw thickness or histological alterations, indicating an analgesic effect without affecting tumor growth. Regarding the analgesic mechanisms of quercetin, it inhibited the production of hyperalgesic cytokines IL-1β and TNFα and decreased neutrophil recruitment (myeloperoxidase activity) and oxidative stress. Naloxone (opioid receptor antagonist) inhibited quercetin analgesia without interfering with neutrophil recruitment, cytokine production, and oxidative stress. Importantly, cotreatment with morphine and quercetin at doses that were ineffective as single treatment reduced the nociceptive responses. Concluding, quercetin reduces the Ehrlich tumor-induced cancer pain by reducing the production of hyperalgesic cytokines, neutrophil recruitment, and oxidative stress as well as by activating an opioid-dependent analgesic pathway and potentiation of morphine analgesia. Thus, quercetin treatment seems a suitable therapeutic approach for cancer pain that merits further investigation. PMID:26351625

An update on analgesics.

PubMed

Power, I

2011-07-01

Recent introduction of new analgesics into the clinic is best described as a slow process with activity classified into two main areas: improving analgesic efficacy/potency and reducing side-effect profile. This review article describes some of the recent advances with an emphasis on use in the acute setting. In this respect, opioids continue to be the mainstay (but not the only) analgesic and there have been important improvements in their clinical effect profile. For example, tapentadol has been introduced as a mixed opioid and norepinephrine uptake inhibitor which, unlike tramadol, does not require metabolic activation and does not suffer from isomer-dependent pharmacodynamics. Opioid antagonists have received much attention recently either used alone, methylnaltrexone (s.c) or alvimopan (p.o), or in combination, Targinact (oxycodone/naloxone), and appear to be effective in reducing opioid side-effects such as those in the gastrointestinal tract. Other agents where there has been recent development include the use of gabapentin, methylxanthines, and local anaesthetics. An interesting area of translation of basic research is in the inhibition of breakdown of endogenous opioids with opiorphin, targeting of the endocannabinoid system, and the use of ampakines to obtund opioid-induced side-effects. It is clear that there is still much work to be done, but the need for highly efficacious analgesics with good side-effect profile remains.

“Is there any way I can get something for my pain?” Patient strategies for requesting analgesics

PubMed Central

Wilbur, Rachel; McLean, Samuel; Sleath, Betsy

2014-01-01

Objective We examined the direct and indirect means by which patients express a desire for analgesic medication. Methods Back pain patients presenting to an academic ED were invited to participate in a study of patient-provider communication. Audio-recorded encounters were transcribed verbatim and transcripts analyzed using a qualitative approach based on conversation analysis. Results Requests for analgesics were documented in 15 out of 74 interactions (20%). We identified three basic patterns: direct requests, in which the patient explicitly asked for medication; indirect requests, in which the patient hinted at a desire for medication but did not ask for it outright; and no request, in which the provider discussed a prescription without the patient requesting it. Conclusion Most patients did not request analgesics. When they did so, they utilized strategies of mitigation, indirection, and deference that presented themselves as deserving patients while upholding the physician's autonomy. Practice Implications Patients come to the clinical encounter with a variety of expectations, of which a desire for an analgesic may be only part of the picture. Rather than focusing on strategies for inuring providers to inappropriate patient requests, it may be useful to devote clinical resources to examining patients' priorities and expectations for treatment. PMID:25468395

Pain treatment and its cost in old people with dementia: a descriptive analysis from the Registry of Dementias of Girona (ReDeGi).

PubMed

Calvó-Perxas, Laia; López-Pousa, Secundino; Turró-Garriga, Oriol; de Eugenio, Rosa; Linares, Marta; Fernández, Maria Del Mar; Castellanos, Mar; Casas, Isabel; Turón-Estrada, Antoni; Casadevall, Teresa; Coromina, Joan; Vilalta-Franch, Joan; Garre-Olmo, Josep

2013-05-01

Pain prevalence is high among elderly people, and equally prevalent in those with dementia. The aim of this study was to describe the use analgesics, as well as the cost of these treatments in old people with dementia. We used a cross-sectional design using 1186 cases registered by the Registry of Dementias of Girona from 2007 to 2008. All drugs were categorized following the Anatomic Therapeutic Chemical classification and grouped according to the World Health Organization (WHO) analgesic ladder steps. Descriptive statistical methods were used. Analgesics were prescribed to 78.6% (95% CI, 76.2-81.0) of the registered cases. Of them, 80.6% (95% CI, 78.0-83.2) were treated following step 1 of the WHO analgesic ladder, 16.8% (95% CI, 14.4-19.3) following step 2 and 2.6% (95% CI, 1.5-3.6) following step 3. Pain treatment in old people with dementia had a cost of 42.1 € per patient and year, with no significant differences depending on the subtype of dementia. The use of analgesics in our sample was not associated to age or to dementia severity, which are themselves risk factors for increased pain. Moreover, no differences were detected depending on the subtype of dementia.

The analgesic effects of exogenous melatonin in humans.

PubMed

Andersen, Lars Peter Holst

2016-10-01

The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects. In study I, we systematically reviewed all randomized studies investigating clinical effects of perioperative melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic effects of melatonin in surgical patients, equating reductions of 20 mm and 19 mm, respectively on a VAS, compared with placebo. Profound heterogeneity between the included studies was, however, present. In study II, we aimed to investigate the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous melatonin in a validated human inflammatory pain model, the human burn model. The study was performed as a randomized, double blind placebo-controlled crossover study. Primary outcomes were pain during the burn injury and areas of secondary hyperalgesia. No significant effects of exogenous melatonin were observed with respect to primary or secondary outcomes, compared to placebo. Study III and IV estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin demonstrated a t max value of 41 minutes. Bioavailability of oral melatonin was only 3%. Elimination t 1/2 were approximately 45 minutes following both oral and intravenous administration, respectively. High-dose intravenous melatonin was not associated with increased sedation, in terms of simple reaction times, compared to placebo. Similarly, no other adverse effects were reported. In Study V, we aimed to re-analyse data obtained from a randomized analgesic drug trial by a selection of standard statistical test. Furthermore, we presented an integrated assessment method of longitudinally measured pain intensity and opioid consumption. Our analyses documented that the employed statistical method impacted the statistical significance of post-operative analgesic outcomes. Furthermore, the novel integrated assessment method combines two interdependent outcomes, lowers the risk of type 2 errors, increases the statistical power, and provides a more accurate description of post-operative analgesic efficacy. Exogenous melatonin may offer an effective and safe analgesic drug. At this moment, however, the results of human studies have been contradictory. High-quality randomized experimental- and clinical studies are still needed to establish a "genuine" analgesic effect of the drug in humans. Other perioperative effects of exogenous melatonin should also be investigated, before melatonin can be introduced for clinical routine use in surgical patients. Despite promising experimental and clinical findings, several unanswered questions also relate to optimal dosage, timing of administration and administration route of exogenous melatonin.

21 CFR 201.322 - Over-the-counter drug products containing internal analgesic/antipyretic active ingredients...

Code of Federal Regulations, 2010 CFR

2010-04-01

... not limited to, acetaminophen, aspirin, carbaspirin calcium, choline salicylate, ibuprofen, ketoprofen... anti-inflammatory analgesic/antipyretic active ingredients—including but not limited to aspirin...—including but not limited to aspirin, carbaspirin calcium, choline salicylate, ibuprofen, ketoprofen...

Timely pain management in the emergency department.

PubMed

Patrick, Patricia A; Rosenthal, Barry M; Iezzi, Carina A; Brand, Donald A

2015-03-01

Delivering timely pain relief remains a challenge for most emergency departments. To evaluate the effectiveness of a policy aimed at delivering analgesics within 30 min to patients presenting to an emergency department with severe pain. Subjects were aged ≥19 years, had a principal diagnosis of renal colic, hip fracture, or sickle cell disease, reported a pain score ≥8 on a scale of 0 to 10 at triage, and continued to report a score in this range until receiving analgesia. The study compared proportions of patients receiving analgesics within the 30-min target, median time to analgesic administration, and median time to relief of severe pain (decline in pain level to score <8) during 6 months before vs. 6 months after implementation of the new pain management policy. Paradoxically, the median total waiting time to analgesic administration increased from 64 min (n = 75) to 80 min (n = 70) after policy implementation (p = 0.01), and the proportion of patients receiving analgesics within 30 min declined from 17% (13/75) to 7% (5/70) (p = 0.08). Median time to relief of severe pain did not differ significantly between periods (130.5 vs. 153 min; p = 0.31). After implementation of the new pain management policy, the proportion of patients with severe pain receiving analgesics within 30 min actually declined. Although a 30-min target may be unrealistic, it seems reasonable to conclude that something is wrong when patients with notoriously painful conditions must typically wait 1-2 h to obtain relief. Given the millions of individuals who receive care in emergency departments nationwide each year, the suffering caused by delays occurs on a large scale, so creative approaches are clearly needed to overcome the obstacles. Copyright © 2015 Elsevier Inc. All rights reserved.

Postoperative analgesic efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery

PubMed Central

Gandhi, Ranju; Sunder, Rani

2012-01-01

Background: Analgesic efficacy of rectal acetaminophen is variable in different surgical procedures. Little data is available on its efficacy in ophthalmic surgeries. We conducted this prospective, randomized, double blind study to evaluate and compare the efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery over a 24 hour period. Materials and Methods: 135 children scheduled for elective ophthalmic surgery were randomly allocated to one of the three groups, high, low, or control (H, L, or N) and received rectal acetaminophen 40 mg/kg, 20 mg/kg or no rectal drug respectively after induction of general anesthesia. Postoperative observations included recovery score, hourly observational pain score (OPS) up to 8 hours, time to first analgesic demand, and requirement of rescue analgesics and antiemetics over a 24 hour period. Results: Nineteen of 30 (63%) of children in group N required postoperative rescue analgesic versus 5/48 (10%) of group H (P <0.0001) and 10/47 (23%) of group L (P =0.0005) during 24 hour period. Mean time to requirement of first analgesic was 206±185 min in group H, 189±203min in group L, and 196 ±170 min in group N (P=0.985). OPS was significantly lower in group H and L compared to group N during first 8 hours. Requirement of rescue antiemetic was 18.7% in group H as compared to 23% each in group L and group N (P >0.5). Conclusions: Single dose rectal acetaminophen can provide effective postoperative analgesia for pediatric ophthalmic surgery at both high dose (40 mg/kg) and low dose (20 mg/kg) both in early postoperative and over a 24 hour period. PMID:23225924

Attachment styles, pain, and the consumption of analgesics during labor: a prospective observational study.

PubMed

Costa-Martins, José Manuel; Pereira, Marco; Martins, Henriqueta; Moura-Ramos, Mariana; Coelho, Rui; Tavares, Jorge

2014-03-01

Individuals with less secure attachment styles have been shown to experience more pain than people with more secure attachment styles; however, attachment styles have not yet been examined in the context of labor pain and analgesic consumption. The purpose of this prospective observational study was to assess the influence of the mother's attachment style on the perception of labor pain, as assessed by a visual analog scale and analgesic consumption. Eighty-one pregnant women with a mean age of 32 years (standard deviation = 5.1) were assessed during the third trimester of pregnancy and during labor. The physical predictors of labor pain were recorded, and the adult attachment style was assessed with the Adult Attachment Scale-Revised. For labor analgesia, a low dose of patient-controlled epidural analgesia protocol (ropivacaine .6 mg/mL plus sufentanil .5 μg/mL) was used. Women with a secure attachment style reported significantly less labor pain (P < .001) and a significantly lower analgesic consumption during labor (P < .001) than insecurely attached women. These findings suggest that women's attachment style was associated with labor pain and analgesic consumption and support the relevance of the attachment theory as a promising conceptual framework for understanding labor pain. This study showed that women with an insecure attachment style were more likely to report higher pain before patient-controlled epidural analgesia and higher analgesic consumption and to request supplemental analgesia during labor. The assessment of adult attachment has the potential to identify women at high risk of poorly coping with pain during childbirth. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Modeling the Trajectory of Analgesic Demand Over Time After Total Knee Arthroplasty Using the Latent Curve Analysis.

PubMed

Lo, Po-Han; Tsou, Mei-Yung; Chang, Kuang-Yi

2015-09-01

Patient-controlled epidural analgesia (PCEA) is commonly used for pain relief after total knee arthroplasty (TKA). This study aimed to model the trajectory of analgesic demand over time after TKA and explore its influential factors using latent curve analysis. Data were retrospectively collected from 916 patients receiving unilateral or bilateral TKA and postoperative PCEA. PCEA demands during 12-hour intervals for 48 hours were directly retrieved from infusion pumps. Potentially influential factors of PCEA demand, including age, height, weight, body mass index, sex, and infusion pump settings, were also collected. A latent curve analysis with 2 latent variables, the intercept (baseline) and slope (trend), was applied to model the changes in PCEA demand over time. The effects of influential factors on these 2 latent variables were estimated to examine how these factors interacted with time to alter the trajectory of PCEA demand over time. On average, the difference in analgesic demand between the first and second 12-hour intervals was only 15% of that between the first and third 12-hour intervals. No significant difference in PCEA demand was noted between the third and fourth 12-hour intervals. Aging tended to decrease the baseline PCEA demand but body mass index and infusion rate were positively correlated with the baseline. Only sex significantly affected the trend parameter and male individuals tended to have a smoother decreasing trend of analgesic demands over time. Patients receiving bilateral procedures did not consume more analgesics than their unilateral counterparts. Goodness of fit analysis indicated acceptable model fit to the observed data. Latent curve analysis provided valuable information about how analgesic demand after TKA changed over time and how patient characteristics affected its trajectory.

Mechanism-Driven Phase I Translational Study of Trifluoperazine in Adults with Sickle Cell Disease

PubMed Central

Molokie, Robert E.; Wilkie, Diana J.; Wittert, Harriett; Suarez, Marie L.; Yao, Yingwei; Zhao, Zhongsheng; He, Ying; Wang, Zaijie J.

2014-01-01

Recent evidence of neuropathic pain among adults with sickle cell disease (SCD) reveals a need for adjuvant analgesic treatments for these patients. Ca2+/calmodulin protein kinase IIα (CaMKIIα) has a known role in neuropathic pain and trifluoperazine is a potent CaMKIIα inhibitor. The study aim was to determine trifluoperazine's acute effects, primarily on adverse effects and secondarily on pain intensity reduction, in adults with SCD. In a phase I, open-label study of 6 doses of trifluoperazine (0.5, 1, 2, 5, 7.5, 10 mg), we obtained 7-hourly and 24-hour repeated measures of adverse effects, pain intensity, and supplemental opioid analgesics in 18 adults with SCD (18 hemoglobin SS disease, 15 women, average age 35.8 ± 8.9 years, ranged 23-53) each of whom received a single dose. Data were analyzed with descriptive statistics. Subjects reported moderate to severe sedative effects at 7.5 and 10 mg doses, respectively. Eight subjects reported 50% reduction in chronic pain without severe sedation or supplemental opioid analgesics; one of these subjects had dystonia 24.5 hrs after the 10 mg dose. The analgesic effect lasted for at least 24 hrs in 3 subjects. Sedation resolved with caffeine and dystonia resolved with diphenhydramine. Adults with SCD experienced minimal adverse effects at doses under 10 mg. In this molecular mechanism-driven translational study, trifluoperazine shows promise as an analgesic drug that is worthy of further testing in a randomized controlled study of adults with SCD starting at a dose of 1 mg in repeated doses to determine long-term adverse and analgesic effects. PMID:24211787

Comparable effects of exercise and analgesics for pain secondary to knee osteoarthritis: a meta-analysis of trials included in Cochrane systematic reviews.

PubMed

Henriksen, Marius; Hansen, Julie B; Klokker, Louise; Bliddal, Henning; Christensen, Robin

2016-07-01

Evidence of comparative effectiveness of different treatment approaches is important for clinical decision-making, yet absent for most recommended treatments of knee osteoarthritis pain. The objective of this study was to estimate the comparative effectiveness of exercise versus orally administered analgesics for pain in patients with knee osteoarthritis. The Cochrane Database of systematic reviews was searched for meta-analyses of randomized controlled studies comparing exercise or analgesics with a control group (placebo or usual care) and with pain as an outcome. Individual study estimates were identified and effect sizes were calculated from group differences. We combined study-level effects on pain with a random effects meta-analysis and compared effect sizes between exercise trials and trials with analgesic interventions. We included six Cochrane reviews (four pharmacology, two exercise). From these, 54 trials were eligible (20 pharmacology, 34 exercise), with 9806 participants (5627 pharmacology, 4179 exercise). The pooled effect size of pharmacological pain interventions was 0.41 (95% CI: 0.23-0.59) and for exercise 0.46 standardized mean difference (95% CI: 0.34-0.59). There was no statistically significant difference between the two types of intervention (difference: 0.06 standardized mean difference [95% CI: -0.28-0.16; p = 0.61]). This meta-epidemiological study provides indirect evidence that for knee osteoarthritis pain, the effects from exercise and from oral analgesics are comparable. These results may support shared decision-making where a patient for some reason is unable to exercise or who consider exercise as unviable and analgesics as a more feasible choice. PROSPERO registration: CRD42013006924.

Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy.

PubMed

Micov, Ana; Tomić, Maja; Pecikoza, Uroš; Ugrešić, Nenad; Stepanović-Petrović, Radica

2015-07-01

Painful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effectiveness of national guidance in changing analgesic prescribing in primary care from 2002 to 2009: An observational database study

PubMed Central

Bedson, J; Belcher, J; Martino, OI; Ndlovu, M; Rathod, T; Walters, K; Dunn, KM; Jordan, KP

2013-01-01

Background Numerous national guidelines have been issued to assist general practitioners’ safe analgesic prescribing. Their effectiveness is unclear. The objective of this study was to examine trends in general practitioners’ prescribing behaviour in relation to national guidelines. Methods This was a retrospective observational database study of registered adult patients prescribed an analgesic (2002–2009) from the Consultations in Primary Care Archive – 12 North Staffordshire general practices. Prescribing guidance from the UK Medicines Regulatory Health Authority (MHRA) regarding non-steroidal anti-inflammatory drugs (NSAIDs) and co-proxamol, and the National Institute for Health and Clinical Excellence (NICE) osteoarthritis (OA) management guidelines were considered. Analgesic prescribing rates were examined, arranged according to a classification of six equipotent medication groups: (1) basic analgesics; (2)–(5) increasingly potent opioids and (6) NSAIDs. In each quarter from 2002 to 2009, the number of patients per 10,000 registered population receiving a prescription for the first time from each group was determined. Quarters associated with significant changes in the underlying prescribing trend were determined using joinpoint regression. Results A significant decrease in incident co-proxamol and Cox-2 prescribing occurred around the time of the first MHRA advice to stop using them and were rarely prescribed thereafter. The new prescribing of weak analgesics (e.g., co-codamol 8/500) increased at this same time. Initiating topical NSAIDs significantly increased around the time of the NICE OA guidelines. Conclusions Significant prescribing changes occurred when national advice and guidelines were issued. The effectiveness of this advice may vary depending upon the content and method of dissemination. Further evaluation of the optimal methods for delivering prescribing guidance is required. PMID:22865816

Postoperative pain treatment after total knee arthroplasty: A systematic review

PubMed Central

Wetterslev, Mik; Hansen, Signe Elisa; Hansen, Morten Sejer; Mathiesen, Ole; Dahl, Jørgen B.

2017-01-01

Introduction The aim of this systematic review was to document efficacy, safety and quality of evidence of analgesic interventions after total knee arthroplasty (TKA). Methods This PRISMA-compliant and PROSPERO-registered review includes all-language randomized controlled trials of medication-based analgesic interventions after TKA. Bias was evaluated according to Cochrane methodology. Outcomes were opioid consumption (primary), pain scores at rest and during mobilization, adverse events, and length of stay. Interventions investigated in three or more trials were meta-analysed. Outcomes were evaluated using forest plots, Grading of Recommendations Assessment, Development and Evaluation (GRADE), L’Abbe Plots and trial sequential analysis. Results The included 113 trials, investigating 37 different analgesic interventions, were characterized by unclear/high risk of bias, low assay sensitivity and considerable differences in pain assessment tools, basic analgesic regimens, and reporting of adverse events. In meta-analyses single and continuous femoral nerve block (FNB), intrathecal morphine, local infiltration analgesia, intraarticular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and gabapentinoids demonstrated significant analgesic effects. The 24-hour morphine-sparing effects ranged from 4.2 mg (CI: 1.3, 7.2; intraarticular local anaesthetics), to 16.6 mg (CI: 11.2, 22; single FNB). Pain relieving effects at rest at 6 hours ranged from 4 mm (CI: -10, 2; gabapentinoids), to 19 mm (CI: 8, 31; single FNB), and at 24 hours from 3 mm (CI: -2, 8; gabapentinoids), to 16 mm (CI: 8, 23; continuous FNB). GRADE-rated quality of evidence was generally low. Conclusion A low quality of evidence, small sample sizes and heterogeneity of trial designs prohibit designation of an optimal procedure-specific analgesic regimen after TKA. PMID:28273133

Does neonatal pain management in intensive care units differ between night and day? An observational study.

PubMed

Guedj, Romain; Danan, Claude; Daoud, Patrick; Zupan, Véronique; Renolleau, Sylvain; Zana, Elodie; Aizenfisz, Sophie; Lapillonne, Alexandre; de Saint Blanquat, Laure; Granier, Michèle; Durand, Philippe; Castela, Florence; Coursol, Anne; Hubert, Philippe; Cimerman, Patricia; Anand, K J S; Khoshnood, Babak; Carbajal, Ricardo

2014-02-20

To determine whether analgesic use for painful procedures performed in neonates in the neonatal intensive care unit (NICU) differs during nights and days and during each of the 6 h period of the day. Conducted as part of the prospective observational Epidemiology of Painful Procedures in Neonates study which was designed to collect in real time and around-the-clock bedside data on all painful or stressful procedures. 13 NICUs and paediatric intensive care units in the Paris Region, France. All 430 neonates admitted to the participating units during a 6-week period between September 2005 and January 2006. During the first 14 days of admission, data were collected on all painful procedures and analgesic therapy. The five most frequent procedures representing 38 012 of all 42 413 (90%) painful procedures were analysed. Observational study. We compared the use of specific analgesic for procedures performed during each of the 6 h period of a day: morning (7:00 to 12:59), afternoon, early night and late night and during daytime (morning+afternoon) and night-time (early night+late night). 7724 of 38 012 (20.3%) painful procedures were carried out with a specific analgesic treatment. For morning, afternoon, early night and late night, respectively, the use of analgesic was 25.8%, 18.9%, 18.3% and 18%. The relative reduction of analgesia was 18.3%, p<0.01, between daytime and night-time and 28.8%, p<0.001, between morning and the rest of the day. Parental presence, nurses on 8 h shifts and written protocols for analgesia were associated with a decrease in this difference. The substantial differences in the use of analgesics around-the-clock may be questioned on quality of care grounds.

Predictors of Recall Certainty of Dates of Analgesic Medication Use in Pregnancy

PubMed Central

Radin, Rose G.; Mitchell, Allen A.; Werler, Martha M.

2012-01-01

Purpose Recalled dates of medication use are difficult to validate, particularly for over-the-counter (OTC) medications. We evaluated mothers’ recall certainty as an approximation of the accuracy of their recalled exposures. Methods We used data from the Slone Epidemiology Center Birth Defects Study collected by retrospective interview of women about pregnancy medication use. For each medication reported, women were asked to report the dates of their use and how certain they were of their reported dates. For this analysis, 32,107 reports from 14,577 analgesic users were categorized as ‘high’ or ‘low’ recall certainty if they considered a reported date as exact or estimated, respectively. Patterns of analgesic use, maternal demographics, and health behaviors were explored as predictors of high recall certainty of dates of analgesic use. We used log-binomial regression with the generalized estimating equations extension to account for multiple reports per subject in estimating prevalence ratios (PR) and 95% confidence intervals. Results Relative to episodes of short-term routine use (≥4 times/week for ≤30 days), high recall certainty was more likely for episodes of a single dose (prescription PR=1.92 (1.61, 2.27); OTC PR=3.65 (3.03, 4.40)) and less likely for episodes of occasional use (prescription PR=0.10 (0.05, 0.18); OTC PR=0.65 (0.53, 0.79)). The association of chronic routine use with high recall certainty was inverse among prescription analgesics and positive among OTC analgesics (prescription PR=0.56 (0.40, 0.80); OTC PR=2.46 (1.92, 3.42)). Conclusions Some characteristics that were associated with recall accuracy in previous studies were also associated with recall certainty in this study. PMID:22674801

Postoperative analgesic efficacy of ultrasound-guided ilioinguinal-iliohypogastric nerve block compared with medial transverse abdominis plane block in inguinal hernia repair: A prospective, randomised trial.

PubMed

Bhatia, Nidhi; Sen, Indu Mohini; Mandal, Banashree; Batra, Ankita

2018-03-29

Analgesic efficacy of ultrasound-guided transverse abdominis plane block, administered a little more medially, just close to the origin of the transverse abdominis muscle has not yet been investigated in patients undergoing unilateral inguinal hernia repair. We hypothesised that medial transverse abdominis plane block would provide comparable postoperative analgesia to ilioinguinal-iliohypogastric nerve block in inguinal hernia repair patients. This prospective, randomised trial was conducted in 50 ASA I and II male patients≥18 years of age. Patients were randomised into two groups to receive either pre-incisional ipsilateral ultrasound-guided ilioinguinal-iliohypogastric nerve block or medial transverse abdominis plane block, with 0.3ml/kg of 0.25% bupivacaine. Our primary objective was postoperative 24-hour analgesic consumption and secondary outcomes included pain scores, time to first request for rescue analgesic and side effects, if any, in the postoperative period. There was no significant difference in the total postoperative analgesic consumption [group I: 66.04mg; group II: 68.33mg (P value 0.908)]. Time to first request for rescue analgesic was delayed, though statistically non-significant (P value 0.326), following medial transverse abdominis plane block, with excellent pain relief seen in 58.3% patients as opposed to 45.8% patients in ilioinguinal-iliohypogastric nerve block group. Medial transverse abdominis plane block being a novel, simple and easily performed procedure can serve as an useful alternative to ilioinguinal-iliohypogastric nerve block for providing postoperative pain relief in inguinal hernia repair patients. Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Observational evidence that urbanisation and neighbourhood deprivation are associated with escalation in chronic pharmacological pain treatment: a longitudinal population-based study in the Netherlands.

PubMed

Leue, Carsten; Buijs, Servaas; Strik, Jacqueline; Lousberg, Richel; Smit, Jasper; van Kleef, Maarten; van Os, Jim

2012-01-01

To examine, in the light of the association between urban environment and poor mental health, whether urbanisation and neighbourhood deprivation are associated with analgesic escalation in chronic pharmacological pain treatment and whether escalation is associated with prescriptions of psychotropic medication. Longitudinal analysis of a population-based routine dispensing database in the Netherlands. Representative sample of pharmacies, covering 73% of the Dutch nationwide medication consumption in the primary care and hospital outpatient settings. 449 410 patients aged 15-85 years were included, of whom 166 374 were in the Starter group and 283 036 in the Continuation group of chronic analgesic treatment. Escalation of analgesics (ie, change to a higher level of analgesic potency, classified across five levels) in association with urbanisation (five levels) and dichotomous neighbourhood deprivation was analysed over a 6-month observation period. Ordered logistic multivariate model evaluating analgesic treatment. In both Starter and Continuation groups, escalation was positively associated with urbanisation in a dose-response fashion (Starter group: OR (urbanisation level 1 compared with level 5): 1.24, 95% CI 1.18 to 1.30; Continuation group: OR 1.18, 95% CI 1.14 to 1.23). An additional association was apparent with neighbourhood deprivation (Starter group: OR 1.07, 95% CI 1.02 to 1.11; Continuation group: OR 1.04, 95% CI 1.01 to 1.08). Use of somatic and particularly psychotropic co-medication was associated with escalation in both groups. Escalation of chronic analgesic treatment is associated with urban and deprived environments and occurs in a context of adding psychotropic medication prescriptions. These findings suggest that pain outcomes and mental health outcomes share factors that increase risk and remedy suffering.

Pain management following discharge after ambulatory same-day surgery.

PubMed

Watt-Watson, Judy; Chung, Frances; Chan, Vincent W S; McGillion, Michael

2004-05-01

Same-day surgeries are becoming routine for many surgical procedures. However, the degree to which patients need help with pain management at home following laparoscopic cholecystectomy (LC), shoulder, or hand ambulatory day surgery has received minimal examination. This study examined pain and related interference, analgesic use and adverse events, complications and resources utilized, and adequacy of postdischarge information at four time periods. Data were collected from 180 patients by telephone interviews at 24, 48 and 72 hours, and 7 days after discharge. Patients (n = 78 hand, 48 shoulder, 54 LC surgery) were on average 41 years old. For all patients, worst 24-hour pain was reported as moderate to severe at all time periods. Using repeated measures anova demonstrated that shoulder patients had significantly more pain and overall pain-related interference, particularly in sleep and work, from 24 hours to day 7 than did hand or LC patients. The main analgesic taken was acetaminophen (paracetamol) with codeine 30 mg; 50% took no analgesia from 72 hours. About 20% experienced analgesic adverse events within 72 hours, mainly constipation and nausea. Only

The Prescription Pattern of Acetaminophen and Non-Steroidal Anti-Inflammatory Drugs in Patients with Liver Cirrhosis.

PubMed

Hong, Young Mi; Yoon, Ki Tae; Heo, Jeong; Woo, Hyun Young; Lim, Won; An, Dae Seong; Han, Jun Hee; Cho, Mong

2016-10-01

Analgesics, known to be hepatotoxic drugs, are frequently prescribed to patients with liver cirrhosis who are prone to drug-induced liver injury. No guidelines are available regarding the prescription of analgesics in these patients. Therefore, we aimed to evaluate the prescription pattern of most frequently used analgesics in patients with cirrhosis. We assessed the prescription pattern of acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with liver cirrhosis registered in Health Insurance Review Assessment Service database between January 1, 2012 and December 31, 2012. A total of 125,505 patients with liver cirrhosis were registered from January 1, 2012 to December 31, 2012. Of that group, 50,798 (40.5%) patients claimed reimbursement for at least one prescription for acetaminophen or NSAIDs during the one year follow-up period. Overall, NSAIDs (82.7%) were more prescribed than acetaminophen (64.5%). NSAIDs were more prescribed than acetaminophen even in decompensated cirrhosis compared with compensated cirrhosis (71.5% vs. 68.8%, P value < 0.001). There was a marked difference in prescription preference between acetaminophen and NSAIDs among physicians. Internists more frequently prescribed acetaminophen than NSAIDs compared to other physicians (50.9% vs. 76.2%, P < 0.001). Gastroenterologists more frequently prescribed acetaminophen over NSAIDs compared to other internists (80.9% vs. 51.2%, P < 0.001). Analgesics were prescribed in 40.5% of patients with cirrhosis. NSAIDs were more frequently prescribed although they should be avoided. The prescription pattern of analgesics were different significantly among physicians in patients with liver cirrhosis. The harmful effects of NSAIDs in patients with cirrhosis should be reminded to all physicians prescribing analgesics.

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

PubMed

Dualé, Christian; Sierralta, Fernando; Dallel, Radhouane

2007-07-01

One of the possible sites of action of the analgesic effect of morphine is the Nucleus Raphe Magnus, as morphine injected into this structure induces analgesia in transient pain models. In order to test if morphine in the Nucleus Raphe Magnus is also analgesic in a tonic pain model, 5 microg of morphine or saline (control) were microinjected into the Nucleus Raphe Magnus of the rat. Analgesic effects were assessed following nociceptive stimulation using transient heating of the tail (phasic pain) and subcutaneous orofacial injection of 1.5 % formalin (tonic pain). While morphine was strongly analgesic for the tail-flick response (p <0.0001 compared to control), analgesia on the response to formalin was also observed for both early (p = 0.007) and late responses (p = 0.02). However, the response to formalin was not completely blunted. These results suggest that the Nucleus Raphe Magnus is not the exclusive site of action of morphine-induced analgesia in clinical conditions.

Analgesic effects of branding in treatment of headaches.

PubMed Central

Branthwaite, A; Cooper, P

1981-01-01

The effect of branding--that is, the labelling and marketing--of a well-known proprietary analgesic used to treat headaches was studied in a sample of women given a branded or unbranded form with either an inert or an active formulation. The sample was also divided according to whether the subjects were regular users of the brand or users of other brands. The findings showed that branded tablets were overall significantly more effective than unbranded tablets in relieving headaches. Differential effects were observed: the effects of branding were more noticeable one hour after the tablets were taken compared with 30 minutes; in the women given the placebo; and in the users of the brand compared with the users of other brands. It is hypothesised that these effects are due to increased confidence in obtaining relief with a well-known brand, and that branding has an analgesic effect that interacts with the analgesic effects of placebos and active ingredients. PMID:6786566

[Ambulatory laparoscopic cholecystectomy by minilaparoscopy versus traditional multiport ambulatory laparoscopic cholecystectomy. Prospective randomized trial].

PubMed

Planells Roig, Manuel; Arnal Bertomeu, Consuelo; Garcia Espinosa, Rafael; Cervera Delgado, Maria; Carrau Giner, Miguel

2016-02-01

Difference analysis of ambulatorization rate, pain, analgesic requirements and daily activities recovery in patients undergoing laparoscopic cholecystectomy with standard multiport access (CLMP) versus a minilaparoscopic, 3mm size, technique. Prospective randomized trial of 40 consecutive patients undergoing laparoscopic cholecystectomy. Comparison criteria included predictive ultrasound factors of difficult cholecystectomy, previous history of complicated biliary disease and demographics. Results are analyzed in terms of ambulatorization rate, pain, analgesic requirements, postoperative recovery, technical difficulty, hemorrhage intensity, overnight stay, readmission rate and total or partial conversion. Both procedures were similar in surgery time, technical score and hemorrhage score. MLC was associated with similar ambulatorization rate, 85%, and over-night stay 15%, with only 15% partial conversion rate. MLC showed less postoperative pain (P=.026), less analgesic consumption (P=.006) and similar DAR (P=.879). MLC is similar to CLMP in terms of ambulatorization with less postoperative pain and analgesic requirements without differences in postoperative recovery. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Toward an effective peripheral visceral analgesic: responding to the national opioid crisis.

PubMed

Camilleri, Michael

2018-06-01

This minireiew summarizes recent new developments in visceral analgesics. This promising field is important, as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors via biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor, or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs. Other compounds target nonopioid mechanisms, including cannabinoid (CB2), N-methyl-d-aspartate, calcitonin gene-related peptide, estrogen, and adenosine A 2B receptors and transient receptor potential (TRP) channels (TRPV1, TRPV4, and TRPM8). Although current evidence is based predominantly on animal models of visceral pain, early human studies also support the evidence from the basic and animal research. This augurs well for the development of nonaddictive, visceral analgesics for treatment of chronic abdominal pain, an unmet clinical need.

[Hemostatic and analgesic effect of Gonghuan Zhixue Tablet on mice].

PubMed

Fu, Ling-Mei; You, Zhao-Ling; Lei, Lei; Wen, Le-Xi; Chen, Huan-Ming

2004-03-01

To explore the hemostatic and analgesic effect of Gonghuan Zhixue Tablet (GHZXT) on mice and to produce experimental evidence for exploiting new drug for endometrorrhagia caused by Cu-intrauterine contraceptive device (Cu-IUD). Compared with 6-aminocaproic acid and notoginseng, the effects of GHZXT on clotting and bleeding time of mice with capillary method and severed tail were investigated; and compared with aspirin, the analgesic effects of GHZXT on mice were investigated with hot plate and torsive body method. The clotting time of mice was remarkably shortened with a rising of the dosage of GHZXT and the difference between each therapeutic group and distilled water group was remarkable. As compared with distilled water group, the bleeding time of each dosage group of GHZXT was obviously shortened; and each dosage of GHZXT could prolong the time of pain reaction to hot plate and decrease the degree of torsive body of the mice. Pharmacological experiment has proved that GHZXT has evident hemostatic and analgesic function.

Parental Approach to the Prevention and Management of Fever and Pain Following Childhood Immunizations: A Survey Study.

PubMed

Saleh, Ezzeldin; Swamy, Geeta K; Moody, M Anthony; Walter, Emmanuel B

2017-05-01

Antipyretic analgesics are commonly used to prevent and treat adverse events following immunizations. Current practice discourages routine use due to possible blunting of vaccine immune responses. We surveyed 150 parents/caregivers of recently vaccinated 6- and 15-month-old children to determine the prevalence of and beliefs regarding antipyretic analgesics use around vaccinations. 11% used them prophylactically, before vaccination. Use in the first 48 hours after vaccination was 64%, primarily to prevent and/or treat fever and pain. Acetaminophen was administered 2.6 times more frequently than ibuprofen. Ibuprofen was used more in the 15-month compared with the 6-month-old children (28% vs 7.4%, respectively, P = .001). The majority of caregivers disagreed with their use for fever (53%) or pain (59%). Antipyretic analgesic use, including prophylaxis, around vaccinations was common in our study population. Effective interventions are needed to target parents/caregivers to eliminate unnecessary antipyretic analgesic use around vaccination time and foster nonmedication alternatives.

Evaluation of analgesic, antipyretic and anti-inflammatory activity on Cordia dichotoma G. Forst. Leaf.

PubMed

Gupta, Richa; Kaur, Jagjit

2015-01-01

Cordia dichotoma G. Forst. is an important medicinal plant of family Boraginaceae. Traditionally, its leaves are used to treat fever, headache, and joint pain but its medicinal activities have not been proven by research. To evaluate the analgesic, anti-inflammatory, and antipyretic activity of C. dichotoma G. Forst. leaf extract. The various extracts of leaf powder were prepared by using soxhlet apparatus. The methanol extract was selected for pharmacological study. To evaluate analgesic activity, Eddy's hot plate method, to study anti-inflammatory activity, carageenan-induced rat paw edema method, and to study antipyretic activity, yeast-induced pyrexia method was used. SD female rats (180-200 g) were used for the study. In all three tests, the methanol extract high dose (400 mg/kg) was found to be highly significant as compared to standard drug. This study proved the traditional uses of plant leaves and concluded the analgesic, anti-inflammatory, and antipyretic activity of the leaf methanol extract.

Evaluation of analgesic, antipyretic and anti-inflammatory activity on Cordia dichotoma G. Forst. Leaf

PubMed Central

Gupta, Richa; Kaur, Jagjit

2015-01-01

Background: Cordia dichotoma G. Forst. is an important medicinal plant of family Boraginaceae. Traditionally, its leaves are used to treat fever, headache, and joint pain but its medicinal activities have not been proven by research. Objective: To evaluate the analgesic, anti-inflammatory, and antipyretic activity of C. dichotoma G. Forst. leaf extract. Material and Methods: The various extracts of leaf powder were prepared by using soxhlet apparatus. The methanol extract was selected for pharmacological study. To evaluate analgesic activity, Eddy's hot plate method, to study anti-inflammatory activity, carageenan-induced rat paw edema method, and to study antipyretic activity, yeast-induced pyrexia method was used. SD female rats (180-200 g) were used for the study. Results: In all three tests, the methanol extract high dose (400 mg/kg) was found to be highly significant as compared to standard drug. Conclusion: This study proved the traditional uses of plant leaves and concluded the analgesic, anti-inflammatory, and antipyretic activity of the leaf methanol extract. PMID:25598647

A novel analgesic Isolated from a Traditional Chinese Medicine

PubMed Central

Zhang, Yan; Wang, Chaoran; Wang, Lien; Parks, Gregory Scott; Zhang, Xiuli; Guo, Zhimou; Ke, Yanxiong; Li, Kang-Wu; Kim, Mi Kyeong; Vo, Benjamin; Borrelli, Emiliana; Ge, Guangbo; Yang, Ling; Wang, Zhiwei; Garcia-Fuster, M. Julia; Luo, Z. David; Liang, Xinmiao; Civelli, Olivier

2014-01-01

Summary Background Current pain management is limited, in particular, with regard to chronic pain. In an attempt to discover novel analgesics, we combined the approach developed to characterize traditional Chinese medicine (TCM), as part of the “herbalome” project, with the reverse pharmacology approach aimed at discovering new endogenous transmitters and hormones. Results In a plant used for centuries for its analgesic properties, we identify a compound, dehydrocorybulbine (DHCB) that is effective at alleviating thermally induced acute pain. We synthesize DHCB and show that it displays moderate dopamine receptor antagonist activities. By using selective pharmacological compounds and dopamine receptor knockout (KO) mice, we show that DHCB antinociceptive effect is primarily due to its interaction with D2 receptors, at least at low doses. We further show that DHCB is effective against inflammatory pain and injury-induced neuropathic pain and furthermore causes no antinociceptive tolerance. Conclusion Our study casts DHCB as a different type of analgesic compound and as a promising lead in pain management. PMID:24388848

Additive effect of combined application of magnesium and MK-801 on analgesic action of morphine.

PubMed

Bujalska-Zadrożny, Magdalena; Duda, Kamila

2014-01-01

As previously reported, magnesium ions (Mg(2+)) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg(2+) behaves like an N-methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared with that of MK-801. Acute pain was evoked by mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801 (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to acute stimuli or the streptozotocin hyperalgesia but significantly augmented the analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e. magnesium sulphate and MK-801) were applied concomitantly, a clear additive effect on the analgesic action of morphine occurred in both models of pain. Possible explanations of these observations are discussed. © 2014 S. Karger AG, Basel.

The use of virtual reality and audiovisual eyeglass systems as adjunct analgesic techniques: a review of the literature.

PubMed

Wismeijer, Andreas A J; Vingerhoets, Ad J J M

2005-12-01

This review focuses on the application of technologically advanced methods of audiovisual distraction as adjunct analgesic techniques; more specifically, (a) virtual reality (VR) and (b) audiovisual (A/V) eyeglass systems (A/V distraction). It is assumed that distraction taxes the patient's limited attention capacity, resulting in the withdrawal of attention from the noxious stimulus with a subsequent reduction in pain. Twenty studies evaluating the analgesic potential of both methods in different patient groups and in healthy volunteers were identified in the scientific literature. Although the majority of these studies are hampered by serious methodological drawbacks, particularly a small number of participants, the results nevertheless strongly suggest that both VR and A/V distraction can be a very promising analgesic technique that may be used safely and effectively for the reduction of pain and discomfort during medical procedures. An additional important aspect is that few negative side effects have been reported. Directions for future research are presented.

[Analgesic effect of ferulic acid on CCI mice: behavior and neurobiological analysis].

PubMed

Lv, Wei-Hong; Zhang, Lu; Wu, Shu-Juan; Chen, Sai-Zhen; Zhu, Xin-Bo; Pan, Jian-Chun

2013-11-01

To study the analgesic effect of chronic administration with ferulic acid, and preliminarily discuss its mechanism. Thermal hyperalgesia and mechanical allodynia tests were conducted to observe the analgesic effect of chronic administration with ferulic acid on CCI mice. The neurochemical detection method was applied to observe the effect chronic administration with ferulic acid on monoamine neurotransmitter and monoamine oxidase activity. Compared with the normal group, CCI mice showed notable reduction in heat sensation and nociceptive threshold in and mechanical allodynia. Ferulic acid (10, 20, 40 and 80 mg x kg(-1), po) could significantly reverse the situations. In an in-depth study, we found that the reason for these results was that ferulic acid was dose-dependent in increasing 5-HT and NE levels in hippocampus, frontal cortex and amygdale and could inhibit MAO-A activity in mouse brains. These results showed that ferulic acid has the analgesic effect. Its mechanism may be related to the inhibition of monoamine oxidase activity and the increase in monoamine neurotransmitter in mouse brains.

Study of the use of analgesics by patients with headache at a specialized outpatient clinic (ACEF).

PubMed

Chagas, Olga Francis Pita; Éckeli, Fabiola Dach; Bigal, Marcelo E; Silva, Mayko Olinto Amaral da; Speciali, Jose Geraldo

2015-07-01

To evaluate the use of analgesics in headache diagnosed in Outpatients Headache Clinic (ACEF), as well as his involvement in the activities of the patients. 145 patients with headache seen at ACEF during the period August/July 2009/2010 underwent a questionnaire and interview with neurologist responsible for the final diagnosis according to ICHD-II. Relationship Women:Men 7:1. 1) Prevalence: Migraine without aura (52.4%), migraine with aura (12.4%), chronic migraine (15.2%) and medication overuse headache (MOH) (20%). 2) Analgesic drugs used: Compounds with Dipyrone (37%), Dipyrone (23%), Paracetamol (16%) compound with Paracetamol (6%), triptans (6%) and non steroidal anti-inflammatory drugs (12%). There was a significant decrease in the duration of pain and less interference in the activities of the headache patients after the use of analgesics. Prevalence of MOH has been increasing in population level and specialized services. New studies emphasizing the MOH are needed to assist in the improvement of their diagnostic and therapeutic approach.

Parental approach to the prevention and management of fever and pain following childhood immunizations: a survey study

PubMed Central

Saleh, Ezzeldin; Swamy, Geeta K; Moody, M Anthony; Walter, Emmanuel B.

2017-01-01

Antipyretic analgesics are commonly used to prevent and treat adverse events following immunizations. Current practice discourages routine use due to possible blunting of vaccine immune responses. We surveyed 150 parents/caregivers of recently vaccinated 6- and 15-month-old children to determine the prevalence of and beliefs regarding antipyretic analgesics use around vaccinations. 11% used them prophylactically, before vaccination. Use in the first 48 hours after vaccination was 64%, primarily to prevent and/or treat fever and pain. Acetaminophen was administered 2.6 times more frequently than ibuprofen. Ibuprofen was used more in the 15-month compared to the 6-month-old children (28 % vs 7.4 % respectively, p=0.001). The majority of caregivers disagreed with their use for fever (53%) or pain (59%). Antipyretic analgesic use, including prophylaxis, around vaccinations was common in our study population. Effective interventions are needed to target parents/caregivers to eliminate unnecessary antipyretic analgesic use around vaccination time and foster non-medication alternatives. PMID:27798399

Factors affecting the use of postincisional analgesics in dogs and cats by Canadian veterinarians in 2001

PubMed Central

Hewson, Caroline J.; Dohoo, Ian R.

2006-01-01

Abstract Factors affecting the postincisional use of analgesics for ovariohysterectomy (OVH) in dogs and cats were assessed by using data collected from 280 Canadian veterinarians, as part of a national, randomized mail survey (response rate 57.8%). Predictors of analgesic usage identified by logistic regression included the presence of at least 1 animal health technician (AHT) per 2 veterinarians (OR = 2.3, P = 0.004), and the veterinarians’ perception of the pain caused by surgery without analgesia (OR = 1.5, P < 0.001). Linear regression identified the following predictors of veterinarians’ perception of pain: the presence of more than 1 AHT per 2 veterinarians (coefficient = 0.42, P = 0.048) and the number of years since graduation (coefficient = −0.073, P < 0.001). Some of these risk factors are similar to those identified in 1994. The results suggest that continuing education may help to increase analgesic usage. Other important contributors may be client education and a valid method of pain assessment. PMID:16734371

A study of anti-inflammatory and analgesic activity of new 2,4,6-trisubstituted pyrimidines.

PubMed

Yejella, Rajendra Prasad; Atla, Srinivasa Rao

2011-01-01

Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with various substituted aromatic and hetero aromatic aldehydes according to Claisen-Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in quantitative yields. All the newly synthesized pyrimidines were characterized by means of IR, ¹H- and ¹³C-NMR, Electron Ionization (EI)-mass and elemental analyses and screened for anti-inflammatory and analgesic activities by in vivo. 2-amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4-aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent anti-inflammatory and analgesic activity compared with ibuprofen, reference standard. And also it was found that compound 5b identified as lead structure among all in both the activities. Pyrimidines which showed good anti-inflammatory activity also displayed better analgesic activity.

Trends in intentional abuse or misuse of benzodiazepines and opioid analgesics and the associated mortality reported to poison centers across the United States from 2000 to 2014.

PubMed

Calcaterra, S L; Severtson, S G; Bau, G E; Margolin, Z R; Bucher-Bartelson, B; Green, J L; Dart, R C

2018-04-03

Prior works demonstrates an increased risk of death when opioid analgesics and benzodiazepines are used concomitantly to gain a high. Using poison center data, we described trends in abuse or misuse of benzodiazepines and opioid analgesics. We quantified mortality risk associated with abuse or misuse of benzodiazepines, opioid analgesics and the combination of opioid analgesics and benzodiazepines. This was a retrospective chart review of data from the National Poison Data System which collects information from 55 poison centers located across the United States. We identified reported cases of "intentional abuse or misuse" of benzodiazepine and/or opioid analgesic exposures. Poisson regression was used to compare the number of cases from each year between 2001 and 2014 to the year 2000. Logistic regression was used to determine whether cases exposed to both benzodiazepines and opioids had greater odds of death relative to cases exposed to opioid analgesics alone. From 2000 to 2014, there were 125,485 benzodiazepine exposures and 84,627 opioid exposures among "intentional abuse or misuse" cases. Of the benzodiazepine exposures, 17.3% (n = 21,660) also involved an opioid. In 2010, exposures involving both opioids and benzodiazepines were 4.26-fold (95% CI: 3.87-4.70; p < .001) higher than in 2000. The risk of death was 1.55 (95% CI: 1.01-2.37; p = .04) times greater among those who used both an opioid and a benzodiazepine compared to opioids alone. This association held after adjusting for gender and age. Intentional abuse or misuse of benzodiazepines and opioids in combination increased significantly from 2000 to 2014. Benzodiazepine abuse or misuse far exceeded cases of opioid abuse or misuse. Death was greater with co-abuse or misuse of benzodiazepines and opioids. Population-level campaigns to inform the public about the risk of death with co-abuse or misuse of benzodiazepines and opioids are urgently needed to address this overdose epidemic.

Prevention of addiction in pain management

DOEpatents

Dewey, Stephen L.; Brodie, Jonathan D.; Ashby, Jr., Charles R.

2005-09-06

The present invention provides a composition for treating pain. The composition includes a pharmaceutically acceptable analgesic and a GABAergic agent, such as gamma vinyl GABA, effective in reducing or eliminating the addictive liability of the analgesic. The invention also includes a method for reducing or eliminating the addictive

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

21 CFR 341.40 - Permitted combinations of active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ingredients, or any aspirin and antacid combination provided that the product is labeled according to § 341.85... combination of acetaminophen with other analgesic-antipyretic active ingredients, or any aspirin and antacid... other analgesic-antipyretic active ingredients, or any aspirin and antacid combination provided that the...

Battlefield pain management: A view of 17 years in Israel Defense Forces.

PubMed

Benov, Avi; Salas, Margaux M; Nakar, Helit; Antebi, Ben; Tarif, Bader; Yitzhak, Avraham; Glassberg, Elon

2017-07-01

Pain control in trauma is an integral part of treatment in combat casualty care (CCC). More soldiers injured on the battlefield will need analgesics for pain than those who will need lifesaving interventions (LSI). It has been shown that early treatment of pain improves outcomes after traumatic injury, whereas inadequate treatment leads to higher rates of PTSD. The purpose of this article is to report the Israel Defense Forces Medical Corps (IDF-MC) experience with point of injury (POI) use of analgesia. All cases documented in the IDF Trauma Registry (ITR) between January 1997 and December 2014 were examined. All cases of POI pain medications were extracted. Data collection included mechanism of injury, wound distribution, pain medication administered, mortality, and provider type. Of 8,576 patients, 1,056 (12.3%) patients who had at least one documented pain management treatment were included in this study. Demographics of the study population included 94.2% men and 5.8% women with a median age of 21 years. Injury mechanisms included 40.3% blast injuries (n = 426) and 29% gunshot injuries (306). Of 1,513 injured body regions reported, 52% (787) were extremity wounds (upper and lower), 23% (353) were truncal wounds, and 17.7% (268) were head and neck injuries. A total of 1,469 episodes of analgesic treatment were reported. The most common types of analgesics were morphine (74.7%, 1,097 episodes), ketamine (9.6%, 141 episodes), and fentanyl (13.6%, 200 episodes). Of the patients, 39% (413) received more than one type of analgesic. In 90.5% of cases, analgesia was administered by a physician or a paramedic. Over the span of the study period (1997-2014), types of analgesics given by providers at POI had changed, as fentanyl was introduced to providers. A total of 801 LSIs were performed on 379 (35.9%) patients receiving analgesia, and no adverse events were found in any of the casualties. Most casualties at POI did not receive any analgesics while on the battlefield. The most common analgesics administered at POI were opioids and the most common route of administration was intravenously. This study provides evidence that over time analgesic administration has gained acceptance and has been more common place on the battlefield. Increasingly, more casualties are receiving pain management treatment early in CCC along with LSIs. We hope that this shift will impact CCC by reducing PTSD and overall morbidity resulting from inadequate management of acute pain.

Paracetamol, aspirin and indomethacin display endocrine disrupting properties in the adult human testis in vitro.

PubMed

Albert, O; Desdoits-Lethimonier, C; Lesné, L; Legrand, A; Guillé, F; Bensalah, K; Dejucq-Rainsford, N; Jégou, B

2013-07-01

Do mild analgesics affect the endocrine system of the human adult testis? Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. Our studies were performed in vitro. We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes.

Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Motov, Sergey; Yasavolian, Matthew; Likourezos, Antonios; Pushkar, Illya; Hossain, Rukhsana; Drapkin, Jefferson; Cohen, Victor; Filk, Nicholas; Smith, Andrew; Huang, Felix; Rockoff, Bradley; Homel, Peter; Fromm, Christian

2017-08-01

Nonsteroidal anti-inflammatory drugs are used extensively for the management of acute and chronic pain, with ketorolac tromethamine being one of the most frequently used parenteral analgesics in the emergency department (ED). The drugs may commonly be used at doses above their analgesic ceiling, offering no incremental analgesic advantage while potentially adding risk of harm. We evaluate the analgesic efficacy of 3 doses of intravenous ketorolac in ED patients with acute pain. We conducted a randomized, double-blind trial to assess the analgesic efficacy of 3 doses of intravenous ketorolac (10, 15, and 30 mg) in patients aged 18 to 65 years and presenting to the ED with moderate to severe acute pain, defined by a numeric rating scale score greater than or equal to 5. We excluded patients with peptic ulcer disease, gastrointestinal hemorrhage, renal or hepatic insufficiency, allergies to nonsteroidal anti-inflammatory drugs, pregnancy or breastfeeding, systolic blood pressure less than 90 or greater than 180 mm Hg, and pulse rate less than 50 or greater than 150 beats/min. Primary outcome was pain reduction at 30 minutes. We recorded pain scores at baseline and up to 120 minutes. Intravenous morphine 0.1 mg/kg was administered as a rescue analgesic if subjects still desired additional pain medication at 30 minutes after the study drug was administered. Data analyses included mixed-model regression and ANOVA. We enrolled 240 subjects (80 in each dose group). At 30 minutes, substantial pain reduction was demonstrated without any differences between the groups (95% confidence intervals 4.5 to 5.7 for the 10-mg group, 4.5 to 5.6 for the 15-mg group, and 4.2 to 5.4 for the 30-mg group). The mean numeric rating scale pain scores at baseline were 7.7, 7.5, and 7.8 and improved to 5.1, 5.0, and 4.8, respectively, at 30 minutes. Rates of rescue analgesia were similar, and there were no serious adverse events. Secondary outcomes showed similar rates of adverse effects per group, of which the most common were dizziness, nausea, and headache. Ketorolac has similar analgesic efficacy at intravenous doses of 10, 15, and 30 mg, showing that intravenous ketorolac administered at the analgesic ceiling dose (10 mg) provided effective pain relief to ED patients with moderate to severe pain without increased adverse effects. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999–2010

PubMed Central

Bachhuber, Marcus A.; Saloner, Brendan; Cunningham, Chinazo O.; Barry, Colleen L.

2015-01-01

IMPORTANCE Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them. OBJECTIVE To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality. DESIGN, SETTING, AND PARTICIPANTS A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included. EXPOSURES Presence of a law establishing a medical cannabis program in the state. MAIN OUTCOMES AND MEASURES Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate. RESULTS Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, −37.5% to −9.5%; P = .003) compared with states without medical cannabis laws. Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (−19.9%; 95% CI, −30.6% to −7.7%; P = .002), year 2 (−25.2%; 95% CI, −40.6% to −5.9%; P = .01), year 3 (−23.6%; 95% CI, −41.1% to −1.0%; P = .04), year 4 (−20.2%; 95% CI, −33.6% to −4.0%; P = .02), year 5 (−33.7%; 95% CI, −50.9% to −10.4%; P = .008), and year 6 (−33.3%; 95% CI, −44.7% to −19.6%; P < .001). In secondary analyses, the findings remained similar. CONCLUSIONS AND RELEVANCE Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose. PMID:25154332

Impact of analgesics on executive function and memory in the Alzheimer's Disease Neuroimaging Initiative Database.

PubMed

Doan, Lisa; Choi, Daniel; Kline, Richard

2017-10-01

Pain is common in older adults but may be undertreated in part due to concerns about medication toxicity. Analgesics may affect cognition. In this retrospective cohort study, we used the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to examine the interaction of cognitive status and medications, especially non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesized NSAID use would be associated with cognition and that this could be mediated through changes in brain structure. In this post hoc analysis of the ADNI database, subjects were selected by searching the "concurrent medications log" for analgesic medications. Subjects were included if the analgesic was listed on the medication log prior to enrollment in ADNI and throughout the study. Subjects taking analgesics, particularly NSAIDs, at each study visit were compared to control subjects taking no analgesics. Using descriptive statistics as well as univariate, multivariate and repeated measure ANOVA, we explored the relationship between NSAID use and scores for executive function and memory related cognitive activities. We further took advantage of the extensive magnetic resonance imaging (MRI) data available in ADNI to test whether cognitive change was associated with brain structure. The multitude of imaging variables was compressed into a small number of features (five eigenvectors (EV)) using principal component analysis. There were 87 NSAID users, 373 controls, and 71 taking other analgesics. NSAID use was associated with higher executive function scores for cognitively normal (NL) subjects as well as subjects with mild cognitive impairment (MCI). NSAID use was also associated with higher memory scores, but for NL females only. We analysed MRI data using principal component analysis to generate a set of five EVs. Examining NL and MCI subjects, one EV had significantly larger values in subjects taking NSAIDs versus control. This EV was one of two EVs which significantly correlated with composite executive function and memory scores as well as cognitive diagnosis. NSAID use was associated with higher executive function, and memory scores in certain subjects and larger cortical volumes in particular regions. Limitations of the study include secondary analysis of existing data and the possibility of confounding. These results suggest it is important to consider the secondary effects of medications when choosing a treatment regimen. Further prospective studies are needed to examine the role of analgesics on cognition and whether NSAIDs act through cortical dimension changes and how they are related to gender and cognitive diagnosis. Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Use of opioid pain relievers following extraction of third molars.

PubMed

Weiland, Breanna M; Wach, Anthony G; Kanar, Brent P; Castele, Matthew T; Sosovicka, Mark F; Cooke, Matthew R; Moore, Paul A

2015-02-01

Following extraction of third molars, it is common practice for oral and maxillofacial surgeons to provide a prescription for an opioid-containing analgesic such as hydrocodone with acetaminophen. Because the instructions for use most often indicate that these analgesics are to be taken "as needed for pain," it is unknown how many of the prescribed postoperative analgesic tablets are needed and actually taken. Therefore, an assessment of patient pain experiences and actual opioid analgesic usage was carried out using structured telephone interviews of patients performed 1 and 7 days following their thirdmolar extraction surgery. Forty-eight adolescents and young adults, ages 15 to 30 years, participated in this assessment. A review of the surgeon's notes indicated that the median number of prescribed opioid-containing analgesics (ie, Vicodin®, Norco®, Lorcet®, Percocet®) was 20 tablets (range 10 to 40). The median consumption during the first 24 hours was reported to be three tablets (range 0 to 10), and the total consumption for all 7 days was eight tablets (range 0 to 34). Four patients reported nausea or vomiting in the first 24 hours, and six patients reported nausea or vomiting during the following 6 days of recovery. The initial prescriptions provided adequate relief for 45 of the 48 patients. Higher consumption of opioid pain relievers (OPRs) was associated with a longer duration of surgery and the occurrence of postoperative infections.

Face-to-face comparison of the predictive validity of two models of neuropathic pain in the rat: analgesic activity of pregabalin, tramadol and duloxetine.

PubMed

Le Cudennec, Camille; Castagné, Vincent

2014-07-15

We compared the preclinical analgesic activity of three marketed drugs with different pharmacological properties, pregabalin, tramadol and duloxetine, described as effective against neuropathic pain in the clinic. These drugs were tested against evoked pain in two different neuropathic models in the rat, the Bennett (CCI) and the Chung (SNL) models. The selected endpoints were tactile allodynia, tactile hyperalgesia, heat hyperalgesia and cold allodynia. Although all three drugs displayed analgesic activity, the effects observed varied according to the behavioral evaluation. Pregabalin showed clear analgesic effects against cold allodynia and tactile hyperalgesia in both the CCI and Chung models. Tramadol was active against all four endpoints in the Chung model with similar effects in the CCI model, apart from tactile allodynia. Duloxetine inhibited tactile allodynia and heat hyperalgesia in both neuropathic pain models. It also displayed efficacy against tactile hyperalgesia in the CCI model and against cold allodynia in the Chung model. These data confirm that the CCI and the Chung models of neuropathic pain do not detect the activity of analgesics with the same sensitivity. Furthermore, the mode of stimulation (tactile or thermal) and the type of endpoint (allodynia or hyperalgesia) can further influence the observed efficacy of gold standards as well as novel compounds developed for treating neuropathic pain symptoms. Copyright © 2014. Published by Elsevier B.V.

Analgesic and Anti-Inflammatory Activities of the Methanol Extract from Pogostemon cablin

PubMed Central

Lu, Tsung-Chun; Liao, Jung-Chun; Huang, Tai-Hung; Lin, Ying-Chih; Liu, Chia-Yu; Chiu, Yung-jia; Peng, Wen-Huang

2011-01-01

Pogostemon cablin (PC) is a herbal medicine traditionally applied to treat not only common cold, nausea and diarrhea but also headache and fever. The aim of this study was to investigate the analgesic and anti-inflammatory properties of standardized PC methanol extract (PCMeOH) in vivo. Investigations were performed in mice with two analgesic models. One was acetic acid-induced writhing response and the other formalin-induced paw licking. The anti-inflammatory effect was tested by λ-carrageenan (Carr)-induced mice paw edema. These analgesic experimental results indicated that PCMeOH (1.0 g/kg) decreased the acetic acid-induced writhing responses and PCMeOH (0.5 and 1.0 g/kg) decreased the licking time in the second phase of the formalin test. Moreover, Carr-induced paw edema inflammation was significantly reduced in a dose-dependent manner when PCMeOH (0.5 and 1.0 g/kg) was administered 3 and 4 h after the Carr injection. Mechanistic studies showed that PCMeOH decreased the levels of malondialdehyde in the edema paw by increasing the activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase and glutathione reductase, in the liver and decreasing the cyclooxygenase 2 and tumor necrosis factor-α activities in the edema paw. This study has demonstrated the analgesic and anti-inflammatory effects of PCMeOH, thus verifying its popular use in traditional medicine. PMID:19933324

Nonsteroidal Anti-Inflammatory Drugs and Analgesics Use by Kidney Transplant Recipients.

PubMed

Mulka-Gierek, Maria; Foroncewicz, Bartosz; Pączek, Leszek; Wawiórko, Elżbieta; Kamińska, Joanna; Kosieradzki, Maciej; Małkowski, Piotr; Małczuk, Bianka; Nazarewski, Sławomir; Mucha, Krzysztof

2018-03-02

BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics are the most commonly used drugs and are increasingly available over-the-counter (OTC). In certain groups of patients, including kidney transplant recipients, their use may be complicated by adverse effects or drug interactions. The aim of our study was to assess the causes and frequency of OTC NSAIDs or analgesics use, as well as the awareness of related side effects. MATERIAL AND METHODS We enrolled 94 randomly selected kidney transplant recipients, who represented 5% of all kidney transplant recipients at our center. An anonymous survey consisting of 23 multiple-choice questions was administered voluntarily and anonymously. RESULTS In all, 63% of study patients confirmed taking the OTC painkillers; 22% of these patients took these drugs at least several times a week, and 4% took these drugs daily. For 38% of the study kidney transplant recipients, NSAIDs or analgesics were reported to be the only way to manage their pain. In addition, 30% of study patients were unaware of the risks associated with these drugs, despite the fact that 89% of the study patients consider physicians the best source of information. CONCLUSIONS Our study found that 63% of kidney transplant recipients regularly took OTC painkillers and 30% were unaware of the potential adverse effects. This necessitates continuous, ongoing education of kidney transplant recipients about the risks of OTC NSAIDs or analgesics use.

Preemptive, preventive, multimodal analgesia: what do they really mean?

PubMed

Rosero, Eric B; Joshi, Girish P

2014-10-01

To improve postoperative pain management, several concepts have been developed, including preemptive analgesia, preventive analgesia, and multimodal analgesia. This article will discuss the role of these concepts in improving perioperative pain management. Preemptive analgesia refers to the administration of an analgesic treatment before the surgical insult or tissue injury. Several randomized clinical trials have, however, provided equivocal evidence regarding the benefits of preincisional compared with postincisional analgesic administration. Current general consensus, therefore, indicates that use of preemptive analgesia does not translate into consistent clinical benefits after surgery. Preventive analgesia is a wider concept where the timing of analgesic administration in relation to the surgical incision is not critical. The aim of preventive analgesia is to minimize sensitization induced by noxious stimuli arising throughout the perioperative period. Multimodal analgesia consists of the administration of 2 or more drugs that act by different mechanisms for providing analgesia. These drugs may be administered via the same route or by different routes. Thus, the aim of multimodal analgesia is to improve pain relief while reducing opioid requirements and opioid-related adverse effects. Analgesic modalities currently available for postoperative pain control include opioids, local anesthetic techniques [local anesthetic infiltration, peripheral nerve blocks, and neuraxial blocks (epidural and paravertebral)], acetaminophen, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2-specific inhibitors as well as analgesic adjuncts such as steroids, ketamine, α-2 agonists, and anticonvulsants.

Analgesic effects of glycoproteins from Panax ginseng root in mice.

PubMed

Wang, Ying; Chen, Yinghong; Xu, Hong; Luo, Haoming; Jiang, Ruizhi

2013-07-30

The root of Panax ginseng C.A. Mey has various beneficial pharmacological effects. The present study aimed to evaluate the analgesic activities of glycoproteins from the root of Panax ginseng C.A. Mey in mice. Glycoproteins were isolated and purified from the root of Panax ginseng C.A. Mey. Physicochemical properties and molecular mass were determined by chemical assay and HPLC. Acetic acid-induced writhing and hot-plate tests were employed to study the analgesic effect of glycoproteins and compared with that of aspirin or morphine. The locomotor activity was tested in mice by using actophometer. Four glycoproteins were obtained. The glycoproteins which protein content was the highest (73.04%) displayed dose-dependent analgesic effect. In writhing test, the glycoproteins significantly inhibited writhes (P<0.001) at the dose of 20 mg/kg by intraperitoneal injection. In hot-plate test, only at the dose of 20 mg/kg prolong the hot-plate latency (P<0.05, at 30 min). In the locomotor activity test, the glycoproteins were significant decrease of motility counts at the dose of 20 and 40 mg/kg. These findings collectively indicate that the glycoproteins from the root of Panax ginseng C.A. Mey exhibited significant analgesic activities and the proteins were the active site, providing evidence for its pharmacal use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

PubMed Central

2010-01-01

Background In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain. Method We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery. Results Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04). Conclusions Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance. Trial Registration This study was registered at ClinicalTrials.gov. # NCT00279513 PMID:20380750

Analgesic efficacy of lysine clonixinate plus tramadol versus tramadol in multiple doses following impacted third molar surgery.

PubMed

Perez-Urizar, J; Martínez-Rider, R; Torres-Roque, I; Garrocho-Rangel, A; Pozos-Guillen, A

2014-03-01

This study compared the analgesic and anti-inflammatory efficacy, trismus control, and tolerability of the combination of lysine clonixinate and tramadol (LCT) versus tramadol (T) alone after surgical removal of impacted mandibular third molars. This study was a double-blind, randomized clinical trial, including two study groups of 20 patients each, who exhibited acute pain subsequent to surgical extraction of two mandibular third molars. Pain intensity was quantified over a 96-h period using a visual analogue scale and a 5-point verbal rating scale. Secondary indicators of analgesic and anti-inflammatory efficacy, trismus control, and tolerability were determined. Patients administered LCT exhibited better therapeutic effects that those administered T. Fifty percent of patients in the LCT group rated this therapy as 'excellent analgesia' compared with only 10% in the T group. The onset of the analgesic effect of LCT was significantly faster, without any therapeutic failures. There were no significant differences between the groups with regard to anti-inflammatory effect or trismus. The results of this study suggest that the postsurgical analgesic efficacy of LCT in combination (LC 125 mg + T 25 mg) is superior to that obtained with T alone, administered at the standard dose of 50 mg, for up to 96 h after the extraction of both impacted mandibular third molars. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Analgesic use of inhaled methoxyflurane: Evaluation of its potential nephrotoxicity.

PubMed

Dayan, A D

2016-01-01

Methoxyflurane is a volatile, halogenated analgesic, self-administered in a controlled low dose from the Penthrox(®) inhaler for short-term pain relief. It was formerly used in significantly higher doses to produce anaesthesia, when it caused a specific type of dose-related renal tubular damage. The pathogenesis of the renal damage and clinical use of methoxyflurane are discussed here with evidence that a low but effective analgesic dose is not associated with the risk of renal adverse effects. The maximum dose employed to produce analgesia is limited to methoxyflurane 6 mL/day and 15 mL/week, producing a minimum alveolar concentration (MAC) of 0.59 MAC-hours. Renal damage is due to the metabolism of methoxyflurane and release of fluoride ions. Exposure of humans to methoxyflurane ≤2.0 MAC-hours, resulting in serum fluoride ≤40 µmol/L, has not been associated with renal tubular toxicity. The safety margin of analgesic use of methoxyflurane in the Penthrox ((®)) inhaler is at least 2.7- to 8-fold, based on methoxyflurane MAC-hours or serum fluoride level, with clinical experience suggesting it is higher. It is concluded from clinical experience in emergency medicine, surgical procedures and various experimental and laboratory investigations that the analgesic use of methoxyflurane in subanaesthetic doses in the Penthrox inhaler does not carry a risk of nephrotoxicity. © The Author(s) 2015.

Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats

PubMed Central

Kim, Taemin; Seol, Dong Rim; Hahm, Suk-Chan; Ko, Cheolwoong; Kim, Eun-Hye; Chun, Keyoungjin; Kim, Junesun; Lim, Tae-Hong

2015-01-01

The present study examined the analgesic effects of slow-releasing bupivacaine from hydrogel on chronic arthritic pain in rats. Osteoarthritis (OA) was induced by monosodium iodoacetate (MIA) injection into the right knee joint. Hydrogel (HG: 20, 30, and 50 μL) and temperature-sensitive hydrogel containing bupivacaine (T-gel: 20, 30, and 50 μL) were injected intra-articularly 14 days after MIA injection. Behavioral tests were conducted. The rats showed a significant decrease in weight load and paw withdrawal threshold (PWT). Intra-articular 0.5% bupivacaine (10 and 20 μL) significantly reversed MIA-induced decreased PWT, with no effect on weight load. In normal rats, hydrogel did not produce significant changes in PWT but at 30 and 50 μL slightly decreased weight bearing; T-gel did not cause any changes in both the weight load and PWT. In OA rats, T-gel at 20 μL had a significant analgesic effect for 2 days, even though T-gel at 50 μL further reduced the weight load, demonstrating that intra-articular T-gel (20 μL) has long-lasting analgesic effects in OA rats. Thus, T-gel designed to deliver analgesics into the joint cavity could be an effective therapeutic tool in the clinical setting. PMID:26881207

HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in a rat model of bone cancer pain by restoring μ-opioid receptor in spinal cord.

PubMed

Hou, Xinran; Weng, Yingqi; Ouyang, Bihan; Ding, Zhuofeng; Song, Zongbin; Zou, Wangyuan; Huang, Changsheng; Guo, Qulian

2017-08-15

Bone cancer pain (BCP) is a common complication with inadequate management in patients suffering from advanced cancer. Histone deacetylase inhibitors showed significant analgesic effect in multiple inflammatory and neuropathic pain models, but their effect in bone cancer pain has never been explored. In this study, we utilized a BCP rat model with intra-tibial inoculation of Walker 256 mammary gland carcinoma cells, which developed progressive mechanical hypersensitivity but not thermal hypersensitivity. Intrathecal application of trichostatin A (TSA), a classic pan-HDAC inhibitor, ameliorated tactile hypersensitivity and enhanced the analgesic effect of morphine in BCP rats. The analgesic effect of TSA was blocked by co-administration of CTAP, a specific MOR antagonist, confirming the involvement of mu-opioid receptor (MOR). A reduction of MOR expression was observed in the lumbar spinal cord of BCP rats and TSA treatment was able to partially reverse it. In vitro study in PC12 cells also demonstrated the dose-dependent enhancement of MOR expression by TSA treatment. Taking all into consideration, we could draw the conclusion that HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in BCP rats, probably by restoring MOR expression in spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the effects of sedation and general anesthesia in surgically assisted rapid palatal expansion.

PubMed

Satilmis, Tulin; Ugurlu, Faysal; Garip, Hasan; Sener, Bedrettin C; Goker, Kamil

2011-06-01

To compare the effects of sedation and general anesthesia for surgically assisted rapid palatal expansion (SARPE). This randomized prospective study included 30 patients who were scheduled for SARPE, and was performed between January 2008 to February 2010 in the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Marmara University, Istanbul, Turkey. Patients were allocated into Group S - midazolam + fentanyl sedation (n=15), and Group G - general anesthesia (n=15). Hemodynamic parameters, duration of anesthesia, surgery, recovery time, time to discharge, visual analogue scale (VAS) pain scores at 30 minutes (min), one hour (hr), 4 hours, 12 hours, and 24 hours, first consumption of analgesic time, total amount of consumption of analgesics, patient and surgeon satisfaction, nausea, and vomiting were recorded. Analgesic time was significantly longer in Group S (p=0.008), and total analgesic consumption was significantly lower in Group S than in Group G (p=0.031). Patient satisfaction was statistically higher in Group S (p=0.035). At 30 min, one hr, and 12 hrs, VAS satisfaction scores in Group S were statistically lower than those in Group G, and at 4 hrs and 24 hrs there was no statistical difference in VAS scores for both groups. The use of sedation for outpatient SARPE resulted in lower pain scores at discharge, lower analgesic consumption, and greater patient satisfaction.

Opioid, calcium, and adrenergic receptor involvement in protopine analgesia.

PubMed

Xu, Q; Jin, R L; Wu, Y Y

1993-11-01

The analgesic effect of protopine (Pro), an alkaloid isolated from Papaveraceae, was confirmed by tail-pinch and hot-plate tests when given sc 10-40 mg.kg-1, and 20-40 mg.kg-1 inhibited the spontaneous movements of mice. Pro 40 mg.kg-1 increased the sleeping rate, prolonged the sleeping duration, and shortened the sleeping latency in mice hypnotized by ip pentobarbital sodium 30 mg.kg-1. Pro 10-40 mg.kg-1 did not affect the inflammatory reaction induced by xylene and egg white. An icv injection of Pro 20-200 micrograms/mouse showed a remarkable analgesic effect in mice. The icv pretreatment of naloxone 2 micrograms blocked the analgesic effect completely. CaCl2 40 micrograms/mouse (ICV) or methotrexate 10 mg.kg-1 (ip), an agonist of Ca2+ channel, showed a complete blockade of the analgesia, while nifedipine 100 mg.kg-1(po), a blocker of Ca2+ channel, enhanced the analgesic effect. The ip pretreatment of reserpine 4 mg.kg-1 reduced the Pro analgesia. Phentolamine 10 mg.kg-1(ip), an alpha-adrenergic blocker, tended to weaken the analgesia, but propranolol 10 mg.kg-1(ip), a beta-blocker, did not affect it. These results suggest that Pro displays its analgesic effect mainly through the opioid and calcium systems and partly through the adrenergic mechanism.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

PubMed

Bernabe-Garcia, Mariela; López-Alarcon, Mardia; Salgado-Sosa, Alfredo; Villegas-Silva, Raul; Maldonado-Hernandez, Jorge; Rodríguez-Cruz, Maricela; Rivas-Ruiz, Rodolfo; Chavez-Sanchez, Luis; Blanco-Favela, Francisco A; Mancilla-Ramirez, Javier; Gordillo-Alvarez, Virginia; Madrigal-Muñiz, Olivia

2016-01-01

Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 μg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (β = -27 μg/kg, p = 0.028; R2 model = 0.90) for shorter duration (β = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects. © 2016 S. Karger AG, Basel.

Transformation of Lactuca sativa L. with rol C gene results in increased antioxidant potential and enhanced analgesic, anti-inflammatory and antidepressant activities in vivo.

PubMed

Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Sajid, Moniba; Kayani, Waqas Khan; Mirza, Bushra

2016-12-01

Lettuce is an important edible crop which possesses various medicinal properties. In this study Lactuca sativa L. (cv Grand Rapids) was transformed by Agrobacterium-mediated transformation with rol C gene. Transgene integration and expression was confirmed through PCR and semiquantitative RT-PCR. The transformed extracts were evaluated for their in vitro antioxidant and in vivo analgesic, anti-inflammatory and antidepressant activities in rats. The transformed plants showed 53-98 % increase in total phenolic and 45-58 % increase in total flavonoid contents compared with untransformed plants. Results of total reducing power and total antioxidant capacity exhibited 90-118 and 61-75 % increase in transformed plants, respectively. In contrast to control, DPPH, lipid peroxidation and DNA protection assay showed up to 37, 20 and 50 % enhancement in transformed plants, respectively. The extracts showed similar but significant enhancement behavior in hot plate analgesic and carrageenan-induced hind paw edema test. The transformed extracts showed 72.1 and 78.5 % increase for analgesic and anti-inflammatory activities, respectively. The transformants of rol C gene exhibited prominent antidepressant activity with 64-73 % increase compared with untransformed plants. In conclusion, the present work suggests that transformation with rol C gene can be used to generate lettuce with enhanced medicinally important properties, such as antioxidant, analgesic, anti-inflammatory and antidepressant potential.

Identification and Quantitative Analysis of Acetaminophen, Acetylsalicylic Acid, and Caffeine in Commercial Analgesic Tablets by LC-MS

ERIC Educational Resources Information Center

Fenk, Christopher J.; Hickman, Nicole M.; Fincke, Melissa A.; Motry, Douglas H.; Lavine, Barry

2010-01-01

An undergraduate LC-MS experiment is described for the identification and quantitative determination of acetaminophen, acetylsalicylic acid, and caffeine in commercial analgesic tablets. This inquiry-based experimental procedure requires minimal sample preparation and provides good analytical results. Students are provided sufficient background…

77 FR 73289 - Hazardous Substances and Articles; Administration and Enforcement Regulations: Revisions to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

... recommends this approach to manufacturers who are labeling substances to indicate a hazard. Accordingly, the... test animals. Additionally, the routine use of topical anesthetics, systemic analgesics, and humane..., systemic analgesics, and humane endpoints to avoid or minimize pain and distress in ocular safety testing...

Castration is no laughing matter, nitrous oxide can’t even help

USDA-ARS?s Scientific Manuscript database

Castration of pigs is necessary since no other viable alternative is yet available. However, castration is painful and analgesics are being considered to relieve pain. Inhalant gases with analgesic properties allow for a fast induction, short-term and reversible effects, and are a needle-free option...

High Performance Liquid Chromatography of Some Analgesic Compounds: An Instrumental Analysis Experiment.

ERIC Educational Resources Information Center

Haddad, Paul; And Others

1983-01-01

Background information, procedures, and results are provided for an experiment demonstrating techniques of solvent selection, gradient elution, pH control, and ion-pairing in the analysis of an analgesic mixture using reversed-phase liquid chromatography on an octadecylsilane column. Although developed using sophisticated/expensive equipment, less…

78 FR 42088 - Anesthetic and Analgesic Drug Products Advisory Committee; Cancellation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Anesthetic and Analgesic Drug Products Advisory Committee; Cancellation AGENCY: Food and Drug Administration..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31...

Maternal use of mild analgesics during pregnancy associated with reduced anogenital distance in sons: a cohort study of 1027 mother-child pairs.

PubMed

Lind, Dorte Vesterholm; Main, Katharina M; Kyhl, Henriette Boye; Kristensen, David Møbjerg; Toppari, Jorma; Andersen, Helle Raun; Andersen, Marianne Skovsager; Skakkebæk, Niels E; Jensen, Tina Kold

2017-01-01

Is maternal use of mild analgesics in pregnancy associated with anogenital distance (AGD)-the distance from the anus to the genitals-in the offspring? Maternal use of mild analgesics [especially simultaneous use of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs)] during pregnancy was associated with a shorter AGD in boys whereas no effect was found in girls. Mild analgesics including paracetamol (acetaminophen) and NSAIDs (e.g. ibuprofen and acetyl salicylic acid) have endocrine disrupting properties and in utero exposure reduces AGD in male rats. In humans, maternal exposure has been associated with cryptorchidism and hypospadias in male offspring but no studies have examined AGD. A prospective birth cohort study. Between 2010 and 2012, 2500 pregnant women were recruited from the Odense Child Cohort. Children were examined 3 months after the expected date of birth. Pregnant women were asked about use of medication including mild analgesics (paracetamol and NSAID) during pregnancy at recruitment (gestational age (GA) week 10-27) and at GA week 28. AGD and penile width were measured 3 months after expected date of birth by trained personnel. A total of 1027 women answered both questionnaires and their children were examined. Associations between prenatal exposure to mild analgesics and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age SD score. A total of 40% of the women reported use of paracetamol and/or NSAIDs (4.4%) during the first 28 weeks of pregnancy. Exposure to analgesics during pregnancy was associated with a reduced AGD in boys, although statistically significant only for NSAIDs. The association was significant among 20 boys exposed to both paracetamol and NSAIDs (AGD -4.1 mm; CI 95%: -6.4; -1.7). Maternal intake of analgesics did not show any clear association with AGD in female offspring. No effect on penile width was found. Only 27 boys and 18 girls were exposed to NSAIDs and most of them were also exposed to paracetamol. This makes it impossible to distinguish between exposures to NSAIDs alone and a potential mixture effect. Moreover, use of mild analgesics was self-reported up to 2 months after intake, which could have caused misclassification of exposure but is probably not associated with AGD as this was unknown to the women at time of reply to the questionnaire thereby underestimating the association. Confounding by indication may also explain our findings, as the condition for which the analgesic was taken may be associated with a reduction in AGD, rather than the use of the analgesic medication. This is the first study to report such an association in humans and further studies are needed to confirm our findings. A negative association was observed between exposure to analgesics during pregnancy and AGD in boys, suggesting disruption of androgen action. The health implications of a shorter AGD are still uncertain, but in cross-sectional studies among adult men a shorter AGD is associated with poorer semen quality and lower testosterone. As 41% of the women used these painkillers the finding are of public health importance and pregnant women should be advised about the potentially harmful effects of painkiller use. The study was funded by the Danish Environmental Protection Agency by way of the Center on Endocrine Disruptors Danish Center for Hormone Disrupting Chemicals, the Danish Foundation for Scientific Innovation and Technology (09-067180), the Danish Research Council (4004-00352B_FSS), Novo Nordic Foundation (NNF15OC0017734), Ronald McDonald Children Foundation, K.A. Rohde's and wife's Foundation, Odense University Hospital and Region of Southern Denmark, Municipality of Odense, the Danish Council for Strategic Research, Program Commission on Health, Food and Welfare (2101-08-0058), Odense University Hospital Research Foundation and Odense Patient data Exploratory Network (OPEN). The authors declare they have no competing interests. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Rabbit analgesia.

PubMed

Barter, Linda S

2011-01-01

With the increasing popularity of rabbits as household pets, the complexity of diagnostic and surgical procedures performed on rabbits is increasing, along with the frequency of routine surgical procedures. More practitioners are faced with the need to provide adequate analgesia for this species. Preemptive analgesia prior to planned surgical interventions may reduce nervous system changes in response to noxious input, as well as reduce postoperative pain levels and analgesic drug requirements. Concurrent administration of analgesic drugs to anesthetized rabbits undergoing painful procedures is warranted both pre- and intraoperatively as well as postoperatively. This article discusses the neuropharmacologic and pharmacologic aspects of pain in rabbits, and reviews current protocols for the use of analgesic drugs. Published by Elsevier Inc.

Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.

PubMed

Li, C H; Tseng, L F; Ferrara, P; Yamashiro, D

1980-04-01

Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27-3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency.

Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.

PubMed Central

Li, C H; Tseng, L F; Ferrara, P; Yamashiro, D

1980-01-01

Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27-3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency. PMID:6246537

Anti-inflammatory, analgesic and antipyretic activities of loxoprofen sodium given intramuscularly in animals.

PubMed

Hyun, J E; Li, D W; Lee, E B; Jeong, C S

2001-12-01

The evaluation of the anti-inflammatory, analgesic and antipyretic activities of loxoprofen sodium given in intramuscular route was investigated as compared to oral application in rats and mice. The intramuscular ED50 values of loxoprofen sodium in carrageenan edema and vascular permeability tests are 1.15 and 7.8 mg/kg, respectively, which represent more potent than in case of oral application. Its therapeutic effects in adjuvant arthritis were shown at 6 mg/kg i.m. and 3mg/kg p.o. Analgesic effect was shown to be more potent as given intramuscularly. Similar potency of antipyretic effects was shown in both administration routes. Considerably weak gastric damages were observed in intramuscular application.

Regulation of opioid receptor signalling: Implications for the development of analgesic tolerance

PubMed Central

2011-01-01

Opiate drugs are the most effective analgesics available but their clinical use is restricted by severe side effects. Some of these undesired actions appear after repeated administration and are related to adaptive changes directed at counteracting the consequences of sustained opioid receptor activation. Here we will discuss adaptations that contribute to the development of tolerance. The focus of the first part of the review is set on molecular mechanisms involved in the regulation of opioid receptor signalling in heterologous expression systems and neurons. In the second part we assess how adaptations that take place in vivo may contribute to analgesic tolerance developed during repeated opioid administration. PMID:21663702

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-21

..., but not limited to, specific research designs and methodological features so as to inform the future... clinical trials. Many experts in analgesic drug development believe that it is the design of the clinical trials that is at fault in this situation and that better trial designs will yield more successful...

[Comparison of analgesic effect between locally vinegar-processed preparation of fresh rhizoma Corydalis and traditionally vinegar-processed rhizoma Corydalis].

PubMed

Liu, L; Li, G; Zhu, F; Wang, L; Wang, Y

1990-11-01

Hot plate and writhing methods were used in the comparison of the analgesic effect of vinegar-processed fresh tuber corydalis and the traditionally vinegar-processed Rhizoma Corydalis. The result shows that the effect of the former is stronger than that of the latter.

THE EFFECT OF AN ANALGESIC AGENT ON MUSCULAR WORK DECREMENT

DTIC Science & Technology

observations might lead to the conclusion that the pain caused by ischemia limits the endurance of the muscle contraction . An analgesic agent, known to...reduce ischemic pain was shown to have no effect on the endurance or strength of a tonic muscle contraction . This was interpreted as demonstrating a lack

Analysis of Currently Available Analgesic Tablets by Modern Liquid Chromatography: An Undergraduate Laboratory Introduction to HPLC.

ERIC Educational Resources Information Center

Kagel, R. A.; Farwell, S. O.

1983-01-01

Background information, procedures, and results, are provided for an undergraduate experiment in which analgesic tablets are analyzed using liquid chromatography. The experiment, an improved, modified version of the Waters Associates Inc. experiment, is simple to prepare, requiring little glassware and minimal sample manipulation by students. (JN)

Predictors of Nurses' Intentions to Administer As-Needed Opioid Analgesics for Pain Relief to Postoperative Orthopaedic Patients in the Acute Care Setting.

PubMed

Taylor, Colleen Y; Sheu, Jiunn-Jye; Chen, Huey-Shys; Glassman, Tavis; Dake, Joseph

Patients undergoing orthopaedic surgery experience severe postoperative pain that is frequently undertreated. No study was found that examined the predictors of nurses' intentions to administer as needed (PRN) opioid analgesics for postoperative pain relief. The purpose of this study was to determine what constructs from the Integrated Behavioral Model (IBM) can predict nurses' intentions to administer PRN opioid analgesics for pain relief to hospitalized postoperative orthopaedic patients. A nonexperimental, cross-sectional quantitative format was used. The sample consisted of 800 nurses. Data collection was done by survey. Path analysis revealed the significant predictors of nurses' intention to administer opioid analgesics to be self-efficacy (β= 0.15), normative beliefs (β= 0.21), and salience (importance) of the behavior (β= 0.25). The study showed that the IBM constructs are useful for predicting intentions toward performance of a professional behavior. The inclusion of self-efficacy, underlying beliefs, and salience of the behavior was new and unique contributions to the existing body of knowledge.

Correlation between the cumulative analgesic effect of electroacupuncture intervention and synaptic plasticity of hypothalamic paraventricular nucleus neurons in rats with sciatica☆

PubMed Central

Xu, Qiuling; Liu, Tao; Chen, Shuping; Gao, Yonghui; Wang, Junying; Qiao, Lina; Liu, Junling

2013-01-01

In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic effect of repeated electroacupuncture stimulation at bilateral Zusanli (ST36) and Yanglingquan (GB34). In addition, associated synaptic changes in neurons in the paraventricular nucleus of the hypothalamus were examined. Results indicate that the thermal pain threshold (paw withdrawal latency) was significantly increased in rats subjected to 2-week electroacupuncture intervention compared with 2-day electroacupuncture, but the analgesic effect was weakened remarkably in ovariectomized rats with chronic constrictive injury. 2-week electroacupuncture intervention substantially reversed the chronic constrictive injury-induced increase in the synaptic cleft width and thinning of the postsynaptic density. These findings indicate that repeated electroacupuncture at bilateral Zusanli and Yanglingquan has a cumulative analgesic effect and can effectively relieve chronic neuropathic pain by remodeling the synaptic structure of the hypothalamic paraventricular nucleus. PMID:25206591

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

PubMed

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.

Study of pharmacological activities of methanol extract of Jatropha gossypifolia fruits.

PubMed

Apu, Apurba Sarker; Hossain, Faruq; Rizwan, Farhana; Bhuyan, Shakhawat Hossan; Matin, Maima; Jamaluddin, A T M

2012-12-01

The present study was carried out to investigate the possible in vivo analgesic, neuropharmacological and anti-diarrheal activities of the methanol extract of Jatropha gossypifolia fruits. The analgesic activity was measured by acetic acid induced writhing inhibition test. The neuropharmacological activities were evaluated by hole cross, hole-board, and elevated plus-maze (EPM) tests and the anti-diarrheal activity was assessed by castor oil induced diarrhea inhibition method. The extract showed highly significant (P < 0.001) analgesic activity with % inhibitions of writhing response at doses 200 and 400 mg/kg body weight were 77.86% and 71.25%, respectively. The extract at both doses showed significant (P < 0.05) sedative effect in-hole cross test. In-hole board test, the extract showed highly significant (P < 0.001) anxiolytic activity at lower dose whereas this activity was observed at higher dose in EPM test. The extract also showed highly significant (P < 0.001) anti-diarrheal activity. The findings of the study clearly indicate the presence of significant analgesic, neuropharmacological and anti-diarrheal properties of the plant, which demands further investigation including, compound isolation.

Anti-diarrhoea and analgesic activities of the methanol extract and its fractions of Jasminum amplexicaule Buch.-Ham. (Oleaceae).

PubMed

Jia, Qiang; Su, Weiwei; Peng, Wei; Li, Peibo; Wang, Yonggang

2008-09-26

Jasminum amplexicaule Buch.-Ham. (Oleaceae) has been commonly used in the traditional medicine in dysentery, diarrhoea and bellyache in China. In the present work, the methanol extract of Jasminum amplexicaule and different fractions of this extract were studied for anti-diarrhoea and analgesic activities. The anti-diarrhoea activities were investigated using castor oil-induced, magnesium sulphate-induced diarrhoea models, antienteropooling assay and gastrointestinal motility models in mice. The analgesic activities were studied using hot-plate, writhing and formalin models in mice. At the doses of 100, 200 and 400mg/kg, the methanol extract (ME) showed significant and dose-dependent anti-diarrhoea and analgesic activity in these models. The chloroform fraction (CHF), ethyl acetate fraction (EAF) and the residual methanol fraction (RMF) exhibited similar activity using a dose of 200mg/kg in these models. The pharmacological activities of the n-butanol fraction (BUF) were lesser than the ME extract and other fractions. These results may support the fact that this plant is traditionally used to cure diarrhoea and pain.

Consequences of dextropropoxyphene market withdrawal in elderly patients with chronic pain.

PubMed

Becquemont, Laurent; Delespierre, Tiba; Bauduceau, Bernard; Benattar-Zibi, Linda; Berrut, Gilles; Corruble, Emmanuelle; Danchin, Nicolas; Derumeaux, Geneviève; Doucet, Jean; Falissard, Bruno; Forette, Francoise; Hanon, Olivier; Pasquier, Florence; Pinget, Michel; Ourabah, Rissane; Bucher, Sophie; Lazkani, Aida; Piedvache, Celine; Bertin, Philippe

2014-10-01

Describe the consequences of dextropropoxyphene (DXP) market withdrawal on analgesic prescriptions and on the quality of therapeutic management of chronic pain. From a cohort of non-institutionalised elderly patients with chronic pain recruited by general practitioners, we selected patients who were treated with DXP daily for at least 6 months just prior to DXP market withdrawal and who had an evaluation of pain and its impact on daily activities before and after DXP withdrawal. One hundred three patients took DXP daily for chronic pain. Immediately after DXP market withdrawal, 42 (40.8%), 55 (53.4%) and 3 (2.9%) patients were treated with step 1, 2 and 3 analgesics, respectively, and 3 patients (2.9%) were no longer receiving any analgesic medication. Among the 55 patients who continued on step 2 analgesics, 37 were treated with tramadol, 14 with codeine and 9 with opium. Pain intensity and the impact of pain on daily activities remained stable. DXP market withdrawal had no consequences on the intensity or impact of chronic pain in elderly patients.

The studies of anti-inflammatory and analgesic activities and pharmacokinetics of Oxytropis falcate Bunge extraction after transdermal administration in rats.

PubMed

Chen, Zhi-peng; Qu, Min-ming; Chen, Hong-xuan; Liu, Dan; Xiao, Yan-yu; Chen, Jun; Lu, Tu-lin; Cai, Bao-chang

2011-04-01

The aim of this study was to evaluate the activities of anti-inflammatory and analgesic of the total flavonoids extraction from Oxytropis falcate Bunge (FEO) after transdermal administration. The pharmacokinetics and absolute bioavailability of FEO in rat, furthermore, was studied. Firstly, the anti-inflammatory and analgesic effects of the FEO were studied by xylene-induced ear edema, adjuvant-induced joint inflammation law in rats, acetic acid-induced writhing and hot-plate tests in mice. Secondly, we developed a sensitive and specific HPLC method to analyze 2', 4'-dihydroxychalcone (TFC, the mainly ingredient of FEO) in rat plasma to study the pharmacokinetic of TEC. The results showed FEO has anti-inflammatory and analgesic property in a dose-dependent manner, and that the high dose group (90.6 mg/kg) of FEO appeared more significantly effective than the positive drug. From the pharmacokinetic studies of TFC in rats, we got the main pharmacokinetic parameters of TFC, providing a basis for the future studies in clinic. Copyright © 2010 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2011-12-06

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

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

PubMed

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

2012-07-26

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

Antagonism of stress-induced analgesia by D-phenylalanine, an anti-enkephalinase.

PubMed

Bodnar, R J; Lattner, M; Wallace, M M

1980-12-01

Methionine- and leucine-enkephalin produce mild and transient analgesic effects, presumably because of enzymatic degradation. Administration of high (250 mg/kg) doses of D-phenylalanine retards the degradation process and elicits analgesia which is reversed by naloxone and which summates with electroacupuncture analgesia. The present study evaluated D-phenylalanine's dose-dependent effects upon a non-opioid analgesic treatment, cold-water swims (CWS), and compared this with morphine. following determination of flinch-jump baselines, three groups of rats received respectively either 25, 50 or 100 mg/kg of D-phenylalanine intraperitoneally in three conditions: alone, with CWS (2 degrees C for 3.5 min), and with morphine (5 mg/kg, SC). Parallel controls with saline were also tested. Simultaneous exposure with each minimally analgesic dose of D-phenylalanine reduced significantly the analgesic, but not hypothermic effects of CWS. By contrast, morphine analgesia was unaffected by D-phenylalanine. These data provide further support that different pain-inhibitory systems mediate CWS and morphine analgesia and suggest that activation of one system is capable of exerting collateral inhibition upon the other.

New drugs for pain management in advanced cancer patients.

PubMed

Mercadante, Sebastiano

2017-04-01

Advanced cancer patients represent a frail population, often requiring aggressive pain management, particularly in the late stage of disease, when untreated pain is one the most important causes of suffering. Areas covered: In the last decade, a series of new analgesics have been introduced in the market to offer additional options amongst existent drugs. The characteristics of these drugs, their efficacy and tolerability are examined on the basis of existent studies. Expert opinion: Although new analgesic preparations have been developed in recent years, no specific drug has provided a better analgesic performance in comparison with others. Some technologies have been developed to increase the safety or decrease the opioid-related adverse effects, with some molecules providing extra-opioid analgesia. However, existing studies did not present relevant advantages over traditional opioids. The new formulations developed to provide a rapid and non-invasive analgesia for breakthrough pain have really changed the approach to this phenomenon, characterized by a specific temporal pattern requiring a short onset, and duration of the analgesic effect. The availability of new drugs, indeed, may enlarge the possibilities of individualizing treatment, according to specific clinical needs and individual response.

[Analgesic efficacy and clinical safety of intraperitoneal instillation combined with rectus sheath block using ropivacaine for pain relief after laparoscopic gynecological surgery].

PubMed

Yakoshi, Chihiro; Hashimoto, Hiroshi; Niwa, Hidetomo; Kitayama, Masatou; Kudo, Tsuyoshi; Kudo, Mihoko; Hirota, Kazuyoshi

2014-03-01

The aim of this study was to evaluate the analgesic efficacy and safety of rectus sheath block combined with intraperitoneal instillation using two doses of ropivacaine in patients undergoing laparoscopic gynecological surgery. Altogether 53 consenting women were randomized to receive intraperitoneal infiltration with 0.25% ropivacaine or 0.5% ropivacaine followed by rectus sheath block with 0.375% ropivacaine. The outcomes of clinical safety were measured using plasma concentration of local anesthetics and occurrence of toxic symptoms. The analgesic efficacy was assessed using numerical rating scales for pain and morphine consumption up to 24 hours after surgery. Patients' baseline characteristics, surgical factors, and analgesic outcomes were comparable between the two groups. Although peak plasma concentration of ropivacaine was significantly higher in patients receiving 0.5% ropivacaine, none of analyzed concentrations was above the toxic ones. Besides, no patients showed any symptoms of local anesthetic toxicity. The present study showed that the combination of rectus sheath block with intraperitoneal instillation of ropivacaine was safe and potent enough to relieve pain after laparoscopic surgery.

Novel technique of abdominal wall nerve block for laparoscopic colostomy: Rectus sheath block with transperitoneal approach.

PubMed

Nagata, Jun; Watanabe, Jun; Sawatsubashi, Yusuke; Akiyama, Masaki; Arase, Koichi; Minagawa, Noritaka; Torigoe, Takayuki; Hamada, Kotaro; Nakayama, Yoshifumi; Hirata, Keiji

2017-08-27

A 62-year-old man who had acute rectal obstruction due to a large rectal cancer is presented. He underwent emergency laparoscopic colostomy. We used the laparoscopic puncture needle to inject analgesia with the novel transperitoneal approach. In this procedure, both ultrasound and laparoscopic images assisted with the accurate injection of analgesic to the correct layer. The combination of laparoscopic visualization and ultrasound imaging ensured infiltration of analgesic into the correct layer without causing damage to the bowel. Twenty-four hours postoperatively, the patient's pain intensity as assessed by the numeric rating scale was 0-1 during coughing, and a continuous intravenous analgesic was not needed. Colostomy is often necessary in colon obstruction. Epidural anesthesia for postoperative pain cannot be used in patients with a coagulation disorder. We report the use of a novel laparoscopic rectus sheath block for colostomy. There has been no literature described about the nerve block with transperitoneal approach. The laparoscopic rectus sheath block was performed safely and had enough analgesic efficacy for postoperative pain. This technique could be considered as an optional anesthetic regimen in acute situations.

Advanced Analgesic Drug Delivery and Nanobiotechnology.

PubMed

Stoicea, Nicoleta; Fiorda-Diaz, Juan; Joseph, Nicholas; Shabsigh, Muhammad; Arias-Morales, Carlos; Gonzalez-Zacarias, Alicia A; Mavarez-Martinez, Ana; Marjoribanks, Stephen; Bergese, Sergio D

2017-07-01

Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.

Management of vaso-occlusive pain in children with sickle cell disease.

PubMed

Jacob, Eufemia; Miaskowski, Christine; Savedra, Marilyn; Beyer, Judith E; Treadwell, Marsha; Styles, Lori

2003-04-01

A descriptive, longitudinal design was used to evaluate the pain management strategies used in children with sickle cell disease who were experiencing pain during a vaso-occlusive episode. A list of the medications (name, amount, mode of delivery, and frequency) prescribed and administered for pain management for each participant was recorded on the Medication Quantification Scale Worksheet, starting from day 1 of hospitalization to the day of discharge. Children were asked once each evening to provide three separate ratings of how much the pain medication helped them during the day, evening, and night using a 0-to-10 rating scale. Using patient-controlled analgesia (PCA), children self-administered only 35% of the analgesic medications that were prescribed and reported little pain relief. No significant relationships were found between changes in pain relief scores and the amount of analgesics administered. Clinicians need to monitor the amount of analgesics delivered in relationship to pain relief and assist children to titrate PCA administration of analgesics to achieve optimal pain control, or to advocate for changes in the PCA regimen when children cannot assume control of pain management.

Arylhydrazone derivatives of naproxen as new analgesic and anti-inflammatory agents: Design, synthesis and molecular docking studies.

PubMed

Azizian, Homa; Mousavi, Zahra; Faraji, Hamidreza; Tajik, Mohammad; Bagherzadeh, Kowsar; Bayat, Peyman; Shafiee, Abbas; Almasirad, Ali

2016-06-01

A series of new arylidenehydrazone derivatives of naproxen were synthesized and evaluated for their analgesic and anti-inflammatory activities. Some of the synthesized analogues showed comparable activities when compared against naproxen for their analgesic and anti-inflammatory properties. 2-(6-methoxy-2-naphthyl)-N'-[(pyridine-4-yl)methylene]propanoic acid hydrazide 4j was found to be the most active analgesic agent. 2-(6-methoxy-2-naphthyl)-N'-[4-nitrobenzylidene]propanoic acid hydrazide 4g showed highest anti-inflammatory activity in comparison to the naproxen. Molecular modeling study of the synthesized compounds suggested that the designed molecules were well located and bound to the COX-1 and COX-2 active sites. Compound 4g showed the highest selectivity for COX-2 (RCOX-2/COX-1=1.94) and higher affinity rather than naproxen in COX-2 active site (RCOX-2/naproxen=1.28). Moreover, the structural analyses confirmed that the E-ap rotamer is the preferred structure for the arylidenehydrazone derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of common analgesic medications and ovarian cancer survival: results from a pooled analysis in the Ovarian Cancer Association Consortium.

PubMed

Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas; Trabert, Britton; Beeghly-Fadiel, Alicia; Schildkraut, Joellen M; Moysich, Kirsten B; deFazio, Anna; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Jensen, Allan; Kjær, Susanne K; Høgdall, Estrid; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Bandera, Elisa V; Paddock, Lisa E; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M

2017-04-25

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82-0.98)). Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted.

Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection.

PubMed

Mora, Andrea L; Salazar, Miguel; Pablo-Caeiro, Juan; Frost, Craig P; Yadav, Yashoo; DuPont, Herbert L; Garey, Kevin W

2012-04-01

Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P < 0.0001). One hundred of 21,396 (0.47%) patients who did not receive opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P < 0.0001). Similar results were observed using a multivariate Cox proportional hazard model. Moderate to high use of opioid analgesics were associated with an increased risk of CDI.

Novel polymeric bioerodable microparticles for prolonged-release intrathecal delivery of analgesic agents for relief of intractable cancer-related pain.

PubMed

Han, Felicity Y; Thurecht, Kristofer J; Lam, Ai-Leen; Whittaker, Andrew K; Smith, Maree T

2015-07-01

Intractable cancer-related pain complicated by a neuropathic component due to nerve impingement is poorly alleviated even by escalating doses of a strong opioid analgesic. To address this unmet medical need, we developed sustained-release, bioerodable, hydromorphone (potent strong opioid)- and ketamine (analgesic adjuvant)-loaded microparticles for intrathecal (i.t.) coadministration. Drug-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared using a water-in-oil-in-water method with evaporation. Encapsulation efficiency of hydromorphone and ketamine in PLGA (50:50) microparticles was 26% and 56%, respectively. Microparticles had the desired size range (20-60 μm) and in vitro release was prolonged at ≥28 days. Microparticles were stable for ≥6 months when stored refrigerated protected from light in a desiccator. Desirably, i.t. injected fluorescent dye-labeled PLGA microparticles in rats remained in the lumbar region for ≥7 days. In a rat model of neuropathic pain, i.t. coinjection of hydromorphone- and ketamine-loaded microparticles (each 1 mg) produced analgesia for 8 h only. Possible explanations include inadequate release of ketamine and/or hydromorphone into the spinal fluid, and/or insufficient ketamine loading to prevent development of analgesic tolerance to the released hydromorphone. As sub-analgesic doses of i.t. ketamine at 24-48 h intervals restored analgesia on each occasion, insufficient ketamine loading appears problematic. We will investigate these issues in future work. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

The Effect of Skin Traction on Preoperative Pain and Need for Analgesics in Patients With Intertrochanteric Fractures: A Randomized Clinical Trial

PubMed Central

Manafi Rasi, Alireza; Amoozadeh, Farzad; Khani, Salim; Kamrani Rad, Amin; Sazegar, Ali

2015-01-01

Background: Preoperative skin traction is applied for many patients with hip fracture. However, the efficacy of this modality in pain relief is controversial. Objectives: The aim of the current study was to investigate the effects of skin traction on pain in patients with intertrochanteric fractures. Patients and Methods: A total of 40 patients contributed in this randomized clinical trial. Patients were randomly allocated into two equal groups: the skin traction (3 kg) and control groups. The severity of pain was recorded at admission and 30 minutes, one, six, 12, and 24 hours after skin traction application utilizing a Visual Analogue Scale (VAS). In addition, the number of requests for analgesics was recorded. Finally, the mean severity of pain in each measurement and the mean number of analgesic requests were compared between the two groups. Results: The severity of pain was significantly decreased in skin traction group only at the end of the first day after traction application (2.7 ± 0.8 vs. 3.3 ± 0.9; P = 0.042), while there was no significant difference between the two groups in other pain measurements. The number of requests for analgesics was the same between the two groups. Conclusions: Although skin traction had no effect on analgesic consumption, it significantly decreased the pain at the end of the first day. The application of skin traction in patients with intertrochanteric fractures is recommended. PMID:26401491

ANALGESIC EFFECT OF INTRATHECAL BACLOFEN BOLUS ON NEUROPATHIC PAIN IN SPINAL CORD INJURY PATIENTS.

PubMed

Kumru, Hatice; Benito-Penalva, Jesus; Kofler, Markus; Vidal, Joan

2018-05-18

GABA-ergic neurons are widely distributed throughout the central nervous system, including the spinal cord which is important for the transmission of pain impulses to the brain. Here we hypothesized that intrathecal baclofen (ITB) which is a GABA analogue might exert analgesic effects on neuropathic pain, which could be related to subtypes of pain in spinal cord injury (SCI). SCI patients with a cervical or thoracic lesion and neuropathic pain were randomized to receive either a single ITB bolus or placebo. Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory (NPSI), and Brief Pain Inventory (BPI) were obtained for assessment of neuropathic pain. Spasticity was assessed using Modified Ashworth Scale and visual analogue scale. Evaluations were performed at baseline, and 4, 8, and 24 hours after application of ITB or placebo. Eight patients received ITB, 5 placebo. Neuropathic pain improved significantly in the ITB group based on NRS, BPI, and NPSI, which revealed an effect on all subtypes of pain. Spasticity declined significantly. In the placebo group, there was neither significant change in pain nor in spasticity. An ITB bolus exerted a significant analgesic effect on all subtypes of neuropathic pain in SCI patients. ITB has analgesic effects on all subtypes of neuropathic pain and can improve interference of neuropathic pain with activities of daily living. ITB might be a promising analgesic treatment to control neuropathic pain. Copyright © 2018. Published by Elsevier Inc.

Analgesic and anti-inflammatory activities of 80% methanol root extract of Jasminum abyssinicum Hochst. ex. Dc. (Oleaceae) in mice.

PubMed

Tadiwos, Yohannes; Nedi, Teshome; Engidawork, Ephrem

2017-04-18

Pain and inflammation are associated with the pathophysiology of various clinical conditions. Most analgesic and anti-inflammatory drugs available in the market present a wide range of problems. The current study was aimed at investigating the analgesic and anti-inflammatory activity of 80% methanol extract of J. abyssinicum root. The analgesic activity was determined using tail-flick test and acetic acid induced writhing, whereas anti-inflammatory activity was determined by carrageenan induced paw edema and formalin induced pedal edema, carried out in vivo. The test group received three different doses of the extract (50mg/kg, 100mg/kg and 200mg/kg) orally. The positive control group received diclofenac (10mg/kg), aspirin (100mg/kg or 150mg/kg) or morphine (20mg/kg) orally. The negative control group received vehicle (2% Tween 80, 10ml/kg) orally. Furthermore, preliminary phytochemical screening was carried out. Oral administration of J. abbysinicum 80% methanol extract (at all doses) significantly (p<0.001) inhibit pain sensation in the pain models. Similarly, the extract demonstrated anti-inflammatory effect in the inflammation models in mice. Preliminary phytochemical screening showed the presence of saponins, flavonoids, terpenoids, triterpenens and glycosides. The data obtained from the present study indicates that the extract possessed a significant analgesic and anti-inflammatory activity, upholding the folkloric use of the plant. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models.

PubMed

Woode, Eric; Ameyaw, Elvis O; Boakye-Gyasi, Eric; Abotsi, Wonder K M

2012-10-01

Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg(-1), p.o.) and XA (10-100 mg kg(-1), p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg(-1), i.p.) and diclofenac (1-10 mg kg(-1), i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

A descriptive feasibility study to evaluate scheduled oral analgesic dosing at home for the management of postoperative pain in preschool children following tonsillectomy.

PubMed

Sutters, Kimberly A; Holdridge-Zeuner, Danielle; Waite, Steven; Paul, Steven M; Savedra, Marilyn C; Lanier, Brent; Mahoney, Karla; Miaskowski, Christine

2012-03-01

The purpose of this study, in a sample of preschool children (ages 3-5 years; N = 47), was to evaluate the feasibility of scheduled analgesic dosing following outpatient tonsillectomy in order to optimize pain management. Parents were instructed to give their child acetaminophen with hydrocodone (167 mg/5 mL) every 4 hours around the clock for the first 3 days following surgery. Parents recorded ratings of their child's pain with/without swallowing using the Faces, Legs, Activity, Cry, and Consolability (FLACC) behavioral pain scale, pain relief ratings, and severity of analgesic side effects in a home diary. Audiotaped interviews were conducted with parents to document descriptions of their experiences in managing their child's pain at home. Mean FLACC scores with/without swallowing were less than two at each measurement time and pain relief scores increased over time. Total analgesic dose decreased, and the number of missed doses increased over the first 3 days after surgery. Moderate-to-severe daytime sedation, nausea, vomiting, and constipation were reported by parents. Study results suggest that acetaminophen with hydrocodone is effective in relieving preschool children's pain following tonsillectomy and that parental adherence to a scheduled analgesic regimen decreases over time. Time-contingent dosing was associated with moderate to severe side effects and should be addressed in discharge teaching with parents. Findings provide insight into parents' perspective of pain management at home following tonsillectomy and methods for relieving their child's pain. Wiley Periodicals, Inc.

Pharmaco-toxicological study of diterpenoids.

PubMed

Delporte, Carla; Backhouse, Nadine; Salinas, Pedro; San-Martín, Aurelio; Bórquez, Jorge; Loyola, Alberto

2003-04-03

Azorella compacta, Azorella yareta and Laretia acaulis (Apiaceae) are native species from the high Andes Mountains, northeastern Chile, and they have being traditionally used to treat asthma, colds and bronchitis, illnesses with inflammation and pain as the main symptoms. Interestingly, there are no scientific reports available on their benefits or toxicity. This study was carried out with the purpose of validating the medicinal use of these species and to discover anti-inflammatory and analgesic new molecules. As a working hypothesis, we have proposed that these medicinal species contain bioactive compounds with anti-inflammatory and analgesic effects. In this context, azorellanol, 13-hydroxy-7-oxoazorellane and 7-deacetylazorellanol, three diterpenoids previously isolated only from these plants, were subjected to farmaco-toxicological evaluation. Their topical anti-inflammatory and analgesic activities along with acute toxicities or innocuosness were also investigated. Our results indicate the absence of toxic and side effects in mice. All compounds presented dose-related inhibition of pain. 13-hydroxy-7-oxoazorellane was the most potent analgesic but it was less effective than sodium naproxen, the reference drug. Azorellanol exhibited the highest topical anti-inflammatory potency on AA (arachidonic acid) and TPA (12-deoxyphorbol 13-tetradecanoate) induced oedema, and it effect was similar to the reference drugs (nimesulide and indomethacin). Probably, its mechanism of action could be explained through the inhibition to cyclo-oxygenase activity. Our results corroborate the anti-inflammatory and analgesic effects of these species, and it justifies their use in folk medicine.

Australian pharmacies prevent potential adverse reactions in patients taking warfarin requesting over-the-counter analgesia.

PubMed

MacFarlane, Brett V; Bergin, Jenny K; Reeves, Peter; Matthews, Andrew

2015-06-01

The objective of this article was to assess if Australian pharmacy staff prevent potential adverse reactions in warfarin patients requesting over-the-counter (OTC) analgesia. Mystery shoppers entered 170 pharmacies across Australia to request OTC analgesia for a hypothetical patient with a wrist injury who currently takes warfarin following a heart valve replacement. The request was made to the first pharmacist or non-pharmacist staff member to approach the mystery shopper. The interaction was audio-taped and assessed by a pharmacist. The OTC analgesic recommended was assessed for the potential to cause an adverse bleeding event. The quality of advice given with the OTC analgesic was assessed against determined criteria. Results were compared with scenarios of similar request type where the hypothetical patient was not taking warfarin. Mystery shoppers enquiring about taking OTC analgesics concomitantly with warfarin had access to the pharmacist in 97.0% of cases. All 170 pharmacies recommended OTC analgesics that were less likely to cause adverse events when taken with warfarin. The advice given and the communication between pharmacy staff and mystery shoppers were of high quality. Australian pharmacies support the quality use of medicines by patients taking warfarin by providing expeditious access to the pharmacist, appropriate recommendations of OTC analgesics, high standards of quality of advice and they communicate in a way to ensure ease of understanding by the consumer. The protocols used by pharmacy staff help prevent potentially serious adverse drug events. © 2014 Royal Pharmaceutical Society.

Analgesic ineffectiveness of lacosamide after spinal nerve ligation and its sodium channel activity in injured neurons.

PubMed

Hagenacker, T; Schäfer, N; Büsselberg, D; Schäfers, M

2013-07-01

Lacosamide is a novel anti-epileptic drug that enhances the slow- and not fast-inactivating state of voltage-gated sodium channels. Lacosamide has demonstrated analgesic efficacy in several animal studies but preclinical studies on neuropathic pain models are rare, and recent clinical trials showed no superior analgesic effects. Here, we examine whether an acute or chronic administration of lacosamide (3-60 mg/kg, i.p.) attenuates pain behaviour induced by spinal nerve ligation (SNL). To validate the inhibitory efficacy of lacosamide on voltage-gated sodium channels, sodium currents in naïve and SNL-injured dorsal root ganglion (DRG) neurons were recorded using whole-cell patch clamping. Lacosamide only marginally attenuated thermal hyperalgesia, but not tactile allodynia when applied once 7 or 14 days after SNL and showed no analgesic effect when applied daily for 19 days. In naïve neurons, 100 μmol/L lacosamide inhibited sodium channel currents by 58% and enhanced the slow inactivation (87% for lacosamide vs. 47% for control). In contrast, lacosamide inhibited sodium currents in injured DRG neurons by only 15%, while the effects on slow inactivation were diminished. Isolated currents from the NaV 1.8 channel subtype were only marginally changed by lacosamide. The reduced effectiveness of lacosamide on voltage-gated sodium channel currents in injured DRG neurons may contribute to the reduced analgesic effect observed for the SNL model. © 2012 European Federation of International Association for the Study of Pain Chapters.

Preconsultation use of analgesics on adults presenting to the emergency department with acute appendicitis

PubMed Central

Chong, C; Wang, T; Chen, C; Ma, H; Chang, H

2004-01-01

Objective: 279 cases of appendicitis were reviewed and compared for the difference between those patients who received pain medication before consulting a surgeon and those who were not treated with analgesics. Methods: All patients aged 15 years and older who underwent appendicectomy for appendicitis between 1 July 2001 and 30 June 2002 were divided into group 1 (those who received preconsultaion use of analgesics) and group 2 (those who were not treated with analgesics). The following measures were compared: age, sex, symptom duration, initial vital signs, white blood cell counts, frequency of imaging studies, time to operative intervention, and operative findings. Continuous and categorical variables were analysed using t and χ2 tests, respectively. Results: A total of 279 patients were included for analysis. Patient details (age, sex, symptom duration) of the two study groups were similar. There was no statistically significant difference between group 1 and group 2 with respect to vital signs (systolic blood pressure, pulse rate, respiratory rate, body temperature), white blood cell counts, and frequency of imaging studies (ultrasound, computed tomography). There was no significant difference in the rate of perforated appendicitis between the two study groups although a shorter median time to operative intervention has been found in the group who received analegesia. Conclusion: The preconsultation use of analgesics in ED patients with a final diagnosis of appendicitis is not associated with a longer delay to operative intervention and is not associated with an increased rate of perforated appendicitis. PMID:14734373

Comparative antipyretic and analgesic activities of Cissampelos pareira Linn. and Cyclea peltata (Lam.) Hook. F. & Thomas.

PubMed

Singh, Suman G; Nishteswar, K; Patel, Bhupesh R; Nariya, Mukesh

2016-01-01

Cissampelos pareira Linn. is considered as an established source of Patha , whereas Cyclea peltata (Lam.) Hook. F. & Thomas is used as a source plant of Patha in the southern part of India. In classical texts, two different varieties of Patha , i.e. Rajpatha ( C. peltata ) and Laghupatha ( C. pareira ), are mentioned which possess almost similar properties. To compare antipyretic and analgesic activities of C. pareira and C. peltata in suitable experimental model. Powder (540 mg/kg) and ethanolic extract (200 mg/kg) of both the test drugs ( C. pareira and C. peltata ) were evaluated for antipyretic activity in Brewer's yeast-induced pyrexia model in rats. Analgesic activity was evaluated by radiant heat model in rats and acetic acid-induced writhing syndrome in mice. Result of the present study had shown that powder of C. pareira (540 mg/kg) has moderate antipyretic activity as compared to the powder of C. peltata and extract of both test drugs. C. pareira powder showed better analgesic effect than ethanolic extract (200 mg/kg) of both the test drugs in radiant heat model in rats, while in acetic acid-induced writhing syndrome, ethanolic extract (280 mg/kg) of both drugs showed pronounced effect as compared to powder form (780 mg/kg) in mice. Both C. pareira and C. peltata exhibited analgesic effects in experimental animals. The effect is more significant in C. peltata treated group compared to C. pareira . Antipyretic effect was observed with the pretreatment of C. pareira .

Comparison of the antinociceptive action of crude Fuzei, the root of Aconitum, and its processed products.

PubMed

Liou, Shorong-Shii; Liu, I-Min; Lai, Mei Chou; Cheng, Juei-Tang

2005-07-14

The antinociceptive effects of crude Fuzei, the root of Aconitum carmichaeli and of Fuzei processed by three different methods were determined in mice and rats using the light tail-flick assay. A dose-dependent and significant increase in pain threshold was found at 60 min post treatment, with doses of 20-60 mg/kg crude Fuzei. The analgesic effects of processed Fuzei (20-60 mg/kg) exhibited a dose-dependent inhibition of tail-flick, but the effects were lower than those produced by crude Fuzei in the same tests. The analgesic effect of Yan-Fuzei, the salt baking product, was the most potent of the processed products and was nearly that provided by crude Fuzei. Although the concentrations of aconitine were significantly lower in the processed Fuzei than in the crude Fuzei, a higher oral LD50 was found for all of the processed Fuzei formulations. Moreover, antinociception of crude Fuzei and its processed products was attenuated but not totally blocked by naloxone at doses sufficient to block opioid mu-receptors. Furthermore, the analgesic effect of crude Fuzei and its processed products was decreased in opioid mu-receptor knockout mice, but the effect remained unaltered in mice with opioid mu-receptors, indicating that the analgesic effect of Fuzei is centrally mediated. These results demonstrate that Fuzei processed by salt baking possesses analgesic effects within a large therapeutic range, probably via a mechanism involving central opioid receptors that mediate the antinociception.

Analgesic effects of ultrasound-guided transverse abdominis plane block using different volumes and concentrations of local analgesics after laparoscopic cholecystectomy.

PubMed

Şahin, Ayça Sultan; Ay, Necmiye; Şahbaz, Nuri Alper; Akay, Mehlika Kocabaş; Demiraran, Yavuz; Derbent, Abdurrahim

2017-02-01

Objective To evaluate the effects of an ultrasound-guided transverse abdominis plane (US-TAP) block used for postoperative pain relief by comparing the efficacy of two different volumes/concentrations of the local anaesthetic bupivacaine in patients undergoing laparoscopic cholecystectomies. Methods This randomized study enrolled patients undergoing laparoscopic cholecystectomies. They were randomized to two groups: group A received a 20 ml US-TAP block (50 mg bupivacaine +10 ml saline solution) and group B received a 30 ml US-TAP block (50 mg bupivacaine + 20 ml saline solution). The intraoperative consumption of remifentanil, the requirement for postoperative rescue analgesics, patient satisfaction scores, postoperative complications, and postoperative pain as measured by a visual analogue scale at 20 min, 12 h, and 24 h were recorded. Results A total of 60 patients enrolled in the study. There were no differences between the two groups with respect to demographic characteristics, duration of anaesthesia and patient satisfaction scores. The intraoperative consumption of remifentanil, postoperative VAS scores (20 min, 12 h and 24 h) and the requirement for postoperative analgesics were all significantly lower in group B who received a larger volume but a lower concentration of local anaesthetic solution compared with group A. Conclusion A US-TAP block can form part of a balanced postoperative analgesic regimen following laparoscopic cholecystectomy.

Analgesic Effects of Toad Cake and Toad-cake-containing Herbal Drugs

PubMed Central

Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Usui, Tomomi; Sudoh, Keiichi

2014-01-01

Objectives: This study was conducted to clarify the analgesic effect of toad cake and toad-cake-containing herbal drugs. Methods: We counted the writhing response of mice after the intraperitoneal administration of acetic acid as a nociceptive pain model and the withdrawal response after the plantar surface stimulation of the hind paw induced by partial sciatic nerve ligation of the mice as a neuropathic pain model to investigate the analgesic effect of toad cake and toad-cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis inhibitory drug 4-chloro- DL-phenylalanine methyl ester hydrochloride (PCPA), the catecholamine biosynthesis inhibitory drug α-methyl- DL-tyrosine methyl ester hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was also conducted. Results: Analgesic effects in a mouse model of nociceptive pain and neuropathic pain were shown by oral administration of toad cake and toad-cake-containing herbal drugs. The effects of toad cake and toad-cake-containing herbal drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in the nociceptive pain model; the analgesic effect of toad-cake-containing herbal drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model. Conclusion: Toad cake and toad-cake-containing herbal drugs have potential for the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or posttraumatic pain, by activation of the central serotonin nervous system. PMID:25780693

Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation.

PubMed

Ur Rahman, Shafiq; Adhikari, Achyut; Ismail, Muhammad; Raza Shah, Muhammad; Khurram, Muhammad; Shahid, Muhammad; Ali, Farman; Haseeb, Abdul; Akbar, Fazal; Iriti, Marcello

2016-08-20

Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC50, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation.

Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

PubMed Central

Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

2018-01-01

Introduction Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED). Methods We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016). Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED. PMID:29760856

The analgesic effect of wound infiltration with local anaesthetics after breast surgery: a qualitative systematic review.

PubMed

Byager, N; Hansen, M S; Mathiesen, O; Dahl, J B

2014-04-01

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. 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 < 0.05) in pain scores and supplemental analgesic consumption. Ten trials including 699 patients were included in the final analysis. Three trials investigated mastectomy, four trials partial or segmental mastectomy, and three trials breast reduction, excision of benign lump and unspecified breast surgery, respectively. Six trials demonstrated a small and short-lasting, but statistically significant reduction of post-operative pain scores, and four trials observed a statistically significant reduction in post-operative, supplemental opioid consumption that was, however, of limited clinical relevance. Wound infiltration with local anaesthetics may have a modest analgesic effect in the first few hours after surgery. Pain after breast surgery is, however, generally mild to moderate, and other non-invasive analgesic methods may be preferable in this surgical population. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Allergic and non-allergic hypersensitivity to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs in children: epidemiology, clinical aspects, pathophysiology, diagnosis and prevention].

PubMed

Ponvert, C

2012-05-01

Non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs are widely used, but suspected allergic reactions to these drugs are rare, especially in children. Most frequent reactions are cutaneous (urticaria, angioedema) and respiratory (rhinitis, asthma). Other reactions (anaphylaxis, potentially harmful toxidermias) are rare. In a few patients, reactions may result from a specific (allergic) hypersensitivity, with positive responses in prick and intradermal tests (anaphylaxis, immediate urticaria and/or angioedema) and in intradermal and patch tests (non-immediate reactions). However, most reactions result from a non-specific (non-allergic) hypersensitivity (intolerance), with a frequent cross-reactivity between the various families of analgesics, antipyretics and nonsteroidal anti-inflammatory drugs, including paracetamol. Based on a convincing clinical history and/or positive responses in challenge tests, intolerance to non-opioid analgesics, antipyretics and nonsteroidal anti-inflammatory drugs has been diagnosed in 13 to 50% of the patients with allergic-like reactions to these drugs. Risk factors are a personal atopy and age. Prevention is based on administration of other (families of) analgesics, antipyretics and nonsteroidal anti-inflammatory drugs in patients with allergic hypersensitivity to these drugs. In patients with non-allergic hypersensitivity, prevention is based on administration of drugs with a low cyclo-oxygenase-1 inhibitory activity (if tolerated). Desensitization is efficient in patients with respiratory reactions, but does not work in patients with mucocutaneous reactions and anaphylaxis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Prescription opioid mortality trends in New York City, 1990–2006: Examining the emergence of an epidemic☆

PubMed Central

Ransome, Yusuf; Keyes, Katherine M.; Koenen, Karestan C.; Tracy, Melissa; Tardiff, Kenneth J.; Vlahov, David; Galea, Sandro

2013-01-01

Background The drug overdose mortality rate tripled between 1990 and 2006; prescription opioids have driven this epidemic. We examined the period 1990–2006 to inform our understanding of how the current prescription opioid overdose epidemic emerged in urban areas. Methods We used data from the Office of the Chief Medical Examiner to examine changes in demographic and spatial patterns in overdose fatalities induced by prescription opioids (i.e., analgesics and methadone) in New York City (NYC) in 1990–2006, and what factors were associated with death from prescription opioids vs. heroin, historically the most prevalent form of opioid overdose in urban areas. Results Analgesic-induced overdose fatalities were the only types of overdose fatalities to increase in 1990–2006 in NYC; the fatality rate increased sevenfold from 0.39 in 1990 to 2.7 per 100,000 persons in 2006. Whites and Latinos were the only racial/ethnic groups to exhibit an increase in overdose-related mortality. Relative to heroin overdose decedents, analgesic and methadone overdose decedents were more likely to be female and to concurrently use psychotherapeutic drugs, but less likely to concurrently use alcohol or cocaine. Analgesic overdose decedents were less likely to be Black or Hispanic, while methadone overdose decedents were more likely to be Black or Hispanic in contrast to heroin overdose decedents. Conclusions The distinct epidemiologic profiles exhibited by analgesic and methadone overdose fatalities highlight the need to define drug-specific public health prevention efforts. PMID:23357743

Language competence and communication skills in 3-year-old children after prenatal exposure to analgesic opioids.

PubMed

Skovlund, Eva; Handal, Marte; Selmer, Randi; Brandlistuen, Ragnhild Eek; Skurtveit, Svetlana

2017-06-01

An increasing consumption of opioids in the general population has been reported in several countries also among pregnant women. Limited information is available regarding the effect of prenatal exposure to analgesic opioids on long-term neurocognitive function in children. The primary aim of the study was to determine the association between prenatal exposure to analgesic opioids and language competence and communication skills at 3 years of age. The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women during the period from 1999 to 2008. Participants reported medication use at pregnancy weeks 17-18 and 30, and 6 months after birth. Children's language competence and communication skills were reported by mothers on validated scales. A total of 45 211 women with 51 679 singleton pregnancies were included. The use of analgesic opioids was reported in 892 pregnancies (1.7%). In adjusted analyses, no association between opioid use and reduced language competence or communication skills was found, OR = 1.04 (95%CI: 0.89-1.22) and OR = 1.10 (95%CI: 0.95-1.27), respectively. Both pain and use of paracetamol were associated with a small reduction in communication skills. No such association was found for language competence. The use of analgesic opioids in pregnant women does not seem to affect language development or communication skills in children at 3 years of age. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Comparative Rates of Mortality and Serious Adverse Effects Among Commonly Prescribed Opioid Analgesics.

PubMed

Murphy, David L; Lebin, Jacob A; Severtson, Stevan G; Olsen, Heather A; Dasgupta, Nabarun; Dart, Richard C

2018-03-26

The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics. The common assumption that more potent opioid analgesics are associated with higher rates of adverse outcomes has not been adequately substantiated. We compared the rate of serious adverse events among commonly prescribed opioid analgesics of varying potency. Serious adverse events (SAEs; defined as death, major medical effect, or hospitalization) resulting from exposure to tablets containing seven opioid analgesics (oxycodone, hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol) captured by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS ® ) System Poison Center Program were evaluated from 2010 through 2016. Rates of SAEs were adjusted for availability through outpatient dispensing data and regressed on morphine milligram equivalents (MME). There were 19,480 cases of SAE during the 7-year study period. Hydrocodone and oxycodone contributed to 77% of SAE cases. Comparing rates of outcome by relative potency, a hierarchy was observed with hydromorphone (8.02 SAEs/100 kg) and tapentadol (0.27 SAE/100 kg) as the highest and lowest rates, reflecting a 30-fold difference among individual opioid products. SAE rate and potency were related linearly-SAEs increased 2.04 per 100 kg drug dispensed for each 1-unit rise in MME (p = 0.004). Linear regression of SAE/100 kg drug dispensed and drug potency identified that MME comprised 96% of the variation observed. In contrast, potency did not explain variation seen using other study denominators (prescriptions dispensed, dosage units dispensed, and the number of individuals filling a prescription). Potency of a prescription opioid analgesic demonstrates a significant, highly positive linear relationship with exposures resulting in SAEs per 100 kg drug dispensed reported to poison centers. Potency should be carefully considered from both individual provider and public health perspectives.

Effect of Dexamethasone on Characteristics of Supraclavicular Nerve Block with Bupivacaine and Ropivacaine: A Prospective, Double-blind, Randomized Control Trial.

PubMed

Bindal, Deeksha; Narang, Neeraj; Mahindra, Rekha; Gupta, Himanshu; Kubre, Jyotsna; Saxena, Anudeep

2018-01-01

Dexamethasone as an adjuvant to bupivacaine and ropivacaine for supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade. However, comparison of effect of dexamethasone (8 mg) when added to these two local anesthetics has not been well studied. This study was conducted to compare analgesic efficacy of dexamethasone as adjuvant to bupivacaine and ropivacaine in SCBP block. Nerve stimulator-guided SCBP block was given to 120 patients, randomly assigned to one of four groups: ( n = 30 in each group) Group B, BD, R, and RD received 30 ml (0.5%) bupivacaine + 2 ml saline, 30 ml (0.5%) bupivacaine + dexamethasone 8 mg, 30 ml (0.5%) ropivacaine + 2 ml saline, and 30 ml (0.5%) ropivacaine + dexamethasone 8 mg, respectively. Time for request of the first rescue analgesic, 24-h analgesic consumption, and different block characteristics were assessed. Student's t -test, Chi-square test, ANOVA were used for statistical analysis. Dexamethasone significantly prolonged time for request of the first rescue analgesic of both ropivacaine (1211.83 ± 32.86 vs. 283.17 ± 7.71 min){ p R, RD < 0.001} and bupivacaine (1205.17 ± 34.32 vs. 364.67 ± 16.50 min) {p B, BD < 0.001}. 24-h requirement for rescue analgesics was more in Groups B and R when compared to Groups BD and RD. The increase in duration of analgesia was more when Groups R and RD (928.66 min) were compared than Groups B and BD (840.5 min). Similar results were seen with onset times and duration of sensory and motor block. The addition of dexamethasone to bupivacaine and ropivacaine in SCBP block prolonged time for first rescue analgesia and reduced the requirement of rescue analgesics with faster onset and prolonged duration of sensory and motor block, with the effect being stronger with ropivacaine.

The diagnostic value of the numeric pain rating scale in older postoperative patients.

PubMed

van Dijk, Jacqueline F M; Kappen, Teus H; van Wijck, Albert J M; Kalkman, Cor J; Schuurmans, Marieke J

2012-11-01

To measure the diagnostic value of the Numeric Rating Scale by comparing it to a Verbal Rating Scale in older patients. Pain management in older patients is an important challenge because of their greater susceptibility to adverse effects of analgesics. Nurses play an important role in applying guidelines for postoperative pain treatment. However, effective pain management is dependent upon valid and reliable pain assessment. Cross-sectional study. In total, 2674 older patients scored their postoperative pain on an 11-point numeric rating scale (NRS) and an adjective scale (VRS) including no pain, little pain, painful but bearable, considerable pain and terrible pain. The diagnostic value of different NRS cut-off values for administering analgesics is determined by an ROC curve. Sensitivity of NRS > 3 for 'unbearable' pain in older patients was 72% with a specificity of 97·2%. With a cut-off point NRS > 4, sensitivity increased to 83%, while specificity was 96·7%. With a cut-off point NRS > 5, sensitivity was 94%, while specificity was 85%. A high proportion (75%) of older old patients (≥ 75 years) with 'painful but bearable' considers NRS 4, 5 and 6 to this VRS category. Using an NRS cut-off point > 3 or > 4, a large group of older patients with 'bearable' pain would incorrectly classified as 'unbearable'. When we make the assumption that bearable pain means no wish for additional analgesics, this misclassification might result in overtreatment with analgesics, while 3% would be undertreated. With NRS cut-off point > 5, 6% have a risk of overtreatment and 15% of undertreatment. Nurses should not rely solely on the NRS score in determining pain treatment; they need to communicate with older patients about their pain, the need for analgesics and eventual misconceptions about analgesics. © 2012 Blackwell Publishing Ltd.

Analgesic effects of oligonol, acupuncture and quantum light therapy on chronic nonbacterial prostatitis.

PubMed

Akdere, Hakan; Oztekin, Ilhan; Arda, Ersan; Aktoz, Tevfik; Turan, Fatma Nesrin; Burgazli, Kamil Mehmet

2015-04-01

Chronic Nonbacterial Prostatitis (CNBP) is a condition that frequently causes long-term pain and a significant decrease in the quality of life. The present study aimed to examine the analgesic effects of oligonol, acupuncture, quantum light therapy and their combinations on estrogen-induced CNBP in rats. This experimental study was conducted in Edirne, Turkey, using a simple randomized allocation. A total of 90 adult male Wistar rats were randomized into 9 groups of 10 rats each: Group I, control; Group II, CNBP, Group III, oligonol only, Group IV, acupuncture only; Group V, quantum only; Group VI, oligonol + quantum; Group VII, acupuncture + oligonol; Group VIII, quantum + acupuncture; Group IX, acupuncture + quantum + oligonol. Oligonol treatment was given at a dose of 60 mg/day for 6 weeks. Conceptual vessels (CV) 3 and 4, and bilaterally urinary bladder (Bl) 32 and 34 points were targeted with 1-hour acupuncture stimulation. The quantum light therapy was applied in 5-minute sessions for 6 weeks (3-times/a week). For pain measurements, mechanical pressure was applied to a point 2 cm distal to the root of the tail to elicit pain and consequent parameters (peak force, latency time of response and total length of measurement) were assessed. Analgesic effects were observed with all treatment regimens; however, the most prominent median analgesic effect was shown in the quantum light therapy in combination with acupuncture for estrogen-induced CNBP (PF1 = 663.9, PF2 = 403.4) (P = 0.012). Furthermore, we observed that monotherapy with quantum light showed a better analgesic efficacy as compared to oligonol and acupuncture monotherapies (PF1 = 1044.6, PF2 = 661.2) (P = 0.018, P = 0.008, P = 0.018; respectively). All treatment modalities showed a significant analgesic effect on CNBP in rats, being most prominent with the quantum light therapy.

A Review of Current and Emerging Approaches to Pain Management in the Emergency Department.

PubMed

Todd, Knox H

2017-12-01

Pain is the most common symptom prompting an emergency department visit and emergency physicians are responsible for managing both acute pain and acute exacerbations of chronic pain resulting from a broad range of illnesses and injuries. The responsibility to treat must be balanced by the duty to limit harm resulting from analgesics. In recent years, opioid-related adverse effects, including overdose and deaths, have increased dramatically in the USA. In response to the US opioid crisis, emergency physicians have broadened their analgesic armamentarium to include a variety of non-opioid approaches. For some of these therapies, sparse evidence exists to support their efficacy for emergency department use. The purpose of this paper is to review historical trends and emerging approaches to emergency department analgesia, with a particular focus on the USA and Canada. We conducted a qualitative review of past and current descriptive studies of emergency department pain practice, as well as clinical trials of emerging pain treatment modalities. The review considers the increasing use of non-opioid and multimodal analgesic therapies, including migraine therapies, regional anesthesia, subdissociative-dose ketamine, nitrous oxide, intravenous lidocaine and gabapentinoids, as well as broad programmatic initiatives promoting the use of non-opioid analgesics and nonpharmacologic interventions. While migraine therapies, regional anesthesia, nitrous oxide and subdissociative-dose ketamine are supported by a relatively robust evidence base, data supporting the emergency department use of intravenous lidocaine, gabapentinoids and various non-pharmacologic analgesic interventions remain sparse. Additional research on the relative safety and efficacy of non-opioid approaches to emergency department analgesia is needed. Despite a limited research base, it is likely that non-opioid analgesic modalities will be employed with increasing frequency. A new generation of emergency physicians is seeking additional training in pain medicine and increasing dialogue between emergency medicine and pain medicine researchers, educators and clinicians could contribute to better management of emergency department pain.

Concomitant use of analgesics and psychotropics in home-dwelling elderly people – Kuopio 75 + study

PubMed Central

Hartikainen, Sirpa; Mäntyselkä, Pekka; Louhivuori-Laako, Kirsti; Enlund, Hannes; Sulkava, Raimo

2005-01-01

Aims To investigate the extent of concomitant use of analgesic and psychotropic medicines among home-dwelling elderly people aged at least 75 years in Finland. Methods This was a population-based study in Finland, performed as part of Kuopio 75 + study focusing on the clinical epidemiology of diseases, medication and functional capacity. A random sample of 700 persons was drawn from the total population of the city of Kuopio, eastern Finland, aged 75 years on January 1, 1998 (n = 4518). Ninety-nine persons could not be examined and 78 were living in long-term institutions, so that the number of home-dwelling elderly persons amounted to 523. A trained nurse interviewed the participants about their use of medicines, and a geriatrician examined their overall physical and mental status. Dementia and depression were diagnosed according to the DSM IV criteria. Both regular and irregular prescribed and nonprescribed drug use was recorded. Results Every fourth elderly person (27.2%) used analgesics and psychotropics concomitantly, this use becoming twice as common with advancing age (19.6% in the age group 75–79 years, 38.2% among the oldest, aged 85 + years). Concomitant use of psychotropics and opioids also became more common with increasing age (2.8% in age group 75–79 years and 9.6% in the oldest group, aged 85 + years). The use of opioids was nearly twice as common among concomitant users (19.7%) than among those using only analgesics (11.3%). Concomitant users suffered from interfering daily pain and daily pain at rest more commonly than nonusers of analgesics. Depression, sleeping problems and polypharmacy were more common among the concomitant users, who had also had more hip fractures than the rest. Conclusions Concomitant use of analgesics and psychotropics becomes more common with advancing age and is a potential risk factor for adverse drug effects. PMID:16120070

The use of nonsteroidal anti-inflammatory drugs and analgesics by liver transplant recipients.

PubMed

Mulka-Gierek, Maria; Foroncewicz, Bartosz; Florczak, Michał; Pączek, Leszek; Krawczyk, Marek; Mucha, Krzysztof

2016-04-01

This study aimed to assess the reasons and the frequency of the use of over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesics by liver transplant recipients (LTR). Patient awareness of possible drug-related side-effects was also assessed. NSAIDs and analgesics available without prescription belong to the most commonly used class of drugs. However, use of these drugs might be complicated by toxic adverse effects (AEs). Patients at risk for AEs include the transplant recipients. This was a descriptive study. An anonymous survey was carried out in 73 randomly selected LTR, who represented 10% of all LTR at our centre. There were 64% of the patients who confirmed taking NSAIDs or analgesics; 16% of these patients took these drugs at least several times a week and 10% took them daily. For 39% of patients, the only way to manage their pain were OTC NSAIDs or analgesics. As many as 36% of patients were unaware of the risks associated with the use of these drugs. Ninety per cent of LTR consider physicians the most trusted source of drugs information. Our study shows that two-thirds of LTR take OTC NSAIDs or analgesics and one-third are unaware of the AEs associated with these drugs. Therefore, both transplant nurses and doctors should educate their patients about the use and possible AE of these drugs. Considering the high NSAIDs consumption rates, the side effects of these drugs should always be suspected. Especially in patients taking these drugs and referring to medical advisors with specific symptoms, such as: abdominal pain, anaemia, elevated serum creatinine concentration or liver enzymes activity. Awareness of the scale of the problem enables health professionals to cooperate in educating patients. Such practices may reduce uncontrolled abuse of these drugs and related health care costs. © 2016 John Wiley & Sons Ltd.

Association of race and ethnicity with management of abdominal pain in the emergency department.

PubMed

Johnson, Tiffani J; Weaver, Matthew D; Borrero, Sonya; Davis, Esa M; Myaskovsky, Larissa; Zuckerbraun, Noel S; Kraemer, Kevin L

2013-10-01

To determine if race/ethnicity-based differences exist in the management of pediatric abdominal pain in emergency departments (EDs). Secondary analysis of data from the 2006-2009 National Hospital Ambulatory Medical Care Survey regarding 2298 visits by patients ≤ 21 years old who presented to EDs with abdominal pain. Main outcomes were documentation of pain score and receipt of any analgesics, analgesics for severe pain (defined as ≥ 7 on a 10-point scale), and narcotic analgesics. Secondary outcomes included diagnostic tests obtained, length of stay (LOS), 72-hour return visits, and admission. Of patient visits, 70.1% were female, 52.6% were from non-Hispanic white, 23.5% were from non-Hispanic black, 20.6% were from Hispanic, and 3.3% were from "other" racial/ethnic groups; patients' mean age was 14.5 years. Multivariate logistic regression models adjusting for confounders revealed that non-Hispanic black patients were less likely to receive any analgesic (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.43-0.87) or a narcotic analgesic (OR: 0.38; 95% CI: 0.18-0.81) than non-Hispanic white patients (referent group). This finding was also true for non-Hispanic black and "other" race/ethnicity patients with severe pain (ORs [95% CI]: 0.43 [0.22-0.87] and 0.02 [0.00-0.19], respectively). Non-Hispanic black and Hispanic patients were more likely to have a prolonged LOS than non-Hispanic white patients (ORs [95% CI]: 1.68 [1.13-2.51] and 1.64 [1.09-2.47], respectively). No significant race/ethnicity-based disparities were identified in documentation of pain score, use of diagnostic procedures, 72-hour return visits, or hospital admissions. Race/ethnicity-based disparities exist in ED analgesic use and LOS for pediatric abdominal pain. Recognizing these disparities may help investigators eliminate inequalities in care.

Does neonatal pain management in intensive care units differ between night and day? An observational study

PubMed Central

Guedj, Romain; Danan, Claude; Daoud, Patrick; Zupan, Véronique; Renolleau, Sylvain; Zana, Elodie; Aizenfisz, Sophie; Lapillonne, Alexandre; de Saint Blanquat, Laure; Granier, Michèle; Durand, Philippe; Castela, Florence; Coursol, Anne; Hubert, Philippe; Cimerman, Patricia; Anand, K J S; Khoshnood, Babak; Carbajal, Ricardo

2014-01-01

Objective To determine whether analgesic use for painful procedures performed in neonates in the neonatal intensive care unit (NICU) differs during nights and days and during each of the 6 h period of the day. Design Conducted as part of the prospective observational Epidemiology of Painful Procedures in Neonates study which was designed to collect in real time and around-the-clock bedside data on all painful or stressful procedures. Setting 13 NICUs and paediatric intensive care units in the Paris Region, France. Participants All 430 neonates admitted to the participating units during a 6-week period between September 2005 and January 2006. Data collection During the first 14 days of admission, data were collected on all painful procedures and analgesic therapy. The five most frequent procedures representing 38 012 of all 42 413 (90%) painful procedures were analysed. Intervention Observational study. Main outcome assessment We compared the use of specific analgesic for procedures performed during each of the 6 h period of a day: morning (7:00 to 12:59), afternoon, early night and late night and during daytime (morning+afternoon) and night-time (early night+late night). Results 7724 of 38 012 (20.3%) painful procedures were carried out with a specific analgesic treatment. For morning, afternoon, early night and late night, respectively, the use of analgesic was 25.8%, 18.9%, 18.3% and 18%. The relative reduction of analgesia was 18.3%, p<0.01, between daytime and night-time and 28.8%, p<0.001, between morning and the rest of the day. Parental presence, nurses on 8 h shifts and written protocols for analgesia were associated with a decrease in this difference. Conclusions The substantial differences in the use of analgesics around-the-clock may be questioned on quality of care grounds. PMID:24556241

Liposomal bupivacaine versus bupivacaine/epinephrine after video-assisted thoracoscopic wedge resection†.

PubMed

Parascandola, Salvatore A; Ibañez, Jessica; Keir, Graham; Anderson, Jacqueline; Plankey, Michael; Flynn, Deanna; Cody, Candice; De Marchi, Lorenzo; Margolis, Marc; Blair Marshall, M

2017-06-01

The purpose of this research is to compare liposomal bupivacaine and bupivacaine/epinephrine for intercostal blocks related to analgesic use and length of stay following video-assisted thoracoscopic wedge resection. A retrospective study of patients undergoing video-assisted thoracoscopic wedge resection from 2010 to 2015 was performed. We selected patients who stayed longer than 24 h in hospital. Primary outcomes were length of stay and postoperative analgesic use at 12-h intervals from 24 to 72 h. Intercostal blocks were performed with liposomal bupivacaine in 62 patients and bupivacaine/epinephrine in 51 patients. A Wilcoxon signed-rank test evaluated differences in median postoperative analgesic use and length of stay. Those who received liposomal bupivacaine consumed fewer analgesics than those who received bupivacaine/epinephrine, with a statistically significant difference from 24 to 36 h (20.25 vs 45.0 mg; P  = 0.0059) and from 60 to 72 h postoperatively (15.0 vs 33.75 mg; P  = 0.0350). In patients who stayed longer than 72 h, the median cumulative analgesic consumption in those who received liposomal bupivacaine was statistically significantly lower than those who received bupivacaine/epinephrine (120.0 vs 296.5 mg; P  = 0.0414). Median length of stay for the liposomal bupivacaine and bupivacaine/epinephrine groups were 45:05 h and 44:29 h, respectively. There were no adverse events related to blocks performed with liposomal bupivacaine. Thoracic surgery patients who have blocks performed with liposomal bupivacaine require fewer analgesics postoperatively. This may decrease complications related to poor pain control and decrease side effects related to narcotic use in our patient population. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Effect of Two Different Doses of Dexmedetomidine as Adjuvant in Bupivacaine Induced Subarachnoid Block for Elective Abdominal Hysterectomy Operations: A Prospective, Double-blind, Randomized Controlled Study

PubMed Central

Das, Anjan; Halder, Susanta; Chattopadhyay, Surajit; Mandal, Parthajit; Chhaule, Subinay; Banu, Rezina

2015-01-01

Objectives Improvements in perioperative pain management for lower abdominal operations has been shown to reduce morbidity, induce early ambulation, and improve patients’ long-term outcomes. Dexmedetomidine, a selective alpha-2 agonist, has recently been used intrathecally as adjuvant to spinal anesthesia to prolong its efficacy. We compared two different doses of dexmedetomidine added to hyperbaric bupivacaine for spinal anesthesia. The primary endpoints were the onset and duration of sensory and motor block, and duration of analgesia.   Methods A total of 100 patients, aged 35–60 years old, assigned to have elective abdominal hysterectomy under spinal anesthesia were divided into two equally sized groups (D5 and D10) in a randomized, double-blind fashion. The D5 group was intrathecally administered 3ml 0.5% hyperbaric bupivacaine with 5µg dexmedetomidine in 0.5ml of normal saline and the D10 group 3ml 0.5% bupivacaine with 10µg dexmedetomidine in 0.5ml of normal saline. For each patient, sensory and motor block onset times, block durations, time to first analgesic use, total analgesic need, postoperative visual analogue scale (VAS) scores, hemodynamics, and side effects were recorded.   Results Although both groups had a similar demographic profile, sensory and motor block in the D10 group (p<0.050) was earlier than the D5 group. Sensory and motor block duration and time to first analgesic use were significantly longer and the need for rescue analgesics was lower in the D10 group than the D5 group. The 24-hour VAS score was significantly lower in the D10 group (p<0.050). Intergroup hemodynamics were comparable (p>0.050) without any appreciable side effects.   Conclusion Spinal dexmedetomidine increases the sensory and motor block duration and time to first analgesic use, and decreases analgesic consumption in a dose-dependent manner. PMID:26366259

Psychological and drug abuse symptoms associated with nonmedical use of opioid analgesics among adolescents.

PubMed

Boyd, Carol J; Young, Amy; McCabe, Sean E

2014-01-01

Approximately 18% of US adolescents engaged in prescription opioid abuse in 2013. However, this estimate may be misleading because it includes both medical misusers and nonmedical users, and there is evidence that these are 2 groups that differ relative to substance abuse and criminal risk. Thus, this study does not combine medical and nonmedical users; rather, it seeks to better understand the characteristics of nonmedical users. This was a school-based, cross-sectional study that was conducted during 2009-2010 in southeastern Michigan with a sample of 2627 adolescents using a Web-based survey. Three mutually exclusive groups were created based on responses regarding medical and nonmedical use of opioid analgesics. Group 1 had never used an opioid analgesic, Group 2 used an opioid analgesic only as prescribed, and Group 3 nonmedically used an opioid analgesic. In addition, Group 3 was divided into 2 mutually exclusive subgroups (self-treaters and sensation-seekers) based on reasons for nonmedical use. A series of multinomial logistic regressions were conducted to determine if the groups differed on the presence of pain, psychological symptoms (e.g., affective disorder, conduct disorder, attention-deficit/hyperactivity disorder [ADHD]), and drug abuse. Sixty-five percent (65.0%) of the sample was white/Caucasian and 29.5% was African American. The average age was 14.8 years (SD = 1.9). Seventy percent (70.4%; n = 1850) reported no lifetime opioid use, 24.5% (n = 644) were medical users, 3.5% (n = 92) were nonmedical users who used for pain relief only, and 1.6% (n = 41) were classified as nonmedical users for reasons other than for pain relief (e.g., to get high). Both medical users and nonmedical users reported more pain and substance abuse symptoms compared with never users. Those nonmedical users who used opioids for sensation-seeking motivations had greater odds of having psychological symptoms. These data support the need to further consider subgroups of nonmedical users of opioid analgesics.

A Comparison of Three Different Volumes of Levobupivacaine for Caudal Block in Children Undergoing Orchidopexy and Inguinal Hernia Repair.

PubMed

Marjanovic, Vesna; Budic, Ivana; Stevic, Marija; Simic, Dusica

2017-01-01

The aim of this study was to compare the efficacy of 3 different volumes of 0.25% levobupivacaine caudally administered on the effect of intra- and postoperative analgesia in children undergoing orchidopexy and inguinal hernia repair. Forty children, aged 1-7 years, American Society of Anesthesiologists (ASA) physical status I and II, were randomized into 3 different groups according to the applied volumes of 0.25% levobupivacaine: group 1 (n = 13): 0.6 mL∙kg-1; group 2 (n = 10): 0.8 mL∙kg-1; and group 3 (n = 17): 1.0 mL∙kg-1. The age, weight, duration of anesthesia, onset time of intraoperative analgesic, dosage, and addition of intraoperative fentanyl were compared among the groups. The time to first use of the analgesic and the number of patients who required analgesic 24 h after surgery in the time intervals within 6 h, between 6 and 12 h, and between 12 and 24 h postoperatively were evaluated among the groups. Statistical analyses were performed with a Dunnett t test, ANOVA, or Kruskal-Wallis test and χ2 test. Logistic regression analysis was used in order to examine predictive factors on duration of postoperative analgesia. Age, weight, duration of anesthesia, onset time of intraoperative analgesic, dosage, and addition of intraoperative fentanyl were similar among the groups. The time to first analgesic use did not differ among the groups, and logistic regression modelling showed that using the 3 different volumes of levobupivacaine had no predictive influence on duration of postoperative analgesia. The numbers of patients who required analgesics within 6 h (3/2/3), between 6 and 12 h (3/1/3), and between 12 and 24 h (1/0/2) after surgery were similar among the groups. The 3 different volumes of 0.25% levobupivacaine provided the same quality of intra- and postoperative pain relief in pediatric patients undergoing orchidopexy and inguinal hernia repair. © 2017 S. Karger AG, Basel.

Observational evidence that urbanisation and neighbourhood deprivation are associated with escalation in chronic pharmacological pain treatment: a longitudinal population-based study in the Netherlands

PubMed Central

Buijs, Servaas; Strik, Jacqueline; Lousberg, Richel; Smit, Jasper; van Kleef, Maarten; van Os, Jim

2012-01-01

Objective To examine, in the light of the association between urban environment and poor mental health, whether urbanisation and neighbourhood deprivation are associated with analgesic escalation in chronic pharmacological pain treatment and whether escalation is associated with prescriptions of psychotropic medication. Design Longitudinal analysis of a population-based routine dispensing database in the Netherlands. Setting Representative sample of pharmacies, covering 73% of the Dutch nationwide medication consumption in the primary care and hospital outpatient settings. Participants 449 410 patients aged 15–85 years were included, of whom 166 374 were in the Starter group and 283 036 in the Continuation group of chronic analgesic treatment. Main outcome measure Escalation of analgesics (ie, change to a higher level of analgesic potency, classified across five levels) in association with urbanisation (five levels) and dichotomous neighbourhood deprivation was analysed over a 6-month observation period. Methods Ordered logistic multivariate model evaluating analgesic treatment. Results In both Starter and Continuation groups, escalation was positively associated with urbanisation in a dose–response fashion (Starter group: OR (urbanisation level 1 compared with level 5): 1.24, 95% CI 1.18 to 1.30; Continuation group: OR 1.18, 95% CI 1.14 to 1.23). An additional association was apparent with neighbourhood deprivation (Starter group: OR 1.07, 95% CI 1.02 to 1.11; Continuation group: OR 1.04, 95% CI 1.01 to 1.08). Use of somatic and particularly psychotropic co-medication was associated with escalation in both groups. Conclusions Escalation of chronic analgesic treatment is associated with urban and deprived environments and occurs in a context of adding psychotropic medication prescriptions. These findings suggest that pain outcomes and mental health outcomes share factors that increase risk and remedy suffering. PMID:22815464

A naturally-inspired, curcumin-based lecithin formulation (Meriva® formulated as the finished product Algocur®) alleviates the osteo-muscular pain conditions in rugby players.

PubMed

Di Pierro, F; Zacconi, P; Bertuccioli, A; Togni, S; Eggenhoffner, R; Giacomelli, L; Scaltrini, S

2017-11-01

Curcumin is one of the most investigated phytochemical products because of its low toxicity and its broad spectrum of bioactivity, including anti-inflammatory and analgesic properties. A new delivery form of curcumin, resorting to phosphatidylcholine (Meriva®, formulated as the finished product Algocur®) has been developed to increase its bioavailability. In this study, we tested the efficacy and safety of a Meriva®-based product in rugby players suffering by different osteo-muscular pain conditions PATIENTS AND METHODS: In this pilot study, 50 male rugby players with osteo-muscular pain due to traumatic injuries, physical overload or acute episode of chronic pain were recruited and treated with conventional analgesic drugs (n = 25) or Meriva®-based product (n = 25) for a maximum of 10 days. The pain perception and the functio laesa were evaluated at baseline and after 1, 3, 6, 10 and 20 days from the initiation of the treatment protocol. Treatment tolerability, compliance, and adverse events were also reported. During the study, the analgesic effect decreased in both treated group compared to baseline, starting from the third day of treatment. Similarly, the impaired physical function evaluated after 3, 6, 10 and 20 days improved in Meriva®-based product treated group and in subjects treated with conventional analgesic drugs, compared to the baseline condition. The percentage of excellent adherence to treatment or tolerability was higher in the Meriva®-based product treated group. Only 1 (4%) subject treated with Meriva®-based product experienced adverse events whereas 4 (16%) subjects treated with conventional analgesic drugs reported gastric pain as an adverse event. Despite the small sample size and the group heterogeneity, this study suggests that the naturally-derived, curcumin-based delivery form, Meriva® (formulated as the finished product Algocur®), could represent a promising safe, analgesic remedy in painful osteo-muscular conditions associated with intense, high impact, physical activities.

Comparison of Local Wound Infiltration with Ropivacaine Alone or Ropivacaine Plus Dexmedetomidine for Postoperative Pain Relief after Lower Segment Cesarean Section.

PubMed

Bhardwaj, Shaman; Devgan, Sumeet; Sood, Dinesh; Katyal, Sunil

2017-01-01

Dexmedetomidine, α 2 -adrenergic agonist, when coadministered with local anesthetics, improves the speed of onset, duration of analgesia and decreases the dose of local anesthetic used. The aim of this study was to compare the efficacy of local subcutaneous wound infiltration of ropivacaine alone with ropivacaine plus dexmedetomidine for postoperative pain relief following lower segment cesarean section (LSCS). The study was a prospective, randomized control, double-blind study. Sixty female patients belonging to physical status American Society of Anesthesiologists Grade I or II scheduled for LSCS under spinal anesthesia were randomly allocated into two groups of thirty patients each. Group A: local subcutaneous wound infiltration of 0.75% ropivacaine (3 mg/kg) diluted with normal saline to 40 ml. Group B: local subcutaneous wound infiltration of 0.75% ropivacaine (3 mg/kg) plus dexmedetomidine (1.5 μg/kg) of the body weight diluted with normal saline to 40 ml. Standard spinal anesthesia technique was used and LSCS was conducted. The allocated drug was administered by local subcutaneous wound infiltration before closure of the skin. In postoperative period, pain was assessed using visual analog scale (VAS) over a period of 24 h, time of giving first rescue analgesic consumption, mean analgesic consumption, patient satisfaction, and incidence of side effects in 24 h postoperative period was noted. All observations were tabulated and statistically analyzed using Chi-square test and unpaired t -test. A total number of patients requiring rescue analgesic, mean VAS each time rescue analgesic was given, and the mean analgesic required in 24 h postoperative period was lesser in Group B than in Group A. Dexmedetomidine added to ropivacaine for the surgical wound infiltration significantly reduces postoperative pain and rescue analgesic consumption in patients undergoing LSCS. No serious adverse effects were noted.

Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

PubMed Central

Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E.; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard

2017-01-01

Background Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. Methods and Findings We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Conclusions Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful information to enable further investigations in multimorbidity research within the scope of potential interactions and chronic pain. PMID:28046033

Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

PubMed

Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard; Holzer, Barbara M

2017-01-01

Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful information to enable further investigations in multimorbidity research within the scope of potential interactions and chronic pain.

The analgesic effect of therapeutic rTMS is not mediated or predicted by comorbid psychiatric or sleep disorders

PubMed Central

Lindholm, Pauliina; Lamusuo, Salla; Taiminen, Tero; Virtanen, Arja; Pertovaara, Antti; Forssell, Heli; Hagelberg, Nora; Jääskeläinen, Satu

2016-01-01

Abstract Background: Mechanisms underlying alleviation of neuropathic pain by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) and right secondary somatosensory cortex (S2) are only partly known. Patients with chronic neuropathic pain often have comorbidities like depression and sleep problems. Through functional connectivity, rTMS of M1 and S2 may activate dorsolateral prefrontal cortex, the target for treating depression with rTMS. Thus, the analgesic effect of rTMS could be mediated indirectly via improvement of psychiatric comorbidities or sleep. We examined whether rTMS has an independent analgesic effect or whether its clinical benefits depend on effects on mood or sleep. We also evaluated if comorbid psychiatric or sleep disorders predict the treatment outcome. Methods: Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized controlled crossover rTMS study. Patients’ psychiatric history was evaluated by a specialist in psychiatry. Intensity and interference of pain, mood, and the quality of sleep and life were evaluated at baseline and after 2 active (primary somatosensory cortex [S1]/M1 and S2) and placebo rTMS treatments. A logistic regression analysis was done to investigate predictors of treatment outcome. Results: The analgesic effect of the right S2 stimulation was not associated with improvement of psychiatric conditions or sleep, whereas S1/M1 stimulation improved sleep without significant analgesic effect (P = 0.013–0.046 in sleep scores). Psychiatric and sleep disorders were more common in patients than in the general population (P = 0.000–0.001 in sleep scores), but these comorbidities did not predict the rTMS treatment outcome. Conclusion: We conclude that rTMS to the right S2 does not exert its beneficial analgesic effects in chronic neuropathic orofacial pain via indirect improvement of comorbid psychiatric or sleep disorders. PMID:27858874

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

PubMed

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, dihydrocodeine or tramadol is less risky than morphine at its lowest effective dose. Compared to morphine, the efficacy of these drugs varies more from one patient to another, and their multiple pharmacokinetic interactions can be difficult to manage. There is also a sometimes unpredictable risk of serious over-dose. Tramadol has additional adverse effects unrelated to its opioid effects. Weak opioids require at least as much vigilance as morphine, despite the major differences in their reputation and regulation.

The effect of stimulus frequency on the analgesic response to percutaneous electrical nerve stimulation in patients with chronic low back pain.

PubMed

Ghoname, E S; Craig, W F; White, P F; Ahmed, H E; Hamza, M A; Gajraj, N M; Vakharia, A S; Noe, C E

1999-04-01

Low back pain (LBP) is one of the most common medical problems in our society. Increasingly, patients are turning to nonpharmacologic analgesic therapies such as percutaneous electrical nerve stimulation (PENS). We designed this sham-controlled study to compare the effect of three different frequencies of electrical stimulation on the analgesic response to PENS therapy. Sixty-eight consenting patients with LBP secondary to degenerative lumbar disc disease were treated with PENS therapy at 4 Hz, alternating 15 Hz and 30 Hz (15/30 Hz), and 100 Hz, as well as sham-PENS (0 Hz), according to a randomized, cross-over study design. Each treatment was administered for a period of 30 min three times per week for 2 wk. The pre- and posttreatment assessments included the health status survey short form and visual analog scales for pain, physical activity, and quality of sleep. After receiving all four treatments, patients completed a global assessment questionnaire. The sham-PENS treatments failed to produce changes in the degree of pain, physical activity, sleep quality, or daily intake of oral analgesic medications. In contrast, 4-Hz, 15/30-Hz, and 100-Hz stimulation all produced significant decreases in the severity of pain, increases in physical activity, improvements in the quality of sleep, and decreases in oral analgesic requirements (P < 0.01). Of the three frequencies, 15/30 Hz was the most effective in decreasing pain, increasing physical activity, and improving the quality of sleep (P < 0.05). In the global assessment, 40% of the patients reported that 15/30 Hz was the most desirable therapy, and it was also more effective in improving the patient's sense of well-being. We conclude that the frequency of electrical stimulation is an important determinant of the analgesic response to PENS therapy. Alternating stimulation at 15-Hz and 30-Hz frequencies was more effective than either 4 Hz or 100 Hz in improving outcome measures in patients with LBP. The frequency of electrical stimulation seems to be an important determinant of the analgesic efficacy of percutaneous electrical nerve stimulation. Mixed low- and high-frequency stimulation was more effective than either low or high frequencies alone in the treatment of patients with low back pain.

Hair analysis to monitor abuse of analgesic combinations containing butalbital and propyphenazone.

PubMed

Ferrari, Anna; Tiraferri, Ilaria; Palazzoli, Federica; Verri, Patrizia; Vandelli, Daniele; Marchesi, Filippo; Ciccarese, Michela; Licata, Manuela

2015-11-10

Butalbital, a barbiturate, is present in analgesic combinations used by headache sufferers. Overuse/abuse of these combinations may cause dependence, chronic migraine, and medication-overuse headache (MOH). MOH is difficult to manage: it improves interrupting analgesic overuse, but requires monitoring, because relapses are frequent. A gas chromatography-mass spectrometry (GC-MS) method for hair analysis has been developed and validated to document abuse of an analgesic combination containing butalbital and propyphenazone by a patient with MOH. For over ten years the patient managed her headache using eight suppositories/day of an analgesic combination containing butalbital 150mg, caffeine 75mg, and propyphenazone 375mg per suppository. An outpatient detoxification treatment was carried out. After three weeks, the patient reduced the consumption to one suppository/day. At the first control visit, after three months from the beginning of detoxification, the patient increased the use of the combination to four suppositories/day and at the second control visit, after seven months from the beginning of detoxification, she was back to eight suppositories/day. At the two control visits, a hair sample was taken for determination of butalbital and propyphenazone. Moreover blood and urine samples for determination of butalbital were drawn at the beginning of detoxification treatment and at the two control visits. With the segmental analysis of two hair samples the medication history of ten months could be estimated. In the first hair sample, collected at the first control visit, in the distal segment, butalbital and propyphenazone concentrations were, respectively, 17.5ng/mg and 56.0ng/mg, confirming the prolonged abuse; in the proximal segment, concurrently with the detoxification treatment, butalbital and propyphenazone concentrations had reduced respectively to 5.45ng/mg and 11.1ng/mg. The second hair sample, collected at the second control visit, proved the fair course of the detoxification treatment in the distal segment and signalled relapse in the abuse of the analgesic combination in the proximal segment. In the clinical context, hair analysis can be advantageously used to monitor the abuse of analgesic combinations with butalbital, common among headache patients. The validation data showed that GC-MS method developed for determination of butalbital and propyphenazone was rapid, highly sensitive, specific and selective. Copyright © 2015 Elsevier B.V. All rights reserved.

Cycloartanes from Oxyanthus pallidus and derivatives with analgesic activities.

PubMed

Piegang, Basile Nganmegne; Tigoufack, Ignas Bertrand Nzedong; Ngnokam, David; Achounna, Angèle Sorel; Watcho, Pierre; Greffrath, Wolfgang; Treede, Rolf-Detlef; Nguelefack, Télesphore Benoît

2016-03-09

The leaves of Oxyanthus pallidus Hiern (Rubiaceae) are extensively used in the west region of Cameroon as analgesic. These leaves are rich in cycloartanes, a subclass of triterpenes known to possess analgesic and anti-inflammatory properties. The present study aimed at evaluating the analgesic properties of three cycloartanes isolated from Oxyanthus pallidus leaves as well as their aglycones and acetylated derivatives. Three cycloartanes OP3, OP5 and OP6 obtained by successive chromatography of the crude methanol extract of the leaves were hydrolysed to yield respective aglycone AOP1, AOP2, AOP3 and acetylated to HOP1, HOP2 and HOP3 respectively. Formalin-induced pain model was used to evaluate the acute anti-nociceptive properties of these cycloartanes (5 mg/kg, p.o) in mice and to determine the structure-activity relationship. Acute (24 h) and chronic (10 days) anti-hyperalgesic and anti-inflammatory activities of OP5 were evaluated at the doses of 2.5 and 5 mg/kg/day administered orally. OP6 was also evaluated in acute experiments. The antioxidant and hepato-protective activities of OP5 were evaluated at the end of the chronic treatment. The mixture and the individual isolated cycloartanes significantly inhibited both phases of formalin-induced pain with percentage inhibition ranging from 13 to 78%. Acid hydrolysis did not significantly affect their antinociceptive activities while acetylation significantly reduced the effects of these compounds during the second phase of pain. OP5 and OP6 induced acute anti-hyperalgesic activity in formalin-induced mechanical hyperalgesia but not an anti-inflammatory effect. Repeated administration of OP5 for 10 days did not induce any anti-hyperalgesic effect. The evaluation of in vivo antioxidant properties showed that OP5 significantly reduced malondialdehyde and increased superoxide dismutase levels in liver without significantly affecting other oxidative stress and hepatotoxic parameters. Chronic administration of OP5 did not cause gastric ulceration. Cycloartanes isolated from Oxyanthus pallidus possess analgesic effects but lack anti-inflammatory activities. This analgesic effect especially on inflammatory pain may be due to the presence of hydroxyl group in front of the plane. OP5 is devoid of ulcerogenic effect and possess antioxidant properties that might be of benefit to its analgesic properties.

Assessment of the trends in medical use and misuse of opioid analgesics from 2004 to 2011.

PubMed

Atluri, Sairam; Sudarshan, Gururau; Manchikanti, Laxmaiah

2014-01-01

The epidemic of medical use and abuse of opioid analgesics is linked to the economic burden of opioid-related abuse and fatalities in the United States. Multiple studies have estimated the extent to which prescription opioid analgesics contribute to the national drug abuse problem; studies also assessing the trends in medical use and abuse of opioid analgesics have confirmed the relationship between increasing medical use of opioids and increasing fatalities.The available data is limited until 2002. Retrospective analysis of data from 2004 to 2011 from 2 databases: Automation of Reports and Consolidated Orders System (ARCOS) for opioid use data and Drug Abuse Warning Network (DAWN) for drug misuse data. To determine the proportion of drug abuse related to opioid analgesics and the various trends in the medical use and abuse of 8 opioid analgesics commonly used to treat pain: buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone. The data obtained from DAWN is a nationally representative sample of hospital emergency department admissions resulting from drug abuse. Main outcome measure was the identification of trends in the medical use and misuse of opioid analgesics from 2004 to 2011. From 2004 to 2011, there was an increase in the medical use of all opioids except for a 20% decrease in codeine. The abuse of all opioids including codeine increased during this period. Increases in medical use ranged from 2,318% for buprenorphine to 35% for fentanyl, including 140% for hydromorphone, 117% for oxycodone, 73% for hydrocodone, 64% for morphine, and 37% for methadone. The misuse increased 384% for buprenorphine with available data from 2006 to 2011, whereas from 2004 to 2011, it increased 438% for hydromorphone, 263% for oxycodone, 146% for morphine, 107% for hydrocodone, 104% for fentanyl, 82% for methadone, and 39% for codeine. Comparison of opioid use showed an overall increase of 1,448% from 1996 to 2011, with increases of 690% from 1996 to 2004 and 100% from 2004 to 2011. In contrast, misuse increased more dramatically: 4,680% from 1996 to 2011, with increases of 1,372% from 1996 through 2004 and 245% from 2004 to 2011. The number of patients seeking rehabilitation for substance abuse also increased 187% for opioids, whereas it increased 87% for heroin, 40% for marijuana, and decreased 7% for cocaine. Limitations of this assessment include the lack of data from 2003, lack of data available on meperidine, and that the aggregate data systems used in the study did not identify specific formulations or commercial products. The present trend of continued increase in the medical use of opioid analgesics appears to contribute to increases in misuse, resulting in multiple health consequences.

Prazosin for Prophylaxis of Chronic Post Traumatic Headaches in OEF/OIF/OND Service Members and Veterans with Mild TBI

DTIC Science & Technology

2016-10-01

compared to placebo on HA frequency, HA severity and duration, use of abortive /analgesic medications, and HA-related disability. Specific Aim 2: To...the effect of prazosin compared to placebo on post- traumatic HA frequency, severity, duration, use of abortive /analgesic medications, and HA-related

Field Trial of Methoxyflurane, Nitrous Oxide, and Trichloroethylene as Obstetric Analgesics

PubMed Central

Rosen, M.; Mushin, W. W.; Jones, P. L.; Jones, E. V.

1969-01-01

In a field trial of 1,257 patients receiving methoxyflurane, trichloroethylene, and nitrous-oxide/oxygen for the relief of pain in labour methoxyflurane has been shown to have certain advantages which support its use in midwifery practice. The trial confirms our objective method for screening an inhalational agent as an obstetric analgesic. PMID:4895340

An Examination of the Situational Factors Associated with the Misuse of Prescription Analgesics among College Students

ERIC Educational Resources Information Center

Gallucci, Andrew R.; Wynveen, Chris; Hackman, Christine; Meyer, Andrew; Usdan, Stuart

2014-01-01

The current study examined the effect that students' educational environment has on the prevalence and motivations associated with the misuse of prescription analgesics (MPA). A sample of 893 undergraduate students was recruited from one religiously affiliated private university and one public university in the Southern United States. Participants…

Analgesic Effect of Xenon in Rat Model of Inflammatory Pain.

PubMed

Kukushkin, M L; Igon'kina, S I; Potapov, S V; Potapov, A V

2017-02-01

The analgesic effects of inert gas xenon were examined on rats. The formalin model of inflammatory pain, tail-flick test, and hot-plate test revealed the antinociceptive effects of subanesthetizing doses of inhalation anesthetic xenon. Inhalation of 50/50 xenon/oxygen mixture moderated the nociceptive responses during acute and tonic phases of inflammatory pain.

Influence of serotonin on the analgesic effect of granisetron on temporomandibular joint arthritis.

PubMed Central

Voog, Ulle; Alstergren, Per; Leibur, Edvitar; Kallikorm, Riina; Kopp, Sigvard

2004-01-01

The influence of circulating serotonin (5-HT) on the effects of intra-articular administration of granisetron on temporomandibular joint (TMJ) pain was investigated in 11 patients with chronic polyarthritides. An analgesic effect superior to placebo has been shown previously. The change in TMJ movement pain intensity was negatively correlated to circulating 5-HT; that is, the higher the 5-HT before injection, the greater the reduction of pain intensity. The resting pain intensity reduction was not related to 5-HT. In conclusion, this study indicates a stronger short-term analgesic effect on TMJ movement pain by intra-articular administration of the 5-HT3 receptor antagonist granisetron in patients with high levels of circulating 5-HT. PMID:15770056

Modulation of excitatory amino acids pathway: a possible therapeutic approach to chronic daily headache associated with analgesic drugs abuse.

PubMed

Nicolodi, M; Del Bianco, P L; Sicuteri, F

1997-01-01

The use of antagonists of N-methyl-D-aspartate (NMDA) receptors, or the administration of inhibitors of the synthesis or of the release of excitatory amino acids, enables the analgesic drug-dependence associated with chronic daily migraine to be overcome without any physical abstinence sign. Follow-up period indicates that negative modulators of excitatory amino-acid function can induce a stable benefit. The persistent benefit is seemingly due to an inhibitory effect on the process underlying the hyperalgesia state which is a crucial feature of migraine. It can also be suggested that the antagonist activity at NMDA receptor might play a role in very severe non-opioid analgesic drug dependence.

Synthesis, analgesic activity, and binding properties of some epibatidine analogs with a tropine skeleton.

PubMed

Rádl, S; Hafner, W; Budesínsky, M; Hejnová, L; Krejcí, I

2000-06-01

A series of epibatidine analogs and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Also some of their simplified analogs bearing a 3-piperidine moiety are reported. Their receptor binding profiles (5-HT1A, 5-HT1B, M1, M2, neuronal nicotinic receptor) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Some of the compounds, especially those containing an 8-azabicyclo[3.2.1]oct-2-ene moiety possess high afinity for the nicotinic cholinergic receptor. The most analgesically active compounds are also highly toxic. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of compounds 1-9 were compared with that of epibatidine.

Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety.

PubMed

Karrouchi, K; Chemlal, L; Taoufik, J; Cherrah, Y; Radi, S; El Abbes Faouzi, M; Ansar, M

2016-11-01

A series of Schiff bases of 4-amino-1,2,4-triazole derivatives containing pyrazole (5a-h) were synthesized from condensation of 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (3) derivative with various aromatic aldehydes (4a-h). The structures of the synthesized compounds were elucidated by IR, 1 H NMR, 13 C NMR, and mass spectrometry. All the synthesized compounds (5a-h) were screened for their in vivo analgesic and in vitro antioxidant activities revealing significant analgesic and antioxidant properties. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Anti-inflammatory and analgesic activity of Peperomia pellucida (L.) HBK (Piperaceae).

PubMed

de Fátima Arrigoni-Blank, Maria; Dmitrieva, Elena G; Franzotti, Elaine Maria; Antoniolli, Angelo Roberto; Andrade, Márcio Roberto; Marchioro, Murilo

2004-04-01

An aqueous extract of the aerial part of Peperomia pellucida (L.) HBK (Piperaceae) was tested for anti-inflammatory (paw edema induced by carrageenin and arachidonic acid) and analgesic activity (abdominal writhes and hot plate) in rats and mice, respectively. Oral administration of 200 and 400 mg/kg of the aqueous extract exhibited an anti-inflammatory activity in the carrageenin test, which was based on interference with prostaglandin synthesis, as confirmed by the arachidonic acid test. In the abdominal writhing test induced by acetic acid, 400 mg/kg of the plant extract had the highest analgesic activity, whereas in the hot-plate test the best dose was 100 mg/kg. The LD(50) showed that Peperomia pellucida (5000 mg/kg) presented low toxicity.

The discovery and development of analgesics: new mechanisms, new modalities

PubMed Central

Burgess, Gillian; Williams, Dic

2010-01-01

Despite intensive research into pain mechanisms and significant investment in research and development, the majority of analgesics available to prescribers and patients are based on mechanistic classes of compounds that have been known for many years. With considerable ingenuity and innovation, researchers continue to make the best of the mechanistic approaches available, with novel formulations, routes of administration, and combination products. Here we review some of the mechanisms and modalities of analgesics that have recently entered into clinical development, which, coupled with advances in the understanding of the pathophysiology of chronic pain, will hopefully bring the promise of new therapeutics that have the potential to provide improved pain relief for those many patients whose needs remain poorly met. PMID:21041957

Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics

PubMed Central

Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W.; Gutstein, Howard

2015-01-01

Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. SIGNIFICANCE STATEMENT Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. PMID:26468188

Use of prescribed opioid analgesics and co-medication with benzodiazepines in women before, during, and after pregnancy: a population-based cohort study.

PubMed

Handal, Marte; Engeland, Anders; Rønning, Marit; Skurtveit, Svetlana; Furu, Kari

2011-09-01

The aim of the study was to describe the use of prescribed opioid analgesics for noncancer pain and the degree of possible concurrent co-medication with benzodiazepines to women in Norway before, during, and after pregnancy. This was a population-based cohort study based on linkage of two nationwide registries: the Medical Birth Registry of Norway, and the Norwegian Prescription Database. Prescribed opioid analgesics and benzodiazepines issued to women 3 months prior to, during, and 3 months after pregnancies were identified. The study population consisted of 194,937 singleton pregnancies beginning in March 2004 or later and ending before January 2009. About 6% of the women were dispensed opioid analgesics before, during, or after pregnancy. Almost all these women received weak opioids (99%) with short-acting codeine in combination with paracetamol (acetaminophen) as the most frequently dispensed drug. The dispensing of codeine was reduced from 24/1,000 women before pregnancy to 10/1,000 in the last trimester, increasing to 17/1,000 during the breastfeeding period. Most women were dispensed codeine once, and treatment was of short duration (about 1 week). A small group of women (n = 271) were dispensed opioids in all trimesters. Increasing benzodiazepine use was observed as the number of opioid prescriptions increased. The use of opioid analgesics in pregnant women in Norway was dominated by treatment of short duration of the weak opioid codeine. As pregnancy proceeded, opioid use was reduced. However, the increase in opioid use during the nursing period has the potential for serious adverse effects.

Systematic review of the effects of fascia iliaca compartment block on hip fracture patients before operation.

PubMed

Steenberg, J; Møller, A M

2018-06-01

Fascia iliaca compartment block is used for hip fractures in order to reduce pain, the need for systemic analgesia, and prevent delirium, on this basis. This systematic review was conducted to investigate the analgesic and adverse effects of fascia iliaca block on hip fracture in adults when applied before operation. Nine databases were searched from inception until July 2016 yielding 11 randomised and quasi-randomised controlled trials, all using loss of resistance fascia iliaca compartment block, with a total population of 1062 patients. Meta-analyses were conducted comparing the analgesic effect of fascia iliaca compartment block on nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and other nerve blocks, preoperative analgesia consumption, and time to perform spinal anaesthesia compared with opioids and time for block placement. The analgesic effect of fascia iliaca compartment block was superior to that of opioids during movement, resulted in lower preoperative analgesia consumption and a longer time for first request, and reduced time to perform spinal anaesthesia. Block success rate was high and there were very few adverse effects. There is insufficient evidence to conclude anything on preoperative analgesic consumption or first request thereof compared with NSAIDs and other nerve blocks, postoperative analgesic consumption for preoperatively applied fascia iliaca compartment block compared with NSAIDs, opioids and other nerve blocks, incidence and severity of delirium, and length of stay or mortality. Fascia iliaca compartment block is an effective and relatively safe supplement in the preoperative pain management of hip fracture patients. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

A DESCRIPTIVE FEASIBILITY STUDY TO EVALUATE SCHEDULED ORAL ANALGESIC DOSING AT HOME FOR THE MANAGEMENT OF POSTOPERATIVE PAIN IN PRESCHOOL CHILDREN FOLLOWING TONSILLECTOMY

PubMed Central

Sutters, Kimberly A.; Holdridge-Zeuner, Danielle; Waite, Steven; Paul, Steven M.; Savedra, Marilyn C.; Lanier, Brent; Mahoney, Karla; Miaskowski, Christine

2012-01-01

Objectives The purpose of this study, in a sample of preschool children (ages 3 to 5 years; N=47), was to evaluate the feasibility of scheduled analgesic dosing following outpatient tonsillectomy in order to optimize pain management. Methods Parents were instructed to give their child acetaminophen with hydrocodone (167mg/5ml) every 4 hours around-the-clock for the first 3 days following surgery. Parents recorded ratings of their child’s pain with/without swallowing using the Faces, Legs, Activity, Cry, and Consolability (FLACC) behavioral pain scale, pain relief ratings, and severity of analgesic side effects in a home diary. Audiotaped interviews were conducted with parents to document descriptions of their experiences in managing their child’s pain at home. Results Mean FLACC scores with/without swallowing were less than 2 at each measurement time and pain relief scores increased over time. Total analgesic dose decreased and the number of missed doses increased over the first 3 days after surgery. Moderate-to-severe daytime sedation, nausea, vomiting, and constipation were reported by parents. Discussion Study results suggest that acetaminophen with hydrocodone is effective in relieving preschool children’s pain following tonsillectomy, and that parental adherence to a scheduled analgesic regimen decreases over time. Time-contingent dosing was associated with moderate to severe side effects, and should be addressed in discharge teaching with parents. Findings provide insight into parents’ perspective of pain management at home following tonsillectomy and methods for relieving their child’s pain. PMID:22313591

Comparative study of intravenous Tramadol versus Ketorolac for preventing postoperative pain after third molar surgery--a prospective randomized study.

PubMed

Gopalraju, Prathibha; Lalitha, Ramanujapuram Manikarnike; Prasad, Kavitha; Ranganath, Krishnappa

2014-07-01

The aim of this comparative, prospective, randomized, controlled study was to evaluate two different regimens of analgesics: a preoperative intravenous dose of either Tramadol or Ketorolac given 10 min prior to surgery to assess their impact on clinical recovery after third molar surgery. Forty patients requiring surgical extraction of unilateral impacted mandibular third molars similar in position were enrolled in the study. Patients were randomly divided into two groups based on permuting the numbers. Patients in Group 1 and Group 2 were administered either Tramadol 50 mg or Ketorolac 30 mg, intravenously, 10 min prior to surgery. The difference in postoperative pain was assessed by four primary points: pain intensity as measured by a 10 mm visual analogue scale hourly for 12 h, median time to rescue analgesics, number of analgesics consumed and patient's overall 5-point global assessment scale. Throughout the 12 h investigation period, patients treated with Ketorolac reported significantly lower pain intensity scores, significantly longer time to rescue analgesics (Acetaminophen 500 mg) and less intake of postoperative analgesics. In Group 2, 40% of the patient had good overall assessment as compared to Group 1 where only 25% of patients had good overall assessment. The current study shows that pre-emptive use of Inj. Ketorolac 30 mg intravenously can reduce the severity of the postoperative sequelae of asymptomatic impacted mandibular third molar surgery. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Registered Nurses' Knowledge about Adverse Effects of Analgesics when Treating Postoperative Pain in Patients with Dementia.

PubMed

Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi

2015-08-01

Registered nurses (RNs) play a pivotal role in treating pain and preventing and recognizing the adverse effects (AEs) of analgesics in patients with dementia. The purpose of this study was to determine RNs' knowledge of potentially clinically relevant AEs of analgesics. A descriptive, cross-sectional study design was used. In all, 267 RNs treating orthopedic patients, including patients with dementia, in 7 university hospitals and 10 central hospitals in Finland, completed a questionnaire. Analgesics were defined according to the Anatomic Therapeutic Classification as strong opioids, weak opioids, nonsteroidal anti-inflammatory analgesics (NSAIDs), and paracetamol. Definitions of AEs were based on the literature. Logistic regression analysis was applied to analyze which variables predicted nurses' knowledge. The RNs had a clear understanding of the AEs of paracetamol and strong opioids. However, the AEs of NSAIDs, especially renal and cardiovascular AEs, were less well known. The median percentage of correct answers was 87% when asked about strong opioids, 73% for weak opioids, and 60% for NSAIDs. Younger RNs had better knowledge of opioid-related AEs (odds ratio [OR] per 1-year increase, 0.97; 95% confidence interval [CI], 0.94-1.00) and weak opioids (OR, 0.96; 95% CI, 0.93-0.99). This study provides evidence of a deficiency in RNs' knowledge, especially regarding the adverse renal and cardiovascular effects of NSAIDs. Such lack of knowledge indicates that hospitals may need to update the knowledge of older RNs, especially those who treat vulnerable patients with dementia. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Adding pregabalin to a multimodal analgesic regimen does not reduce pain scores following cosmetic surgery: a randomized trial.

PubMed

Chaparro, Luis Enrique; Clarke, Hance; Valdes, Paola A; Mira, Mauricio; Duque, Lorena; Mitsakakis, Nicholas

2012-12-01

Multimodal analgesia increases the chance of successful discharge and pain control after surgery, and pregabalin is being promoted as an effective analgesic, based on placebo-controlled studies. We investigated whether adding pregabalin improved pain control and reduced opioid requests when it was added to a multimodal analgesic regimen for cosmetic surgery. One hundred and ten women who underwent same-day cosmetic surgery were randomized to receive oral pregabalin, 75 mg q12 h for five consecutive days starting the night before surgery, or identical placebos. Participants, outcomes assessors, and the statistician were blinded. The primary outcome was postoperative numerical movement-evoked pain scores at 2, 24, 48, 72, and 96 h after surgery. The secondary outcomes included pain scores at rest; incidence of moderate to severe pain; and analgesic and antiemetic requirements; as well as the incidence of nausea, vomiting, and somnolence. Based on 99 patients who completed the study, we found no difference between the groups in the primary outcome; 72 h after surgery, movement-evoked median pain scores were <4/10 in both groups. We found no differences in opioid requirements (p = 0.95) or anti-inflammatory requirements (p = 0.45), and no difference in opioid-related adverse events. Perioperative pregabalin 75 mg twice a day does not increase benefit when it is added to an already multimodal analgesic regimen for patients undergoing cosmetic surgery. Several factors could explain our findings, including the possibility of publication bias in the current literature.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models

PubMed Central

Woode, Eric; Ameyaw, Elvis O.; Boakye-Gyasi, Eric; Abotsi, Wonder K. M.

2012-01-01

Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg-1, p.o.) and XA (10-100 mg kg-1, p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg-1, i.p.) and diclofenac (1-10 mg kg-1, i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid. PMID:23248562

Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f.) Iwarsson Leaves in Rodent Models

PubMed Central

Alemu, Asnakech

2018-01-01

Background Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test and p < 0.05 was considered significant. Results The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (p < 0.001). Conclusion The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models. PMID:29675050

Analgesic tolerance to morphine is regulated by PPARγ

PubMed Central

de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Stopponi, Serena; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

2014-01-01

Background and Purpose Opioid drugs are potent analgesics. However, their chronic use leads to the rapid development of tolerance to their analgesic effects and subsequent increase of significant side effects, including drug dependence and addiction. Here, we investigated the role of PPARγ in the development of analgesic tolerance to morphine in mice. Experimental Approach We monitored analgesia on alternate days using the tail immersion test. Key Results Daily administration of morphine (30 mg·kg−1, bid) resulted in the rapid development of tolerance to thermal analgesia. Co-administration of pioglitazone (10 and 30 mg·kg−1, bid) significantly attenuated the development and expression of tolerance. However, pretreatment with GW-9662 (5 mg·kg−1, bid), a selective PPARγ antagonist, completely abolished this effect. Injection of GW-9662 and a lower dose of morphine (15 mg·kg−1, bid) accelerated the development of tolerance to its antinociceptive effect. Subsequently, we found that conditional neuronal PPARγ knockout (KO) mice develop a more rapid and pronounced tolerance to morphine antinociception compared with wild-type (WT) controls. Moreover, in PPARγ KO mice, pioglitazone was no longer able to prevent the development of morphine tolerance. Conclusions and Implications Overall, our results demonstrate that PPARγ plays a tonic role in the modulation of morphine tolerance, and its pharmacological activation may help to reduce its development. These findings provide new information about the role of neuronal PPARγ and suggest that combining PPARγ agonists with opioid analgesics may reduce the development of tolerance and possibly attenuate the potential for opioid abuse. PMID:25048682

Comparison of Pain Thresholds and Analgesic Effects of Parecoxib Sodium in Surgical Patients of Different Racial and Religious Backgrounds.

PubMed

Li, Li-Biao; Hu, Yu; Liu, Chao; Gu, Miao-Ning

2015-06-01

To explore the differences of the thresholds of pain and analgesic effects of parecoxib sodium among patients with different racial and religious backgrounds. A total of 48 male patients aged 18 to 38 years who had undergone elective laparoscopic appendectomy under general anesthesia in our centers were enrolled in our study and then divided into 6 groups(n=8 in each group)based on their racial backgrounds(three levels:Mongoloid,Negroid,and Europoid)and religious backgrounds(two levels:without religion background,with religion background).All subjects received the same anesthesia,surgical procedure,and postoperative analgesia with parecoxib sodium. The temperature pain threshold and electrical pain threshold were detected 1h before and after analgesia. The threshold of pain was higher in Europoids than in Negroids and Mongoloids before and after treatment. The temperature pain threshold and electrical pain threshold were not significantly different between subjects with or without religious background(before analgesic therapy:F=251.119,P=0.130,F=275.861,P=0.059;after analgesic therapy:F=308.531,P=0.086,F=180.062,P=0.078). Also,there was no interaction between the racial and religious backgrous in terms of temperature pain threshold and electrical pain threshold(F=13.553,P=0.091,F=22.001,P= 0.089;after analgesic therapy:F=4.624,P=0.089,F=15.935,P=0.094). The threshold of pain differs among individuals with different racial background:it is highest in Europoids,followed by Negroids and Mongoloids. It shows no obvious difference in people with different religious backgrounds.

Effects of Analgesic Use on Inflammation and Hematology in a Murine Model of Venous Thrombosis

PubMed Central

Hish, Gerald A; Diaz, Jose A; Hawley, Angela E; Myers, Daniel D; Lester, Patrick A

2014-01-01

Venous thrombosis (VT) is a significant cause of morbidity and mortality in humans. Surgical animal models are crucial in studies investigating the pathogenesis of this disease and evaluating VT therapies. Because inflammation is critical to both the development and resolution of VT, analgesic medications have the potential to adversely affect multiple parameters of interest in VT research. The objective of this study was to determine how several common analgesics affect key variables in a murine ligation model of deep vein thrombosis. Male C57BL/6 mice were randomly assigned to receive either local (bupivacaine) or systemic parenteral analgesia (buprenorphine, tramadol, or carprofen) or 0.9% NaCl (control). All mice underwent laparotomy and ligation of the inferior vena cava, and treatment was continued until euthanasia at 6 or 48 h after surgery. Analysis of harvested tissues and blood included: hematology, thrombus weight, serum and vein-wall cytokines (IL1β, IL6, IL10, TNFα), soluble P-selectin, and vein-wall leukocyte infiltration. Compared with 0.9% NaCl, all of the analgesics affected multiple parameters important to VT research. Carprofen and tramadol affected the most parameters and should not be used in murine models of VT. Although they affected fewer parameters, a single dose of bupivacaine increased thrombus weight at 6 h, and buprenorphine was associated with reduced vein wall macrophages at 48 h. Although we cannot recommend the use of any of the evaluated analgesic dosages in this mouse model of VT, buprenorphine merits additional investigation to ensure the highest level of laboratory animal care and welfare. PMID:25255071

Reduced anaesthetic requirements and postoperative analgesics in patients undergoing laparoscopic cholecystectomy: premedication with intravenous paracetamol versus ketorolac, a double blind and randomised clinical trial.

PubMed

Medina-Vera, A J; Novoa, L M

2017-02-01

To compare the effects of premedication with intravenous paracetamol versus ketorolac, in decreasing intraoperative anaesthetic and postoperative opioid analgesics requirements in patients undergoing laparoscopic cholecystectomy. An experimental, prospective, comparative, double blind, and randomised clinical trial was conducted to determine intraoperative opioid requirements, and pain and analgesic requirements in the postoperative period in 100 healthy patients undergoing laparoscopic cholecystectomy. They were randomised into 2 groups: Group 1: pre-medicated with paracetamol 1g, and Group 2: with ketorolac 30mg (both administered intravenously 30minutes prior to surgery). There were no statistically significant differences between groups as regards intraoperative remifentanil use (Group 1: 0.0739±0.016μg/kg/min, Group 2: 0.0741±0.018μg/kg/min). The number of patients in Group 2 that had values of VAS>4 points (22.4%) was lower than in Group 1 (28.6%), but with no statistically significant difference. Of the patients who needed postoperative opioid rescue, most required a single rescue and application of analgesics during hospitalisation, that prevailed between 3 and 12hours, without any significant differences between groups. No adverse effects were observed in the study sample. Paracetamol 1g IV given preoperatively decreased anaesthetic requirements and the need for postoperative analgesics similar to the preoperative administration of ketorolac 30mg IV. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

A preliminary evaluation of antihyperglycemic and analgesic activity of Alternanthera sessilis aerial parts

PubMed Central

2014-01-01

Background Alternanthera sessilis is used by folk medicinal practitioners of Bangladesh for alleviation of severe pain. The objective of this study was to scientifically analyze the analgesic (non-narcotic) property of aerial parts of the plant along with antihyperglycemic activity. Methods Antihyperglycemic activity was measured by oral glucose tolerance tests. Analgesic (non-narcotic) activity was determined by observed decreases in abdominal writhings in intraperitoneally administered acetic acid-induced pain model in mice. Results Administration of methanol extract of aerial parts led to dose-dependent and significant reductions in blood glucose levels in glucose-loaded mice. At doses of 50, 100, 200 and 400 mg per kg body weight, the extract reduced blood sugar levels by 22.9, 30.7, 45.4 and 46.1%, respectively compared to control animals. By comparison, a standard antihyperglycemic drug, glibenclamide, when administered at a dose of 10 mg per kg body weight, reduced blood glucose level by 48.9%. In analgesic activity tests, the extract at the above four doses reduced the number of abdominal writhings by 27.6, 37.9, 41.4, and 44.8%, respectively. A standard analgesic drug, aspirin, reduced the number of writhings by 31.0 and 51.7%, respectively, when administered at doses of 200 and 400 mg per kg body weight. Conclusion The results validate the folk medicinal use of the plant to alleviate pain. At the same time, the antihyperglycemic activity result suggests that the plant may be a potential source for blood sugar lowering drug(s). PMID:24885344

[Pharmacist perception of the use of analgesics and their practice on mild-moderate pain. DOLOR-OFF survey].

PubMed

Arrebola, Cristobal; García-Delgado, Pilar; Labrador Barba, Elena; Orera Peña, Maria Luisa; Martínez-Martínez, Fernando

2016-01-01

To examine the use of analgesics, from the perspective of the pharmacist community, and pharmaceutical practice in mild-moderate pain. A cross-sectional, observational study was performed between April and September 2013. 696 community pharmacies in 20 Spanish provinces. Community pharmacists with a minimum professional experience of one year. Characterisation of the demand for analgesics, analgesic users, and pharmaceutical intervention for mild-moderate pain from the perspective of the pharmaceutical community. The main reason why a patient with mild-moderate pain visits a pharmacy is to receive a drug with prescription (45.5%), and the most common condition is headache (35.2%). Ibuprofen and paracetamol are the most commonly used drugs for mild-moderate pain. More than one-third (38.9%) of pharmacists follow a protocol for counselling. A correlation was found between the pharmacist's professional experience and the application of counselling process (Fisher P<.05). Some 87.8% of pharmacists checked two indicators from the dispensing service, and only 1.3% did not check any. Referral to a physician was made by 14.8% of pharmacists, with the main reason being the detection of alarm indicators. Protocols need to be designed and adapted to the characteristics of the 3 profiles identified, in order to increase the efficiency of pharmaceutical services in mild-moderate pain relief. Practical and specific training in pain are required to implement services to ensure the correct and systemic use of analgesics and positive clinical outcomes. Copyright © 2016. Publicado por Elsevier España, S.L.U.

Biomedicine of Enkephalin-Derived Glycopeptide Analgesics

NASA Astrophysics Data System (ADS)

Polt, Robin

The incorporation of glycosides into peptide neurotransmitters imparts drug-like character to the neurotransmitter "message" via "membrane hopping". The importance of the glycopeptide-membrane interaction is emphasized, and the biousian theory is briefly explained. Application of this approach to enkephalins, the endogenous opioid peptides, leads to potent analgesic compounds capable of systemic delivery. The clinical applications of these compounds are advocated by the author.

Central analgesic activity of the aqueous and ethanolic extracts of the leaves of Albizia lebbeck: role of the GABAergic and serotonergic pathways.

PubMed

Meshram, Girish G; Kumar, Anil; Rizvi, Waseem; Tripathi, C D; Khan, R A

2015-01-01

Albizia lebbeck Benth. is extensively used in Indian traditional medicine for treating several painful and inflammatory disorders. The possible central analgesic activity and the underlying mechanism of action of the aqueous (AE) and ethanolic extracts (EE) of the leaves of A. lebbeck were investigated in Wistar rats using Eddy's hot plate and the tail flick tests. In order to investigate the underlying mechanism of action, rats were pretreated with naloxone, bicuculline or methysergide and then were administered a per os (p.o.) dose of AE or EE. AE and EE caused a significant (p<0.05) elevation in the mean basal reaction time in the hot plate method and an increase in the latency time in the tail flick method. In rats pretreated with bicuculline and methysergide, a significant (p<0.05) reduction in the analgesic activity was observed in comparison to AE and EE. Thus, AE and EE exhibited significant central analgesic activity and act possibly via the GABAergic and serotonergic pathways. The flavonoids and saponins found in the leaves could be responsible for the observed effect.

The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region☆

PubMed Central

Xu, Qiuling; Liu, Tao; Chen, Shuping; Gao, Yonghui; Wang, Junying; Qiao, Lina; Liu, Junling

2012-01-01

In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanli (ST36) and Yanglingquan (GB34) once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold (paw withdrawal latency) was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptic cleft width and thinning of the postsynaptic density, and it significantly suppressed the down-regulation of intracellular calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. PMID:25657670

Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances

PubMed Central

Mahdizadeh, Shahla; Khaleghi Ghadiri, Maryam; Gorji, Ali

2015-01-01

Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain. PMID:26101752

Tramadol/Paracetamol Fixed-Dose Combination for Chronic Pain Management in Family Practice: A Clinical Review

PubMed Central

Morón Merchante, Ignacio; Pergolizzi, Joseph V.; van de Laar, Mart; Mellinghoff, Hans-Ulrich; O'Brien, Joanne; Perrot, Serge; Raffa, Robert B.

2013-01-01

The family practitioner plays an important role in the prevention, diagnosis, and early management of chronic pain. He/she is generally the first to be consulted, the one most familiar with the patients and their medical history, and is likely the first to be alerted in case of inadequate pain control or safety and tolerability issues. The family practitioner should therefore be at the center of the multidisciplinary team involved in a patient's pain management. The most frequent indications associated with chronic pain in family practice are of musculoskeletal origin, and the pain is often multimechanistic. Fixed-dose combination analgesics combine compounds with different mechanisms of action; their broader analgesic spectrum and potentially synergistic analgesic efficacy and improved benefit/risk ratio might thus be useful. A pain specialist meeting held in November 2010 agreed that the fixed-dose combination tramadol/paracetamol might be a useful pharmacological option for chronic pain management in family practice. The combination is effective in a variety of pain conditions with generally good tolerability. Particularly in elderly patients, it might be considered as an alternative to conventional analgesics such as NSAIDs, which should be used rarely with caution in this population. PMID:24959571

[Pain therapy].

PubMed

Donnadieu, S; Djian, M C

1998-12-12

NEW OPIOID ANALGESICS: Progress in pain reliet has recently been achieved with the introduction of new opioid analgesics such as tramadol and the pediatric preparation of codeine phosphate as well as powerful long-release opioids which can be administered per os, or percutaneously for transdermal fentanyl. CO-ANALGESICS: Other drugs, mainly antidepressants and anti-convulsants, can be usefully combined with analgesics. New serotonin uptake inhibitors and anticonvulsants (gabapentin and lamotrigin) have the advantage of better tolerance. None of these drugs has marketing approval in France for their pain relieving effects. The same is true for clonidine and neostigmine which, after spinal infusion, potentialize opioids and for ketamine which can relieve neuropathy pain by dissociative anesthesia. NEW ANTI-MIGRAINE DRUGS: New drugs have been developed for specific types of pain such as migraine. The new "triptans" are tolerated better than sumatriptan and is reimbursed by the national social security. REFRACTORY NEUROPATHY PAIN: Indications for electrical stimulation techniques conducted in a neurosurgery unit have been identified. Stimulators may be implanted in spinal or supra-spinal localizations. REGULATORY ASPECTS: New legislation has reorganized health care for pain relief in France. The new texts take into consideration personnel training, the health care network and progress in therapeutics.

The Global Opioid Policy Initiative: a wealth of information, but what is next?

PubMed

Scholten, Willem

2014-03-01

Recently, the outcomes were published of the Global Opioid Policy Initiative, evaluating the availability, cost of opioid medicines and the regulatory barriers that are possibly impeding access for the management of cancer pain in developing countries. Other studies have shown that the vast majority of the world population has no access to opioid analgesics. This study shows by country which opioid medicines are available, what they cost to the patient, and investigates the presence of barriers for access to these medicines. Data from the project will be an important resource for those who advocate for improved access to opioid analgesics. Yet, like so often, many more aspects of inadequate opioid analgesic consumption require exploration and reporting, including legislative barriers. The last publication on the project is a "What's next?" that is over focusing on palliative care, forgetting that outside palliative care is also a huge need for opioid analgesics in moderate and severe pain. While promoting access to palliative care and pain management, their recognition as a human right by UN bodies would be of great help. Moreover, WHO's Access to Controlled Medicines Programme, could be an important programme to support the countries in making these improvements.

Spinal Reflexes and Windup In Vitro: Effects of Analgesics and Anesthetics.

PubMed

Rivera-Arconada, Ivan; Roza, Carolina; Lopez-Garcia, Jose A

2016-02-01

The spinal cord is the first relay center for nociceptive information. Following peripheral injury, the spinal cord sensitizes. A sign of spinal sensitization is the hyper-reflexia which develops shortly after injury and can be detected in the isolated spinal cord as a "memory of pain." In this context, it is easy to understand that many analgesic compounds target spinally located sites of action to attain analgesia. In vitro isolated spinal cord preparations have been used for a number of years, and experience on the effects of compounds of diverse pharmacological families on spinal function has accumulated. Recently, we have proposed that the detailed study of spinal segmental reflexes in vitro may produce data relevant to the evaluation of the analgesic potential of novel compounds. In this review, we describe the main features of segmental reflexes obtained in vitro and discuss the effects of compounds of diverse chemical nature and pharmacological properties on such reflexes. Our aim was to compare the different profiles of action of the compounds on segmental reflexes in order to extract clues that may be helpful for pharmacological characterization of novel analgesics. © 2015 John Wiley & Sons Ltd.

A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.

PubMed

Wu, Ping; Liang, Qin; Feng, Pei; Li, Chunyan; Yang, Chunguang; Liang, Hongsuo; Tang, Huaibo; Shuai, Cijun

2017-04-03

The seeds of Strychnos nux -vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnos nux - vomica . Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.

Methoxyflurane: a review with emphasis on its role in dental practice.

PubMed

Kingon, A; Yap, T; Bonanno, C; Sambrook, P; McCullough, M

2016-06-01

Methoxyflurane was developed as an anaesthetic agent and introduced into clinical practice in 1960. It soon became evident that it possessed analgesic properties that other drugs did not. Due to toxicity concerns, it lost favour in general anaesthesia and had been largely abandoned by the late 1970s. The manufacturer withdrew it in 1999, and the Food and Drug Administration in the United States did not renew its licence in 2005. It has also been withdrawn by the European Union. However, it continues to be used in Australasia, primarily as an inhaled self-administered analgesic by emergency services immediately following trauma. It has become attractive for use in dental practice, likely due to its effectiveness as an analgesic and its additional sedative qualities. Its acceptance is controversial as its use in dentistry is largely elective. Despite its good safety record in analgesic doses, adverse reactions have been recorded. Practitioners should be well aware of risks associated with its use before considering administration, and carefully assess whether or not there are equally good alternative options that do not the carry the same risks. Methoxyflurane is reviewed below with an emphasis on its use in dental practice. © 2016 Australian Dental Association.

Three Newly Approved Analgesics: An Update

PubMed Central

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 formulation of diclofenac potassium, which is a nonsteroidal anti-inflammatory drug (NSAID), and its putative mechanism of action is through inhibition of cyclooxygenase enzymes. This novel formulation of diclofenac allows for improved absorption at lower doses. Liposomal bupivacaine is a new formulation of bupivacaine intended for single-dose infiltration at the surgical site for postoperative analgesia. Bupivacaine is slowly released from this liposomal vehicle and can provide prolonged analgesia at the surgical site. By utilizing NSAIDs and local anesthetics to decrease the transmission of afferent pain signals, less opioid analgesics are needed to achieve analgesia. Since drug-related adverse events are frequently dose related, lower doses from different drug classes may be employed to reduce the incidence of adverse effects, while producing synergistic analgesia as part of a multimodal analgesic approach to acute pain. PMID:24423420

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

PubMed Central

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

2012-01-01

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