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.

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.

Intervertebral Foramen Injection of Ozone Relieves Mechanical Allodynia and Enhances Analgesic Effect of Gabapentin in Animal Model of Neuropathic Pain.

PubMed

Luo, Wen-Jun; Yang, Fan; Yang, Fei; Sun, Wei; Zheng, Wei; Wang, Xiao-Liang; Wu, Fang-Fang; Wang, Jiang-Lin; Wang, Jia-Shuang; Guan, Su-Min; Chen, Jun

2017-07-01

In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. Experimental trial in rats. Institute for Biomedical Sciences of Pain. By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (< 48 hours) inhibiting or antagonizing at Nav1.8 (A-803467), CXCR4 (AMD3100), mTOR (rapamycin), and histone deacetylase (MGCD0103); (3) combined use of systemic gabapentin and IVF ozone produced a synergistic analgesic effect in rats with neuropathic pain. Evaluation of the possible analgesic effects of the intraplantar injection of ozone was not performed. In the present study, we provided a line of evidence for the first time that IVF injection of ozone selectively relieved neuropathic pain but not inflammatory pain, and enhanced the analgesic effect of gabapentin. Chronic pain, neuropathic pain, inflammatory pain, ozone therapy, interventional therapy, gabapentin, spared nerve injury, bee venom, complete Freud's adjuvant.

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

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

Comparative clinical evaluation of the immediate and late analgesic effect of GaAlAs diode lasers of 830 and 660 nm in the treatment of dentine pain: preliminary results

NASA Astrophysics Data System (ADS)

Ladalardo, Thereza C.; Mangabeira Albernaz, Pedro L.; Brugnera, Aldo, Jr.; Zanin, Fatima A. A.; Siqueira, Jose T.; Pinheiro, Antonio L. B.

2002-06-01

In this comparative clinical study, we aimed at evaluating the immediate and late analgesic effect of GaAlAs diode lasers of 660 nm and 830 nm in treatment of dentine pain. We used GaAlAs diode lasers of 660 nm and 830 nm with 35 mW, continuous wave emission, spot size 1 mm2 and a dosage of 4 joules/cm2 applied to the cervical dentine surface. In total 4 treatment sessions were performed at intervals of 7 days in a period of 4 consecutive weeks. A total of 40 teeth treated were divided into two groups comprising 20 teeth each: one group irradiated with a 660 nm wavelength laser, and the other one with a 830 nm wavelength laser. By means of a quantitative visual analogue scale (V.A.S.), we measured the sensitive responses to cold stimulus pre- treatment, and at a follow-up period of 15 and 30 minutes post-treatment in both groups in order to evaluate the immediate analgesic effect. The late effect was evaluated at a follow-up period of 15 and 30 days. Using the GaAlAs diode laser of 660 nm wavelength resulted in better levels of dentine desensitization, at both immediate and late analgesic effect analysis compared with the use of the GaAlAs diode laser of 830 nm wavelength.

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.

[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.

In Vitro and In Vivo Characterization of the New Analgesic Combination Beta-Caryophyllene and Docosahexaenoic Acid

PubMed Central

Fiorenzani, Paolo; Lamponi, Stefania; Magnani, Agnese; Ceccarelli, Ilaria; Aloisi, Anna Maria

2014-01-01

Beta-caryophyllene (BCP) and docosahexaenoic acid (DHA) are components of several plants with documented anti-inflammatory and analgesic effects in animal pain models. In the present study, in vitro and in vivo tests were carried out to evaluate their effects, alone or in combination, during long-lasting administration in a model of persistent pain. IR spectra of the two compounds were obtained to determine their chemical stability and then in vitro toxicity was evaluated in fibroblasts and astrocytes. In the in vivo tests, the analgesic effects of BCP and BCP+DHA were determined in male rats subjected to a model of persistent recurrent pain (three repetitions of the formalin test once a week) to mimic recurrent pain. Both substances were administered per os in almond oil for 2 weeks. Gonadal hormones were determined at the end of the tests to evaluate treatment-induced effects on their levels. BCP changed fibroblast and astrocyte survival in a dose-dependent manner and the effect was counteracted by DHA coadministration. In the in vivo tests, pain responses were significantly decreased in the BCP and BCP+DHA groups with respect to OIL after 1 and 2 weeks of treatment. Estradiol and testosterone levels were increased only in the BCP group. In conclusion, BCP alone or at lower concentration in combination with DHA was efficacious in modulating pain, showing a clear analgesic activity. PMID:25097659

[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.

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

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 .

Evaluation of anti-inflammatory and analgesic activity of a novel rigid 3, 4-dihydroxy chalcone in mice.

PubMed

Heidari, M R; Foroumadi, A; Amirabadi, A; Samzadeh-Kermani, A; Azimzadeh, B S; Eskandarizadeh, A

2009-08-01

There have been many reports indicating the analgesic and anti-inflammatory effects of 3,4-dihydroxychalcones. We have designed and synthesized a rigid 3,4-dihydroxychalcone (RDHC) as a possible drug effecting inflammation and nociception. The analgesic and anti-inflammatory effects were evaluated by formalin and hot-plate tests, respectively. The results showed that RDHC induced significant antinociceptive and anti-inflammatory effects (P < 0.01). Maximum analgesia (63.7%) was observed at 37.5 mg/kg in the first phase of the formalin test. The effect of RDHC was higher in the chronic phase (inflammation phase) of the formalin test (86.4%, P < 0.01). In addition, a significant analgesia (maximum possible effect; MPE = 30.1%) was observed in the hot plate test 45 min after injection of 37.5 mg/kg RDHC (P < 0.01). As a result of our findings, this new RDHC could be suggested for further pharmacological studies.

Topical Anti-Inflammatory and Analgesic Effects of Multiple Applications of S(+)-Flurbiprofen Plaster (SFPP) in a Rat Adjuvant-Induced Arthritis Model.

PubMed

Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-06-01

Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)-flurbiprofen plaster (SFPP), a novel Nonsteroidal anti-inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant-induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)-1 and COX-2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti-inflammatory effects clinically. Drug Dev Res 77 : 206-211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

Topical Anti‐Inflammatory and Analgesic Effects of Multiple Applications of S(+)‐Flurbiprofen Plaster (SFPP) in a Rat Adjuvant‐Induced Arthritis Model

PubMed Central

Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-01-01

Abstract Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)‐flurbiprofen plaster (SFPP), a novel Nonsteroidal anti‐inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant‐induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)−1 and COX‐2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti‐inflammatory effects clinically. Drug Dev Res 77 : 206–211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc. PMID:27241582

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.

[Placebo-controlled blinded study of postoperative pain therapy with carprofen and levomethadone in dogs with fractures].

PubMed

Wacker, Katja; Nolte, Ingo; Kramer, Sabine

2005-01-01

It was the aim of this placebo-controlled study to evaluate the analgesic efficacy of the NASAID carprofen and the pure m-agonist levomthadone over a five-day postoperative evaluation period in dogs with fractures of the humerus or the femur (n = 30). Pain and sedation evaluation was carried out with a visual analogues system (VAS) and with the aid of a numerical estimation scale(NRS). The degree of lameness, the pain treshhold, the glucose and cortisol concentration curves as well as the respiration and heart rate and the systolic blood pressure were used as further pain indicators and to identify drug side effects. The levomethadon group displayed the lowest degree of pain on postoperative examination on the first day. On days 2 to 5, the carprofen group showed the lowest degree of pain in comparison to the placebo group. The levomethadon- and the carprofen group showed no statistically proven differences from day 2 on. Due to great variations in the pain scores and comparatively high median pain score especially on the first day of this study, the efficacy of all analgesics evaluated here must be regarded as insufficient in many cases. Only the parameter nociceptive pain treshhold showed a little, the degree of lameness, the glucose and cortisol levels showed no close correlation to the VAS and NRS pain scores and were therefore of little usefulness as postoperative pain indicators. No relevant clinical side effects caused by the used analgesics were detected in the kidney, the liver, the gastrointestinal tract and the circulatory system in this study. Rather, traumatically induced elevation of enzyme levels improves or normalised until the 5th day of the study. In addition, no negative effect on wound healing was noted, especially for carprofen. Therefore, the evaluated analgesics seems to be adequate for postoperative pain therapy also in fracture patients (trauma patients). However, the efficacy of all analgesics evaluated here must be regarded as insufficient in many cases.

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.

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.

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.

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.

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

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.

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.

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.

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

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1969-01-01

This report—the second of a series on codeine and its alternates for pain and cough relief—contains a detailed evaluation of experimental and clinical data on newer substances having analgesic properties comparable to and in approximately the same range as those of codeine. The data are discussed under the headings: analgesic effects in animals; clinical usefulness; side-effects with particular reference to dependence and abuse liability. PMID:4894737

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.

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

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.

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.

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

Use of multicriteria decision analysis for assessing the benefit and risk of over-the-counter analgesics.

PubMed

Moore, Andrew; Crossley, Anne; Ng, Bernard; Phillips, Lawrence; Sancak, Özgür; Rainsford, K D

2017-10-01

To test the ability of a multicriteria decision analysis (MCDA) model to incorporate disparate data sources of varying quality along with clinical judgement in a benefit-risk assessment of six well-known pain-relief drugs. Six over-the-counter (OTC) analgesics were evaluated against three favourable effects and eight unfavourable effects by seven experts who specialise in the relief of pain, two in a 2-day facilitated workshop whose input data and judgements were later peer-reviewed by five additional experts. Ibuprofen salts and solubilised emerged with the best benefit-risk profile, followed by naproxen, ibuprofen acid, diclofenac, paracetamol and aspirin. Multicriteria decision analysis enabled participants to evaluate the OTC analgesics against a range of favourable and unfavourable effects in a group setting that enabled all issues to be openly aired and debated. The model was easily communicated and understood by the peer reviewers, so the model should be comprehensible to physicians, pharmacists and other health professionals. © 2017 Royal Pharmaceutical Society.

Analgesic, anti-inflammatory and anti-pyretic activities of Caesalpinia decapetala

PubMed Central

Parveen, Amna; Sajid Hamid Akash, Muhammad; Rehman, Kanwal; Mahmood, Qaisar; Qadir, Muhammad Imran

2014-01-01

Introduction: In many pathological conditions, pain, inflammation and fever are interdependent to each other. Due to the use of synthetic drugs, many unwanted effects usually appear. Various studies have been conducted on Caesalpinia decapetala (C. decapetala) to evaluate its effects in the treatment of various diseases but no sufficient scientific literature is available online to prove its analgesic, anti-inflammatory and anti-pyretic activities. Methods: The analgesic, anti-inflammatory and anti-pyretic activities of 70% aqueous methanolic and n-hexane extracts of C. decapetala was evaluated using Swiss albino mice (20-30 g). Results: The results showed that aqueous methanolic extract of C. decapetala at the dose of 100 mg/kg exhibited significant (p< 0.05) activities in various pain models including acetic acid-induced writhing (18.4 ± 0.53), formalin-induced licking (275 ± 4.18) and hot plate method (2.3 ± 0.0328); whereas,  n-hexane extract showed its effects in acetic acid-induced writhing (20 ± 0.31), formalin-induced licking (293 ± 1.20) and hot plate method (2.224 ± 0.029) compared to the effects observed in control group animals. Similarly, the aqueous methanolic extract of C. decapetala after 2 h of treatment exhibited more significant anti-inflammatory (0.66 ± 0.06) and anti-pyretic (38.81 ± 0.05) activities compared to the control group animals. Conclusion: From the findings of our present study, we concluded that the aqueous methanolic extract of C. decapetala has stronger analgesic, anti-inflammatory and anti-pyretic effects than its n-hexane extract. Further studies are required to investigate the active constituents of C. decapetala that exhibit analgesic, anti-inflammatory and anti-pyretic activities. PMID:24790898

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.

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.

Analgesic and anti-inflammatory effects of the dry matter of culture broth of Termitomyces albuminosus and its extracts.

PubMed

Lu, Yi-Yu; Ao, Zong-Hua; Lu, Zhen-Ming; Xu, Hong-Yu; Zhang, Xiao-Mei; Dou, Wen-Fang; Xu, Zheng-Hong

2008-12-08

The objectives of this study were to investigate the analgesic and anti-inflammatory effects of the dry matter of culture broth (DMCB) of Termitomyces albuminosus in submerged culture and its crude saponin extract (CSE) and crude polysaccharide extract (CPE). The analgesic effects of DMCB, CSE and CPE were evaluated with models of acetic acid-induced writhing response and formalin test in mouse. The anti-inflammatory effects of DMCB, CSE and CPE were evaluated by using models of xylene-induced mouse ear swelling and carrageen-induced mouse paw edema. The DMCB, CSE and CPE significantly decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. Treatment of DMCB (1000mg/kg), CSE (200mg/kg) or CPE (200mg/kg) inhibited the mouse ear swelling by 61.8%, 79.0% and 81.6%, respectively. In the carrageen-induced mouse paw edema test, the group treated with indomethacin showed the strongest inhibition of edema formation by 77.8% in the third hour after carrageenan administration, while DMCB (1000mg/kg), CSE (200mg/kg) and CPE (200mg/kg) showed 48.4%, 55.6% and 40.5%, respectively. The results suggested that DMCB of Termitomyces albuminosus possessed the analgesic and anti-inflammatory activities. Saponins and polysaccharides were proposed to be the major active constituents of Termitomyces albuminosus in submerged culture.

Rubus occidentalis analgesic effect in a rat model of incisional pain.

PubMed

Choi, Geun Joo; Kang, Hyun; Kim, Won Joong; Kwon, Ji Wung; Kim, Beom Gyu; Choi, Yoo Shin; Cha, Young Joo; Ko, Jin Soo

2016-11-01

The purpose of this study was to evaluate the analgesic effect of Rubus occidentalis extract (ROE) in a rat model of incisional pain. The involved mechanisms and proinflammatory cytokine response were also examined. To investigate the analgesic effect, rats were intraperitoneally administered with normal saline or various doses of ROE before or after a plantar incision. To evaluate the involved mechanism, rats were intraperitoneally administered yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine after a plantar incision; ROE was then administered intraperitoneally. The mechanical withdrawal threshold (MWT) was tested with von Frey filaments at various time points. To determine the inflammatory response, serum levels of interleukin (IL)-1β or IL-6 were measured. The MWTs significantly increased at 15 min after postincisional administration of 300 mg/kg ROE when compared with those in the control group. This elevation was observed for up to 45 min. Overall, MWTs increased in proportion to ROE dosage; however, ROEs administered before the incision produced no significant change in the MWT. The analgesic effect of ROE was significantly antagonized by mecamylamine, naloxone, and yohimbine, and agonized by dexmedetomidine. Administration of ROE inhibited the postincisional increase in serum IL-1β and IL-6. Intraperitoneal administration of ROE after surgery induces antinociceptive effects in a rat model of postoperative pain, and its effects on mechanical hyperalgesia may be associated with α 2 -adrenergic, nicotinic cholinergic, and opioid receptors. Copyright © 2016 Elsevier Inc. All rights reserved.

Intravenous flurbiprofen axetil enhances analgesic effect of opioids in patients with refractory cancer pain by increasing plasma β-endorphin.

PubMed

Wu, Ting-Ting; Wang, Zhi-Gang; Ou, Wu-Ling; Wang, Jun; Yao, Guo-Qing; Yang, Bo; Rao, Zhi-Guo; Gao, Jian-Fei; Zhang, Bi-Cheng

2014-01-01

The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma β-endorphin levels in cancer patients. A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma β-endorphin levels were measured by radioimmunoassay. With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma β-endorphin levels. After the treatment, plasma β-endorphin level in group B was 62.4±13.5 pg/ml, which was higher than that in group A (45.8±11.2 pg/ml) (p<0.05). Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma β-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

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

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

Making the decision to stop pain: Probability and magnitude effects of expected pain relief on the choice of analgesics.

PubMed

Lin, C

2013-04-01

Pain is a major ailment that motivates individuals to look for treatment. Despite its enormous clinical relevance, very little is known about the factors that influence our preference of an analgesic (or pain-relieving treatment). The current study investigated the influence of the information regarding the probability and the magnitude of the expected analgesic effect on preference of analgesic options. Twenty-four healthy volunteers were instructed to imagine pain across different scenarios and choose between two hypothetical analgesics that differed in their probabilities to successfully relieve pain and the magnitude of their expected analgesic effects. The conservative analgesic was more reliable but less potent than the radical analgesic, whereas the radical analgesic was less reliable but more potent than the conservative analgesic. Consistent with the predictions of prospect theory, a larger proportion of the participants chose the radical analgesic when the overall probability of both analgesics decreased, and when the potency of the radical analgesic was expected to be stronger relative to the conservative analgesic. At the individual level, individuals' relative imagined pain relief (radical analgesic/conservative analgesic) predicted their preference for the radical analgesic. Our findings revealed that preference of analgesic options is mediated by the overall probability of analgesic effect and the relative potency of analgesics. The expected relief one imagines to obtain from analgesics would guide preference. The findings highlight the importance for clinicians to understand how patients subjectively frame the probability and magnitude factors related to decision making in medical context. © 2012 European Federation of International Association for the Study of Pain Chapters.

[Evaluation of the inhibitory effect of extracts from leaves of Renealmia alpinia Rottb. Maas (Zingiberaceae) on the venom of Bothrops asper (mapaná)].

PubMed

Patiño, Arley Camilo; López, Jéssica; Aristizábal, Mónica; Quintana, Juan Carlos; Benjumea, Dora

2012-09-01

Traditional medicine is an invaluable source of research into new medicines as a supplement for the treatment of snakebite, considered as a serious public health problem worldwide. The extracts of the medicinal plant, Renealmia alpina, have been used traditionally by indigenous people of Chocó (Colombia) against Bothrops asper snakebite, a snake responsible for the majority of snakebite accidents in Colombia. The ability of extracts of R. alpinia leaves was tested for its ability to neutralize the hemorrhagic, coagulant and proteolytic effects of the snakebite venom of B. asper. The acute toxicity tests and analgesic activity of R. alpina were evaluated in vivo. In addition, tests were undertaken in in vitro conditions to demonstrate inhibition of coagulant, haemolytic and proteolytic activity of the B. asper venom. Results. Renealmia alpinia extracts had no toxic effects in experimental animals and also provided analgesic and antiophidian effects and protection against the lethal effects of the venom of B. asper. Renealmia. alpinia was an effective therapeutic alternative in association with antivenom treatment in the event of a B. asper snakebite accident. It was demonstrated to protect against the lethal effects and provided analgesic properties as well.

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

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.

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

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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...

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

Evaluation of acute toxicity, sedative and analgesic effects of Taverniera glabra methanolic extract on mice.

PubMed

Marvi, -; Iqbal, Javeid; Muhammad, Shafi; Ahmad, Mansoor

2016-11-01

Present study was conducted on crude methanolic extract of stem and root of Taverniera glabra. In Pakistan T. glabra is found in the region of Balochistan only. T. glabra has numerous therapeutic uses in traditional medicine and it is also used for the pain relief. Current study was carried out to evaluate acute toxicity, analgesic and CNS depressant activity of the plant. Acute toxicity was carried out by oral administration of the T. glabra extract from 250 to 2000mg/kg oral dose. Analgesic activity was carried out by acetic acid induced writhing test and formalin test. Central Nervous System (CNS) depressant activity was carried out by exploratory activities (open field activity, cage crossing activity, rearing test) and forced swimming test. Oral administration of the methanolic extract of T. glabra was nontoxic at the dose of 1500mg/kg in the acute toxicity test. Exploratory behavior of mice treated with the methanolic extract of T. glabra showed sedative effects (P<0.05) in open field, cage crossing, traction and rearing test, particularly at the dose of 500mg as compared with standard drug Diazepam. In forced swimming test, mobility time was significantly (P<0.05) increased at 500mg/kg oral dose, and results were significant as compared with control. Methanolic extract of T. glabra produced significant (P<0.05) analgesic effects at the dose of 500mg/kg in the acetic acid induced writhing test and the formalin test. In conclusion, results show that the crude methanolic extract of T. glabra possess sedative as well as potent analgesic effects. Present pharmacological studies are the first ever studies conducted on the methanolic extract of T. glabra.

Repetitive transcranial magnetic stimulation of the left premotor/dorsolateral prefrontal cortex does not have analgesic effect on central poststroke pain.

PubMed

de Oliveira, Rogério Adas Ayres; de Andrade, Daniel Ciampi; Mendonça, Melina; Barros, Rafael; Luvisoto, Tatiana; Myczkowski, Martin Luiz; Marcolin, Marco Antonio; Teixeira, Manoel Jacobsen

2014-12-01

Central poststroke pain (CPSP) is caused by an encephalic vascular lesion of the somatosensory pathways and is commonly refractory to current pharmacologic treatments. Repetitive transcranial magnetic stimulation (rTMS) of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) can change thermal pain threshold toward analgesia in healthy subjects and has analgesic effects in acute postoperative pain as well as in fibromyalgia patients. However, its effect on neuropathic pain and in CPSP, in particular, has not been assessed. The aim of this prospective, double-blind, placebo-controlled study was to evaluate the analgesic effect of PMC/DLPFC rTMS in CPSP patients. Patients were randomized into 2 groups, active (a-) rTMS and sham (s-) rTMS, and were treated with 10 daily sessions of rTMS over the left PMC/DLPFC (10 Hz, 1,250 pulses/d). Outcomes were assessed at baseline, during the stimulation phase, and at 1, 2, and 4 weeks after the last stimulation. The main outcome was pain intensity changes measured by the visual analog scale on the last stimulation day compared to baseline. Interim analysis was scheduled when the first half of the patients completed the study. The study was terminated because of a significant lack of efficacy of the active arm after 21 patients completed the whole treatment and follow-up phases. rTMS of the left PMC/DLPFC did not improve pain in CPSP. The aim of this double-blind, placebo-controlled study was to evaluate the analgesic effects of rTMS to the PMC/DLPFC in CPSP patients. An interim analysis showed a consistent lack of analgesic effect, and the study was terminated. rTMS of the PMC/DLPFC is not effective in relieving CPSP. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

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

[Study on relationship of dose-effect and time-effect of APA microencapsulated bovine chromaffin cells on pain treatment].

PubMed

Hui, Jianfeng; Li, Tao; Du, Zhi; Song, Jichang

2011-12-01

This study was to investigate the relationship of dose-effect and time-effect of Alginate-Polylysine-Alginate (APA) microencapsulated bovine chromaffin cells on the treatment of pain model rats. Using a rat model of painful peripheral neuropathy, the antinociceptive effects of APA microencapsulated bovine cells transplanted into the subarachnoid space was evaluated by cold allodynia test and hot hyperalgesia test. Compared with control group, the withdrawal difference with cell number 50 thousands groups, 100 thousands groups and 200 thousands groups was reduced (P < 0.05), and the difference decreased with the cells increases, indicating a significant analgesic effect. There was no significant difference between 400 thousands groups and 200 thousands groups. This analgesic effect maintained longer than 12 weeks. There was a positive correlation between the analgesic effect and the quantity of APA microencapsulated bovine chromaffin cells which were transplanted to treat pain model rats, and the effective antinociception remained longer than 12 weeks.

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.

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.

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 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.

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.

Ilex paraguariensis Promotes Orofacial Pain Relief After Formalin Injection: Involvement of Noradrenergic Pathway.

PubMed

de Carvalho, Eudislaine Fonseca; de Oliveira, Simone Kobe; Nardi, Viviane Koepp; Gelinski, Tathiana Carla; Bortoluzzi, Marcelo Carlos; Maraschin, Marcelo; Nardi, Geisson Marcos

2016-03-01

Drinking mate or chimarrão, a hot infusion of Ilex paraguariensis (ILEX) leaves, is a common habit in Southern South America that has a social and almost ritualistic role. It has been used as a stimulant beverage in South America and analgesic in regions of Argentina for treatment of headache and others painful inflammatory conditions such as arthritis and rheumatism. The aim of this study was to evaluate the pharmacological activity of I. paraguariensis infusion (ILEX) on orofacial nociception model induced by formalin, and study its mechanism of action. The analgesic effect of ILEX was assessed through writhing test, paw formalin test, paw edema induced by carrageenan, and orofacial pain induced by formalin. To study the action mechanism of ILEX, opioidergic, dopaminergic, nitrergic, and adrenergic pathways were investigated. The high-performance liquid chromatography analysis of ILEX infusion revealed caffeine and theobromine. The treatment with ILEX reduced the number of writhing. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan. Different from formalin paw test, ILEX was able to reduce the orofacial reactivity to formalin in 31.8% (70.4 ± 2.5 s; first phase), and 20% (127.3 ± 18.9 s; second phase). The analgesic effect of ILEX results from the modulation of noradrenergic pathways since prazosin (α1-adrenoceptor antagonist, 0.15 mg/kg; intraperitoneal) reversed the analgesic effect of ILEX. The present report demonstrates that analgesic effect of ILEX in orofacial formalin test is due mainly to modulation of noradrenergic pathways. Ilex paraguariensis (ILEX) has been used as a stimulant beverage in South America and analgesic in regions of Argentina for the treatment of headache and others painful inflammatory conditions such arthritis and rheumatism.The aim of this study was to evaluate the pharmacological activity of ILEX on orofacial nociception model induced by formalin, and study its mechanism of action.ILEX reduced the number of writhing and orofacial reactivity to formalin in mice. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan.The analgesic effect of ILEX results from the modulation of noradrenergic pathways. Abbreviation Used: ILEX: Infusion of Ilex paraguariensis, NSAIDs: Nonsteroidal anti-inflammatory drugs, L-NOARG: L-NG-nitro-arginine, UV: Ultraviolet, i.p.: Intraperitoneal, NOS: Nitric Oxide Synthase, Analysis of variance, S.E.M.: Standard error of mean, HPLC: High-performance liquid chromatography, NO: Nitric Oxide, v.o.: Oral route, DCQ: dicaffeoylquinic acid, BMS: Burning mouth syndrome, PBS: Phosphate-buffered saline.

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.

Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model.

PubMed

Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-02-01

Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti-inflammatory drug) patch, SFPP (S(+)-flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)-flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant-induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX-1 (IC50  = 8.97 nM) and COX-2 (IC50  = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

Analgesic Effect of the Newly Developed S(+)‐Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant‐Induced Arthritis Model

PubMed Central

Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-01-01

ABSTRACT Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant‐induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX‐1 (IC50 = 8.97 nM) and COX‐2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20–28, 2016. © 2016 Wiley Periodicals, Inc. PMID:26763139

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 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.

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.

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.

Factors influencing use of analgesics among construction workers in the Ga-Eastmunicipality of the Greater Accra region, Ghana.

PubMed

Badzi, Caroline D; Ackumey, Mercy M

2017-12-01

Analgesics also known as painkillers are widely used for pain relief. There are severe health implications associated with excessive use of analgesics. This paper examines factors influencing the use of analgesics among construction workers in the Ga-East Municipality (GEM) of the Greater Accra region of Ghana. This is a cross-sectional study involving 206 construction workers randomly sampled from 7 construction sites in the GEM. A structured questionnaire was used to elicit responses on knowledge of analgesics, types of analgesics used and factors influencing the use of analgesics. Chi-square test analysis was used to examine factors influencing analgesic use. The majority of workers were aged between 15 to 44 years (89.8%) and 51.9 percent of respondents had completed Junior high school. Many respondents (68.0%) used Brand 1 a locally manufactured analgesic with paracetamol, aspirin and caffeine as the active ingredients and 31.6 percent of respondents had no knowledge of possible side effects of continuous use of analgesics. Chi square analysis showed that age was significantly associated with use of analgesics (p<0.01). Knowledge of the types of analgesics, dosage and side effects did not influence use (p>0.05). Television and radio advertisements influenced use of analgesics (p<0.01). Knowledge on analgesic use and knowledge of probable serious side effects was inadequate. Pharmacists and chemists involvement in education of clients of the side effects of analgesics is highly recommended to minimise misuse. The Food and Drugs Authority should regulate the proliferation of advertisements for analgesics in the media. None declared.

IL4-10 fusion protein has chondroprotective, anti-inflammatory and potentially analgesic effects in the treatment of osteoarthritis.

PubMed

Steen-Louws, C; Popov-Celeketic, J; Mastbergen, S C; Coeleveld, K; Hack, C E; Eijkelkamp, N; Tryfonidou, M; Spruijt, S; van Roon, J A G; Lafeber, F P J G

2018-05-26

Effective disease-modifying drugs for osteoarthritis (DMOAD) should preferably have chondroprotective, anti-inflammatory, and analgesic activity combined in a single molecule. We developed a fusion protein of IL4 and IL10 (IL4-10 FP), in which the biological activity of both cytokines is preserved. The present study evaluates the chondroprotective, anti-inflammatory, and analgesic activity of IL4-10 FP in in vitro and in vivo models of osteoarthritis. Human osteoarthritic cartilage tissue and synovial tissue were cultured with IL4-10 FP. Cartilage proteoglycan turnover and release of pro-inflammatory, catabolic, and pain mediators by cartilage and synovial tissue were measured. The analgesic effect of intra-articularly injected IL4-10 FP was evaluated in a canine model of osteoarthritis by force-plate analysis. IL4-10 FP increased synthesis (P = 0.018) and decreased release (P = 0.018) of proteoglycans by osteoarthritic cartilage. Release of pro-inflammatory IL6 and IL8 by cartilage and synovial tissue was reduced in the presence of IL4-10 FP (all P < 0.05). The release of MMP3 by osteoarthritic cartilage and synovial tissue was decreased (P = 0.018 and 0.028) whereas TIMP1 production was not significantly changed. Furthermore, IL4-10 FP protected cartilage against destructive properties of synovial tissue mediators shown by the increased cartilage proteoglycan synthesis (P = 0.0235) and reduced proteoglycan release (P = 0.0163). Finally, intra-articular injection of IL4-10 FP improved the deficient joint loading in dogs with experimentally induced osteoarthritis. The results of current preliminary study suggest that IL4-10 FP has DMOAD potentials since it shows chondroprotective and anti-inflammatory effects in vitro, as well as potentially analgesic effect in a canine in vivo model of osteoarthritis. Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

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.

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.

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.

Phytochemical screening and study of antioxidant, antimicrobial, antidiabetic, anti-inflammatory and analgesic activities of extracts from stem wood of Pterocarpus marsupium Roxburgh.

PubMed

Pant, Dipak Raj; Pant, Narayan Dutt; Saru, Dil Bahadur; Yadav, Uday Narayan; Khanal, Dharma Prasad

2017-01-01

The main aims of the study were to evaluate the phytochemical constituents and to study the antioxidant, antimicrobial, antidiabetic, anti-inflammatory, and analgesic activities of extracts from stem wood of Pterocarpus marsupium . Ethanol, acetone and isopropyl alcohol (IPA) (1:1) extracts of stem wood of P. marsupium were subjected to phytochemical screening and analysis of biological activities from August 2015 to January 2016. The antioxidant assay was carried out using 2, 2-diphenyl-1-picrylhydrazyl scavenging method, antimicrobial activity testing by cup diffusion method, antidiabetic test evaluation by oral glucose tolerance test in mice, anti-inflammatory effect was evaluated by hind paw edema method in mice and analgesic test evaluation by a chemical writhing method in mice. The results of the study revealed that P. marsupium is a source of various phytoconstituents such as alkaloids, glycosides, saponins, tannins, proteins, carbohydrates, cardiac glycosides, flavonoids, and terpenoids. Both the acetone and IPA extract as well as the ethanol extract of stem wood of P. marsupium exhibited a dose-dependent antioxidant activity. Acetone and IPA extract showed antibacterial activity against Gram-positive bacteria, while the ethanolic extract was found to possess antidiabetic activity. The antidiabetic activity of the extract was found to be time and dose-dependent. Similarly, the acetone and IPA extract was found to have anti-inflammatory activity, which was also time and dose-dependent. Furthermore, the ethanolic extract showed analgesic activity, which was dose-dependent. The ethanolic extract was found to be nontoxic. Thus, this study laid sufficient background for the further research on extracts from stem wood of P. marsupium for identification, subsequent purification and isolation of compounds having antibacterial, antidiabetic, anti-inflammatory, and analgesic activities.

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

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 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.

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.

Persistent pain after motor vehicle collision: comparative effectiveness of opioids vs nonsteroidal antiinflammatory drugs prescribed from the emergency department-a propensity matched analysis.

PubMed

Beaudoin, Francesca L; Gutman, Roee; Merchant, Roland C; Clark, Melissa A; Swor, Robert A; Jones, Jeffrey S; Lee, David C; Peak, David A; Domeier, Robert M; Rathlev, Niels K; McLean, Samuel A

2017-02-01

Each year millions of Americans present to the emergency department (ED) for care after a motor vehicle collision (MVC); the majority (>90%) are discharged to home after evaluation. Acute musculoskeletal pain is the norm in this population, and such patients are typically discharged to home with prescriptions for oral opioid analgesics or nonsteroidal antiinflammatory drugs (NSAIDs). The influence of acute pain management on subsequent pain outcomes in this common ED population is unknown. We evaluated the effect of opioid analgesics vs NSAIDs initiated from the ED on the presence of moderate to severe musculoskeletal pain and ongoing opioid use at 6 weeks in a large cohort of adult ED patients presenting to the ED after MVC (n = 948). The effect of opioids vs NSAIDs was evaluated using an innovative quasi-experimental design method using propensity scores to account for covariate imbalances between the 2 treatment groups. No difference in risk for moderate to severe musculoskeletal pain at 6 weeks was observed between those discharged with opioid analgesics vs NSAIDs (risk difference = 7.2% [95% confidence interval: -5.2% to 19.5%]). However, at follow-up participants prescribed opioids were more likely than those prescribed NSAIDs to report use of prescription opioids medications at week 6 (risk difference = 17.5% [95% confidence interval: 5.8%-29.3%]). These results suggest that analgesic choice at ED discharge does not influence the development of persistent moderate to severe musculoskeletal pain 6 weeks after an MVC, but may result in continued use of prescription opioids. Supported by NIAMS R01AR056328 and AHRQ 5K12HS022998.

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.

Long-term effects of octreotide on pituitary gigantism: its analgesic action on cluster headache.

PubMed

Otsuka, Fumio; Mizobuchi, Satoshi; Ogura, Toshio; Sato, Kenji; Yokoyama, Masataka; Makino, Hirofumi

2004-10-01

We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.

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.

Lack of synergistic interaction between the two mechanisms of action of tapentadol in gastrointestinal transit.

PubMed

Cowan, A; Raffa, R B; Tallarida, C S; Tallarida, R J; Christoph, T; Schröder, W; Tzschentke, T M

2014-09-01

A multi-mechanistic approach offers potential enhancement of analgesic efficacy, but therapeutic gain could be offset by an increase in adverse events. The centrally acting analgesic tapentadol [(-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride] combines μ-opioid receptor (MOR) agonism and neuronal noradrenaline reuptake inhibition (NRI), both of which contribute to its analgesic effects. Previously, isobolographic analysis of occupation-effect data and a theoretically equivalent methodology determining interactions from the effect scale demonstrated pronounced synergistic interaction between the two mechanisms of action of tapentadol in two models of antinociception (low-intensity tail-flick and spinal nerve ligation). The present study investigated the nature of interaction of the two mechanisms on a surrogate measure for gastrointestinal adverse effect (inhibition of gastrointestinal transit). Dose-response curves were generated in rats for tapentadol alone or in combination with the opioid receptor antagonist, naloxone, or the α2 -adrenoceptor antagonist, yohimbine, to reveal the effect of tapentadol based upon MOR agonism, NRI, and combined mechanisms. The dose-effect curve of tapentadol was shifted to the right by both antagonists, thereby providing data to distinguish between MOR agonism and NRI. Analysis revealed a simple additive interaction between the two mechanisms on this endpoint, in contrast to the synergistic interaction previously demonstrated for antinociception. We believe this is the first published evaluation of mechanistic interaction for a surrogate measure of adverse effect of a single compound with two mechanisms of action, and the results suggest that there is a greater separation between the analgesic and gastrointestinal effects of tapentadol than expected based upon its analgesic efficacy. © 2014 European Pain Federation - EFIC®

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.

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.

Low power radiofrequency electromagnetic radiation for the treatment of pain due to osteoarthritis of the knee.

PubMed

Alcidi, L; Beneforti, E; Maresca, M; Santosuosso, U; Zoppi, M

2007-01-01

To investigate the analgesic effect of low power radiofrequency electromagnetic radiation (RF) in osteoarthritis (OA) of the knee. In a randomized study on 40 patients the analgesic effect of RF was compared with the effect of transcutaneous electrical nerve stimulation (TENS). RF and TENS applications were repeated every day for a period of 5 days. The therapeutic effect was evaluated by a visual analogue scale (VAS) and by Lequesne's index: tests were performed before, immediately after and 30 days after therapy. RF therapy induced a statistically significant and long lasting decrease of VAS and of Lequesne's index; TENS induced a decrease of VAS and of Lequesne's index which was not statistically significant. A therapeutic effect of RF was therefore demonstrated on pain and disability due to knee OA. This effect was better than the effect of TENS, which is a largely used analgesic technique. Such a difference of the therapeutic effect may be due to the fact that TENS acts only on superficial tissues and nerve terminals, while RF acts increasing superficial and deep tissue temperature.

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1968-01-01

This report—the first of a series on codeine and its alternates for pain and cough relief—presents a detailed evaluation of experimental and clinical data concerning the analgesic action of codeine (the antitussive action will be assessed separately). The authors discuss the pharmacology of the drug, including side-effects and toxicity; effects on the respiratory, circulatory, digestive and urinary systems; tolerance, dependence and liability to abuse; metabolic effects; and mechanism of action. Though codeine is generally more toxic than morphine to animals on account of its convulsant action, it is less toxic to man, possibly because it produces less respiratory depression. Again, tolerance to its analgesic effects has been demonstrated in several animal species, but dependence in man is observed far less frequently than it is with morphine, and the abstinence syndrome is less intense. From their extensive review of the evidence available, the authors conclude that codeine is a good analgesic and that little risk to public health is likely to arise from its clinical use to relieve pain. PMID:4972938

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.

Prescribing pattern of analgesics in orthopedic in-patient department at tertiary care hospital in Guwahati, Assam, Northeast India

PubMed Central

Choudhury, Dwijen Kumar; Bezbaruah, Babul Kumar

2016-01-01

Objectives: The aim of this study is to evaluate the prescribing pattern of analgesics and analyze the rational use of analgesic in orthopedic in-patient department of tertiary care teaching hospital, Guwahati, Assam. Subjects and Methods: An observational and cross-sectional study was carried out for 1 month from April to May 2014. Collected data included age, sex, diagnosis and line of management during the study. The generic name and the average cost of treatment per patient were evaluated using Indian Drug Review, 2014. The prescribed drugs were assessed with respective National Model List of Essential Medicines (NLEM), 2011 and the rationality of prescriptions was determined using the World Health Organization indicators of drug utilization. The patients’ details were recorded in a predeigned data collection form and results were analyzed by descriptive statistics. Results: Out of 200 patients, 123 were male and 77 were female. The average number of analgesic per prescription was 1.46. In this study, 55.5% of patients had received single analgesic. Diclofenac was the most commonly prescribed analgesic (43.49%). During hospitalization, majority of the patients have received parenteral preparation. Gastroprotective agents and antimicrobials were frequently prescribed along with analgesics. Out of 292 analgesics prescribed, 183 (62.67%) were from the NLEM, India. Furthermore, 176 (57.19%) analgesics were prescribed by generic name. The average cost of treatment per patient was 2151.72 INR. Utilization of analgesic in terms of defined daily dose/100 bed-days was 104.01. Conclusion: The percentages of analgesics prescribing from NLEM and the use of analgesic by generic name were found satisfactory. Regular educational interventions to improve prescribing practices among physicians at different levels may further promote rational prescribing. PMID:27756947

Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract of Piper betle leaves.

PubMed

Alam, Badrul; Akter, Fahima; Parvin, Nahida; Sharmin Pia, Rashna; Akter, Sharmin; Chowdhury, Jesmin; Sifath-E-Jahan, Kazi; Haque, Ekramul

2013-01-01

The present study was designed to evaluate the antioxidant, analgesic, and anti-inflammatory activities of the methanolic extract of Piper betle leaves (MPBL). MPBL was evaluated for anti-inflammatory activity using carrageenan-induced hind paw edema model. Analgesic activity of MPBL was evaluated by hot plate, writhing, and formalin tests. Total phenolic and flavonoids content, total antioxidant activity, scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, peroxynitrate (ONOO) as well as inhibition of total ROS generation, and assessment of reducing power were used to evaluate antioxidant potential of MPBL. The extract of MPBL, at the dose of 100 and 200 mg/kg, produced a significant (p<0.05) increase in pain threshold in hot plate method whereas significantly (p<0.05) reduced the writhing caused by acetic acid and the number of licks induced by formalin in a dose-dependent manner. The same ranges of doses of MPBL caused significant (p<0.05) inhibition of carrageenan-induced paw edema after 4 h in a dose-dependent manner. In DPPH, ONOO(-), and total ROS scavenging method, MPBL showed good antioxidant potentiality with the IC50 value of 16.33±1.02, 25.16±0.61 , and 41.72±0.48 µg/ml, respectively with a significant (p<0.05) good reducing power. The findings of the study suggested that MPBL has strong analgesic, anti-inflammatory, and antioxidant effects, conforming the traditional use of this plant for inflammatory pain alleviation to its antioxidant potentiality.

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.

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

Anticholinesterase, antioxidant, analgesic and anti-inflammatory activity assessment of Xeranthemum annuum L. and isolation of two cyanogenic compounds.

PubMed

Orhan, Ilkay Erdogan; Gulyurdu, Fulya; Kupeli Akkol, Esra; Senol, Fatma Sezer; Arabaci Anul, Serap; Tatli, Iffet Irem

2016-11-01

Xeranthemum annuum L. (Asteraceae) (XA) is an ornamental and medicinal species with limited bioactivity and phytochemical data. Identification of anticholinesterase, antioxidant, anti-inflammatory and analgesic effects of the flower and root-stem (R-S) extracts of XA. Anticholinesterase (at 100 μg mL -1 ) and antioxidant (at 1000 μg mL -1 ) effects of various extracts were evaluated via microtiter assays, while anti-inflammatory and analgesic effects of the R-S extracts were tested using carrageenan-induced hind paw oedema (100 and 200 mg kg -1 ) and p-benzoquinone (PBQ) writhing models (200 mg kg -1 ) in male Swiss albino mice. The R-S ethanol extract of XA was subjected to isolation studies using conventional chromatographic methods. Most of the extracts showed inhibition over 85% against butyrylcholinesterase and no inhibition towards acetylcholinesterase. The flower chloroform and the R-S ethyl acetate extracts were most effective (97.85 ± 0.94% and 96.89 ± 1.09%, respectively). The R-S ethanol extract displayed a remarkable scavenging activity against DPPH (77.33 ± 1.99%) and in FRAP assay, while the hexane extract of the R-S parts possessed the highest metal-chelating capacity (72.79 ± 0.33%). The chloroform extract of the R-S caused a significant analgesic effect (24.4%) in PBQ writhing model. No anti-inflammatory effect was observed. Isolation of zierin and zierin xyloside, which were inactive in anticholinesterase assays, was achieved from the R-S ethanol extract. This is the first report of anticholinesterase, antioxidant, analgesic and anti-inflammatory activities and isolation of zierin and zierin xyloside from XA. Therefore, XA seems to contain antioxidant and BChE-inhibiting compounds.

Antipyretic and analgesic effects of zaltoprofen for the treatment of acute upper respiratory tract infection: verification of a noninferiority hypothesis using loxoprofen sodium.

PubMed

Azuma, Arata; Kudoh, Shoji; Nakashima, Mitsuyoshi; Nagatake, Tsuyoshi

2011-01-01

A multicenter, placebo-controlled, double-dummy, randomized, parallel-group, double-blind study was conducted to verify the hypothesis of noninferiority for single-dose administration of zaltoprofen 160 mg, a nonsteroidal anti-inflammatory drug, compared with loxoprofen sodium 60 mg (loxoprofen), in terms of antipyretic and analgesic effects in patients with acute upper respiratory tract infection. The eligible 330 patients were assigned to one of 3 groups: zaltoprofen 160 mg, loxoprofen 60 mg and placebo. The analysis set consisted of 322 patients. Antipyretic effects were assessed by measuring body temperature, and analgesic effects were evaluated using a visual analog scale (VAS) for 4 h under the control of study staff. A detection kit for influenza virus A and B antigens was used to determine the presence of influenza virus infection. Compared with immediately before administration and with the placebo group, significant decreases in body temperature and summary VAS pain scores were noted in both the zaltoprofen and loxoprofen groups at 4 h after drug administration. Based on the degree of decrease in body temperature and the summary VAS pain scores up to 4 h after administration, noninferiority in terms of antipyretic and analgesic effects of zaltoprofen compared with those of loxoprofen was confirmed after single administration. Similar antipyretic and analgesic effects were also confirmed in influenza virus antigen-positive patients (73 patients). No clinical concerns were identified regarding safety. Zaltoprofen and loxoprofen are confirmed to be safe and useful for patients with acute upper respiratory tract infection, including those with influenza infection. Copyright © 2011 S. Karger AG, Basel.

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

Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation.

PubMed

Nidhi, Malviya; Patro, M Nagaraju; Kusumvalli, Somisetty; Kusumdevi, Vemula

2016-01-01

Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion-evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box-Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN "S8" were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in C max and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized.

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.

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.

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.

Comparison of the analgesic effect of intravenous acetaminophen with that of flurbiprofen axetil on post-breast surgery pain: a randomized controlled trial.

PubMed

Nonaka, Takahiro; Hara, Marie; Miyamoto, Chisato; Sugita, Michiko; Yamamoto, Tatsuo

2016-06-01

Acetaminophen is known to be a relatively weak analgesic with fewer side effects than nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to determine whether intravenous (iv) acetaminophen produces comparable analgesic effects to those of flurbiprofen (positive control drug), an intravenously injectable NSAID, after partial mastectomies. The primary outcome assessed was pain intensity during the first 24 h after the operation, and the secondary outcome was the satisfaction rating at discharge. After obtaining Institutional Ethics Committee approval, a series of 40 consecutive female patients who were scheduled for partial mastectomies were enrolled. Participants were randomly divided into two groups: an acetaminophen (1000 mg × 3) group (group A) and a flurbiprofen (50 mg × 3) group (group F). Each drug was administered 15 min before the end of surgery, and at 6 and 12 h after the operation. Postoperative pain was evaluated using a 100-mm visual analog scale (VAS) at 3, 6, and 24 h postoperatively. Satisfaction rating was evaluated on a 5-point scale (very good, good, well, bad, and very bad). VAS scores (mm) with movement in groups A and F at 3, 6, and 24 h after the surgery were 22 vs. 28, 14 vs. 24, and 12 vs. 20.5 (median), respectively, with no significant differences between the two groups. Eighteen of 20 patients in group A and 20 of 20 patients in group F expressed a satisfaction rating of greater than good. Acetaminophen produces an equivalent analgesic effect to flurbiprofen in post-partial mastectomy patients.

Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen: novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance.

PubMed

Uzgören-Baran, Ayşe; Tel, Banu Cahide; Sarıgöl, Deniz; Oztürk, Elif İnci; Kazkayası, Inci; Okay, Gürol; Ertan, Mevlüt; Tozkoparan, Birsen

2012-11-01

In an effort to establish new candidates with improved analgesic and anti-inflammatory activities and lower ulcerogenic risk, a series of thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one derivatives of ibuprofen were synthesized. All compounds were evaluated for their in vivo anti-inflammatory and analgesic activities in mice. Furthermore, the ulcerogenic risks of the compounds were determined. In general, none of the compounds represent a risk for developing stomach injury as much as observed in the reference drugs ibuprofen and indomethacin. The compounds carrying a 3-phenyl-2-propenylidene (1a), (biphenyl-4-yl)methylidene (1f) and (1-methylpyrrol-2-yl)methylidene (1n) at the 6th position of the fused ring have been evaluated as potential analgesic/anti-inflammatory agents without a gastrointestinal side effect. These new compounds, therefore, deserve further attention to develop new lead drugs. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery

PubMed Central

Muraoka, Wataru; Nishizawa, Daisuke; Fukuda, Kenichi; Kasai, Shinya; Hasegawa, Junko; Wajima, Koichi; Nakagawa, Taneaki

2016-01-01

Background Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment. PMID:28256933

Anti-allergic rhinitis effect of caffeoylxanthiazonoside isolated from fruits of Xanthium strumarium L. in rodent animals.

PubMed

Peng, Wei; Ming, Qian-Liang; Han, Ping; Zhang, Qiao-Yan; Jiang, Yi-Ping; Zheng, Cheng-Jian; Han, Ting; Qin, Lu-Ping

2014-05-15

The fruits of Xanthium strumarium L. (Asteraceae) have been used extensively in China for treatment of various diseases such as allergic rhinitis (AR), tympanitis, urticaria and arthritis or ozena. This study was designed to systemically investigate the effects of the caffeoylxanthiazonoside (CXT) isolated from fruits of X. strumarium on AR in rodent animals. Animals were orally administered with CXT. Anti-allergic activity of CXT was evaluated by passive cutaneous anaphylaxis test (PCA); acetic acid-induced writhing tests were used to evaluate the analgesic effects of CXT; acetic acid-induced vascular permeability tests were performed to evaluate anti-inflammatory effect of CXT. Then, the model AR in rats was established to evaluate the effects of CXT on AR with the following tests: the sneezing and nasal scratching frequencies, IgE level in serum, and histopathological examinations. Our results demonstrated that CXT had favorable anti-allergic, anti-inflammatory and analgesic effects. Additionally, we found that CXT was helpful to ameliorate the nasal symptoms and to down-regulate IgE levels in AR rats. Thus, we suggested that CXT can be treated as a candidate for treating AR. Copyright © 2014 Elsevier GmbH. All rights reserved.

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.

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

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.

In vivo analgesic and anti-inflammatory activities of ursolic acid and oleanoic acid from Miconia albicans (Melastomataceae).

PubMed

Vasconcelos, Maria Anita L; Royo, Vanessa A; Ferreira, Daniele S; Crotti, Antonio E Miller; Andrade e Silva, Márcio L; Carvalho, José Carlos T; Bastos, Jairo Kenupp; Cunha, Wilson R

2006-01-01

The aim of this work was to use in vivo models to evaluate the analgesic and anti-inflammatory activities of ursolic acid (UA) and oleanoic acid (OA), the major compounds isolated as an isomeric mixture from the crude methylene chloride extract of Miconia albicans aerial parts in an attempt to clarify if these compounds are responsible for the analgesic properties displayed by this plant. Ursolic acid inhibited abdominal constriction in a dose-dependent manner, and the result obtained at a content of 40 mg kg(-1) was similar to that produced by administration of acetylsalicylic acid at a content of 100 mg kg(-1). Both acids reduced the number of paw licks in the second phase of the formalin test, and both of them displayed a significant anti-inflammatory effect at a content of 40 mg kg(-1). It is noteworthy that the administration of the isolated mixture, containing 65% ursolic acid/35% oleanolic acid, did not display significant analgesic and anti-inflammatory activities. On the basis of the obtained results, considering that the mixture of UA and OA was poorly active, it is suggested that other compounds, rather than UA and OA, should be responsible for the evaluated activities in the crude extract, since the crude extract samples displayed good activities.

Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic

PubMed Central

Devabhakthuni, Sandeep

2013-01-01

The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects. PMID:24665213

Qualitative phytochemical screening and evaluation of anti-inflammatory, analgesic and antipyretic activities of Microcos paniculata barks and fruits.

PubMed

Aziz, Md Abdullah

2015-05-01

The main objectives of this study were to qualitatively evaluate the profile of phytochemical constituents present in methanolic extract of Microcos paniculata bark (BME) and fruit (FME), as well as to evaluate their anti-inflammatory, analgesic and antipyretic activities. Phytochemical constituents of BME and FME were determined by different qualitative tests such as Molisch's test, Fehling's test, alkaloid test, frothing test, FeCl3 test, alkali test, Salkowski's test and Baljet test. The anti-inflammatory, analgesic and antipyretic activities of the extracts were evaluated through proteinase-inhibitory assay, xylene-induced ear edema test, cotton pellet-induced granuloma formation in mice, formalin test, acetic acid-induced writhing test, tail immersion test and Brewer's yeast-induced pyrexia in mice. M. paniculata extracts revealed the presence of carbohydrates, alkaloids, saponins, tannins, flavonoids and triterpenoids. All of the extracts showed significant (P<0.05, vs aspirin group) proteinase-inhibitory activity, whereas the highest effect elicited by plant extracts was exhibited by the BME (75.94% proteinase inhibition activity) with a half-maximal inhibitory concentration (IC50) of 61.31 μg/mL. Each extract at the doses of 200 and 400 mg/kg body weight showed significant (P<0.05, vs control) percentage inhibition of ear edema and granuloma formation. These extracts significantly (P<0.05, vs control) reduced the paw licking and abdominal writhing of mice. In addition, BME 400 mg/kg, and FME at 200 and 400 mg/kg showed significant (P<0.05, vs control) analgesic activities at 60 min in the tail immersion test. Again, the significant (P<0.05, vs control) post-treatment antipyretic activities were found by BME 200 and 400 mg/kg and FME 400 mg/kg respectively. Study results indicate that M. paniculata may provide a source of plant compounds with anti-inflammatory, analgesic and antipyretic activities.

Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract of Piper betle leaves

PubMed Central

Alam, Badrul; Akter, Fahima; Parvin, Nahida; Sharmin Pia, Rashna; Akter, Sharmin; Chowdhury, Jesmin; Sifath-E-Jahan, Kazi; Haque, Ekramul

2013-01-01

Objective: The present study was designed to evaluate the antioxidant, analgesic, and anti-inflammatory activities of the methanolic extract of Piper betle leaves (MPBL). Materials and Methods: MPBL was evaluated for anti-inflammatory activity using carrageenan-induced hind paw edema model. Analgesic activity of MPBL was evaluated by hot plate, writhing, and formalin tests. Total phenolic and flavonoids content, total antioxidant activity, scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, peroxynitrate (ONOO) as well as inhibition of total ROS generation, and assessment of reducing power were used to evaluate antioxidant potential of MPBL. Results: The extract of MPBL, at the dose of 100 and 200 mg/kg, produced a significant (p<0.05) increase in pain threshold in hot plate method whereas significantly (p<0.05) reduced the writhing caused by acetic acid and the number of licks induced by formalin in a dose-dependent manner. The same ranges of doses of MPBL caused significant (p<0.05) inhibition of carrageenan-induced paw edema after 4 h in a dose-dependent manner. In DPPH, ONOO-, and total ROS scavenging method, MPBL showed good antioxidant potentiality with the IC50 value of 16.33±1.02, 25.16±0.61 , and 41.72±0.48 µg/ml, respectively with a significant (p<0.05) good reducing power. Conclusion: The findings of the study suggested that MPBL has strong analgesic, anti-inflammatory, and antioxidant effects, conforming the traditional use of this plant for inflammatory pain alleviation to its antioxidant potentiality. PMID:25050265

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 Techniques in Hip and Knee Arthroplasty: From the Daily Practice to Evidence-Based Medicine

PubMed Central

Anastase, Denisa Madalina; Cionac Florescu, Simona; Munteanu, Ana Maria; Ursu, Traian; Stoica, Cristian Ioan

2014-01-01

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are major orthopedic surgery models, addressing mainly ageing populations with multiple comorbidities and treatments, ASA II–IV, which may complicate the perioperative period. Therefore effective management of postoperative pain should allow rapid mobilization of the patient with shortening of hospitalization and social reintegration. In our review we propose an evaluation of the main analgesics models used today in the postoperative period. Their comparative analysis shows the benefits and side effects of each of these methods and guides us to how to use evidence-based medicine in our daily practice. PMID:25484894

[The ECAD_O project: clinical caring epidemiology of pain in the hospital: the nurses' contribution].

PubMed

Sichetti, Daniela; Di Biagio, Katiuscia; Anino, Nadia; Buttà, Rosalia; Venturi, Cristina; Bandieri, Elena; Ripamonti, Carla; Tognoni, Gianni; Romero, Marilena

2009-01-01

ECAD_O is a project aimed to establish a surveillance of pain treatment--as part of routine care and as a hospital pharmacovigilance activity--with the following objectives: to assess in each participant ward prevalence of patients exposed to analgesics; to describe the pharmacological management schedules; to document the perception of health-care professionals on the effectiveness of treatment administered; to identify groups of patients whose pain is undertreated, through the activation of a collaborative protocol. A multicentre (48 hospitals) and multidisciplinary (nurses, clinicians, pharmacists) cross-sectional survey was conducted in 6 index-days. Epidemiological, clinical and therapeutic data were collected and heath-care professionals (nurses or clinicians) were asked about their perception on the effectiveness of treatment administered and the reasons of non-effectiveness. In the 164 participant wards (61 surgery, 46 medicine, 28 oncology, 22 orthopaedics, 7 other) 3854 patients (20.9% of inpatients) were exposed to analgesics. The majority of patients (84.3%) received analgesics around-the-clock. Opioid analgesics were administered around-the-clock (64.7%; 2103/3250) as well as only as needed (27.1%; 164/604). According to health-care professionals, analgesic therapy administered was not effective in 516 patients (13.4% of sample). Inspite of this evaluation, 288 patients did not receive rescue therapy, because it was not prescribed (180 patients) or not administered even if prescribed (108 patients). The establishment of a surveillance scheme which could be adopted in the routine conditions of care to monitor the quality of pain control has been successfully tested on the basis of multidisciplinary teams where the nurse personnel plays a key role.

Analgesic and anti-inflammatory activity of podophyllotoxin derivatives.

PubMed

Guerrero, Estela; Abad, Andrés; Montenegro, Gisela; Del Olmo, Esther; López-Pérez, José Luis; San Feliciano, Arturo

2013-05-01

Podophyllotoxin is a natural product that inhibits the polymerization of tubulin and has served as a prototype for the development of diverse antitumor agents in clinical use, such as etoposide, teniposide and etopophos. Reumacon, another semisynthetic derivative, reached its clinical phase for the treatment of rheumatoid arthritis. This study investigated the analgesic and anti-inflammatory properties of three compound derivatives from podophyllotoxin. During a phytochemical study performed on Juniperus thurifera Linne (Cupressaceae) leaves, among other products, several cyclolignans, such as podophyllotoxin, deoxypodophyllotoxin, deoxypicropodophyllotoxin and thuriferic acid were isolated. These compounds, obtained afterwards through semisynthesis, were assayed as analgesic and anti-inflammatory agents. Additionally, the cytotoxic activity of thuriferic acid was evaluated in three cancer cell lines, P-388, A-549 and HT-29, and these data were compared with previous cytotoxicity results obtained for the other three compounds. Analgesic activity results showed that deoxypicropodophyllin is as effective as deoxypodophyllotoxin to inhibit nociceptive perception induced by acetic acid in mice (77.8% ± 4.1% and 71.3% ± 6.5%, respectively), while its cytotoxicity [1.01 × 10(-7) (GI50 M)] is 100-fold less. Other set of experiments showed that thuriferic acid, a derivative of podophyllotoxin a thousand times less citotoxic [1.21 × 10(-5) (GI50 M)] than deoxypodophyllotoxin, caused significant inhibition of paw edema development in the carrageenan-induced inflammation test (63.4% ± 3.3%), effect comparable to those of deoxypodophyllotoxin (66.3% ± 4.4%), and the standard drug indomethacin (61.5% ± 2.5%). We conclude that deoxypicropodophyllotoxin and thuriferic acid are effective in reducing edema formation. However, deoxypicropodophyllin is more related with analgesic activity than anti-inflammatory effect.

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

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-01-01

Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. PMID:27286745

Subcutaneous infiltration of doxylamine on cutaneous analgesia in rats.

PubMed

Hung, Ching-Hsia; Shieh, Ja-Ping; Chiu, Chong-Chi; Wang, Jhi-Joung; Chen, Yu-Wen

2018-06-01

We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED 50 )), the relative potency was bupivacaine (0.41 (0.36-0.48) mmol)> doxylamine (7.39 (6.91-7.91)mmol) (p<0.01). On an equipotent basis (ED 25 , ED 50 and ED 75 ), subcutaneous doxylamine resulted in greater duration of action (p<0.01) than bupivacaine at producing cutaneous analgesia. The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Toxicity assessment and analgesic activity investigation of aqueous acetone extracts of Sida acuta Burn f . and Sida cordifolia L. (Malvaceae), medicinal plants of Burkina Faso

PubMed Central

2012-01-01

Background Sida acuta Burn f. and Sida cordifolia L. (Malvaceae) are traditionally used in Burkina Faso to treat several ailments, mainly pains, including abdominal infections and associated diseases. Despite the extensive use of these plants in traditional health care, literature provides little information regarding their toxicity and the pharmacology. This work was therefore designed to investigate the toxicological effects of aqueous acetone extracts of Sida acuta Burn f. and Sida cordifolia L. Furthermore, their analgesic capacity was assessed, in order to assess the efficiency of the traditional use of these two medicinal plants from Burkina Faso. Method For acute toxicity test, mice were injected different doses of each extract by intraperitoneal route and the LD50 values were determined. For the subchronic toxicity evaluation, Wistar albinos rats were treated by gavage during 28 days at different doses of aqueous acetone extracts and then haematological and biochemical parameters were determined. The analgesic effect was evaluated in mice by the acetic-acid writhing test and by the formalin test. Results For the acute toxicity test, the LD50 values of 3.2 g/kg and 3.4 g/kg respectively for S. acuta Burn f. and S. cordifolia L. were obtained. Concerning the haematological and biochemical parameters, data varied widely (increase or decrease) according to dose of extracts and weight of rats and did not show clinical correlations. The extracts have produced significant analgesic effects by the acetic acid writhing test and by the hot plate method (p <0.05) and a dose-dependent inhibition was observed. Conclusion The overall results of this study may justify the traditional uses of S. acuta and S. cordifolia . PMID:22883637

Toxicity assessment and analgesic activity investigation of aqueous acetone extracts of Sida acuta Burn f . and Sida cordifolia L. (Malvaceae), medicinal plants of Burkina Faso.

PubMed

Konaté, Kiessoun; Bassolé, Imaël Henri Nestor; Hilou, Adama; Aworet-Samseny, Raïssa R R; Souza, Alain; Barro, Nicolas; Dicko, Mamoudou H; Datté, Jacques Y; M'Batchi, Bertrand

2012-08-11

Sida acuta Burn f. and Sida cordifolia L. (Malvaceae) are traditionally used in Burkina Faso to treat several ailments, mainly pains, including abdominal infections and associated diseases. Despite the extensive use of these plants in traditional health care, literature provides little information regarding their toxicity and the pharmacology. This work was therefore designed to investigate the toxicological effects of aqueous acetone extracts of Sida acuta Burn f. and Sida cordifolia L. Furthermore, their analgesic capacity was assessed, in order to assess the efficiency of the traditional use of these two medicinal plants from Burkina Faso. For acute toxicity test, mice were injected different doses of each extract by intraperitoneal route and the LD50 values were determined. For the subchronic toxicity evaluation, Wistar albinos rats were treated by gavage during 28 days at different doses of aqueous acetone extracts and then haematological and biochemical parameters were determined. The analgesic effect was evaluated in mice by the acetic-acid writhing test and by the formalin test. For the acute toxicity test, the LD50 values of 3.2 g/kg and 3.4 g/kg respectively for S. acuta Burn f. and S. cordifolia L. were obtained. Concerning the haematological and biochemical parameters, data varied widely (increase or decrease) according to dose of extracts and weight of rats and did not show clinical correlations. The extracts have produced significant analgesic effects by the acetic acid writhing test and by the hot plate method (p <0.05) and a dose-dependent inhibition was observed. The overall results of this study may justify the traditional uses of S. acuta and S. cordifolia .

Analgesic and anti-inflammatory effects of UP1304, a botanical composite containing standardized extracts of Curcuma longa and Morus alba.

PubMed

Yimam, Mesfin; Lee, Young-Chul; Moore, Breanna; Jiao, Ping; Hong, Mei; Nam, Jeong-Bum; Kim, Mi-Ran; Hyun, Eu-Jin; Chu, Min; Brownell, Lidia; Jia, Qi

2016-01-01

Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma longa and the root bark of Morus alba, on rats with carrageenan-induced paw edema. A plant library was screened for bradykinin receptor antagonists. In vivo, the anti-inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation. Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. In vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 μg/mL for bradykinin B1 inhibition was calculated for the organic extract of C. longa. Curcumin showed Ki values of 2.73 and 58 μg/mL for bradykinin receptors B1 and B2, respectively. Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.

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

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

Is There a Role for Intravenous Subdissociative-Dose Ketamine Administered as an Adjunct to Opioids or as a Single Agent for Acute Pain Management in the Emergency Department?

PubMed

Motov, Sergey; Rosenbaum, Steven; Vilke, Gary M; Nakajima, Yuko

2016-12-01

Whether acute or chronic, emergency physicians frequently encounter patients reporting pain. It is the responsibility of the emergency physician to assess and evaluate, and if appropriate, safely and effectively reduce pain. Recently, analgesics other than opioids are being considered in an effort to provide safe alternatives for pain management in the emergency department (ED). Opioids have significant adverse effects such as respiratory depression, hypotension, and sedation, to say nothing of their potential for abuse. Although ketamine has long been used in the ED for procedural sedation and rapid sequence intubation, it is used infrequently for analgesia. Recent evidence suggests that ketamine use in subdissociative doses proves to be effective for pain control and serves as a feasible alternative to traditional opioids. This paper evaluates ketamine's analgesic effectiveness and safety in the ED. This is a literature review of randomized controlled trials, systematic reviews, meta-analyses, and observational studies evaluating ketamine for pain control in the ED setting. Based on these search parameters, eight studies were included in the final analysis and graded based on the American Academy of Emergency Medicine Clinical Practice Committee manuscript review process. A total of eight papers were reviewed in detail and graded. Recommendations were given based upon this review process. Subdissociative-dose ketamine (low-dose ketamine) is effective and safe to use alone or in combination with opioid analgesics for the treatment of acute pain in the ED. Its use is associated with higher rates of minor, but well-tolerated adverse side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

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.

Analgesic properties of the aqueous and ethanol extracts of the leaves of Kalanchoe crenata (Crassulaceae).

PubMed

Nguelefack, T B; Fotio, A L; Watcho, P; Wansi, S L; Dimo, T; Kamanyi, A

2004-05-01

The aqueous and ethanol extracts of the dry leaves of Kalanchoe crenata (300 and 600 mg/kg) were evaluated for their analgesic properties on the pain induced by acetic acid, formalin and heat in mice and by pressure on rats. The ethanol extract of K. crenata at a dose of 600 mg/kg produced an inhibition of 61.13% on pain induced by acetic acid and 50.13% for that induced by formalin. An inhibition of 67.18% was observed on pain induced by heat 45 min after the administration of the extract. The aqueous extract administered at a dose of 600 mg/kg produced a maximum effect of 25% on pain induced by pressure. These activities were similar to those produced by a paracetamol-codeine association, while indomethacin exhibited a protective effect only against the writhing test. Our results suggest that the leaves of K. crenata could be a source of analgesic compounds. Copyright 2004 John Wiley & Sons, Ltd.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

PubMed Central

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

2009-01-01

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

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.

Mumijo attenuates chemically induced inflammatory pain in mice.

PubMed

Malekzadeh, Golnaz; Dashti-Rahmatabadi, Mohammad Hossein; Zanbagh, Samira; Akhavi Mirab-bashii, Atefehsadat

2015-01-01

Mumijo (shilajit) has been well known in traditional medicine as a remedy for a number of diseases, such as bone fractures, wounds, inflammation, and headache. It is also widely used as an analgesic agent in folk medicine, but no scientific documentation exists concerning that effect. The current study was conducted to evaluate the ability of mumijo to reduce sensitivity to painful stimuli when compared with morphine sulfate and sodium diclofenac. A total of 176 animals were randomly and equally divided into 2 groups with 88 mice each-one for formalin test and the other for writhing test. For each test, the animals were allocated into 10 equal groups, based on the dosage of the analgesic, plus a negative control group, with 8 mice in each group. The analgesic effect of mumijo extract in doses of 0.75, 7.5, 75, and 750 mg/kg was assessed and compared witha group receiving distilled water-the negative control group, and that for groups receiving 1, 2, or 4 mg/kg of morphine sulfate or 10, 20, or 30 mg/kg of sodium diclofenac-the positive control groups. The results showed a significant decrease in pain intensity for all mice receiving doses of mumijo extract during a 1-h formalin test when compared with the distilled water group. For all the mumijo groups except the one receiving 750 mg/kg, the analgesic effect was significantly lower than that for the morphine sulfate group receiving 4 mg/kg. No significant differences existed between all mumijo and all diclofenac groups. In a writhing test, a significant inhibition of the pain response induced by acetic acid also occurred in all 4 mumijo-administered groups as opposed to the group receiving distilled water. No significant differences existed between the writhing response in groups receiving 75 and 750 mg/kg of mumijo and any doses of diclofenac or morphine. The comparison among the different doses of mumijo in the formalin test did not show any significant differences, but in the writhing test, the maximum dose showed a more effective analgesic action. The findings indicated a significant analgesic effect for mumijo extract on chronic pain in mice, occurring in a dose-independent manner.

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

Intravenous Lidocaine: Old-School Drug, New Purpose—Reduction of Intractable Pain in Patients with Chemotherapy Induced Peripheral Neuropathy

PubMed Central

van der Wal, Selina E. I.; Smedes, Lotte A.; Radema, Sandra A.; van Alfen, Nens; Steegers, Monique A. H.

2017-01-01

Background. Treatment of intractable pain due to chemotherapy induced peripheral neuropathy (CIPN) is a challenge. Intravenous (iv) lidocaine has shown to be a treatment option for neuropathic pain of different etiologies. Methods. Lidocaine (1.5 mg/kg in 10 minutes followed by 1.5 mg/kg/h over 5 hours) was administered in nine patients with CIPN, and analgesic effect was evaluated during infusion and after discharge. The immediate effect of lidocaine on pressure pain thresholds (PPT) and the extent of the stocking and glove distribution of sensory abnormalities (cold and pinprick) were assessed. Results. Lidocaine had a significant direct analgesic effect in 8 out of 9 patients (P = 0.01) with a pain intensity difference of >30%. Pain reduction persisted in 5 patients for an average of 23 days. Lidocaine did not influence mean PPT, but there was a tendency that the extent of sensory abnormalities decreased after lidocaine. Conclusion. Iv lidocaine has direct analgesic effect in CIPN with a moderate long-term effect and seems to influence the area of cold and pinprick perception. Additional research is needed, using a control group and larger sample sizes to confirm these results. PMID:28458593

14-Alkoxy- and 14-acyloxypyridomorphinans: μ agonist/δ antagonist opioid analgesics with diminished tolerance and dependence side effects.

PubMed

Ananthan, Subramaniam; Saini, Surendra K; Dersch, Christina M; Xu, Heng; McGlinchey, Nicholas; Giuvelis, Denise; Bilsky, Edward J; Rothman, Richard B

2012-10-11

In the search for opioid ligands with mixed functional activity, a series of 5'-(4-chlorophenyl)-4,5α-epoxypyridomorphinans possessing alkoxy or acyloxy groups at C-14 was synthesized and evaluated. In this series, the affinity and functional activity of the ligands were found to be influenced by the nature of the substituent at C-14 as well as by the substituent at N-17. Whereas the incorporation of a 3-phenylpropoxy group at C-14 on N-methylpyridomorhinan gave a dual MOR agonist/DOR agonist 17h, its incorporation on N-cyclopropylmethylpyridomorphinan gave a MOR agonist/DOR antagonist 17d. Interestingly, 17d, in contrast to 17h, did not produce tolerance or dependence effects upon prolonged treatment in cells expressing MOR and DOR. Moreover, 17d displayed greatly diminished analgesic tolerance as compared to morphine upon repeated administration, thus supporting the hypothesis that ligands with MOR agonist/DOR antagonist functional activity could emerge as novel analgesics devoid of tolerance, dependence, and related side effects.

Pharmacogenetics in obstetric anesthesia.

PubMed

Landau, Ruth; Kraft, John C

2010-06-01

Genomic research in pain, anesthesia and analgesia generated some hope that pharmacogenetics may guide anesthesiologists to provide effective medicine in a 'tailored' manner. Within the field of obstetric anesthesia, relatively few studies have evaluated the effect of polymorphisms on the perception of labor or postcesarean pain or the response to analgesics for childbirth. Because of the multifactorial nature of labor and delivery pain and particularly challenging clinical context, many consider that 'titration of drugs to the desired effect works just fine'. With recent evidence highlighting an association between severe postdelivery pain and persistent pain, early recognition of an increased susceptibility for acute pain has become particularly relevant. Neuraxial labor analgesia is influenced by a common polymorphism of the mu-opioid receptor gene. This polymorphism also affects the analgesic response to systemic opioids for postcesarean pain and other types of surgeries. Finally, the risk for persistent pain after cesarean deliveries may be associated with a certain genetic profile. Although still premature to anticipate clinical implications and a change in practice based on these recent discoveries, genetic variability clearly appears to affect pain perception, response to analgesics and predisposition for the development of chronic pain.

Wet cupping therapy improves local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis.

PubMed

Meng, Xiang-Wen; Wang, Ying; Piao, Sheng-Ai; Lv, Wen-Tao; Zhu, Cheng-Hui; Mu, Ming-Yuan; Li, Dan-Dan; Liu, Hua-Peng; Guo, Yi

2018-01-15

To observe wet cupping therapy (WCT) on local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS). Fifty-seven NT-CS patients were randomly divided into WCT group and Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group (30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated with acupuncture for 10 min. The treatment effificacies were evaluated with a Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB 21) acupoints (affected side) was observed with a laser speckle flflowmetry, and its variations before and after treatment in both groups were compared as well. In both groups, the VAS scores signifificantly decreased after the intervention (P<0.01), while the blood perfusion at the two acupoints signifificantly increased after intervention (P<0.05); however, the increasement magnitude caused by WCT was obvious compared with JA (P<0.05). WCT could improve analgesic effects in patients with NT-CS, which might be related to increasing local blood perfusion of acupunct points.

14-Alkoxy- and 14-Acyloxypyridomorphinans: Mu Agonist/Delta Antagonist Opioid Analgesics with Diminished Tolerance and Dependence Side Effects

PubMed Central

Ananthan, Subramaniam; Saini, Surendra K.; Dersch, Christina M.; Xu, Heng; McGlinchey, Nicholas; Giuvelis, Denise; Bilsky, Edward J.; Rothman, Richard B.

2012-01-01

In the search for opioid ligands with mixed functional activity, a series of 5′-(4-chlorophenyl)-4,5α-epoxypyridomorphinans possessing alkoxy or acyloxy groups at C-14 was synthesized and evaluated. In this series, the affinity and functional activity of the ligands were found to be influenced by the nature of the substituent at C-14 as well as by the substituent at N-17. Whereas the incorporation of a 3-phenylpropoxy group at C-14 on N-methylpyridomorhinan gave a dual MOR agonist/DOR agonist 17h its incorporation on N-cyclopropylmethylpyridomorphinan gave a MOR agonist/DOR antagonist 17d. Interestingly, 17d, in contrast to 17h, did not produce tolerance or dependence effects on prolonged treatment in cells expressing MOR and DOR. Moreover, 17d displayed greatly diminished analgesic tolerance as compared to morphine on repeated administration, thus supporting the hypothesis that ligands with MOR agonist/DOR antagonist functional activity could emerge as novel analgesics devoid of tolerance, dependence and related side effects. PMID:23016952

Fluorine bearing sydnones with styryl ketone group: synthesis and their possible analgesic and anti-inflammatory activities.

PubMed

Deshpande, Shreenivas Ramachandrarao; Pai, Karkala Vasantakumar

2012-04-01

In continuation of structure activity relationship studies, a panel of fluorine containing sydnones with styryl ketone group 4-[1-oxo-3-(substituted aryl)-2-propenyl]-3-(3-chloro-4-fluorophenyl)sydnones 2a-i, was synthesized as better analgesic and anti-inflammatory agents. The title compounds were formed by condensing 4-acetyl-3-(3-chloro-4-fluorophenyl)sydnone with various substituted aryl aldehydes, characterized by spectral studies and evaluated at 100 mg\\kg b.w., p.o. for analgesic, anti-inflammatory and ulcerogenic activities. Compounds 2c and 2e showed good analgesic effect in acetic acid-induced writhing while none showed significant activity in hot plate assay in mice. In carrageenan-induced rat paw oedema test, compound 2c and 2f exhibited good anti-inflammatory effect at 3rd h, whereas compounds 2c, 2e, 2d, 2g and 2h showed activity in croton oil induced ear oedema assay in mice. Compounds 2c and 2e were less ulcerogenic than ibuprofen in rats, when tested by ulcer index method. Compounds with electron attracting substituents such as 2c and 2e were found to be promising in terms of the ratio of efficacy and adverse effect. These compounds generally exhibited better activity than those of earlier series signifying fluorine substitution.

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

PubMed

Matsuura, Wataru; Harada, Shinichi; Tokuyama, Shogo

2016-01-01

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

α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2.

PubMed

Li, Xiao-Jun; Yang, Yan-Jing; Li, Yu-Sang; Zhang, Wei Kevin; Tang, He-Bin

2016-02-17

Frankincense oil and water extracts (FOE, FWE) have long been used for external treatment of inflammation and pain. The present study was conducted to identify the active ingredients responsible for the anti-inflammatory and analgesic effects and to determine the underlying mechanisms. The compositions of FOE and FWE were identified and compared by GC-MS. The anti-inflammatory and analgesic activities of the two extracts and their possible active ingredients (α-pinene, linalool, and 1-octanol) were evaluated and compared in a xylene-induced ear edema model and a formalin-inflamed hind paw model. Inflammatory infiltrates and cyclooxygenase-2 (COX-2) expression in hind paw skin were investigated by histological staining. The contents of α-pinene, linalool, and 1-octanol in FOE were much higher than those in FWE. Mice treated with FOE exhibited greater and faster lessening of swelling and pain than mice treated with FWE. The combination of the three components had more potent pharmacological effects on hind paw inflammation and COX-2 overexpression than the three components used alone. These findings suggest that topical application of FOE or its active ingredients (including α-pinene, linalool, and 1-octanol) exhibit significantly anti-inflammatory and analgesic effects through inhibiting nociceptive stimulus-induced inflammatory infiltrates and COX-2 overexpression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

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.

Assessment of the analgesic, anti-inflammatory and sedative effects of the dichloromethanol extract of Schinus molle.

PubMed

Taylor, A; Oyedeji, O O; Aremu, O; Oyemitan, I; Gwebu, E T; Oyedeji, A O; Nkeh-Chungag, B N

2016-01-01

Determination of the active fraction and compounds of the dichloromethanol extract of Schinus molle seeds and evaluation of their biological effects. Dried seeds of Schinus molle were sequentially extracted in hexane, acetyl acetate and dichloromethane. The dichloromethane extract was separated into two fractions (1 and 2) by column chromatography. Fraction 2 was further separated into its two constituent compounds which were characterized as belonging to the lanosteroid group of compounds. Both factions were tested for their analgesic, anti-inflammatory and sedative effects. The two fractions significantly increased (p<0.05) the tail flick latency though fraction 2 provided better and more long lasting protection against thermal pain. On the other hand, the anti-inflammatory effect of ibuprofen, though inferior to the anti-inflammatory effect of fraction 2 was better than the effects of fraction 1. Fraction 2 significantly (p<0.01) reduced rat paw oedema compared to the saline treatment group throughout the experiments while fraction 2 compared to fraction 1 showed significantly (p<0.01) greater inflammatory effects. On the other hand both fractions lacked significant sedative effects. Given that fraction 2 had only two constituent compounds (isomasticadienonic and Masticatrienonate), one or both of these compounds should be contributing to the observed analgesic and anti-inflammatory effects.

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.

[Evaluation of the effectiveness of patient-controlled analgesia in children with sickle cell anemia from the perspective of healthcare professionals and parents].

PubMed

Turaç, Ayşegül; Rumeli Atıcı, Şebnem

2016-07-01

This study evaluated the efficacy of patient-controlled analgesia (PCA) used by children with sickle cell anemia (SCA) based on the attitudes of parents and healthcare professionals. A total of 86 individuals were involved in the study: 54 parents of children with SCA who were receiving treatment and 32 healthcare providers (doctors, nurses). To evaluate the effectiveness of the PCA method, a questionnaire was prepared to determine the level of knowledge of the participants about the PCA method and their perception of its advantages and disadvantages. According to 65.6% (n=21) of the healthcare providers, PCA should be used during acute phase of pain. The great majority of the participants (93%; n=80) thought that pain was effectively controlled both during the day and at night. PCA reduced the fear of unavailability of analgesic drugs in 83.3% (n=45) of parents and in 87.5% (n=28) of healthcare providers. More parents (37%) reported a reduction in the fear of return of pain than healthcare providers (9.4%) (p<0.05). Most parents (87%; n=47) reported that they preferred to wait until their child complained of severe pain to use on-demand doses of analgesic due to concerns about overdose and addiction. Resolving machine alarms (48%; n=26) and the length of time required to refill the machine (48%; n=26) were reported as disadvantages of PCA method. In this study, parents and healthcare professionals found PCA to be effective in relieving pain in children with SCA; however, fears and biased knowledge of users about the analgesic drug are thought to inhibit reaching sufficient dosage. Educational courses for users about PCA and the drugs used may increase the effectiveness of PCA method.

Pregabalin role in inhibition of morphine analgesic tolerance and physical dependency in rats.

PubMed

Hasanein, Parisa; Shakeri, Saeed

2014-11-05

Pregabalin is recently proposed as analgesic or adjuvant in pain management. While previous preclinical investigations have evaluated pregabalin-opioid interactions, the effect of pregabalin on opioid tolerance and dependency has not yet been studied. Here we evaluated the effects of different doses of pregabalin (50, 100 and 200mg/kg, s.c.) on morphine-induced tolerance and dependency in rats. Adult male Wistar rats were rendered tolerant to analgesic effect of morphine by injection of morphine (10mg/kg, s.c.) twice daily for 7 days. To develop morphine dependence, rats were given escalating doses of morphine. To determine the effect of pregabalin on the development of morphine tolerance and dependence, different doses of pregabalin were administrated before morphine. The tail-flick and naloxone precipitation withdrawal tests were used to evaluate the degree of tolerance and dependence, respectively. Chronic morphine-injected rats showed significant decrements in the percentage maximum possible effect (%MPE) of morphine on the days 5 and 7 (32.5%±3.5, 21.5%±4, respectively) compared to the first day (100%) which showed morphine tolerance. Pregabalin 200mg/kg completely prevented the development of morphine tolerance. In addition, concomitant treatment of morphine with pregabalin attenuated almost all of the naloxone-induced withdrawal signs which include weight loss, jumping, penis licking, teeth chattering, wet dog shakes, rearing, standing, sniffing, face grooming and paw tremor. These data show that pregabaline has a potential anti-tolerant/anti-dependence property against chronic usage of morphine. Therefore, pregabalin appears to be a promising candidate for the treatment of opioid addiction after confirming by future clinical studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Dronabinol and chronic pain: importance of mechanistic considerations.

PubMed

de Vries, Marjan; van Rijckevorsel, Dagmar C M; Wilder-Smith, Oliver H G; van Goor, Harry

2014-08-01

Although medicinal cannabis has been used for many centuries, the therapeutic potential of delta-9-tetrahydrocannabinol (Δ9-THC; international non-proprietary name = dronabinol) in current pain management remains unclear. Several pharmaceutical products with defined natural or synthesized Δ9-THC content have been developed, resulting in increasing numbers of clinical trials investigating the analgesic efficacy of dronabinol in various pain conditions. Different underlying pain mechanisms, including sensitization of nociceptive sensory pathways and alterations in cognitive and autonomic processing, might explain the varying analgesic effects of dronabinol in chronic pain states. The pharmacokinetics, pharmacodynamics and mechanisms of action of products with a defined dronabinol content are summarized. Additionally, randomized clinical trials investigating the analgesic efficacy of pharmaceutical cannabis based products are reviewed for the treatment of chronic nonmalignant pain. We suggest a mechanism-based approach beyond measurement of subjective pain relief to evaluate the therapeutic potential of dronabinol in chronic pain management. Development of objective mechanistic diagnostic biomarkers reflecting altered sensory and cognitive processing in the brain is essential to evaluate dronabinol induced analgesia, and to permit identification of responders and/or non-responders to dronabinol treatment.

Emerging analgesic drugs for Parkinson's disease.

PubMed

Perez-Lloret, Santiago; Rey, María Verónica; Dellapina, Estelle; Pellaprat, Jean; Brefel-Courbon, Christine; Rascol, Olivier

2012-06-01

Pain affects between 40 and 85% of Parkinson's disease (PD) patients. It is a frequently disabling and overlooked feature, which can significantly reduce health-related quality of life. Unfortunately, there are no universally recommended treatments for this condition. Evidence about the efficacy and safety of available analgesic treatments is summarized in this review. Potential targets for upcoming therapies are then discussed in light of what is currently known about the physiopathology of pain in PD. Protocols for efficacy and safety assessment of novel analgesic therapies are discussed. Finally, critical aspects of study protocol design such as patient selection or outcomes to be evaluated are discussed. Preliminary results indicate that duloxetine, cranial electrotherapy stimulation, rotigotine, subthalamic or pallidum nuclei stimulation or lesion or levodopa could be effective for treating pain in PD. Similarly, some case reports indicate that repetitive transcranial magnetic stimulation (rTMS) or apomorphine could be effective for relieving painful off-period dystonia. Clinical trials with rTMS or oxycodone/naloxone prolonged-release tablets for neuropathic pain or botulinum toxin for off-period dystonia are underway. Success of clinical trials about analgesic strategies in PD will depend on the selection of the right PD population to be treated, according to the type of pain, and the proper selection of study outcomes and follow-up of international recommendations.

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.

Low-dose vaporized cannabis significantly improves neuropathic pain.

PubMed

Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Evaluation of thermal antinociceptive effects after intramuscular administration of hydromorphone hydrochloride to American kestrels (Falco sparverius)

USGS Publications Warehouse

Guzman, David Sanchez-Migallon; Drazenovich, Tracy L.; Olsen, Glenn H.; Willits, Neil H.; Paul-Murphy, Joanne R.

2013-01-01

Conclusions and Clinical Relevance—Hydromorphone at the doses evaluated significantly increased the thermal nociception threshold for American kestrels for 3 to 6 hours. Additional studies with other types of stimulation, formulations, dosages, routes of administration, and testing times are needed to fully evaluate the analgesic and adverse effects of hydromorphone in kestrels and other avian species and the use of hydromorphone in clinical settings.

VIPER: Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety

DTIC Science & Technology

2017-10-01

Through analysis of data obtained in the Molecular Signatures of Chronic Pain Subtypes study termed Veterans Integrated Pain Evaluation Research...immune cells (macrophages) to chronic pain while also evaluating novel analgesics in relevant animal models. The current proposal also attempts to...analysis of data obtained in the Molecular Signatures of Chronic Pain Subtypes study termed Veterans Integrated Pain Evaluation Research (VIPER

Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation

PubMed Central

Nidhi, Malviya; Patro, M Nagaraju; Kusumvalli, Somisetty; Kusumdevi, Vemula

2016-01-01

Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion–evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box–Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN “S8” were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in Cmax and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized. PMID:27382279

Effect of submucosal application of tramadol on postoperative pain after third molar surgery.

PubMed

Gönül, Onur; Satılmış, Tülin; Bayram, Ferit; Göçmen, Gökhan; Sipahi, Aysegül; Göker, Kamil

2015-10-14

The aim of this study was to evaluate the effectiveness of submucosal application of tramadol, for acute postoperative facial pain, following the extraction of impacted third molar teeth. This prospective, double-blind, randomised placebo-controlled study included 60 ASA I-II patients undergoing impacted third molar surgery under local anaesthesia. Following the surgical procedure, patients were randomly divided into two groups; group T (1 mg/kg tramadol) and group S (2-mL saline). Treatments were applied submucosally after surgery. Pain after extraction was evaluated using a visual analogue scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 h postoperatively. The time at which the first analgesic drug was taken, the total analgesic dose used, and adverse tissue reactions were also evaluated. In group T, postoperative VAS scores were significantly lower compared to that in group S (p < 0.05). This study demonstrated that post-operative submucosal application of tramadol is an effective method for reducing acute post-operative facial pain after impacted third molar surgery.

Comparison of four different pain relief methods during hysterosalpingography: A randomized controlled study

PubMed Central

Unlu, Bekir Serdar; Yilmazer, Mehmet; Koken, Gulengul; Arioz, Dagistan Tolga; Unlu, Ebru; Baki, Elif Dogan; Kurttay, Cemile; Karacin, Osman

2015-01-01

BACKGROUND: Hysterosalpingography (HSG) is the most commonly used method for evaluating the anatomy and patency of the uterine cavity and fallopian tubes, and is an important tool in the evaluation of infertility. The most frequent side effect is the pain associated with the procedure. OBJECTIVES: To evaluate four analgesic methods to determine the most useful method for reducing discomfort associated with HSG. METHODS: In the present prospective study, 75 patients undergoing HSG for evaluation of infertility were randomly assigned to four groups: 550 mg of a nonsteroidal anti-inflammatory drug (NSAID) (group 1); 550 mg NSAID + paracervical block (group 2); 550 mg NSAID + paracervical analgesic cream (group 3); or 550 mg NSAID + intrauterine analgesic instillation (group 4). A visual analogue scale was used to assess the pain perception at five predefined steps. RESULTS: Instillation of the liquids used for HSG was found to be the most painful step of HSG, and this step was where the only significant difference among groups was observed. When comparing visual analogue scale scores, group 2 and group 3 reported significantly less pain than the other groups. Group 1 reported significantly higher mean (± SD) scores (7.2±1.6) compared with groups 2 and 3 (4.7±2.5 and 3.8±2.4, respectively) (P<0.001). In addition, group 2 reported significantly less pain than group 4 (4.7±2.5 versus 6.7±1.8, respectively) (P<0.02). CONCLUSIONS: For effective pain relief during HSG, in addition to 550 mg NSAID, local application of lidocaine cream to the posterior fornix of the cervix uteri and paracervical lidocaine injection into the cervix uteri appear to be the most effective methods. PMID:25848848

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

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

Mediating Effect of Family Caregivers' Hesitancy to Use Analgesics on Homecare Cancer Patients' Analgesic Adherence.

PubMed

Lee, Bih-O; Liu, Yi; Wang, Yi-Hsien; Hsu, Hsin-Tien; Chen, Chien-Liang; Chou, Pi-Ling; Hsu, Wen-Chung

2015-12-01

Family caregivers play an increasingly critical role in cancer patients' symptom management as the number of cancer patients receiving home care grows. However, there is a lack of research measuring the impact of the family caregivers' hesitancy to use analgesics on analgesic adherence and the resulting influence on patient pain intensity. To examine whether family caregivers' hesitancy to use analgesics is a mediator that influences patient adherence and investigate how analgesic regimen adherence affects pain intensity. This study used a cross-sectional and descriptive design. One hundred seventy-six patient-family caregiver dyads (N = 352) were recruited from one local hospital in southern Taiwan. Instruments included the Short Version of the Barriers Questionnaire-Taiwan, the Morisky Medication Adherence Measure-Taiwan, the Brief Pain Inventory-Chinese, and demographic and illness questionnaires. A one-way analysis of variance and post hoc comparisons were performed to assess the influence of analgesic regimen adherence on pain intensity. Sobel tests were used to examine mediating effects. Family caregivers' hesitancy to use analgesics was a significant mediator between patient barriers to use analgesics and patient analgesic regimen adherence (P < 0.0001). Patients with low and moderate adherence levels reported significantly higher levels of pain severity (F = 3.83, P < 0.05). This study showed that family caregivers' hesitancy to use analgesics was a significant mediator associated with their hesitancy to use analgesics and the patients' analgesic adherence. It is important for health care providers to consider family caregivers' hesitancy to use analgesics when attempting to improve adherence to pain management regimens in clinical practice. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

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.

Anti-nociceptive properties in rodents and the possibility of using polyphenol-rich fractions from sida urens L. (Malvaceae) against of dental caries bacteria.

PubMed

Konaté, Kiessoun; Zerbo, Patrice; Ouédraogo, Maurice; Dibala, Crépin I; Adama, Hilou; Sytar, Oksana; Brestic, Marian; Barro, Nicolas

2013-06-21

Sida urens L. (Malvaceae) is in flora of Asian medicinal herbs and used traditionally in West of Burkina Faso for the treatment of infectious diseases and particularly used against, dental caries bacteria, fever, pain and possesses analgesic properties. This study was conducted to reveal the antibacterial effect against dental caries bacteria on the one hand, and evaluate their analgesic capacity in experimental model with Swiss mice and on the other hand, with an aim to provide a scientific basis for the traditional use of this plant for the management of dental caries bacteria. The antibacterial assays in this study were performed by using inhibition zone diameters, MIC (Minimum inhibitory concentration) and MBC (Minimal bactericidal concentration) methods. On the whole the dental caries bacteria (Gram-positive and Gram-negative bacterial strains) were used. Negative control was prepared using discs impregnated with 10% DMSO in water and commercially available Gentamicin from Alkom Laboratories LTD was used as positive reference standards for all bacterial strains. In acute toxicity test, mice received doses of extract (acetone/water extract) from Sida urens L. by intraperitoneal route and LD50 was determined in Swiss mice. As for analgesic effects, acetic acid writhing method was used in mice. The acetic acid-induced writhing method was used in mice with aim to study analgesic effects. The results showed that the highest antibacterial activities were founded with the polyphenol-rich fractions against all bacterial strains compared to the standard antibiotic. About preliminary study in acute toxicity test, LD50 value obtained was more than 5000 mg/kg b.w. Polyphenol-rich fractions produced significant analgesic effects in acetic acid-induced writhing method and in a dose-dependent inhibition was observed. These results validate the ethno-botanical use of Sida urens L. (Malvaceae) and demonstrate the potential of this herbaceous as a potential antibacterial agent of dental caries that could be effectively used for future health care purposes.

Mechanisms of Analgesic and Anti-Inflammatory Properties of Annona muricata Linn. (Annonaceae) Fruit Extract in Rodents

PubMed Central

Ishola, Ismail O.; Olusayero, Abayomi Micheal; Ochieng, Charles O.

2014-01-01

Abstract Unripe fruit of Annona muricata Linn. (Annonaceae) (soursop) is used in traditional African medicine for the treatment of neuralgia, rheumatism, and arthritic pain. This study sought to investigate the analgesic and anti-inflammatory effects of lyophilized fruit extract of Annona muricata (AM) in rodents. The analgesic activity was evaluated using the mouse writhing, formalin, and hot-plate tests while the anti-inflammatory action was investigated using the carrageenan-induced rat paw edema and xylene-induced ear edema tests. Pretreatment with AM (50, 100, and 200 mg/kg, p.o.) produced dose-dependent (P<.001) inhibition of writhes and formalin-induced pain in the late phase. AM and morphine produced time-course increase in pain threshold in hot-plate test. However, the analgesic effect elicited by AM was reversed (P<.05) by naloxone pretreatment. Similarly, the time-dependent increase in paw circumference induced by carrageenan was inhibited by AM treatment with peak effect (0.23±0.10 cm; P<.001, 200 mg/kg; 6 h), which was comparatively similar to that of diclofenac treated. Further, the xylene-induced ear edema was significantly reduced by AM (50 or 100 mg/kg) pretreatment; however, the anti-inflammatory effect elicited by AM was prevented by pretreatment of mice with NG-nitro-l-arginine (20 mg/kg, i.p., nitric-oxide synthase inhibitor) 15 min before AM (200 mg/kg, p.o.). The in vitro cyclooxygenase assay also showed that AM produced concentration-dependent inhibition of both cyclooxygenase (COX)-1 and COX-2 activity by 39.44%±0.05% and 55.71%±0.12%, respectively, at 100 μg/mL. In conclusion, A. muricata possesses analgesic effect through interaction with opioidergic pathway and anti-inflammatory property through inhibition of chemical mediators of inflammation. PMID:25133801

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

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.

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

Antioxidant, antinociceptive, and anti-inflammatory effects of carotenoids extracted from dried pepper (Capsicum annuum L.).

PubMed

Hernández-Ortega, Marcela; Ortiz-Moreno, Alicia; Hernández-Navarro, María Dolores; Chamorro-Cevallos, Germán; Dorantes-Alvarez, Lidia; Necoechea-Mondragón, Hugo

2012-01-01

Carotenoids extracted from dried peppers were evaluated for their antioxidant, analgesic, and anti-inflammatory activities. Peppers had a substantial carotenoid content: guajillo 3406 ± 4 μg/g, pasilla 2933 ± 1 μg/g, and ancho 1437 ± 6 μg/g of sample in dry weight basis. A complex mixture of carotenoids was discovered in each pepper extract. The TLC analysis revealed the presence of chlorophylls in the pigment extract from pasilla and ancho peppers. Guajillo pepper carotenoid extracts exhibited good antioxidant activity and had the best scavenging capacity for the DPPH(+) cation (24.2%). They also exhibited significant peripheral analgesic activity at 5, 20, and 80 mg/kg and induced central analgesia at 80 mg/kg. The results suggest that the carotenoids in dried guajillo peppers have significant analgesic and anti-inflammatory benefits and could be useful for pain and inflammation relief.

Antioxidant, Antinociceptive, and Anti-Inflammatory Effects of Carotenoids Extracted from Dried Pepper (Capsicum annuum L.)

PubMed Central

Hernández-Ortega, Marcela; Ortiz-Moreno, Alicia; Hernández-Navarro, María Dolores; Chamorro-Cevallos, Germán; Dorantes-Alvarez, Lidia; Necoechea-Mondragón, Hugo

2012-01-01

Carotenoids extracted from dried peppers were evaluated for their antioxidant, analgesic, and anti-inflammatory activities. Peppers had a substantial carotenoid content: guajillo 3406 ± 4 μg/g, pasilla 2933 ± 1 μg/g, and ancho 1437 ± 6 μg/g of sample in dry weight basis. A complex mixture of carotenoids was discovered in each pepper extract. The TLC analysis revealed the presence of chlorophylls in the pigment extract from pasilla and ancho peppers. Guajillo pepper carotenoid extracts exhibited good antioxidant activity and had the best scavenging capacity for the DPPH+ cation (24.2%). They also exhibited significant peripheral analgesic activity at 5, 20, and 80 mg/kg and induced central analgesia at 80 mg/kg. The results suggest that the carotenoids in dried guajillo peppers have significant analgesic and anti-inflammatory benefits and could be useful for pain and inflammation relief. PMID:23091348

The PECS II block as a major analgesic component for clavicle operations: A description of 7 case reports.

PubMed

Schuitemaker R, J B; Sala-Blanch, X; Rodriguez-Pérez, C L; Mayoral R, J T; López-Pantaleon, L A; Sánchez-Cohen, A P

2018-01-01

Clavicle fractures correspond to 35% of traumatic fractures of the shoulder girdle. Regional anaesthesia has shown better analgesic results than systemic treatment for perioperative management. Innervation of the clavicle is complex, at present its knowledge raises controversy. The lateral pectoral nerve through the innervating musculature predominantly participates in the lateral and anterior part of the clavicle. The following report of 7 cases describes the effective postoperative analgesia of modified PEC II block in patients with middle third clavicle fracture or acromioclavicular dislocation who underwent a modified PEC II block for postoperative pain management, in the context of a multimodal analgesia. The potential advantage of this management over other analgesic procedures should be evaluated in specific clinical trials. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

DNA binding, anti-inflammatory and analgesic evaluation of metal complexes of N/S/O donor ligands; Synthesis, spectral characterization

NASA Astrophysics Data System (ADS)

Kumar Naik, K. H.; Ashok, B.; Naik, Nagaraja; Mulla, Jameel Ahmed S.; Prakasha, Avinash

2015-04-01

Transition metal complexes containing tri-dentate NSN donor ligands i.e., 5-((1(aminomethyl)cyclohexyl)methyl)-1,3,4-thiadiazol-2-amine (AMTA) (2) and 5-(2-aminophenyl)-1,3,4-thiadiazol-2-amine (ATA) (4i-ii) have been synthesized. The newly synthesized ligands and their respective complexes were characterized by elemental analysis, molar conductance measurement and various spectral studies [infrared (IR), electronic, and NMR (for ligands only)]. Metal complexes are like [M(AMTA)2], [M(ATA)2] type, where M = Mn(II), Co(II) and Cu(II). The proposed geometries of the complexes are octahedral in nature. The synthesized ligands and their complexes were exhibits effective anti-inflammatory, analgesic and DNA binding activities. All the tested compounds exhibited significant analgesic activity, whereas the compound 4i, 4(ia) and 4(iib) is equipotent with Diclofenac sodium.

A novel ropivacaine-loaded in situ forming implant prolongs the effect of local analgesia in rats

PubMed Central

Lu, Lei; Zhang, Wei; Wu, Xin; Wang, Xiaoyu; Zhang, Min; Zhu, Quangang; Ding, Xueying; Xu, Zhiyun

2012-01-01

Introduction Prolonged postoperative analgesia cannot be achieved by a single injection of local anesthetic solution. The objective of this study was to optimize the formulation of a ropivacaine hydrochloride (Ropi-HCl) loaded in situ forming implant (ISI) by addition of different co-solvents, and evaluate the in vitro release of Ropi-HCl, and the analgesic effect and toxicity of the optimized formulation in rats. Material and methods Triacetin (TA), benzyl benzoate (BB) and polyethylene glycol 400 (PEG 400) were used as additives and added to the solvent of N-methyl-2-pyrrolidone (NMP). Drug release to the surface and inner structural properties of the formed implant were evaluated by scanning electron microscopy (SEM). The analgesic effect was determined by injection near the rat sciatic nerve. Results The solvent system added with TA or BB significantly decreased the burst release, whereas PEG 400 increased the Ropi-HCl burst release from the formulation. Over 70% of the incorporated Ropi-HCl was released from all formulations in 14 days in the in vitro assay. The SEM showed that the surface of NMP-BB formulation was less porous and more homogeneous, compared with the other formulations. Compared with Ropi-HCl injection, the optimized formulation (NMP-BB) significantly prolonged the analgesic effect in 48 h (p < 0.05), with a mild degree of motor block from 3 h to 12 h. Histological evaluation of the injection site revealed only mild inflammatory infiltration without obvious pathological nerve alterations. Conclusions The biodegradable Ropi-HCl-loaded ISI system with NMP-BB may prove to be an attractive and safe alternative for the delivery of parenteral local anesthetics to prolong pain relief. PMID:24049519

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

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.

Factors influencing the postoperative use of analgesics in dogs and cats by Canadian veterinarians.

PubMed

Dohoo, S E; Dohoo, I R

1996-09-01

Four hundred and seventeen Canadian veterinarians were surveyed to determine their postoperative use of analgesics in dogs and cats following 6 categories of surgeries, and their opinion toward pain perception and perceived complications associated with the postoperative use of potent opioid analgesics. Three hundred and seventeen (76%) returned the questionnaire. An analgesic user was defined as a veterinarian who administers analgesics to at least 50% of dogs or 50% of cats following abdominal surgery, excluding ovariohysterectomy. The veterinarians responding exhibited a bimodal distribution of analgesic use, with 49.5% being defined as analgesic users. These veterinarians tended to use analgesics in 100% of animals following abdominal surgery. Veterinarians defined as analgesic nonusers rarely used postoperative analgesics following any abdominal surgery. Pain perception was defined as the average of pain rankings (on a scale of 1 to 10) following abdominal surgery, or the value for dogs or cats if the veterinarian worked with only 1 of the 2 species. Maximum concern about the risks associated with the postoperative use of potent opioid agonists was defined as the highest ranking assigned to any of the 7 risks evaluated in either dogs or cats. Logistic regression analysis identified the pain perception score and the maximum concern regarding the use of potent opioid agonists in the postoperative period as the 2 factors that distinguished analgesic users from analgesic nonusers. This model correctly classified 68% of veterinarians as analgesic users or nonusers. Linear regression analysis identified gender and the presence of an animal health technologist in the practice as the 2 factors that influenced pain perception by veterinarians. Linear regression analysis identified working with an animal health technologist, graduation within the past 10 years, and attendance at continuing education as factors that influenced maximum concern about the postoperative use of opioid agonists.

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

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.

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

Analgesic effect of the neuropeptide cortistatin in murine models of arthritic inflammatory pain.

PubMed

Morell, Maria; Souza-Moreira, Luciana; Caro, Marta; O'Valle, Francisco; Forte-Lago, Irene; de Lecea, Luis; Gonzalez-Rey, Elena; Delgado, Mario

2013-05-01

To investigate the role of the antiinflammatory neuropeptide cortistatin in chronic pain evoked by joint inflammation. Thermal and mechanical hyperalgesia was evoked in mouse knee joints by intraplantar injection of tumor necrosis factor α and intraarticular infusion of Freund's complete adjuvant, and the analgesic effects of cortistatin, administered centrally, peripherally, and systemically, were assessed. In addition, the effects of cortistatin on the production of nociceptive peptides and the activation of pain signaling were assayed in dorsal root ganglion cultures and in inflammatory pain models. The role of endogenous cortistatin in pain sensitization and perpetuation of chronic inflammatory states was evaluated in cortistatin-deficient mice. Finally, the effect of noxious/inflammatory stimuli in the production of cortistatin by the peripheral nociceptive system was assayed in vitro and in vivo. Expression of cortistatin was observed in peptidergic nociceptors of the peripheral nociceptive system, and endogenous cortistatin was found to participate in the tuning of pain sensitization, especially in pathologic inflammatory conditions. Results showed that cortistatin acted both peripherally and centrally to reduce the tactile allodynia and heat hyperalgesia evoked by arthritis and peripheral tissue inflammation in mice, via mechanisms that were independent of its antiinflammatory action. These mechanisms involved direct action on nociceptive neurons and regulation of central sensitization. The analgesic effects of cortistatin in murine arthritic pain were linked to binding of the neuropeptide to somatostatin and ghrelin receptors, activation of the G protein subunit Gαi , impairment of ERK signaling, and decreased production of calcitonin gene-related peptide in primary nociceptors. These findings indicate that cortistatin is an antiinflammatory factor with potent analgesic effects that may offer a new approach to pain therapy in pathologic inflammatory states, including osteoarthritis and rheumatoid arthritis. Copyright © 2013 by the American College of Rheumatology.

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.

An Integrative Review of Interventions to Support Parents When Managing Their Child's Pain at Home.

PubMed

Parker, Roses; McKeever, Stephen; Wiseman, Theresa; Twycross, Alison

2018-04-01

To identify interventions aimed at helping parents manage their child's pain at home and to establish which aspects of interventions were effective. Integrative narrative review. MEDLINE, CINAHL Plus, PsychINFO, PsychArticles, AMED, PubMed, Scopus and Web of Knowledge databases were searched in 2016. This narrative synthesis followed Centre for Reviews and Dissemination and Economic and Social Research Council guidance. Reasons attributed to intervention success were analyzed using content analysis. From 2,534 papers, 17 were included. A majority were randomized controlled trials (n = 13) and most addressed postoperative pain (n = 15). A range of interventions were found that directly targeted parents, including child-parent interactions and health care professional-parent interactions, as well as complex interventions. Three studies were successful in reducing child pain at home and seven in increasing appropriate analgesic drug administration. Analysis of reasons attributed to interventions success revealed characteristics of interventions, components of parental pain management, and key features of research that aid researchers in designing and evaluating interventions. Risk of bias was present because of inadequate randomization, lack of a control group, and underpowered studies. Nurses should be aware that targeting parents directly is the most effective way of reducing child pain at home. Nurses need to advocate for effective analgesics for their child patients because the ineffectiveness of many interventions was attributed to inadequate analgesic drugs. Once this is achieved, success in increasing analgesic drug administration is most likely reached via parent-targeted interventions and those targeting health care professional-parent interactions. Successful interventions will be tailored to the child and adequately powered. Including a measure of sedation will ensure sedation is not mistaken for analgesic effectiveness. Interventions should address multiple facets of pain management and include a measure of pain over a period as opposed to a snapshot in time. Copyright © 2017 American Society for Pain Management Nursing. 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®.

Opening of brain blood barrier induced by red light and central analgesic improvement of cobra neurotoxin.

PubMed

Ye, Yong; Li, Yue; Fang, Fei

2014-05-05

Cobra neurotoxin (NT) has central analgesic effects, but it is difficult to pass through brain blood barrier (BBB). A novel method of red light induction is designed to help NT across BBB, which is based on photosensitizer activation by red light to generate reactive oxygen species (ROS) to open BBB. The effects were evaluated on cell models and animals in vivo with illumination by semiconductor laser at 670nm on photosensitizer pheophorbide isolated from silkworm excrement. Brain microvascular endothelial cells and astrocytes were co-cultured to build up BBB cell model. The radioactivity of (125)I-NT was measured in cells and tissues for NT permeation. Three ways of cranial irradiation, nasal cavity and intravascular irradiation were tested with combined injection of (125)I-NT 20μg/kg and pheophorbide 100μg/kg to rats, and organs of rats were separated and determined the radioactivity. Paw pressure test in rats, hot plate and writhing test in mice were applied to appraise the analgesic effects. NT across BBB cell model increased with time of illumination, and reached stable level after 60min. So did ROS in cells. NT mainly distributed in liver and kidney of rats, significantly increased in brain after illumination, and improved analgesic effects. Excitation of pheophorbide at red light produces ROS to open BBB, help NT enter brain, and enhance its central action. This research provides a new method for drug across BBB to improve its central role. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

"Protective premedication": a comparative study of acetaminophen, gabapentin and combination of acetaminophen with gabapentin for post-operative analgesia.

PubMed

Syal, Kartik; Goma, Mandeep; Dogra, Ravi K; Ohri, Anil; Gupta, Ashok K; Goel, Ashok

2010-10-01

We carried out a study to evaluate the effects of protective premedication with Acetaminophen, Gabapentin and combination of Acetaminophen with Gabapentin on post-operative analgesia in patients undergoing open cholecys-tectomy under general anesthesia. PATIENTS #ENTITYSTARTX00026; The study was conducted in a double-blind randomized and controlled manner in 120 consenting patients of either sex belonging to ASA physical status grade I and II, between the age groups of 20 to 50 years, weighing between 40 to 65 kg and undergoing elective surgery (open cholecystectomy) under general anesthesia. The patients were divided into 4 groups: 1: placebo, 2: Acetaminophen 1000 mg, 3: 1200 mg Gabapentin, 4: Acetaminphen 1000 mg plus 1200 mg Gabapentin. The drugs were given two hours before induction. Time, number and total amount of rescue analgesic (tramadol) and VAS score at rest and on movement. Side effects like any episode of nausea/vomiting and level of sedation were noted. Premedication with antihyperalgesic and analgesic agents helps to decrease postoperative pain scores. Gabapentin premedication is effective for providing better postoperative pain relief with lower and delayed requirements of rescue analgesics, but causes more episodes of nausea and vomiting and higher levels of sedation.

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.

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

Regular intake of non-opioid analgesics is associated with an increased risk of restless legs syndrome in patients maintained on antidepressants.

PubMed

Leutgeb, U; Martus, P

2002-08-30

To evaluate prevalence and risk factors of restless legs syndrome (RLS) in secondary-care patients maintained on tricyclic and serotonin reuptake inhibiting antidepressants. A total of 243 subjects with affective and anxiety disorders were interviewed for symptoms of RLS before and after at least 6 months of antidepressant pharmacotherapy within a naturalistic study. Logistic regression analysis was applied to adjust for the effects of age, gender, comorbidities, and the most frequent co-medications. The overall prevalence of RLS was 27%. In the RLS-affected patients, regular use or overuse of non-opioid analgesics frequently combined with caffeine was the major risk factor which significantly correlated with psychiatric and medical comorbidity. In a subsample of 172 patients who had seldom taken analgesics the prevalence of RLS was 9%, which corresponds with its prevalence in the general population. Neither antidepressants nor neuroleptics but non-opioid analgesics appear to be a major risk factor of RLS. Their regular use should be considered in studies of RLS-patients on psychotropic or other drugs. In this sample of secondary-care patients, ICD-10 classified depression or anxiety per se did not appear to be a risk factor of RLS.

Study of pharmacological activities of methanol extract of Jatropha gossypifolia fruits

PubMed Central

Apu, Apurba Sarker; Hossain, Faruq; Rizwan, Farhana; Bhuyan, Shakhawat Hossan; Matin, Maima; Jamaluddin, A.T.M

2012-01-01

Objective: 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. Materials and Methods: 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. Findings: 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. Conclusion: 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. PMID:24808665

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.

Analgesic effects of tramadol, carprofen or multimodal analgesia in rats undergoing ventral laparotomy.

PubMed

Zegre Cannon, Coralie; Kissling, Grace E; Goulding, David R; King-Herbert, Angela P; Blankenship-Paris, Terry

2011-03-01

In this study, the authors evaluated the analgesic efficacy of tramadol (an opioid-like analgesic), carprofen (a nonsteroidal anti-inflammatory drug) and a combination of both drugs (multimodal therapy) in a rat laparotomy model. The authors randomly assigned rats to undergo either surgery (abdominal laparotomy with visceral manipulation and anesthesia) or anesthesia only. Rats in each group were treated with tramadol (12.5 mg per kg body weight), carprofen (5 mg per kg body weight), a combination of tramadol and carprofen (12.5 mg per kg body weight and 5 mg per kg body weight, respectively) or saline (anesthesia control group only; 5 mg per kg body weight). The authors administered analgesia 10 min before anesthesia, 4 h after surgery or (for the rats that received anesthesia only) anesthesia and 24 h after surgery or anesthesia. They measured locomotor activity, running wheel activity, feed and water consumption, body weight and fecal corticosterone concentration of each animal before and after surgery. Clinical observations were made after surgery or anesthesia to evaluate signs of pain and distress. The authors found that carprofen, tramadol and a combination of carprofen and tramadol were all acceptable analgesia regimens for a rat laparotomy model.

Anti-nociceptive efficacy of carprofen, levomethadone and buprenorphine for pain relief in cats following major orthopaedic surgery.

PubMed

Möllenhoff, A; Nolte, I; Kramer, S

2005-05-01

A placebo-controlled, randomized blind study was conducted in cats (n = 60) after fracture repair to compare the analgesic effects as well as the side-effects of carprofen, buprenorphine and levomethadone during a 5-day treatment. Cats with severe shock symptoms or increases in blood urea nitrogen (BUN) and creatinine were excluded from the study. The cats were randomly assigned to four groups (n= 15). In group 1, carprofen was administered upon extubation at an initial dose of 4 mg/kg body weight, followed by one-third of that dose three times daily on days 2 to 5. In group 2, buprenorphine was administered in a single dose of 0.01 mg/kg body weight upon extubation and subsequently every 8 h. Levomethadone (group 3) was applied according to the same scheme at a dosage of 0.3 mg/kg body weight each time. The placebo (group 4) was given at the same time intervals as the opioids. Examinations were carried out prior to anaesthesia, between 30 min and 8 h after extubation, and on the following 4 days, 1 h after administration of the analgesics or the placebo as well as 1 h before the next administration. Pain and sedation evaluation was carried out with a visual analogue system (VAS) and with the aid of a numerical estimation scale (NRS). Pain was also scored by measuring mechanical nociceptive threshold of traumatized tissue. Plasma glucose and cortisol concentration, heart rate, respiration rate, blood pressure and body temperature were measured. Furthermore, a complete blood count and clinical chemistry including BUN, creatinine, alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), arterial blood pressure (AP), total protein and electrolytes of the cats were checked on the day of admission as well as on the last day of this study (day 5). Defaecation and urination as well as wound healing were monitored. On the basis of the mechanical nociceptive threshold of the traumatized tissue, concentrations of plasma glucose and cortisol and pain assessment using NRS and VAS, carprofen was found to have better anti-nociceptive efficacy when compared with the two opioid analgesics, while the analgesic effect of levomethadone was similar to that of buprenorphine. However, the carprofen group also showed comparably high median NRS and VAS pain scores in addition to occasional broad deviations from the group mean on the first post-operative treatment day. Sedative effects were detected for buprenorphine and levomethadone; in addition, symptoms of central excitation were noted with levomethadone. There was no indication of any clinically relevant respiratory depressive or cardiovascular effects, nor of any undesired renal, gastrointestinal or hepatic effects of the analgesics applied. However, the somewhat insensitive examination methods did not permit sufficient evaluation of side-effects, particularly on the gastrointestinal tract and the kidneys. It was found that carprofen and buprenorphine were well-tolerated analgesics for a 5-day administration in the cat, whereas levomethadone caused central excitation in some cases in the dosage scheme used here. However, it was apparent that none of the tested analgesics induced sufficient analgesia in the post-operative phase. For this reason, suitable methods must be found to improve analgesia, particularly in the immediate post-operative phase.

Effects of over-the-counter sales restriction of antibiotics on substitution with medicines for symptoms relief of cold in Mexico and Brazil: time series analysis.

PubMed

Santa-Ana-Tellez, Yared; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Wirtz, Veronika J

2016-11-01

We evaluated changes in the use of non-steroidal anti-inflammatory drugs (NSAIDs), non-opioid analgesics and cough and cold medicines and its relation with the use of antibiotics after the over-the-counter (OTC) antibiotic sales restrictions in Mexico and Brazil. IMS Health provided retail quarterly data from the private sectors in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. Data of each active substance of antibiotics, easily accessible medicines perceived as antibiotics substitutes (cough and cold medicines, analgesics and NSAIDs-the latter two being combined in the analyses), and medicines to control for external factors that can affect the medicines usage trend (antihypertensives) were converted from kilograms to defined daily doses per 1000 inhabitants days (DDD/TID). Interrupted time series were used to estimate changes in level of medicines use at the intervention point and slope after the regulation. The Gregory-Hansen cointegration test was used to explore the relation between the use of antibiotics and perceived substitutes. After the regulation in Mexico NSAIDs-analgesics usage level increased by 1.1 DDD/TID with a slope increase of 0.2 DDD/TID per quarter and the cough and cold medicines usage level increased by 0.4 DDD/TID. In Brazil NSAIDs-analgesics usage level increased by 1.9 DDD/TID, and cough and cold medicines did not change. In the two countries, NSAIDs-analgesics usage changes were related with antibiotic usage changes; in Mexico cough and cold medicines usage changes had a relation with the antibiotics usage changes. These results showed a substitution effect on the use of other medicines, especially NSAIDs and analgesics, after reinforcement of OTC antibiotics sales restrictions. These regulations aimed to improve the antibiotics use and as a consequence reduce antimicrobial resistance; however, this type of policies should be comprehensive and take into account the potential substitution effects on the use of other medicines. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Analgesic effect and clinical tolerability of the combination of paracetamol 500 mg and caffeine 50 mg versus paracetamol 400 mg and dextropropoxyphene 30 mg in back pain].

PubMed

Kuntz, D; Brossel, R

1996-09-07

A double-blind randomized multicentric study was performed to test the hypothesis that the analgesic effect of paracetamol-cafeine is equivalent to that of paracetamol-dextropropoxyphen in patients suffering from pain due to osteoarthritis of the spine. Rhumatologists included 124 patients who were randomized into two groups of 62 each. Pain was measured daily during the seven-day treatment Huskisson's Analog Visual Scales; 112 were per protocol and evaluable. The two treatment groups were statistically similar for demographics, vital signs, medical and treatment history. A majority of them had pain located at the lumbar spine only; the other patients had either pain at the cervical or dorsal spine or at several sites. At the end of the week there was a major reduction in pain level: 51.2% in patients given paracetamol-cafeine and 47.0% in those given paracetamol-dextropropoxyphen. The main criteria of efficacy--the percentage of success (decrease of pain > 50%)--was similar in the two groups as well in the intention-to-treat population (p = 0.01) as the per protocol population (p = 0.028). Kinetics of pain decrease during the first day of treatment were assessed with an hourly evaluation during the six first hours and at the 12th hour. There was no difference between the two groups. There was no serious adverse event and the frequency and intensity of the adverse events were similar in the two groups. The potentializing action of cafeine on paracetamol-induced pain relief enables a degree of pain relief equivalent to that of a combination using an analgesic with a peripheral action, paracetamol, and another with a central action, dextropoxyphen. The fact that the paracetamol-cafeine combination does not have a central action avoids secondary effects induced by central analgesics (drowsiness, constipation) in patients with osteoarthritis back pain.

Comparison of perioperative analgesic efficacy between methadone and butorphanol in cats.

PubMed

Warne, Leon N; Beths, Thierry; Holm, Merete; Bauquier, Sébastien H

2013-09-15

To compare the perioperative analgesic effect between methadone and butorphanol in cats. Randomized controlled clinical trial. 22 healthy female domestic cats. Cats admitted for ovariohysterectomy were allocated to a butorphanol group (n = 10) or methadone group (12) and premedicated with butorphanol (0.4 mg/kg [0.18 mg/lb], SC) or methadone (0.6 mg/kg [0.27 mg/lb], SC), respectively, in combination with acepromazine (0.02 mg/kg [0.01 mg/lb], SC). Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. A multidimensional composite scale was used to conduct pain assessments prior to premedication and 5, 20, 60, 120, 180, 240, 300, and 360 minutes after extubation or until rescue analgesia was given. Groups were compared to evaluate isoflurane requirement, propofol requirement, pain scores, and requirement for rescue analgesia. Propofol and isoflurane requirements and preoperative pain scores were not different between groups. During recovery, dysphoria prevented pain evaluation at 5 minutes. Pain scores at 20 minutes were significantly lower in the methadone group, and 6 of 10 cats in the butorphanol group received rescue analgesia, making subsequent pain score comparisons inapplicable. After 6 hours, only 3 of 12 cats in the methadone group had received rescue analgesia. In the present study, methadone appeared to be a better postoperative analgesic than butorphanol and provided effective analgesia for 6 hours following ovariohysterectomy in most cats.

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.

Do analgesics improve functioning in patients with chronic low back pain? An explorative triple-blinded RCT.

PubMed

Schiphorst Preuper, Henrica R; Geertzen, Jan H B; van Wijhe, Marten; Boonstra, Anne M; Molmans, Barbara H W; Dijkstra, Pieter U; Reneman, Michiel F

2014-04-01

TREATMENT of patients with chronic low back pain (CLBP) aims to reduce disability, improve functional capacity, and participation. Time contingent prescription of analgesics is a treatment modality in CLBP. The impact of analgesics on functional capacity is unknown. Aim of the study was to explore the effect of analgesics on functioning measured by functional capacity evaluation, and self-reported disability in patients with CLBP. Explorative Randomized Placebo-Controlled Clinical Trial was performed in an outpatient pain rehabilitation setting on patients waiting for rehabilitation. Included patients had low back pain lasting >3 months, visual analogue scale worst pain ≥4.0 cm, and age >18 years. Outcome measures before (T0) and after treatment (T1): functional capacity, pain intensity, Roland Morris Disability Questionnaire. T1: global perceived pain relief. Patient characteristics and psychological questionnaires were assessed. Fifty patients were included in this study and were randomly assigned to 2 weeks treatment or placebo. acetaminophen/tramadol 325 mg/37.5 mg per capsule. Dose: maximum acetaminophen 1,950 mg and tramadol 225 mg per day; treatment and placebo titrated identically. Compliance and side-effects were monitored. TREATMENT effects between groups over time were compared. One patient (treatment group) was lost to follow-up. Forty-nine patients remained in the study. TREATMENT effects in primary outcomes did not differ significantly between groups. A subgroup of 10 (42%) patients (treatment group) reported global pain relief (responders) who reduced self-reported disability (p < 0.05). Responders had significantly lower catastrophizing scores. Overall treatment effects were small and non-significant. A subgroup, however, reported improved functioning as a result of treatment. Responders had lower catastrophizing scores.

Suprascapular and Interscalene Nerve Block for Shoulder Surgery: A Systematic Review and Meta-analysis.

PubMed

Hussain, Nasir; Goldar, Ghazaleh; Ragina, Neli; Banfield, Laura; Laffey, John G; Abdallah, Faraj W

2017-12-01

Interscalene block provides optimal shoulder surgery analgesia, but concerns over its associated risks have prompted the search for alternatives. Suprascapular block was recently proposed as an interscalene block alternative, but evidence of its comparative analgesic effect is conflicting. This meta-analysis compares the analgesic effect and safety of suprascapular block versus interscalene block for shoulder surgery. Databases were searched for randomized trials comparing interscalene block with suprascapular block for shoulder surgery. Postoperative 24-h cumulative oral morphine consumption and the difference in the area under curve for pooled rest pain scores were designated as primary outcomes. Analgesic and safety outcomes, particularly block-related and respiratory complications, were evaluated as secondary outcomes. Results were pooled using random-effects modeling. Data from 16 studies (1,152 patients) were analyzed. Interscalene block and suprascapular block were not different in 24-h morphine consumption. The difference in area under the curve of pain scores for the 24-h interval favored interscalene block by 1.1 cm/h, but this difference was not clinically important. Compared with suprascapular block, interscalene block reduced postoperative pain but not opioid consumption during recovery room stay by a weighted mean difference (95% CI) of 1.5 cm (0.6 to 2.5 cm; P < 0.0001). Pain scores were not different at any other time. In contrast, suprascapular block reduced the odds of block-related and respiratory complications. This review suggests that there are no clinically meaningful analgesic differences between suprascapular block and interscalene block except for interscalene block providing better pain control during recovery room stay; however, suprascapular block has fewer side effects. These findings suggest that suprascapular block may be considered an effective and safe interscalene block alternative for shoulder surgery.

[Conservative treatment of nonspecific, chronic low back pain : Evidence of the efficacy - a systematic literature review].

PubMed

Bredow, J; Bloess, K; Oppermann, J; Boese, C K; Löhrer, L; Eysel, P

2016-07-01

Non-specific chronic low back pain (NSCLBP): Which conservative therapy shows an evident effectiveness - A review of the current literature. Our results are based on literature reviews of current randomised control studies, reviews and meta-analysis drawn from the Cochrane Library and Medline-Database between the years 2004 until 2015. German and English Studies were included. We focused on different conservative Treatments of NSCLBP, which are listed at, the NVL-Guidelines. Based on the given evidence we evaluated their effectiveness. As part of the review we identified 4657 Publications, 85 were included in this study. Therapeutic options such as bed rest, TENS, Massage, Spine Supports, Back Schools and Antidepressants showed no evident effectiveness. Injections, NSAR analgesic therapy, Thermotherapy and Opioid analgesic therapy indicated a short-time effectiveness. A long term success (> 6 weeks) however, can not be shown. Only the Movement therapy can, in the summation of the included studies, postulate an evident (Evidence Level I) long-term effect treating NSCLBP. Only a few therapy options indicate a significant evident effectiveness for treating NSCLBP conservatively. At short notice methods such as injection therapy, thermo-therapy and analgesic therapies with NSAR and/or opioids help coping the acute phase. In the long term only movement therapy seems to provide an evident effectiveness. In the case of therapy-refractory NSCLBP a multimodal therapy should be considered.

Perioperative analgesia for patients undergoing endoscopic sinus surgery: an evidence-based review.

PubMed

Svider, Peter F; Nguyen, Brandon; Yuhan, Brian; Zuliani, Giancarlo; Eloy, Jean Anderson; Folbe, Adam J

2018-04-12

Misuse and diversion of prescription opioids have been critical in facilitating the opioid epidemic. Our objective was to perform a systematic evidence-based review delineating perioperative regimens (including opioid alternatives) evaluated for endoscopic sinus surgery. PubMed/MEDLINE, Cochrane Library, and EmBase databases were evaluated for studies detailing analgesics employed after endoscopic sinus surgery. Studies were assessed for level of evidence. Bias risk was evaluated using the Cochrane Bias tool and GRADE criteria. Medication, administration, adverse effects, pain scores, and rescue analgesic consumption were evaluated. A summary of evidence detailing benefits, harm, and cost was prepared. Thirty-two studies encompassing 1812 patients were included. The GRADE criteria determined the overall evidence to be of moderate quality. Perioperative acetaminophen had few adverse events and reduced immediate need for opioid rescue after sinus surgery; studies evaluating acetaminophen demonstrate a preponderance of benefit over harm. Nonsteroidal anti-inflammatory drugs (NSAIDs) also reduce postoperative opioid consumption, although a small portion of patients undergoing sinus surgery harbor the potential for NSAID intolerance. The aggregate level of evidence for studies evaluating NSAIDs was grade A, whereas the aggregate grade of evidence for several other agents was grade B. There is evidence supporting the use of NSAIDs and gabapentin for the control of pain after endoscopic sinus surgery. Acetaminophen, α-agonists, and local anesthetics are also viable options for postoperative analgesia. Familiarity with these data is essential to facilitate the use of opioid alternatives. Further large-scale, multi-institutional, randomized trials are needed to provide conclusive recommendations for these perioperative analgesics. © 2018 ARS-AAOA, LLC.

Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

PubMed

Gao, Mingxiang; Li, Jinyu; Nie, Cunbin; Song, Beibei; Yan, Lin; Qian, Hai

2018-05-15

Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H 2 S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H 2 S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B 9 , containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H 2 S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B 9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H 2 S-releasing capability. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

PubMed

Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-09-01

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P < .0004). Psychoactive and subjective effects were dose-dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. Because the 2 active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

OnabotulinumtoxinA effectiveness on chronic migraine, negative emotional states and sleep quality: a single-center prospective cohort study.

PubMed

Aydinlar, Elif Ilgaz; Dikmen, Pinar Yalinay; Kosak, Seda; Kocaman, Ayse Sagduyu

2017-12-01

OnabotulinumtoxinA (OnabotA) is considered effective in in patients with chronic migraine (CM) who failed on traditional therapies. This study was designed to evaluate the effect of OnabotA injection series on migraine outcome, negative emotional states and sleep quality in patients with CM. A total of 190 patients with CM (mean (SD) age: 39.3 (10.2) years; 87.9% were female) were included. Data on Pittsburgh sleep quality index (PSQI), headache frequency and severity, number of analgesics used, Migraine Disability Assessment Scale. (MIDAS) scores and Depression, Anxiety and Stress Scale (DASS-21) were evaluated at baseline (visit 1) and 4 consecutive follow up visits, each conducted after OnabotA injection series; at week 12 (visit 2), week 24 (visit 3), week 36 (visit 4) and week 48 (visit 5) to evaluate change from baseline to follow up. From baseline to visit 5, significant decrease was noted in least square (LS) mean headache frequency (from 19.5 to 8.4, p = 0.002), headache severity (from 8.1 to 6.1, p = 0.017), number of analgesics (from 26.9 to 10.4, p = 0.023) and MIDAS scores (from 67.3 to 18.5, p < 0.001). No significant change from baseline was noted in global PSOI and DASS-21 scores throughout the study. Our findings revealed that OnabotA therapy was associated with significant improvement in migraine outcome leading to decrease in headache frequency and severity, number of analgesics used and MIDAS scores. While no significant change was noted in overall sleep quality and prevalence of negative emotional states, patients without negative emotional states at baseline showed improved sleep quality throughout the study.

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis.

PubMed

Kawakami, Hiromasa; Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24-0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04-5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. University Hospital Medical Information Network Clinical Trials Registry UMIN000025344.

[Evaluate the efficacy of combination therapy of ultrasound and currents of TENS professionally active in patients with pain of the lumbar spine].

PubMed

Krukowska, Jolanta; Dudkiewicz, Iwona; Balcerzak, Ewa; Linek, Przemysław; Kulma, Dariusz; Miller, Elibieta

2014-01-01

Back pain most often affects people whose work is related to the load while performing activities related to lifting and in addition to the method and type of work performed, as well as office workers. The aim of the study is to evaluate the efficacy of combination therapy of ultrasound and TENS in the analgesic effect in patients with disorders of the lumbar spine. The study group consisted of 115 patients aged from 24 to 65 years (mean 45.22 +/- 10.38 years) with pain complaints in the lumbar degenerative against overload and, as a result of long-term work involved in taking a forced static position or sitting. Twice (before and after treatment) pain intensity was assessed using of the modified questionnaire of indicators according to Laitinen and scale VAS and physical fitness bythe Oswestry questionnaire (ODI--Oswestry Disability Index). It has been demonstrated greater analgesic efficacy of combination therapy than the monotherapy, which had a characterizing effect on the improvement of mobility of patients according to the Oswestry questionnaire. Afterthe completion of the combination therapy was observed the highly statistical higher than in the monotherapy groups, reducing the intensity and frequency of pain, increase physical activity and reduce quantities medications you are taking. Combination antiretroviral the action of ultrasound and currentsTENS has a more effective analgesic effect and improve the efficiency of patients with pain in the lumbar spine than monotherapy with ultrasound or TENS currents. Enables faster recovery professional and social activity and a reduction in sickness absence at work.

Methadone Reverses Analgesic Tolerance Induced by Morphine Pretreatment

PubMed Central

Posa, Luca; Accarie, Alison; Marie, Nicolas

2016-01-01

Background: Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin reduces tolerance to morphine. So far, no studies have been conducted to evaluate the ability of methadone to reduce morphine tolerance in morphine-pretreated animals, a treatment sequence that could be encountered in opiate rotation protocol. We investigated the ability of methadone (a mu opioid receptor internalizing agonist used in therapy) to reverse morphine tolerance and the associated cellular mechanisms in the periaqueductal gray matter, a region involved in pain control. Methods: We measured analgesic response following a challenge dose of morphine in the hot plate test and investigated regulation of mu opioid receptor (coupling and endocytosis) and some cellular mechanisms involved in tolerance such as adenylate cyclase superactivation and changes in N-methyl-d-aspartate receptor subunits expression and phosphorylation state. Results: A chronic treatment with morphine promoted tolerance to its analgesic effects and was associated with a lack of mu opioid receptor endocytosis, adenylate cyclase overshoot, NR2A and NR2B downregulation, and phosphorylation of NR1. We reported that a methadone treatment in morphine-treated mice reversed morphine tolerance to analgesia by promoting mu opioid receptor endocytosis and blocking cellular mechanisms of tolerance. Conclusions: Our data might lead to rational strategies to tackle opiate tolerance in the frame of opiate rotation. PMID:26390873

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.

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.

Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial.

PubMed

Cengiz, Pelin; Gokcinar, Derya; Karabeyoglu, Isil; Topcu, Hulya; Cicek, Gizem Selen; Gogus, Nermin

2014-05-01

To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. A randomized, double-blind comparative study. Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6 μg/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects.

Effects of Acute Administration of Ketorolac on Mammalian Vestibular Sensory Evoked Potentials

PubMed Central

Gaines, G Christopher; Jones, Timothy A

2013-01-01

The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use as a supplemental analgesic during major surgery in anesthetized rodents. The use of ketorolac during surgery is believed to reduce the anesthetic dose required to achieve and maintain an adequate surgical plane, thus improving the physiologic condition and survival of animals during long experimental procedures. Ketorolac has reported side effects that include dizziness, ear pain, hearing loss, tinnitus, and vertigo in humans, but ketorolac has not been reported to affect the vestibular system in animals. To investigate this possibility, we evaluated the acute effects of ketorolac on vestibular compound action potentials in C57BL/6 mice. Linear vestibular sensory-evoked potentials (VsEP) were recorded during the administration of ketorolac at doses 3 to 14 times the effective analgesic dose. VsEP results for ketorolac were compared with those from a control group maintained under anesthesia for the same period. Ketorolac did not significantly affect the temporal profiles of response latencies and amplitudes or the rate of change in response measures over time between controls and ketorolac-treated mice. These findings demonstrate that ketorolac can be used as an analgesic to supplement anesthesia in mice without concerns of modifying the amplitudes and latencies of the linear VsEP. PMID:23562034

Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Identification of a Potent and Centrally Acting μ Opioid Analgesic with Reduced Abuse Liability.

PubMed

Crowley, Rachel Saylor; Riley, Andrew P; Sherwood, Alexander M; Groer, Chad E; Shivaperumal, Nirajmohan; Biscaia, Miguel; Paton, Kelly; Schneider, Sebastian; Provasi, Davide; Kivell, Bronwyn M; Filizola, Marta; Prisinzano, Thomas E

2016-12-22

Opioids are widely used to treat millions suffering from pain, but their analgesic utility is limited due to associated side effects. Herein we report the development and evaluation of a chemical probe exhibiting analgesia and reduced opioid-induced side effects. This compound, kurkinorin (5), is a potent and selective μ-opioid receptor (MOR) agonist (EC 50 = 1.2 nM, >8000 μ/κ selectivity). 5 is a biased activator of MOR-induced G-protein signaling over β-arrestin-2 recruitment. Metadynamics simulations of 5's binding to a MOR crystal structure suggest energetically preferred binding modes that differ from crystallographic ligands. In vivo studies with 5 demonstrate centrally mediated antinociception, significantly reduced rewarding effects, tolerance, and sedation. We propose that this novel MOR agonist may represent a valuable tool in distinguishing the pathways involved in MOR-induced analgesia from its side effects.

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®

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.

Analgesic Effect of Topical Sodium Diclofenac before Retinal Photocoagulation for Diabetic Retinopathy: A Randomized Double-masked Placebo-controlled Intraindividual Crossover Clinical Trial.

PubMed

Ramezani, Alireza; Entezari, Morteza; Shahbazi, Mohammad Mehdi; Semnani, Yosef; Nikkhah, Homayoun; Yaseri, Mehdi

2017-04-01

To evaluate the analgesic effect of topical sodium diclofenac 0.1% before retinal laser photocoagulation for diabetic retinopathy. Diabetic patients who were candidates for peripheral laser photocoagulation were included in a randomized, placebo-controlled, intraindividual, two-period, and crossover clinical trial. At the first session and based on randomization, one eye received topical sodium diclofenac 0.1% and the other eye received an artificial tear drop (as placebo) three times before laser treatment. At the second session, eyes were given the alternate drug. Patients scored their pain using visual analogue scale (max, 10 cm) at both sessions. Patients and the surgeon were blinded to the drops given. Difference of pain level was the main outcome measure. A total of 200 eyes of 100 patients were enrolled. Both treatments were matched regarding the applied laser. Pain sensation based on visual analogue scale was 5.6 ± 3.0 in the treated group and 5.5 ± 3.0 in the control group. The calculated treatment effect was 0.15 (95% confidence interval, -0.27 to 0.58; p = 0.486). The estimated period effect was 0.24 ( p = 0.530) and the carryover effect was not significant ( p = 0.283). Pretreatment with topical sodium diclofenac 0.1% does not have any analgesic effect during peripheral retinal laser photocoagulation in diabetic patients.

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.

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.

Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis.

PubMed

Malek, Sarah; Sample, Susannah J; Schwartz, Zeev; Nemke, Brett; Jacobson, Peer B; Cozzi, Elizabeth M; Schaefer, Susan L; Bleedorn, Jason A; Holzman, Gerianne; Muir, Peter

2012-10-04

Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 - transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen - non-steroidal anti-inflammatory drug (NSAID), Tramadol - synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. Acute hyperthermia developed after ABT-116 treatment (P < 0.001). Treatment with carprofen (P ≤ 0.01) and tramadol (P ≤ 0.001) led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01). Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P < 0.001). Questionnaire score and activity count at the end of treatment were correlated with age, clinical severity at trial entry, and outcome measure baseline status (SR ≥ ±0.40, P ≤ 0.005). Placebo treatment effects were evident with all variables studied. Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs.

Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis

PubMed Central

2012-01-01

Background Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 – transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen – non-steroidal anti-inflammatory drug (NSAID), Tramadol - synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. Results Acute hyperthermia developed after ABT-116 treatment (P < 0.001). Treatment with carprofen (P ≤ 0.01) and tramadol (P ≤ 0.001) led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01). Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P < 0.001). Questionnaire score and activity count at the end of treatment were correlated with age, clinical severity at trial entry, and outcome measure baseline status (SR ≥ ±0.40, P ≤ 0.005). Placebo treatment effects were evident with all variables studied. Conclusion Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs. PMID:23035739

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

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

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.

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.

The analgesic, anti-inflammatory and calcium antagonist potential of Tanacetum artemisioides.

PubMed

Bukhari, Ishfaq Ali; Khan, Rafeeq Alam; Gilani, Anwar-ul Hassan; Shah, Abdul Jabbar; Hussain, Javid; Ahmad, Viqar Uddin

2007-03-01

Several species of the genus Tanacetum are traditionally used in a variety of health conditions including pain, inflammation, respiratory and gastrointestinal disorders. In the current investigation, we evaluated the plant extract of T. artemisioides and some of its pure compounds (flavonoids) for analgesic, anti-inflammatory and calcium antagonist effects in various in-vivo and in vitro studies. Using the actetic acid induced writhing test, intraperitoneal (i.p) administration of the plant extract (25-50 mg/kg) and its flavonoid compounds TA-1 and TA-2 (1-5 mg/kg ) exhibited significant analgesic actvity. The maximum analgesic effect observed with the crude extract of the plant was 71% at 50 mg/kg, while that of compounds TA-1 and TA-2 (5 mg/kg i.p) was 75 and 47%, respectively. The plant extract and its pure compounds caused inhbition of formalin induced paw licking in mice predominatly in the second phase of the test. Diclofenac sodium, a standard reference compound, showed a simlar effect in these chemical induced pain models. In the carrgeenan induced rat paw edema assay, the plant extract (50-200 mg/kg i.p) demonstrated significant (P< 0.01) anti-inflammatory activity which was comparable to that obtained with diclofenac sodium and indomethacin. In isolated rabbit jejunum preprations the plant extract showed an atropine sensitive dose-dependent (0.10-1.0 mg/mL) spasmogenic activity followed by a spasmolytic effect at the next higher doses (3-5 mg/mL). The crude extract of the plant also inhibited the high K+-induced contractions, indicating a calcium channel blocking (CCB) activity, which was further confirmed when the plant extract caused a rightward shift in the Ca++ concentration response curves in the isolated rabbit jejunum preparations, similar to that seen with verapamil. The flavonoid compounds isolated from the plant were devoid of any activity in the isolated tissue preparations. These results indicate that the plant extract of T. artemisioides possesses analgesic, anti-inflammatory and CCB activities. The flavonoid compounds of the plant may have a role in its observed analgesic and antiinflammatory activities, while the CCB activity of the plant may be attributed to some other chemical constituents present. Moreover the findings support the traditional reputation of the genus Tanacetum for its therapeutic benefits in pain and inflammatory conditions.

Ginger (Zingiber officinale) as an Analgesic and Ergogenic Aid in Sport: A Systemic Review.

PubMed

Wilson, Patrick B

2015-10-01

Ginger is a popular spice used to treat a variety of maladies, including pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used by athletes to manage and prevent pain; unfortunately, NSAIDs contribute to substantial adverse effects, including gastrointestinal (GI) dysfunction, exercise-induced bronchoconstriction, hyponatremia, impairment of connective tissue remodeling, endurance competition withdrawal, and cardiovascular disease. Ginger, however, may act as a promoter of GI integrity and as a bronchodilator. Given these potentially positive effects of ginger, a systematic review of randomized trials was performed to assess the evidence for ginger as an analgesic and ergogenic aid for exercise training and sport. Among 7 studies examining ginger as an analgesic, the evidence indicates that roughly 2 g·d(-1) of ginger may modestly reduce muscle pain stemming from eccentric resistance exercise and prolonged running, particularly if taken for a minimum of 5 days. Among 9 studies examining ginger as an ergogenic aid, no discernable effects on body composition, metabolic rate, oxygen consumption, isometric force generation, or perceived exertion were observed. Limited data suggest that ginger may accelerate recovery of maximal strength after eccentric resistance exercise and reduce the inflammatory response to cardiorespiratory exercise. Major limitations to the research include the use of untrained individuals, insufficient reporting on adverse events, and no direct comparisons with NSAID ingestion. While ginger taken over 1-2 weeks may reduce pain from eccentric resistance exercise and prolonged running, more research is needed to evaluate its safety and efficacy as an analgesic for a wide range of athletic endeavors.

Abdominal pain, cramping or discomfort impairs quality of life in women: An internet-based observational pilot study focussing on impact of treatment.

PubMed

Enck, Paul; Koehler, Ursula; Weigmann, Harald; Mueller-Lissner, Stefan

2017-03-01

Background  Abdominal pain, cramping, and discomfort (APCD) are experienced by up to 30 % of adults in Europe. Objective  To assess the impact of APCD on quality of life (QoL) and to investigate the effectiveness, tolerability, and impact on QoL of hyoscine butylbromide (HBB, Buscopan ® ) compared with STW 5 (Iberogast ® ) or analgesics in women with APCD. Methods  An internet-based observational pilot study was conducted in Germany in women who had predominantly used HBB, STW 5, or analgesics (n = 240 per treatment) to treat APCD. This online survey included questions on QoL, effectiveness, and tolerability. Results  A total of 720 completed questionnaires was evaluated. APCD had a major impact on QoL, with 96 % of women reporting that daily activities were disrupted at least sometimes, and 44 % at least often. Other aspects of QoL, such as quality of work, eating habits, and social activities, were also affected in most women. After taking their medication of choice, 91 % of women in the HBB group reported they could "very often" or "often" continue with their daily activities, compared with 84 % and 85 % in the STW 5 and analgesic groups, respectively (p < 0.05 for both comparisons). HBB was perceived to be the "best solution" to overcome APCD symptoms "very often" or "often" by more women (86 %) than STW 5 (75 %) and analgesics (74 %) (p < 0.05 for both comparisons). Conclusion  Women with APCD have impaired QoL. All treatments were considered effective by the majority of participants. Compared with STW 5 or analgesics, HBB was reported to facilitate return to daily activities more frequently. © Georg Thieme Verlag KG Stuttgart · New York.

The Analgesic Effects of Morphine and Tramadol Added to Intra-articular Levobupivacaine-Tenoxicam Combination for Arthroscopic Knee Surgery on Postoperative Pain; a Randomized Clinical Trial

PubMed Central

Oral, Ebru Gelici; Hanci, Ayse; Ulufer Sivrikaya, Gulcihan; Dobrucali, Hale; Turkoglu Kilinc, Leyla

2015-01-01

Background: Arthroscopic knee surgery is commonly performed as an outpatient procedure and is often associated with postoperative pain. Objectives: We aimed to compare the effects of intra-articular levobupivacaine-tenoxicam-tramadol and levobupivacaine-tenoxicam-morphine combinations on postoperative pain in patients undergoing elective arthroscopic knee surgery. Materials and Methods: A total of 90 ASA I-II patients undergoing elective arthroscopic meniscectomy under general anesthesia were enrolled. The participants were randomly allocated to three groups to receive the following intra-articular medications after completion of the surgery and before deflation of the tourniquet: Group S, 20 mL of saline; Group T, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 100 mg of tramadol in 20 mL saline; and Group M, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 4 mg of morphine in 20 mL saline. Visual analogue scale values at rest (VASr) and at active flexion of knee (VASa) at postoperation hours 1, 2, 4, 8, 12, and 24, duration of analgesia, total analgesic consumption, and number of rescue analgesia at 24 hours were evaluated. Results: VASr and VASa were significantly higher in group S in comparison to other groups (P < 0.05). Duration of analgesia was significantly longer in Group T and Group M than in Group S (P < 0.05). The difference between group T and group M was also significant (P < 0.05). Number of rescue analgesia and total analgesic consumption at postoperative hour 24 was significantly fewer in group M compared with other groups (P < 0.05). Conclusions: Intra-articular levobupivacaine-tenoxicam-morphine combination provides effective pain relief, longer analgesic duration, and less analgesic requirement when compared with intra-articular levobupivacaine-tenoxicam-tramadol combination and saline after knee arthroscopic surgery. PMID:26161321

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.

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.

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.

Anti-nociceptive properties in rodents and the possibility of using polyphenol-rich fractions from sida urens L. (Malvaceae) against of dental caries bacteria

PubMed Central

2013-01-01

Background Sida urens L. (Malvaceae) is in flora of Asian medicinal herbs and used traditionally in West of Burkina Faso for the treatment of infectious diseases and particularly used against, dental caries bacteria, fever, pain and possesses analgesic properties. This study was conducted to reveal the antibacterial effect against dental caries bacteria on the one hand, and evaluate their analgesic capacity in experimental model with Swiss mice and on the other hand, with an aim to provide a scientific basis for the traditional use of this plant for the management of dental caries bacteria. Method The antibacterial assays in this study were performed by using inhibition zone diameters, MIC (Minimum inhibitory concentration) and MBC (Minimal bactericidal concentration) methods. On the whole the dental caries bacteria (Gram-positive and Gram-negative bacterial strains) were used. Negative control was prepared using discs impregnated with 10% DMSO in water and commercially available Gentamicin from Alkom Laboratories LTD was used as positive reference standards for all bacterial strains. In acute toxicity test, mice received doses of extract (acetone/water extract) from Sida urens L. by intraperitoneal route and LD50 was determined in Swiss mice. As for analgesic effects, acetic acid writhing method was used in mice. The acetic acid-induced writhing method was used in mice with aim to study analgesic effects. Results The results showed that the highest antibacterial activities were founded with the polyphenol-rich fractions against all bacterial strains compared to the standard antibiotic. About preliminary study in acute toxicity test, LD50 value obtained was more than 5000 mg/kg b.w. Polyphenol-rich fractions produced significant analgesic effects in acetic acid-induced writhing method and in a dose-dependent inhibition was observed. Conclusion These results validate the ethno-botanical use of Sida urens L. (Malvaceae) and demonstrate the potential of this herbaceous as a potential antibacterial agent of dental caries that could be effectively used for future health care purposes. PMID:23787152

A prospective randomized study comparing percutaneous nephrolithotomy under combined spinal-epidural anesthesia with percutaneous nephrolithotomy under general anesthesia.

PubMed

Singh, Vishwajeet; Sinha, Rahul Janak; Sankhwar, S N; Malik, Anita

2011-01-01

A prospective randomized study was executed to compare the surgical parameters and stone clearance in patients who underwent percutaneous nephrolithotomy (PNL) under combined spinal-epidural anesthesia (CSEA) versus those who underwent PNL under general anesthesia (GA). Between January 2008 to December 2009, 64 patients with renal calculi were randomized into 2 groups and evaluated for the purpose of this study. Group 1 consisted of patients who underwent PNL under CSEA and Group 2 consisted of patients who underwent PNL under GA. The operative time, stone clearance rate, visual pain analog score, mean analgesic dose and mean hospital stay were compared amongst other parameters. The difference between visual pain analog score after the operation and the dose of analgesic requirement was significant on statistical analysis between both groups. PNL under CSEA is as effective and safe as PNL under GA. Patients who undergo PNL under CESA require lesser analgesic dose and have a shorter hospital stay. Copyright © 2011 S. Karger AG, Basel.

Comparison of two combinations of opioid and non-opioid analgesics for acute periradicular abscess: a randomized clinical trial.

PubMed

Santini, Manuela Favarin; Rosa, Ricardo Abreu da; Ferreira, Maria Beatriz Cardoso; Fischer, Maria Isabel; Souza, Erick Miranda; Só, Marcus Vinícius Reis

2017-01-01

Acute periradicular abscess is a condition characterized by the formation and propagation of pus in the periapical tissues and generally associated with debilitating pain. The aim of this study was to compare the overall analgesic effectiveness of two combinations of opioid and non-opioid analgesics for acute periradicular abscess. This study included 26 patients who sought emergency care in a Brazilian dental school. The patients were randomly divided into two groups: Co/Ac - oral prescription of codeine (30 mg) plus acetaminophen (500 mg), every 4 h, for 3 days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg) plus acetaminophen (500 mg) on the same schedule. Two factors were evaluated: (1) pain scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after treatment, using the Visual Analogue Scale; and (2) the occurrence of adverse effects. In both groups, there was a reduction in pain scores over time. For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48, and 72 hours after treatment (P<0.05). In the Tr/Ac group, the scores significantly decreased over time from time point 6 h (P<0.05). Comparing the pain at each time point, the groups were not significantly different (P>0.05), i.e., both treatments were effective in controlling pain caused by APA; however, the combination of Tr/Ac caused more adverse reactions as two patients had to stop using the medication. This study suggests that, considering both analgesic efficacy and safety, the combination of codeine and acetaminophen is more effective to control moderate to severe pain from acute periradicular abscesses.

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.

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.

[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.

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.

Evaluation of antinociceptive and anti-inflammatory properties of methanolic crude extract of Lophopetalum javanicum (bark).

PubMed

Ansari, Prawej; Badhan, Sanjeeda Sarmin; Azam, Shofiul; Sultana, Nasrin; Anwar, Sabbir; Mohamed Abdurahman, Mohamed Sheikh; Hannan, J M A

2016-06-01

The aim of the current study was to investigate the scientific basis of the traditional application of Lophopetalum javanicum for measuring anti-inflammatory and analgesic activity and phytochemical screening. Present study includes the preliminary screening of the phytochemical composition and in vivo analgesic and anti-inflammatory activity of methanolic extract of L. javanicum (MELJ). Hot-plate test and tail immersion method were used to investigate acute analgesic effects of L. javanicum, and the potency in inhibition of chronic inflammation in mice was tested by carrageenan-induced paw edema and formalin-induced edema method. One hour after the administration of carrageenan, rat's paw was inflamed, and after treating it with 500 mg/kg dose, increase in the significant inhibitory effect on paw was observed. At the third hour after carrageenan injection, extreme inhibition (55.61%±0.015%; p<0.001) resulted by methanolic extract. By using hot plate method, it was found that L. javanicum increases pain tolerance time up to 17.89±0.079 min, whereas the compared standard's interval was 21.48±0.397 min. In tail immersion method, the pain threshold was 3.02±0.074 (p<0.001) at 400 mg/kg by L. javanicum at 90 min of experiment. This study manifested that the methanolic extract of L. javanicum is efficient in inhibiting pain mediators to release, and conceivably, this report should get priority while searching for a new analgesic and anti-inflammatory agent.

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

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

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 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.

Effects of Shilajit on the development of tolerance to morphine in mice.

PubMed

Tiwari, P; Ramarao, P; Ghosal, S

2001-03-01

Effects of concomitant administration of Processed Shilajit (PS, 0.1 and 1 mg/kg, i.p.), in Swiss mice were evaluated on the development of tolerance to morphine induced analgesia in the hot plate test. Chronic administration of morphine (10 mg/kg, i.p., b.i.d.) to mice over a duration of 10 days resulted in the development of tolerance to the analgesic effect of morphine. Concomitant administration of PS with morphine, from day 6 to day 10, resulted in a significant inhibition of the development of tolerance to morphine (10 mg/kg, i.p.) induced analgesia. Processed Shilajit per se, in the doses used, did not elicit any significant analgesia in mice; nor did the chronic concomitant administration of Processed Shilajit alter the morphine-induced analgesia. These findings with Processed Shilajit indicate its potential as a prospective modifier of analgesic tolerance to morphine. Copyright 2001 John Wiley & Sons, Ltd.

[Botulinum toxin for the treatment of pain syndromes].

PubMed

Ferreira, Joaquim J; Couto, Marina; Costa, João; Coelho, Miguel; Rosa, Mário M; Sampaio, Cristina

2006-01-01

Although botulinum toxin (BoNT) is being used for therapeutic purposes for more than 20 years, the list of potential new indications continues to increase and includes various pain syndromes. The pain relief experienced by patients with dystonia and spasticity from intramuscular BoNT injections suggested that other chronic skeletal-muscles pain conditions may also benefit. BoNT inhibits the release of acetylcholine at the neuromuscular junction thereby reducing striatal muscle contractions and the proposed analgesic property was initially attributed to muscular relaxation. A specific analgesic BoNT effect is difficult to conclude from studies where pain is conditioned by other associated symptoms like dystonia, muscle contraction or spasticity. One alternative is to critically appraise clinical trials where BoNT was studied as the active intervention and pain evaluated as an outcome. From this analysis there is convincing evidence for the effectiveness of BoNT in the treatment of pain associated with cervical dystonia. For all other pain syndromes there have been relatively few, small sized, placebo-controlled studies (myofascial pain syndrome, chronic neck and low back pain, piriformis syndrome and fibromyalgia) and the results of these studies have been contradictory or non conclusive. To establish the analgesic properties of BoNT there is a need for appropriately designed, exploratory randomized controlled studies in well accepted human models of nociceptive or neuropathic pain. This does not exclude the subsequent need to conduct pragmatic trials to evaluate the effectiveness of BoNT in conditions where the improvement of pain or any associated clinical sign or symptom may be of clinical relevance.

A hydro-ethanolic extract of Synedrella nodiflora (L.) Gaertn ameliorates hyperalgesia and allodynia in vincristine-induced neuropathic pain in rats.

PubMed

Amoateng, Patrick; Adjei, Samuel; Osei-Safo, Dorcas; Ameyaw, Elvis Ofori; Ahedor, Believe; N'guessan, Benoit Banga; Nyarko, Alexander Kwadwo

2015-07-01

The hydro-ethanolic extract of Synedrella nodiflora (L.) Gaertn whole plant has demonstrated analgesic effects in acute pain models. The extract has also demonstrated anticonvulsant effects in murine models of experimental epilepsy. The present study illustrates an evaluation of the hydro-ethanolic extract of the plant for possible analgesic properties in hyperalgesia and allodynia associated with vincristine-induced neuropathy in rats. Neuropathic pain was induced in Sprague-Dawley rats by injecting 100 μg/kg of vincristine sulphate on alternative days for 6 days (days 0, 2, 4, 8, 10 and 12). Vincristine-induced cold allodynia, mechanical hyperalgesia and thermal hyperalgesia were measured pre-vincristine administration and on days 15, 17 and 19 post-vincristine administration. The rats were then treated with S. nodiflora extract (SNE) (100, 300 and 1000 mg/kg), pregabalin (10, 30 and 100 mg/kg) and distilled water as vehicle daily for 5 days and pain thresholds were measured on alternate days for 3 days. SNE and pregabalin produced analgesic properties observed as increased paw withdrawal latencies to mechanical, tactile, cold water stimuli and thermal hyperalgesic tests during the 5 days of treatment. The findings suggest that hydro-ethanolic extract of S. nodiflora possesses anti-hyperalgesic and anti-allodynic effects in vincristine-induced neuropathic pain in rats.

“Protective Premedication”: A Comparative Study of Acetaminophen, Gabapentin and Combination of Acetaminophen with Gabapentin for Post-Operative Analgesia

PubMed Central

Syal, Kartik; Goma, Mandeep; Dogra, Ravi K; Ohri, Anil; Gupta, Ashok K; Goel, Ashok

2010-01-01

Background: We carried out a study to evaluate the effects of protective premedication with Acetaminophen, Gabapentin and combination of Acetaminophen with Gabapentin on post-operative analgesia in patients undergoing open cholecys-tectomy under general anesthesia. Patients & Methods: The study was conducted in a double-blind randomized and controlled manner in 120 consenting patients of either sex belonging to ASA physical status grade I and II, between the age groups of 20 to 50 years, weighing between 40 to 65 kg and undergoing elective surgery (open cholecystectomy) under general anesthesia. The patients were divided into 4 groups: 1: placebo, 2: Acetaminophen 1000 mg, 3: 1200 mg Gabapentin, 4: Acetaminphen 1000 mg plus 1200 mg Gabapentin. The drugs were given two hours before induction. Time, number and total amount of rescue analgesic (tramadol) and VAS score at rest and on movement. Side effects like any episode of nausea/vomiting and level of sedation were noted. Results: Premedication with antihyperalgesic and analgesic agents helps to decrease postoperative pain scores. Gabapentin premedication is effective for providing better postoperative pain relief with lower and delayed requirements of rescue analgesics, but causes more episodes of nausea and vomiting and higher levels of sedation. PMID:21547185

Involvement of spinal orexin A in the electroacupuncture analgesia in a rat model of post-laparotomy pain.

PubMed

Feng, Xiao-Ming; Mi, Wen-Li; Xia, Fang; Mao-Ying, Qi-Liang; Jiang, Jian-Wei; Xiao, Sheng; Wang, Zhi-Fu; Wang, Yan-Qing; Wu, Gen-Cheng

2012-11-22

Orexin A (OXA, hypocretin/hcrt 1) is a newly discovered potential analgesic substance. However, whether OXA is involved in acupuncture analgesia remains unknown. The present study was designed to investigate the involvement of spinal OXA in electroacupuncture (EA) analgesia. A modified rat model of post-laparotomy pain was adopted and evaluated. Von Frey filaments were used to measure mechanical allodynia of the hind paw and abdomen. EA at 2/15 Hz or 2/100 Hz was performed once on the bilateral ST36 and SP6 for 30 min perioperatively. SB-334867, a selective orexin 1 receptor (OX1R) antagonist with a higher affinity for OXA than OXB, was intrathecally injected to observe its effect on EA analgesia. OXA at 0.3 nmol and EA at 2/15 Hz produced respective analgesic effects on the model (P<0.05). Pre-surgical intrathecal administered of SB-334867 30 nmol antagonized OXA analgesia and attenuated the analgesic effect of EA (P<0.05). However, SB-334867 did not block fentanyl-induced analgesia (P>0.05). In addition, naloxone, a selective opioid receptor antagonist, failed to antagonize OXA-induced analgesia (P>0.05). The results of the present study indicate the involvement of OXA in EA analgesia via OX1R in an opioid-independent way.

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

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.

(-)-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.

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

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

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.

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.

Searching for pain information, education, and support on the Internet.

PubMed

Colón, Yvette

2013-03-01

Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topics addressed in this issue are searching for pain information, education, support, and providers on the Internet and evaluating online information.

Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway.

PubMed

De, Soumita; Maroo, Niteeka; Saha, Piu; Hazra, Samik; Chatterjee, Mitali

2013-01-01

The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action. Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA) and generation of reactive oxygen species (ROS) was measured by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate. PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001). In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01. The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration.

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...

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

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

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.

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.

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

Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: A randomized controlled trial

PubMed Central

Beaulieu, André D; Peloso, Paul M; Haraoui, Boulos; Bensen, William; Thomson, Glen; Wade, John; Quigley, Patricia; Eisenhoffer, John; Harsanyi, Zoltan; Darke, Andrew C

2008-01-01

OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR) tramadol and sustained-release (SR) diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees. METHODS: Patients with at least moderate pain intensity, and having received analgesics over the past three months, underwent a two-to seven-day washout of current analgesics before initiation of 200 mg CR tramadol or 75 mg SR diclofenac. During the eight-week study, patients returned to the clinic biweekly. CR tramadol doses were titrated to a maximum of 200 mg, 300 mg or 400 mg per day. SR diclofenac doses were titrated to 75 mg or 100 mg once daily, or 75 mg twice a day based on pain relief and the presence of side effects. For rescue analgesic, patients took acetaminophen as needed, up to 650 mg three times a day. RESULTS: Forty-five patients on CR tramadol and 52 patients on SR diclofenac were evaluable. Significant improvements from prestudy treatment were shown for visual analogue scale pain (P=0.0001), stiffness (P<0.0005) and physical function (P=0.0001) scores for both treatments. There were no significant differences between the two treatments in the Western Ontario and McMaster Universities subscales, overall pain, pain and sleep, or the clinical effectiveness evaluation. Overall incidence of adverse events was similar in both groups, with more opioid-related adverse events with CR tramadol, and two serious adverse events occurring with the use of SR diclofenac. CONCLUSIONS: CR tramadol is as effective as SR diclofenac in the treatment of pain due to knee or hip osteoarthritis, with the potential for fewer of the serious side effects that characterize nonsteroidal anti-inflammatory drug administration. PMID:18443672

The analgesic efficacy of ultrasound-guided transversus abdominis plane block on postoperative pain and morphine consumption in varicocelectomy.

PubMed

Ömür, Dilek; Oğuzalp, Hüseyin; Kiraz, Hasan A; Ekin, Serpil; Alan, Cabir; Ersay, Ahmet R; Hancı, Volkan

2016-06-01

To evaluate the analgesic effect of transversus abdominis plane (TAP) block administered before varicocele surgery. This study was completed at the Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, between January 2011 and April 2013. In a prospective, double blind, randomized, placebo controlled clinical study, 40 male patients scheduled for elective varicocele operations were randomized to group T (treatment group) or group C (controls). After receiving general anesthesia, group T received a TAP block using 20 mL 0.25% bupivacaine on the operation side, whereas group C received a control block using 20 mL 0.9% Sodium chloride. During the first 24 hours after surgery, the patient pain was evaluated using the visual analogue scale (VAS) at rest and while coughing. Postoperative patient controlled analgesia morphine consumption, VAS scores, and side effects were recorded. Of 34 patients, Group T (n=18) had significantly lower VAS pain scores than Group C (n=16) both at rest and while coughing. The total morphine consumed was  lower (7.7 ± 4.0) versus 21.6 ± 12.4 mg, p less than 0.001) in the 24 hours after surgery. As part of a multimodal analgesic regime after varicocelectomy surgery, morphine consumption and VAS pain scores were significantly lower among those receiving 20 mL 0.25% bupivacaine administered for a TAP block than among controls.

Clinical Evaluation of a Novel Technology for Oral Patient-Controlled Analgesia, the PCoA® Acute Device, for Hospitalized Patients with Postoperative Pain, in Pilot Feasibility Study.

PubMed

Wirz, Stefan; Conrad, Stefan; Shtrichman, Ronit; Schimo, Kai; Hoffmann, Eva

2017-01-01

Acute postoperative pain delays recovery and increases morbidity and mortality. Traditional administration of postoperative analgesics by nurses is often inefficient. The present study evaluated the safety, efficacy, and usability of a novel, patient-controlled analgesic dispenser, the PCoA Acute. A controlled pilot study was conducted at three medical centers. Patients scheduled for elective surgery were enrolled into two groups, both taking oral analgesics: a control group ( n = 43), opioids dispensed by nurses, and a test group ( n = 27), opioids dispensed via the PCoA Acute. Pill intake data were recorded. Pain ratings at rest and during movement were surveyed. No severe adverse events were recorded. Average pill intake time was reduced from 8 : 58 minutes in the control group to 1 : 17 minutes in the test group ( P value < 0.05). The test group took 67% more pills than the control group, indicating enhanced compliance. Pain scores were significantly lower for patients in the test group ( P value < 0.05). Over 90% of PCoA Acute users were satisfied with its use. The study confirmed that PCoA Acute is safe and effective. It is well accepted by patients and medical staff. Its use can optimize pain medication administration.

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

PubMed Central

Garzón, Javier; de la Torre-Madrid, Elena; Rodríguez-Muñoz, María; Vicente-Sánchez, Ana; Sánchez-Blázquez, Pilar

2009-01-01

Background Although the systemic administration of cannabinoids produces antinociception, their chronic use leads to analgesic tolerance as well as cross-tolerance to morphine. These effects are mediated by cannabinoids binding to peripheral, spinal and supraspinal CB1 and CB2 receptors, making it difficult to determine the relevance of each receptor type to these phenomena. However, in the brain, the CB1 receptors (CB1Rs) are expressed at high levels in neurons, whereas the expression of CB2Rs is marginal. Thus, CB1Rs mediate the effects of smoked cannabis and are also implicated in emotional behaviors. We have analyzed the production of supraspinal analgesia and the development of tolerance at CB1Rs by the direct injection of a series of cannabinoids into the brain. The influence of the activation of CB1Rs on supraspinal analgesia evoked by morphine was also evaluated. Results Intracerebroventricular (icv) administration of cannabinoid receptor agonists, WIN55,212-2, ACEA or methanandamide, generated a dose-dependent analgesia. Notably, a single administration of these compounds brought about profound analgesic tolerance that lasted for more than 14 days. This decrease in the effect of cannabinoid receptor agonists was not mediated by depletion of CB1Rs or the loss of regulated G proteins, but, nevertheless, it was accompanied by reduced morphine analgesia. On the other hand, acute morphine administration produced tolerance that lasted only 3 days and did not affect the CB1R. We found that both neural mu-opioid receptors (MORs) and CB1Rs interact with the HINT1-RGSZ module, thereby regulating pertussis toxin-insensitive Gz proteins. In mice with reduced levels of these Gz proteins, the CB1R agonists produced no such desensitization or morphine cross-tolerance. On the other hand, experimental enhancement of Gz signaling enabled an acute icv administration of morphine to produce a long-lasting tolerance at MORs that persisted for more than 2 weeks, and it also impaired the analgesic effects of cannabinoids. Conclusion In the brain, cannabinoids can produce analgesic tolerance that is not associated with the loss of surface CB1Rs or their uncoupling from regulated transduction. Neural specific Gz proteins are essential mediators of the analgesic effects of supraspinal CB1R agonists and morphine. These Gz proteins are also responsible for the long-term analgesic tolerance produced by single doses of these agonists, as well as for the cross-tolerance between CB1Rs and MORs. PMID:19284549

Subacute arsenic exposure through drinking water reduces the pharmacodynamic effects of ketoprofen in male rats.

PubMed

Ahmad, Wasif; Prawez, Shahid; Chanderashekara, H H; Tandan, Surendra Kumar; Sankar, Palanisamy; Sarkar, Souvendra Nath

2012-03-01

We evaluated the modulatory role of the groundwater contaminant arsenic on the pharmacodynamic responses of the nonsteroidal analgesic-antipyretic drug ketoprofen and the major pro-inflammatory mediators linked to the mechanism of ketoprofen's therapeutic effects. Rats were pre-exposed to sodium arsenite (0.4, 4 and 40 ppm) through drinking water for 28 days. The pharmacological effects of orally administered ketoprofen (5 mg/kg) were evaluated the following day. Pain, inflammation and pyretic responses were, respectively, assessed through formalin-induced nociception, carrageenan-induced inflammation and lipopolysaccharide-induced pyrexia. Arsenic inhibited ketoprofen's analgesic, anti-inflammatory and antipyretic effects. Further, arsenic enhanced cyclooxygenase-1 and cyclooxygenase-2 activities and tumor necrosis factor-α, interleukin-1β and prostaglandin-E(2) production in hind paw muscle. These results suggest a functional antagonism of ketoprofen by arsenic. This may relate to arsenic-mediated local release of tumor necrosis factor-α and interleukin-1β, which causes cyclooxygenase induction and consequent prostaglandin-E(2) release. In conclusion, subacute exposure to environmentally relevant concentrations of arsenic through drinking water may aggravate pain, inflammation and pyrexia and thereby, may reduce the therapeutic efficacy of ketoprofen. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Minimum Effective Concentration of Bupivacaine in Ultrasound-Guided Femoral Nerve Block after Arthroscopic Knee Meniscectomy: A Randomized, Double-Blind, Controlled Trial.

PubMed

Moura, Ed Carlos Rey; de Oliveira Honda, Claudio A; Bringel, Roberto Cesar Teixeira; Leal, Plinio da Cunha; Filho, Gasper de Jesus Lopes; Sakata, Rioko Kinmiko

2016-01-01

Adequate analgesia is important for early hospital discharge after meniscectomy. A femoral nerve block may reduce the need for systemic analgesics, with fewer side effects; however, motor block can occur. Ultrasound-guided femoral nerve block may reduce the required local anesthetic concentration, preventing motor block. The primary objective of this study was to determine the lowest effective analgesic concentration of bupivacaine in 50% (EC50) and in 90% (EC90) of patients for a successful ultrasound-guided femoral nerve block in arthroscopic knee meniscectomy. This was a prospective, randomized, double-blind, controlled trial. This study was conducted at Hospital São Domingos. A total of 52 patients undergoing arthroscopic knee meniscectomy were submitted to ultrasound-guided femoral nerve block using 22 mL bupivacaine. The bupivacaine concentration given to a study patient was determined by the response of the previous patient (a biased-coin design up-down sequential method). If the previous patient had a negative response, the bupivacaine concentration was increased by 0.05% for the next case. If the previous patient had a positive response, the next patient was randomized to receive the same bupivacaine concentration (with a probability of 0.89) or to have a decrease by 0.05% (with a probability of 0.11). A successful block was defined by a numerical pain intensity scale score < 4 (0 = no pain; 10 = worst imaginable pain) in 3 different evaluations. If the pain intensity score was = 4 (moderate or severe pain) at any time, the block was considered failed. General anesthesia was induced with 30 µg/kg alfentanil and 2 mg/kg propofol, followed by propofol maintanance, plus remifentanil if needed. Postoperative analgesia supplementation was performed with dipyrone; ketoprofen and tramadol were given if needed. The following parameters were evaluated: numerical pain intensity score, duration of analgesia, supplementary analgesic dose in 24 hours, and need for intraoperative remifentanil. The EC50 was 0.160 (95% CI: 0.150 - 0.189), and EC90 was 0.271 (95% CI: 0.196 - 0.300). There was no difference in numerical pain intensity score for the different concentrations of bupivacaine. A successful block was achieved in 45 patients, with no difference according to bupivacaine concentration. Time to first analgesic supplementation dose was longer for bupivacaine concentrations = 0.3% (543.8 ± 283.8 min.), compared to 0.25% (391.3 ± 177.8 min.) and < 0.25% (302.3 ± 210.1 min.). There were no differences in supplementary analgesic dose in 24 hours nor in the use of intraoperative remifentanil according to bupivacaine concentration. The analgesic effect was measured only during the first 2 hours. Bupivacaine EC50 for ultrasound-guided femoral nerve block was 0.160 (95% CI: 0.150 - 0.189), and EC90 was 0.271 (95% CI: 0.196 - 0.300).

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

Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle.

PubMed

Paulino, Niraldo; Dantas, Andreia Pires; Bankova, Vassya; Longhi, Daniela Taggliari; Scremin, Amarilis; de Castro, Solange Lisboa; Calixto, João Batista

2003-11-01

Propolis is a bee product, which has long been used in folk medicine for the management of different diseases. In this study we evaluated the analgesic and anti-inflammatory effects of a standard ethanolic extract of Bulgarian propolis (Et-Blg) in mice and its in vitro effect on airway smooth muscle. Et-Blg inhibited acetic acid-induced abdominal contortions with an ID(50) = 7.4 +/- 0.7 mg. kg(-1). In the formalin test, the extract caused a significant reduction in pain in mice treated with 100 mg. kg(-1) Et-Blg during the neurogenic phase and for the inflammatory phase with all doses of the extract, with an ID(50) = 2.5 +/- 0.4 mg. kg(-1). Et-Blg inhibited also the capsaicin-induced ear edema in mice; however, this extract was ineffective when assessed in the tail-flick and hot-plate thermal assays. The analgesic effect of Et-Blg was associated with the inhibition of inflammatory responses and not to a simple irritation of nervous terminals. In vitro, this extract inhibited the contraction of trachea smooth muscle induced by histamine (IC(50) = 50 +/- 5 microg. mL(-1)), capsaicin (IC(50) = 26.8 +/- 3 microg. mL(-1)), 80 mM KCl (IC(50) = 27.8 +/- 3 microg. mL(-1)), and carbachol (IC(50) = 54 +/- 2 microg. mL(-1)).

Intravenous parecoxib sodium as an analgesic alternative to morphine in acute trauma pain in the emergency department.

PubMed

Baharuddin, Kamarul Aryffin; Rahman, Nik Hisamuddin Na; Wahab, Shaik Farid Abdull; Halim, Nurkhairulnizam A; Ahmad, Rashidi

2014-01-03

Parecoxib sodium is the first parenteral COX-2 inhibitor used for pain management licensed for postoperative pain. However, no study has assessed the usage of parecoxib for acute traumatic pain in the emergency department (ED). The objective of this study was to investigate a potential alternative analgesic agent in the ED by determining the mean reduction of pain score between acute traumatic pain patients who were administered with intravenous (IV) parecoxib sodium versus IV morphine sulfate. The onset of perceptible analgesic effect and side effects were also evaluated. A randomized, double-blinded study comparing IV parecoxib 40 mg versus IV morphine at 0.10 mg/kg was conducted in adult patients presented with acute traumatic pain with numeric rating scale (NRS) of 6 or more within 6 hours of injury. Patients were randomized using a computer-generated randomization plan. Drug preparation and dispensing were performed by a pharmacist. Periodic assessment of blood pressure, pulse rate, oxygen saturation, and NRS were taken at 0, 5, 15, and 30 minute intervals after the administration of the study drug. The primary outcome was the reduction of NRS. Side effect and drug evaluation was conducted within 30 minutes of drug administration. There was no statistically significant difference in the reduction of mean NRS between patients in the IV parecoxib group or IV morphine group (P = 0.095). The mean NRS for patients treated with IV morphine were 7.1 at 0 minutes, 4.5 at 5 minutes, 3.1 at 15 minutes, and 2.0 at 30 minutes. Whereas mean NRS for patients who received IV parecoxib were 7.8 at 0 minutes, 5.7 at 5 minutes, 4.7 at 15 minutes, and 3.9 at 30 minutes. The onset of perceptible analgesic effects could be seen as early as 5 minutes. Dizziness was experienced in 42.9% of patients who received IV morphine compared to none in the parecoxib group. There was non-significant trend toward superiority of IV morphine over IV parecoxib. Looking at its effectiveness and the lack of opioid-related side-effects, the usage of IV parecoxib sodium may be extended further to a variety of cases in the ED.

Intravenous parecoxib sodium as an analgesic alternative to morphine in acute trauma pain in the emergency department

PubMed Central

2014-01-01

Background Parecoxib sodium is the first parenteral COX-2 inhibitor used for pain management licensed for postoperative pain. However, no study has assessed the usage of parecoxib for acute traumatic pain in the emergency department (ED). The objective of this study was to investigate a potential alternative analgesic agent in the ED by determining the mean reduction of pain score between acute traumatic pain patients who were administered with intravenous (IV) parecoxib sodium versus IV morphine sulfate. The onset of perceptible analgesic effect and side effects were also evaluated. Methods A randomized, double-blinded study comparing IV parecoxib 40 mg versus IV morphine at 0.10 mg/kg was conducted in adult patients presented with acute traumatic pain with numeric rating scale (NRS) of 6 or more within 6 hours of injury. Patients were randomized using a computer-generated randomization plan. Drug preparation and dispensing were performed by a pharmacist. Periodic assessment of blood pressure, pulse rate, oxygen saturation, and NRS were taken at 0, 5, 15, and 30 minute intervals after the administration of the study drug. The primary outcome was the reduction of NRS. Side effect and drug evaluation was conducted within 30 minutes of drug administration. Results There was no statistically significant difference in the reduction of mean NRS between patients in the IV parecoxib group or IV morphine group (P = 0.095). The mean NRS for patients treated with IV morphine were 7.1 at 0 minutes, 4.5 at 5 minutes, 3.1 at 15 minutes, and 2.0 at 30 minutes. Whereas mean NRS for patients who received IV parecoxib were 7.8 at 0 minutes, 5.7 at 5 minutes, 4.7 at 15 minutes, and 3.9 at 30 minutes. The onset of perceptible analgesic effects could be seen as early as 5 minutes. Dizziness was experienced in 42.9% of patients who received IV morphine compared to none in the parecoxib group. Conclusions There was non-significant trend toward superiority of IV morphine over IV parecoxib. Looking at its effectiveness and the lack of opioid-related side-effects, the usage of IV parecoxib sodium may be extended further to a variety of cases in the ED. PMID:24386899

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.

Role of Sigma-1 Receptor/p38 MAPK Inhibition in Acupoint Catgut Embedding-Mediated Analgesic Effects in Complete Freund's Adjuvant-Induced Inflammatory Pain.

PubMed

Du, Kairong; Wang, Xue; Chi, Laiting; Li, Wenzhi

2017-08-01

The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia. Rats were prepared with intrathecal catheter implantation. ACE was applied to bilateral "Kunlun" (BL60), "Zusanli" (ST36), and "Sanyinjiao" (SP6) acupoints in the rat model of inflammatory pain (complete Freund's adjuvant [CFA] intraplantar injection). Then, Sig-1R agonist PRE084 or saline was intrathecally given daily. The paw withdrawal thresholds and paw edema were measured before CFA injection and at 1, 3, and 5 day after CFA injection. Western bolt was used to evaluate the protein expression of spinal Sig-1R, p38MAPK, and extracellular signal-regulated kinase (ERK), and immunohistochemistry of Sig-1R was detected at 1, 3, and 5 days after CFA injection. ACE exhibited specific analgesic effects. ACE increased paw withdrawal thresholds and markedly decreased CFA-induced paw edema at 1, 3, and 5 days. ACE downregulated the protein expression of Sig-1R, which was increased significantly at 1, 3, and 5 days after CFA injection. ACE decreased the expression of p38 MAPK and ERK at 1 and 3 days but not at 5 days. However, an injection of Sig-1R agonist PRE084 markedly reversed these alterations, except ERK expression. The present study demonstrated that ACE exhibited antihyperalgesic effects via the inhibition of the Sig-1R that modulated p38 MAPK, but not ERK, expression in the CFA-induced inflammatory pain model in rats.

Effects of dexmedetomidine infusion during spinal anesthesia on hemodynamics and sedation

PubMed Central

Tarıkçı Kılıç, Ebru; Aydın, Gaye

2018-01-01

ABSTRACT Background: We evaluated the effects of intravenous dexmedetomidine during spinal anesthesia on hemodynamics, respiratory rate, oxygen saturation, sedpain, and compared them with those of saline infusion. Sixty American Society of Anesthesiologists physical status I and II cases were randomly divided into two groups. Patients were connected to the monitor after premedication, and spinal anesthesia was administered. Sensory and motor blockades were assessed using pinprick test and Bromage scale, respectively. Group I received dexmedetomidine infusion and Group II received saline infusion. Throughout the infusion process, hemodynamic data, respiratory rate, oxygen saturation, sedation, pain, Bromage score, amnesia, bispectral index, and side effects were recorded. Postoperative hemodynamic measurements, oxygen saturation, sedation, pain scores were obtained. Sedation and pain were evaluated using the Ramsay and visual analog scales, respectively. Analgesics were administered in cases with high scores on the visual analog scale. Postoperative analgesic consumption, side effects, treatments were recorded. No significant differences were found between the groups with respect to oxygen saturation, respiratory rate, pain, and side effects in the intraoperative period. Time to onset of sensorial block, maximum sensorial block, onset of motor block, and maximum motor block; bispectral index values; and apex heartbeat until 80 min of infusion, systolic arterial blood pressure until 90 min, and diastolic arterial blood pressure until 50 min were lower, whereas amnesia and sedation levels were higher in dexmedetomidine group. Postoperative pain and analgesic requirement were not different. Apex heartbeat at 15 min and systolic arterial blood pressure at 30 min were lower and sedation scores were higher in the dexmedetomidine infusion group. We demonstrated dexmedetomidine infusion had a hemodynamic depressant effect intraoperatively whereas it had no significant effect on peripheral oxygen saturation, respiratory rate, visual analog scale scores, and side effects. Dexmedetomidine infusion enhanced motor and sensory blockade quality and induced amnesia and sedation. PMID:29457538

[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.

Prospective double-blind clinical trial evaluating the effectiveness of Bromelain in the third molar extraction postoperative period.

PubMed

de la Barrera-Núñez, M-C; Yáñez-Vico, R-M; Batista-Cruzado, A; Heurtebise-Saavedra, J-M; Castillo-de Oyagüe, R; Torres-Lagares, D

2014-03-01

To evaluate the anti-inflammatory and analgesic effect of Bromelain (pineapple extract) administered orally in the postoperative after extraction of impacted lower molars. This is a prospective, placebo-controlled, unicentric, double-blind study; the sample size was 34 patients. The pre and postoperative outcomes, evaluated on the third (D3) and eighth day (D8), included inflamtion, pain and oral aperture, as well as the need for analgesics. One group received Bromelain 150mg per day for three days and 100mg on days 4 to 7. The other group received placebo in the same dosage. All outcomes werrecorded quantitatively and analyzed with the Mann-Whitney U test for independent samples. Although there were no statistically significant differences between the treatment groups, a trend towards less inflammation and improved oral aperture was observed in the group that received Bromelain, compared to the group that received placebo. This trend can be attributed completely to random reasons, since there is no statistical difference in the results. Further studies are necessary to analyze different administration patterns and doses of Bromelain for the use in the postoperative of impacted third molars.

Efficacy of ketamine in improving pain after tonsillectomy in children: meta-analysis.

PubMed

Cho, Hye Kyung; Kim, Kyu Won; Jeong, Yeon Min; Lee, Ho Seok; Lee, Yeon Ji; Hwang, Se Hwan

2014-01-01

The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children. Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0-24 hours after leaving the operation room were included in the analysis. The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics. Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study.

Pharmacokinetics and pharmacodynamics of glycyrrhetinic acid with Paeoniflorin after transdermal administration in dysmenorrhea model mice.

PubMed

Ding, Xue; Sun, Yuming; Wang, Qing; Pu, Tingting; Li, Xiaohui; Pan, Yaqing; Yang, Yang

2016-07-15

Glycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine. The aim of this work was to investigate the combinatory analgesic effect of GA and PF after percutaneous administration and to define their pharmacokinetic/pharmacodynamic (PK/PD) characteristics. GA and PF were produced to transdermal patches based on previous research, and the permeation parameters of GA and PF in the patches were investigated with in vitro experiments. Dysmenorrhea model mice were then produced to compare the analgesic effects of the patches with different proportions of GA-PF. In the in vivo assessment, the number of writhes exhibited by the dysmenorrhea mice was recorded at designated time points, and skin, muscle under skin and plasma samples were collected, for assessments of drug distribution, pharmacokinetics parameters and PK/PD characteristics. In dysmenorrhea mice, GA-PF and meloxicam (the positive control drug) could relieve pain to equal degrees. Specifically, a single dose of the optimized patches (10%GA-10%PF, wt) exerted a steady analgesic effect for 48h in dysmenorrhea mice, but this effect lagged behind the changes in the plasma concentration. Evaluation with the Bliss Independence criterion revealed that the two ingredients displayed a synergistic effect. Then the PK/PD relationship of GA in this compound preparation was defined with this synergistic effect. The preparation might be suitable for topical spasmolysis and anti-inflammatory therapy. Copyright © 2016 Elsevier GmbH. All rights reserved.

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.

EVALUATION OF EFFECTIVENESS IN A NOVEL WOUND HEALING OINTMENT-CROCODILE OIL BURN OINTMENT

PubMed Central

Li, Hua-Liang; Deng, Yi-Tao; Zhang, Zi-Ran; Fu, Qi-Rui; Zheng, Ya-Hui; Cao, Xing-Mei; Nie, Jing; Fu, Li-Wen; Chen, Li-Ping; Xiong, You-Xiong; Shen, Dong-Yan; Chen, Qing-Xi

2017-01-01

Background: Crocodile oil and its products are used as ointments for burns and scalds in traditional medicines. A new ointment formulation - crocodile oil burn ointment (COBO) was developed to provide more efficient wound healing activity. The purpose of the study was to evaluate the burn healing efficacy of this new formulation by employing deep second-degree burns in a Wistar rat model. The analgesic and anti-inflammatory activities of COBO were also studied to provide some evidences for its further use. Materials and methods: The wound healing potential of this formulation was evaluated by employing a deep second-degree burn rat model and the efficiency was comparatively assessed against a reference ointment - (1% wt/wt) silver sulfadiazine (SSD). After 28 days, the animals were euthanized and the wounds were removed for transversal and longitudinal histological studies. Acetic acid-induced writhing in mice was used to evaluate the analgesic activity and its anti-inflammatory activity was observed in xylene -induced edema in mice. Results: COBO enhanced the burn wound healing (20.5±1.3 d) as indicated by significant decrease in wound closure time compared with the burn control (25.0±2.16 d) (P<0.01). Hair follicles played an importance role in the physiological functions of the skin, and their growth in the wound could be revealed for the skin regeneration situation. Histological results showed that the hair follicles were well-distributed in the post-burn skin of COBO treatment group, and the amounts of total, active, primary and secondary hair follicles in post-burn 28-day skin of COBO treatment groups were more than those in burn control and SSD groups. On the other hand, the analgesic and anti-inflammatory activity of COBO were much better than those of control group, while they were very close to those of moist exposed burn ointment (MEBO). Conclusions: COBO accelerated wound closure, reduced inflammation, and had analgesic effects compared with SSD in deep second degree rat burn model. These findings suggest that COBO would be a potential therapy for treating human burns. Abbreviations: COBO, crocodile oil burn ointment; SSD, silver sulfadiazine; MEBO, moist exposed burn ointment; TCM, traditional Chinese medicine; CHM, Chinese herbal medicine; GC-MS, gas chromatography-mass spectrometry. PMID:28480384

EVALUATION OF EFFECTIVENESS IN A NOVEL WOUND HEALING OINTMENT-CROCODILE OIL BURN OINTMENT.

PubMed

Li, Hua-Liang; Deng, Yi-Tao; Zhang, Zi-Ran; Fu, Qi-Rui; Zheng, Ya-Hui; Cao, Xing-Mei; Nie, Jing; Fu, Li-Wen; Chen, Li-Ping; Xiong, You-Xiong; Shen, Dong-Yan; Chen, Qing-Xi

2017-01-01

Crocodile oil and its products are used as ointments for burns and scalds in traditional medicines. A new ointment formulation - crocodile oil burn ointment (COBO) was developed to provide more efficient wound healing activity. The purpose of the study was to evaluate the burn healing efficacy of this new formulation by employing deep second-degree burns in a Wistar rat model. The analgesic and anti-inflammatory activities of COBO were also studied to provide some evidences for its further use. The wound healing potential of this formulation was evaluated by employing a deep second-degree burn rat model and the efficiency was comparatively assessed against a reference ointment - (1% wt/wt) silver sulfadiazine (SSD). After 28 days, the animals were euthanized and the wounds were removed for transversal and longitudinal histological studies. Acetic acid-induced writhing in mice was used to evaluate the analgesic activity and its anti-inflammatory activity was observed in xylene -induced edema in mice. COBO enhanced the burn wound healing (20.5±1.3 d) as indicated by significant decrease in wound closure time compared with the burn control (25.0±2.16 d) ( P <0.01). Hair follicles played an importance role in the physiological functions of the skin, and their growth in the wound could be revealed for the skin regeneration situation. Histological results showed that the hair follicles were well-distributed in the post-burn skin of COBO treatment group, and the amounts of total, active, primary and secondary hair follicles in post-burn 28-day skin of COBO treatment groups were more than those in burn control and SSD groups. On the other hand, the analgesic and anti-inflammatory activity of COBO were much better than those of control group, while they were very close to those of moist exposed burn ointment (MEBO). COBO accelerated wound closure, reduced inflammation, and had analgesic effects compared with SSD in deep second degree rat burn model. These findings suggest that COBO would be a potential therapy for treating human burns. Abbreviations: COBO, crocodile oil burn ointment; SSD, silver sulfadiazine; MEBO, moist exposed burn ointment; TCM, traditional Chinese medicine; CHM, Chinese herbal medicine; GC-MS, gas chromatography-mass spectrometry.

Too Deep or Not Too Deep?: A Propensity-Matched Comparison of the Analgesic Effects of a Superficial Versus Deep Serratus Fascial Plane Block for Ambulatory Breast Cancer Surgery.

PubMed

Abdallah, Faraj W; Cil, Tulin; MacLean, David; Madjdpour, Caveh; Escallon, Jaime; Semple, John; Brull, Richard

2018-07-01

Serratus fascial plane block can reduce pain following breast surgery, but the question of whether to inject the local anesthetic superficial or deep to the serratus muscle has not been answered. This cohort study compares the analgesic benefits of superficial versus deep serratus plane blocks in ambulatory breast cancer surgery patients at Women's College Hospital between February 2014 and December 2016. We tested the joint hypothesis that deep serratus block is noninferior to superficial serratus block for postoperative in-hospital (pre-discharge) opioid consumption and pain severity. One hundred sixty-six patients were propensity matched among 2 groups (83/group): superficial and deep serratus blocks. The cohort was used to evaluate the effect of blocks on postoperative oral morphine equivalent consumption and area under the curve for rest pain scores. We considered deep serratus block to be noninferior to superficial serratus block if it were noninferior for both outcomes, within 15 mg morphine and 4 cm·h units margins. Other outcomes included intraoperative fentanyl requirements, time to first analgesic request, recovery room stay, and incidence of postoperative nausea and vomiting. Deep serratus block was associated with postoperative morphine consumption and pain scores area under the curve that were noninferior to those of the superficial serratus block. Intraoperative fentanyl requirements, time to first analgesic request, recovery room stay, and postoperative nausea and vomiting were not different between blocks. The postoperative in-hospital analgesia associated with deep serratus block is as effective (within an acceptable margin) as superficial serratus block following ambulatory breast cancer surgery. These new findings are important to inform both current clinical practices and future prospective studies.

The Effect of Acupressure at Spleen 6 Acupuncture Point on the Anxiety Level and Sedative and Analgesics Consumption of Women during Labor: A Randomized, Single-blind Clinical Trial

PubMed Central

Samadi, Parisa; Alipour, Zahra; Lamyian, Minoor

2018-01-01

Background: Labor pain is the most severe pain women would experience, which could lead to loss of emotional control that plays a key role in creating a traumatic delivery experience and psychological disorders. The goal of this study was to evaluate the effect of acupressure on anxiety level and sedative and analgesics consumption in women during labor. Materials and Methods: This study was a randomized, single-blind clinical trial performed at Maryam Hospital in Tehran, Iran. One hundred and thirty-one pregnant women in Labor Ward were selected by convenience sampling. Subjects were randomly allocated to three groups, namely experimental group (pressure group), control group 1(touh group) and, control group 2 (routine care group). The study data were gathered using demographic information form, and assessed with Faces Anxiety Scale (FAS). For participants belonging to the experimental group, pressure was applied to the Spleen 6 acupoint for 30 min, and for those with only light touch was applied to the Spleen 6 acupoint for 30 min. The collected data were analyzed using Statistical Package for the Social Sciences 16 and descriptive statistics. Results: There was a significant difference between the three groups in terms of the mean of anxiety after 30 min of starting the intervention and 30 min after termination of the intervention; the anxiety of the experimental group was significantly decreased (p = 0.03). Sedative and analgesics consumption was significantly lower in the experimental group compared to the other groups (p = 0.006). Conclusions: This study showed that compression of the Spleen 6 acupoint was an effective complementary method to decrease maternal anxiety and analgesic consumption, especially pethidine. PMID:29628954

Evaluation of analgesic, anti-inflammatory, anti-depressant and anti-coagulant properties of Lactuca sativa (CV. Grand Rapids) plant tissues and cell suspension in rats.

PubMed

Ismail, Hammad; Mirza, Bushra

2015-06-27

Lactuca sativa (lettuce) has been traditionally used for relieving pain, inflammation, stomach problems including indigestion and lack of appetite. Moreover, the therapeutic significance of L. sativa includes its anticonvulsant, sedative-hypnotic and antioxidant properties. In the present study, the MC (methanol and chloroform; 1:1) and aqueous extracts of seed and leaf along with cell suspension exudate were prepared. These extracts were explored for their analgesic, anti-inflammatory, antidepressant and anticoagulant effects by hot plate analgesic assay; carrageenan induced hind paw edema test, forced swimming test and capillary method for blood clotting respectively in a rat model. The results were analyzed using one-way Analysis of Variance (ANOVA) followed by Turkey multiple comparison test. Interestingly, the extracts and the cell suspension exudate showed dual inhibition by reducing pain and inflammation. The results indicated that the aqueous extracts of leaf exhibited highest analgesic and anti-inflammatory activities followed by leaf MC, cell suspension exudate, seed aqueous and seed MC extracts. The current findings show that aqueous and MC extracts of seed have the least immobility time in the forced swimming test, which could act as an anti-depressant on the central nervous system. The leaf extracts and cell suspension exudate also expressed moderate anti-depressant activities. In anticoagulant assay, the coagulation time of aspirin (positive control) and MC extract of leaf was comparable, suggesting strong anti-coagulant effect. Additionally, no abnormal behavior or lethality was observed in any animal tested. Taken together, L. sativa can potentially act as a strong herbal drug due to its multiple pharmaceutical effects and is therefore of interest in drug discovery and development of formulations.

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.

Therapeutic efficacy of bromelain in impacted third molar surgery: a randomized controlled clinical study.

PubMed

Ordesi, Paolo; Pisoni, Luca; Nannei, Pierluigi; Macchi, Maurizia; Borloni, Roberto; Siervo, Sandro

2014-09-01

Bromelain is the name given to a family of proteolytic enzymes obtained from Ananas comosus, the pineapple plant. It is considered a potent anti-inflammatory and antiedematous substance. Surgery of impacted third molars in the outpatient setting is one of the procedures most often associated with postoperative pain and swelling. The aim of this study was to evaluate the efficacy of bromelain in reducing postoperative pain and swelling. 80 patients were recruited to the study from patients attending the Maxillofacial Surgery Unit of the Istituto Stomatologico Italiano, Milan, Italy, for impacted third molar surgery. At time 0 when surgery was performed, patients started simultaneous antibiotic and analgesic therapy. On the following day, patients were divided into two groups. Patients in group 1 were prescribed bromelain. Patients in group 2 were prescribed only the analgesic if required. Three parameters were evaluated: pain, edema, and erythema. The first evaluation visit was performed 3 hours after surgery, the second 48 hours after surgery, and the final evaluation 7 days after surgery. Postoperative pain, edema, and erythema were significantly lower in the study group than in the control group. Analgesic consumption, both in terms of days of treatment and number of tablets taken, was slightly lower in the study group. Only one adverse event was recorded, which occurred in a patient in the control group. The present study demonstrates an important anti-inflammatory and anti-edematous effect of bromelain. Statistical analysis shows that in the group treated with bromelain the inflammatory response was significantly less than in the control group.

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.

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

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.

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.

Perioperative Opioid Analgesics and Hip Arthroscopy: Trends, Risk Factors for Prolonged Use, and Complications.

PubMed

Anciano Granadillo, Victor; Cancienne, Jourdan M; Gwathmey, F Winston; Werner, Brian C

2018-05-02

The purpose of this article is to (1) examine trends in preoperative and prolonged postoperative opioid analgesic use in patient undergoing hip arthroscopy, (2) characterize risk factors for prolonged opioid analgesic use following hip arthroscopy, and (3) explore preoperative and prolonged postoperative opioid analgesic use as independent risk factors for complications following hip arthroscopy. A private insurance database was queried for patients undergoing hip arthroscopy from 2007 to 2015 with a minimum of 6 months of follow-up. Independent risk factors for prolonged opioid analgesic use were determined. Preoperative and prolonged opioid analgesic use as risk factors for complications were examined. There was a significantly decreasing trend in preoperative (P = .002) and prolonged postoperative (P = .009) opioid analgesic use. The most significant risk factor for prolonged postoperative opioid analgesic use was preoperative use (odds ratio [OR], 3.61; P < .0001). Other preoperative prescriptions, including muscle relaxants (OR, 1.5; P < .0001) and anxiolytics (OR, 2.0; P < .0001), were also significant risk factors. Preoperative opioid analgesic use was a significant risk factor for postoperative complications, including emergency room visits (OR, 2.1; P < .0001) and conversion to total hip arthroplasty (THA) (OR, 1.6; P < .0001). Prolonged postoperative opioid analgesic use was associated with a higher risk of revision hip arthroscopy (OR, 1.4; P = .0004) and conversion to THA (OR, 1.8; P < .0001). More than a quarter of patients undergoing hip arthroscopy continue to receive opioid analgesic prescriptions more than 3 months postoperatively. The most significant risk factor for prolonged opioid analgesic use is preoperative opioid analgesic use. Additionally, anxiolytics, substance use or abuse, morbid obesity, and back pain were among the more notable risk factors for prolonged postoperative opioid analgesic use. Preoperative and prolonged postoperative opioid analgesic use was associated with a higher likelihood of several adverse effects/complications. Level III, retrospective comparative study. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Factors associated with a continuous regular analgesic use - a population-based study of more than 45,000 Danish women and men 18-45 years of age.

PubMed

Hargreave, Marie; Andersen, Tina Veje; Nielsen, Ann; Munk, Christian; Liaw, Kai-Li; Kjaer, Susanne K

2010-01-01

Widespread use of and serious adverse effects associated with use of analgesics accentuates the need to consider factors related to analgesic use. The objective of this study was to describe continuous regular analgesics use and examine factors associated with a continuous regular analgesic use. The study was based on data from two surveys and included a random sample of women and men aged 18-45 years from the general Danish population. Information on analgesics use, self-rated health, demographic and lifestyle factors was collected using a self-administered questionnaire. A total of 28,000 women and 33 000 men were invited to participate and 22,199 women (response-rate 81.4%) and 23,080 men (response-rate 71.0%), respectively, were included in the study. Data were analyzed using multivariate logistic regression. We found that 27% of the women and 18% of the men reported a regular monthly use of at least seven analgesic tablets during the last year (continuous regular analgesics use). Besides poor self-rated health we found in both sexes that increasing age, poor self-rated fitness, and smoking were related to a continuous regular analgesics use. Nulliparity, low level of education, overweight/obesity, binge drinking, and abstinence were associated with a continuous regular analgesics use for women, while underweight and marital/cohabiting status were associated with a continuous regular analgesics use only for men. Regular monthly analgesic use during the last year was generally prevalent. Besides self-rated health, several socio-demographic and lifestyle factors were associated with a continuous regular analgesic use, although with some gender differences.

Selective enhancement of fentanyl-induced antinociception by the delta agonist SNC162 but not by ketamine in rhesus monkeys: Further evidence supportive of delta agonists as candidate adjuncts to mu opioid analgesics.

PubMed

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

2010-12-01

Mu-opioid receptor agonists such as fentanyl are effective analgesics, but their clinical use is limited by untoward effects. Adjunct medications may improve the effectiveness and/or safety of opioid analgesics. This study compared interactions between fentanyl and either the noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine or the delta-opioid receptor agonist SNC162 [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-phenyl)methyl]-N,N-diethylbenzamide] in two behavioral assays in rhesus monkeys. An assay of thermal nociception evaluated tail-withdrawal latencies from water heated to 50 and 54°C. An assay of schedule-controlled responding evaluated response rates maintained under a fixed-ratio 30 schedule of food presentation. Effects of each drug alone and of three mixtures of ketamine+fentanyl (22:1, 65:1, 195:1 ketamine/fentanyl) or SNC162+fentanyl (59:1, 176:1, 528:1 SNC162/fentanyl) were evaluated in each assay. All drugs and mixtures dose-dependently decreased rates of food-maintained responding, and drug proportions in the mixtures were based on relative potencies in this assay. Ketamine and SNC162 were inactive in the assay of thermal antinociception, but fentanyl and all mixtures produced dose-dependent antinociception. Drug interactions were evaluated using dose-addition and dose-ratio analysis. Dose-addition analysis revealed that interactions for all ketamine/fentanyl mixtures were additive in both assays. SNC162/fentanyl interactions were usually additive, but one mixture (176:1) produced synergistic antinociception at 50°C. Dose-ratio analysis indicated that ketamine failed to improve the relative potency of fentanyl to produce antinociception vs. rate suppression, whereas two SNC162/fentanyl mixtures (59:1 and 176:1) increased the relative potency of fentanyl to produce antinociception. These results suggest that delta agonists may produce more selective enhancement than ketamine of mu agonist-induced antinociception. Copyright © 2010 Elsevier Inc. All rights reserved.

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.

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.

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.

[The effects of transversus abdominis plane block on analgesic and anesthetic consumption during total abdominal hysterectomy: a randomized controlled study].

PubMed

Karaman, Tugba; Ozsoy, Asker Zeki; Karaman, Serkan; Dogru, Serkan; Tapar, Hakan; Sahin, Aynur; Dogru, Hatice; Suren, Mustafa

A transversus abdominis plane block is a peripheral block method that has been used successfully for pain relief after total abdominal hysterectomy. However, the effects of the combination of the transversus abdominis plane block and general anesthesia on analgesic and anesthetic requirements remain unclear. This randomized placebo-controlled study is aimed to evaluate the effects of transversus abdominis plane block on analgesic and anesthetic consumption during total abdominal hysterectomy under general anesthesia. Sixty-six women undergoing total abdominal hysterectomy were randomized into two groups to receive general anesthesia alone (control group) or with transversus abdominis plane block using 20mL of 0.25% bupivacaine (transversus abdominis plane group). Intraoperative remifentanil and sevoflurane consumption were recorded. We also evaluated the postoperative pain, nausea, quality of recovery scores and rescue analgesic requirement during postoperative 24hours. The total remifentanil and sevoflurane consumption is significantly lower in transversus abdominis plane group; respectively mean (SD) 0.130 (0.25) vs. 0.094 (0.02) mcg.kg -1 .min -1 ; p<0.01 and 0.295 (0.05) vs. 0.243 (0.06) mL.min -1 ; p<0.01. In the postoperative period, pain scores were significantly reduced in transversus abdominis plane group soon after surgery; median (range) 6 (2-10) vs. 3 (0-5); p<0.001, at 2h (5 [3-9] vs. 2.5 [0-6]; p<0.001), at 6h (4 [2-7] vs. 3[0-6], p<0.001), at 12h (3.5 [1-6] vs. 2 [1-5]; p=0.003). The patients in the transversus abdominis plane group had significantly higher QoR-40 scores 190.5 (175-197) vs. 176.5 (141-187); p<0.001). Combining transversus abdominis plane block with general anesthesia can provide reduced opioid and anesthetic consumption and can improve postoperative pain and quality of recovery scores in patients undergoing total abdominal hysterectomy. Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

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.

Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2.

PubMed

Piekielna-Ciesielska, Justyna; Mollica, Adriano; Pieretti, Stefano; Fichna, Jakub; Szymaszkiewicz, Agata; Zielińska, Marta; Kordek, Radzisław; Janecka, Anna

2018-12-01

Opioid peptides and opiate drugs such as morphine, mediate their analgesic effects, but also undesired side effects, mostly through activation of the mu opioid receptor. However, delta- and kappa-opioid receptors can also contribute to the analgesic effects of opioids. Recent findings showed that simultaneous activation of multiple opioid receptors may result in additional analgesia with fewer side effects. Here, we evaluated the pharmacological profile of our formerly developed mixed mu/kappa-opioid receptor ligands, Dmt-c[D-Lys-Phe-Phe-Asp]NH 2 (C-36) and Dmt-c[D-Lys-Phe-p-CF 3 -Phe-Asp]NH 2 (F-81). The ability of these peptides to cross the blood-brain barrier was tested in the parallel artificial membrane permeability (PAMPA) assay. On the basis of the hot-plate test in mice after central and peripheral administration, analog F-81 was selected for the anti-nociceptive and anti-inflammatory activity assessment after peripheral administration.

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

Analgesic and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice

PubMed Central

Tsai, Der-Shiang; Huang, Mei-Hsuen; Tsai, Jen-Chieh; Chang, Yuan-Shuang; Chiu, Yung-Jia; Lin, Yen-Chang

2015-01-01

Abstract In this study, we evaluated the analgesic and anti-inflammatory activities of a 70% ethanol extract from Rosa taiwanensis Nakai (RTEtOH). The analgesic effect was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity was evaluated by λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of RTEtOH was examined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) in the paw edema tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver tissue. The betulinic acid and oleanolic acid contents of RTEtOH were assayed by HPLC. The results showed that RTEtOH decreased the acetic acid-induced writhing responses (1.0 g/kg) and the late phase of the formalin-induced licking time (0.5 and 1.0 g/kg). In the anti-inflammatory models, RTEtOH (0.5 and 1.0 g/kg) reduced the paw edema at 3, 4, and 5 h after λ-carrageenan administration. Moreover, the anti-inflammatory mechanisms might be due to the decreased levels of COX-2, TNF-α, IL-1β, and IL-6, as well as the inhibition of NO and MDA levels through increasing the activities of SOD, GPx, and GRd. The contents of two active compounds, betulinic acid and oleanolic acid, were quantitatively determined. This study demonstrated the analgesic and anti-inflammatory activities of RTEtOH and provided evidence to support its therapeutic use in inflammatory diseases. PMID:25494361

Efficacy of periportal infiltration and intraperitoneal instillation of ropivacaine after laparoscopic surgery in children.

PubMed

Di Pace, Maria Rita; Cimador, Marcello; Catalano, Pieralba; Caruso, Anna; Sergio, Maria; Casuccio, Alessandra; De Grazia, Enrico

2009-12-01

Postoperative pain is less intense after laparoscopic than after open surgery. However, minimally invasive surgery is not a a pain-free procedure. Many trials have been done in adults using intraperitoneal and/or incisional local anesthetic, but similar studies have not yet been reported in the literature in children. The aim of this study was to evaluate the analgesic effect of periportal infiltration and intraperitoneal instillation of ropivacaine in children undergoing laparoscopic surgery. Thirty patients who underwent laparoscopic surgery were randomly allocated to one of three groups. Group A (n = 10) received local infiltration of port sites with 10 mL of ropivacaine. Group B (n = 10) received both an infiltration of port sites with 10 mL of ropivacaine and an intraperitoneal instillation of 10 mL of ropivacaine. Group C did not receive any analgesic treatment. The local anesthetic was always administered at the end of surgery. The degree of postoperative abdominal parietal pain, abdominal visceral pain, and shoulder pain was assessed by using a Wong-Baker pain scale and a Visual Analog Scale (VAS) at 3, 6 12, and 24 hours postoperatively. The following parameters were also evaluated: rescue analgesic treatment, length of hospital stay, and time of return to normal activities. Three hours after operation, patients had low pain scores. Six and 12 hours postoperatively, the abdominal parietal pain was significantly higher (P < 0.0005) in group C than in the other two groups, both treated with an infiltration at the trocar sites; mean intensity of abdominal visceral pain was significantly lower (P < 0.0005) in group B than in groups A and C; the overall incidence of shoulder pain was significantly lower (P < 0.0005) in group B patients than in patients of groups A and C. At 20 hours postoperatively, pain scores were significantly reduced of intensity in all groups. Rescue analgesic treatment was significantly higher in group C, if compared to groups A and B 12 hours after the operation. No statistically significant difference was found in length of hospital stay, but children who received analgesic treatment had a more rapid return to normal activities than untreated patients (P < 0.0005). Our study demonstrates that the combination of local infiltration and intraperitoneal instillation of ropivacaine is more effective for pain relief in children after laparoscopic surgery than the administration of ropivacaine only at the trocar sites.

Seeing an Embodied Virtual Hand is Analgesic Contingent on Colocation.

PubMed

Nierula, Birgit; Martini, Matteo; Matamala-Gomez, Marta; Slater, Mel; Sanchez-Vives, Maria V

2017-06-01

Seeing one's own body has been reported to have analgesic properties. Analgesia has also been described when seeing an embodied virtual body colocated with the real one. However, there is controversy regarding whether this effect holds true when seeing an illusory-owned body part, such as during the rubber-hand illusion. A critical difference between these paradigms is the distance between the real and surrogate body part. Colocation of the real and surrogate arm is possible in an immersive virtual environment, but not during illusory ownership of a rubber arm. The present study aimed at testing whether the distance between a real and a virtual arm can explain such differences in terms of pain modulation. Using a paradigm of embodiment of a virtual body allowed us to evaluate heat pain thresholds at colocation and at a 30-cm distance between the real and the virtual arm. We observed a significantly higher heat pain threshold at colocation than at a 30-cm distance. The analgesic effects of seeing a virtual colocated arm were eliminated by increasing the distance between the real and the virtual arm, which explains why seeing an illusorily owned rubber arm does not consistently result in analgesia. These findings are relevant for the use of virtual reality in pain management. Looking at a virtual body has analgesic properties similar to looking at one's real body. We identify the importance of colocation between a real and a surrogate body for this to occur and thereby resolve a scientific controversy. This information is useful for exploiting immersive virtual reality in pain management. Copyright © 2017. Published by Elsevier Inc.

Derivatives of furanditerpenes from Pterodon genus: Pharmacological studies disclose their potential as chronic pain relief in mice.

PubMed

Spindola, Humberto M; Grando, Rogério; Figueiredo, Mariana C; Basting, Rosana; Queiroz, N C A; de Fátima, Ângelo; de Carvalho, João E; Wang, Zaijie J; Foglio, M A

2017-06-05

Pterodon genus fruits are commercially available at the Brazilian medicinal market used in folk medicine due to their anti-inflammatory, analgesic, and anti-rheumatic effects. Previous studies demonstrated that furanditerpenes possessing vouacapan skeleton, isolated from Pterodon genus, possess expressive antinociceptive activities, with promising moiety for the development of new analgesic products. The antinociceptive properties of compounds 6α,7β-6α-hidroxivouacapan-7β-17β-lactone (HVL) and 6α-oxovouacapan-7β-17β-lactone (OVL), semi-synthetic analogues of furanditerpenes previously reported as analgesic agents were evaluated on animal experimental models (Spindola et al., 2010, 2011). The chemical-induced pain methods used in the present work, demonstrated for the first time that both compounds HVL and OVL have potential as important templates for the development of chronic pain control drugs. The main findings of this work were that both compounds were: effective in the writhing test; reduced paw edema in the carrageenan test; effective in the inflammatory phase of the formalin test corroborating their activity against inflammatory pain conditions; effective on reducing pain through the stimulation of vanilloid receptors sensible to capsaicin (an important pathway for chronic pain maintenance); reduced the pain stimulus caused by PGE 2 injection (a pathway involved in chronic pain hypersensitivity); effective on decreasing mechanical allodynia in the CFA-model, demonstrating their potential use against chronic pain disorders. Copyright © 2017 Elsevier B.V. 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.

A prospective randomized, double-dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of  pain in the ED.

PubMed

Motov, Sergey; Mai, Mo; Pushkar, Illya; Likourezos, Antonios; Drapkin, Jefferson; Yasavolian, Matthew; Brady, Jason; Homel, Peter; Fromm, Christian

2017-08-01

Compare adverse effects and analgesic efficacy of low-dose ketamine for acute pain in the ED administered either by single intravenous push (IVP) or short infusion (SI). Patients 18-65, presenting to ED with acute abdominal, flank, or musculoskeletal pain with initial pain score≥5, were randomized to ketamine 0.3mg/kg by either IVP or SI with placebo double-dummy. Adverse effects were evaluated by Side Effects Rating Scale for Dissociative Anesthetics (SERSDA) and Richmond Agitation-Sedation Scale (RASS) at 5, 15, 30, 60, 90, and 120min post-administration; analgesic efficacy was evaluated by Numerical Rating Scale (NRS). 48 patients enrolled in the study. IVP group had higher overall rates of feeling of unreality on SERSDA scale: 92% versus 54% (difference 37.5%; p=0.008; 95% CI 9.3-59.5%). At 5min median severity of feeling of unreality was 3.0 for IVP versus 0.0 for SI (p=0.001). IVP also showed greater rates of sedation on RASS scale at 5min: median RASS -2.0 versus 0.0 (p=0.01). Decrease in mean pain scores from baseline to 15min was similar across groups: 5.2±3.53 (95% CI 3.7-6.7) for IVP; 5.75±3.48 (95% CI 4.3-7.2) for SI. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication. Low-dose ketamine given as a short infusion is associated with significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of magnesium sulphate on intraoperative neuromuscular blocking agent requirements and postoperative analgesia in children with cerebral palsy.

PubMed

Na, H-S; Lee, J-H; Hwang, J-Y; Ryu, J-H; Han, S-H; Jeon, Y-T; Do, S-H

2010-03-01

In this double-blind, randomized, placebo-controlled study, we evaluated the effects of magnesium sulphate on neuromuscular blocking agent requirements and analgesia in children with cerebral palsy (CP). We randomly divided 61 children with CP undergoing orthopaedic surgery into two groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and 15 mg kg(-1) h(-1) by continuous infusion during the operation. The control group (Group S) received the same amount of isotonic saline. Rocuronium was administered 0.6 mg kg(-1) before intubation and 0.1 mg kg(-1) additionally when train-of-four counts were 2 or more. I.V. fentanyl and ketorolac were used to control postoperative pain. Total infused analgesic volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and 48 h. The rocuronium requirement of Group M was significantly less than that of Group S [0.29 (0.12) vs 0.42 (0.16) mg kg(-1) h(-1), P<0.05]. Cumulative analgesic consumption in Group M was significantly less after operation at 24 and 48 h (P<0.05), and pain scores in Group M were lower than in Group S during the entire postoperative period (P<0.05). Serum magnesium concentrations in Group M were higher until 24 h after operation (P<0.05). The incidence of postoperative nausea and vomiting and rescue drug injections was similar in the two groups. No shivering or adverse effects related to hypermagnesaemia were encountered. I.V. magnesium sulphate reduces rocuronium requirements and postoperative analgesic consumption in children with CP.

Effect of magnesium added to local anesthetics for caudal anesthesia on postoperative pain in pediatric surgical patients: A systematic review and meta-analysis with Trial Sequential Analysis

PubMed Central

Mihara, Takahiro; Nakamura, Nobuhito; Ka, Koui; Goto, Takahisa

2018-01-01

Background Magnesium has been investigated as an adjuvant for neuraxial anesthesia, but the effect of caudal magnesium on postoperative pain is inconsistent. The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of caudal magnesium. Methods We searched six databases, including trial registration sites. Randomized clinical trials reporting the effect of caudal magnesium on postoperative pain after general anesthesia were eligible. The risk ratio for use of rescue analgesics after surgery was combined using a random-effects model. We also assessed adverse events. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Results Four randomized controlled trials (247 patients) evaluated the need for rescue analgesics. In all four trials, 50 mg of magnesium was administered with caudal ropivacaine. The results suggested that the need for rescue analgesia was reduced significantly by caudal magnesium administration (risk ratio 0.45; 95% confidence interval 0.24–0.86). There was considerable heterogeneity as indicated by an I2 value of 62.5%. The Trial Sequential Analysis-adjusted confidence interval was 0.04–5.55, indicating that further trials are required. The quality of evidence was very low. The rate of adverse events was comparable between treatment groups. Conclusion Caudal magnesium may reduce the need for rescue analgesia after surgery, but further randomized clinical trials with a low risk of bias and a low risk of random errors are necessary to assess the effect of caudal magnesium on postoperative pain and adverse events. Trial registration University Hospital Medical Information Network Clinical Trials Registry UMIN000025344. PMID:29293586

Evaluation of transversus abdominis plane block for renal transplant recipients - A meta-analysis and trial sequential analysis of published studies.

PubMed

Singh, Preet Mohinder; Borle, Anuradha; Makkar, Jeetinder Kaur; Trisha, Aanjan; Sinha, Aashish

2018-01-01

Patients undergoing renal transplant (RT) have altered drug/opioid pharmacokinetics. Transversus abdominis plane (TAP) block in renal transplant recipients has been recently evaluated for analgesic and opioid-sparing potential by many trials. The studies comparing TAP-block to conventional analgesic regimens for RT were searched. Comparisons were made for total opioids consumed (as morphine-equivalents) during the first postoperative 24-h (primary objective), intraoperative, and immediate-postoperative period. Pain scores and postoperative nausea-vomiting (PONV) were also evaluated. Trial sequential analysis (TSA) was used to quantify the strength of analysis. Ten-trials with 258 and 237 patients in control and TAP-block group, respectively, were included. TAP-block decreased the 24-h (reported in 9-trials) opioid consumption by 14.61 ± 4.34 mg (reduction by 42.7%, random-effects, P < 0.001, I 2 = 97.82%). Sample size of the present analysis (472) was well past the required "information-size" variable (396) as per the TSA for a power of 85%. Intraoperative opioid consumption also decreased by 2.06 ± 0.63 mg (reduction of 27.8%) (random effects, P < 0.001, I 2 = 98.84%). Pain scores with TAP-block were significantly lower in both early and delayed postoperative phase. Odds ratio for PONV without TAP block was 1.99 ± 1.05 (Fixed-effects, P = 0.04, I 2 = 0%). Publication bias was likely (Egger's test, X-intercept=7.89, P < 0.05). TAP-block significantly lowers the intraoperative and cumulative postoperative 24-h opioid consumption in RT recipients. Persistent and better pain control is achieved when TAP-Block is used. Benefits of TAP block extend beyond the analgesic actions alone as it also decreases the 24-h incidence of postoperative nausea vomiting as well. The technique of the block needs standardization for RT recipients.

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.

Synthesis and Pharmacological Evaluation of New Chemical Entities from Ibuprofen as Novel Analgesic Candidates.

PubMed

Ahmadi, A; Naderi, N; Daniali, M; Kazemi, S; Aazami, S; Alizadeh, N; Nahri-Niknafs, B

2015-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice of drugs that are normally used for the treatment of pain and inflammation. Ibuprofen (I) and its analogues as the most widely used NSAIDs have been synthesized in recent years. In an effort to establish new candidates with improved analgesic properties, derivatives (II-VII) with substituted aromatic as well as aliphatic moieties were synthesized in this experiment and evaluated in formalin test with rats. The results were compared to ibuprofen and control groups. Findings indicated that derivatives with new alkylphenyl rings (VI and VII) had some similar or more analgesic activities relative to the control and ibuprofen groups, respectively; which could be justified as to more alkyl and phenyl groups instead of p-isobutylphenyl moiety in I. © Georg Thieme Verlag KG Stuttgart · New York.

Minocycline encapsulated chitosan nanoparticles for central antinociceptive activity.

PubMed

Nagpal, Kalpana; Singh, S K; Mishra, D N

2015-01-01

The purpose of the study is to explore the central anti-nociceptive activity of brain targeted nanoparticles (NP) of minocycline hydrochloride (MH). The NP were formulated using the modified ionotropic gelation method (MHNP) and were coated with Tween 80 (T80) to target them to brain (cMHNP). The formulated nanoparticles have already been characterized for particle size, zeta potential, drug entrapment efficiency and in vitro drug release. The nanoparticles were then evaluated for pharmacodynamic activity using thermal methods. The pure drug and the formulation, MHNP were not able to show a statistically significant central analgesic activity. cMHNP on the other hand evidenced a significant central analgesic activity. Animal models evidenced that brain targeted nanoparticles may be utilized for effective delivery of central anti-nociceptive effect of MH. Further clinical studies are required to explore the activity for mankind. Copyright © 2014 Elsevier B.V. All rights reserved.

Anesthetics and analgesics in experimental traumatic brain injury: Selection based on experimental objectives

PubMed Central

Rowe, Rachel K.; Harrison, Jordan L.; Thomas, Theresa C.; Pauly, James R.; Adelson, P. David; Lifshitz, Jonathan

2013-01-01

The use of animal modeling in traumatic brain injury (TBI) research is justified by the lack of sufficiently comprehensive in vitro and computer modeling that incorporates all components of the neurovascular unit. Valid animal modeling of TBI requires accurate replication of both the mechanical forces and secondary injury conditions observed in human patients. Regulatory requirements for animal modeling emphasize the administration of appropriate anesthetics and analgesics unless withholding these drugs is scientifically justified. The objective of this review is to present scientific justification for standardizing the use of anesthetics and analgesics, within a study, when modeling TBI in order to preserve study validity. Evidence for the interference of anesthetics and analgesics in the natural course of brain injury calls for consistent consideration of pain management regimens when conducting TBI research. Anesthetics administered at the time of or shortly after induction of brain injury can alter cognitive, motor, and histological outcomes following TBI. A consistent anesthesia protocol based on experimental objectives within each individual study is imperative when conducting TBI studies to control for the confounding effects of anesthesia on outcome parameters. Experimental studies that replicate the clinical condition are essential to gain further understanding and evaluate possible treatments for TBI. However, with animal models of TBI it is essential that investigators assure a uniform drug delivery protocol that minimizes confounding variables, while minimizing pain and suffering. PMID:23877609

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.

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.

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.

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

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

[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.

An isobolographic analysis of the antinociceptive effect of xylopic acid in combination with morphine or diclofenac

PubMed Central

Woode, Eric; Ameyaw, Elvis Ofori; Abotsi, Wonder Kofi Mensah; Boakye-Gyasi, Eric

2015-01-01

Background: A common practice of managing pain globally is the combination of analgesics and this is aimed at facilitating patient compliance, simplifying prescription, and improving efficacy without increasing adverse effects. Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders and xylopic acid (XA) present in the fruit extract have been shown to possess analgesic properties in animals. There is the likelihood of concomitant use of XA and the commonly used analgesics in traditional settings. This study, therefore, evaluated the pharmacologic interaction between XA/morphine and xylopic/diclofenac combinations. Methods: The formalin test and acetic acid writhing test were used to study the antinociceptive activity of XA, morphine, and diclofenac. The isobolographic analysis was used to study the antinociceptive interactions between XA co-administered with morphine or diclofenac. Results: Results obtained revealed that XA (10–100 mg/kg), morphine (1–10 mg/kg), and diclofenac (1–10 mg/kg) produced dose-related antinociception with different potencies in the formalin and acetic acid writhing tests. Isobolographic analysis of XA/morphine and XA/diclofenac combinations revealed potentiation of their antinociceptive effects. The degree of potentiation calculated as interaction index showed synergism for both combinations in all the nociceptive tests. Conclusion: In conclusion, the present study demonstrated synergism for the co-administration of XA with morphine or diclofenac. PMID:26692735

Flavonoids to reduce bleeding and pain after stapled hemorrhoidopexy: a randomized controlled trial.

PubMed

Mlakar, Bostjan; Kosorok, Pavle

2005-08-01

Control of postoperative symptoms is of paramount importance in ambulatory surgery. This trial was conducted to evaluate whether a micronized purified flavonoid fraction (MPFF) (Detralex((R))) reduces postoperative bleeding, pain and consumption of analgesics after ambulatory stapled hemorrhoidopexy, as reported in trials after classic hemorrhoidectomy. Phlebotropic activity, protective effect on the capillaries and anti-inflammatory properties of this drug have been reported in several studies. Sixty-three patients with third-degree hemorrhoids had ambulatory stapled hemorrhoidopexy under spinal anesthesia in the period of one year. The patients were randomized, with 30 receiving Detralex 500 mg (2 tablets 3 times daily for 5 days after the operation) and 33 forming the control group. The patients were asked to daily self-assess the presence of blood on defecation, degree of pain and consumption of analgesics for the first week after the operation. There was no significant difference between the two groups in duration of presence of blood, degree of pain or analgesics requirement. No major complications, such as bleeding requiring transfusion or hospitalization, sepsis, anal stenosis or urgent defecation, were noted in the follow-up period. There were no side effects from Detralex treatment. In our study we could not demonstrate any positive effect of prescribing flavonoids after stapler hemorrhoidopexy. This procedure may not be sufficiently aggressive and is associated with too few postoperative complications to show any protective influence of flavonoids.

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.

Antioedematous and Analgesic Properties of Fertile Fronds of Drynaria quercifolia

PubMed Central

Anuja, G. I.; Latha, P. G.; Shine, V. J.; Suja, S. R.; Shikha, P.; Satheesh Kumar, K.; Rajasekharan, S.

2014-01-01

Inflammation is a complex biological response of tissue cells to harmful stimuli including trauma, tissue necrosis, and infections which plays a key role in the pathophysiology of many deadly diseases. In ethnomedicine Drynaria quercifolia fronds are used to treat inflammation as poultice on swellings and as antibacterial, hepatoprotective, and antipyretic agent. Herein, we have evaluated the antioedematous, antiproliferative, and analgesic properties of the ethanolic extract of fertile fronds of D. quercifolia (FF) by standard procedures. Oral administration of FF produced significant inhibition of carrageenan and histamine induced paw oedema in Wistar rats. FF significantly reduced both wet weight and dry weight of granuloma tissue which shows the inhibitory effect on exudative and proliferative phases of inflammation. FF significantly attenuated acute and delayed phases of formalin induced pain, acetic acid-induced writhing, capsaicin-induced nociception, and hot plate test in mice. Phytochemical analysis revealed the presence of coumarins, flavonoids, glycosides, phenolics, saponins, steroids, tannins, and terpenoids. Total phenolic content was 186 mg/g equivalent of gallic acid. The HPLC estimation showed flavanone glycoside naringin (1.2%) and its aglycone naringenin (0.02%). The presence of potent anti-inflammatory and analgesic principles in FF and their synergistic action may be the reason for the proposed therapeutic effects. PMID:24575313

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.

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 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.

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.

Lidocaine alleviates morphine tolerance via AMPK-SOCS3-dependent neuroinflammation suppression in the spinal cord.

PubMed

Zhang, Yan; Tao, Gao-Jian; Hu, Liang; Qu, Jie; Han, Yuan; Zhang, Guangqin; Qian, Yanning; Jiang, Chun-Yi; Liu, Wen-Tao

2017-11-02

Morphine tolerance is a clinical challenge, and its pathogenesis is closely related to the neuroinflammation mediated by Toll-like receptor 4 (TLR4). In Chinese pain clinic, lidocaine is combined with morphine to treat chronic pain. We found that lidocaine sufficiently inhibited neuroinflammation induced by morphine and improved analgesic tolerance on the basis of non-affecting pain threshold. CD-1 mice were utilized for tail-flick test to evaluate morphine tolerance. The microglial cell line BV-2 was utilized to investigate the mechanism of lidocaine. Neuroinflammation-related cytokines were measured by western blotting and real-time PCR. The level of suppressor of cytokine signaling 3 (SOCS3) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-related signaling pathway was evaluated by western blotting, real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. Lidocaine potentiated an anti-nociceptive effect of morphine and attenuated the chronic analgesic tolerance. Lidocaine suppressed morphine-induced activation of microglia and downregulated inflammatory cytokines, interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) via upregulating SOCS3 by activating AMPK. Lidocaine enhanced AMPK phosphorylation in a calcium-dependent protein kinase kinase β (CaMKKβ)-dependent manner. Furthermore, lidocaine decreased the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and inhibited the nuclear factor-κB (NF-κB) in accordance with the inhibitory effects to TLR4. Lidocaine as a prevalent local anesthetic suppresses morphine tolerance efficiently. AMPK-dependent upregulation of SOCS3 by lidocaine plays a crucial role in the improvement of analgesic tolerance.

Analgesic effects of carprofen and liposome-encapsulated butorphanol tartrate in Hispaniolan parrots (Amazona ventralis) with experimentally induced arthritis.

PubMed

Paul-Murphy, Joanne R; Sladky, Kurt K; Krugner-Higby, Lisa A; Stading, Ben R; Klauer, Julia M; Keuler, Nicholas S; Brown, Carolyn S; Heath, Timothy D

2009-10-01

To evaluate the microcrystalline sodium urate (MSU) method for inducing arthritis in parrots and to compare the analgesic efficacy of long-acting liposome-encapsulated butorphanol (LEBT), carprofen, or a combination of both. 20 Hispaniolan parrots. MSU was injected into a tibiotarsal-tarsometatarsal (intertarsal) joint to induce arthritis (time 0). Four treatments were compared (LEBT [15 mg/kg, SC] administered once at time 0; injections of carprofen [3 mg/kg, IM, q 12 h] starting at time 0; administration of LEBT plus carprofen; and a control treatment of saline [0.9% NaCl] solution). Weight load testing and behavioral scoring were conducted at 0, 2, 6, 26, and 30 hours. Injection of MSU into the intertarsal joint induced arthritis, which resolved within 30 hours. Treatment with LEBT or LEBT plus carprofen resulted in significantly greater weight-bearing load on the limb with induced arthritis, compared with the control treatment. Treatment with carprofen alone caused a slight but nonsignificant improvement in weight-bearing load on the arthritic limb, compared with the control treatment. Behaviors associated with motor activity and weight bearing differed between the control and analgesic treatments. Butorphanol was an effective treatment for pain associated with arthritis, but carprofen administered every 12 hours was insufficient. Injection of MSU to induce arthritis in a single joint was a good method for evaluating tonic pain in parrots, and measurement of the weight-bearing load was accurate for assessment of arthritic pain; however, behavioral changes associated with pain were subtle.

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

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.

Evaluation of analgesic activity of Terminalia arjuna (Roxb.) Wight and Arn bark: A tribal claim.

PubMed

Gupta, Anurag; Nishteswar, K; Shukla, Vinay J; Ashok, B K

2014-01-01

Plants occupy an important place in folk medicine all over the world for centuries and indigenous communities have developed their own specific knowledge on plant resources, uses, management, and conservation. Research interest and activities in the area of ethno medicine have increased tremendously in the last decade. Currently, scientists are evincing keen interest in the scientific evaluation of ethno medical claims. Bark powder of Arjuna (Terminalia arjuna [Roxb.] Wight and Arn) is used by tribals for the management of some painful conditions. To evaluate analgesic activity of T. arjuna bark in rodents. For evaluation of analgesic activity, different experimental models, that is, the acetic acid-induced writhing syndrome in mice, formaldehyde-induced paw licking response and tail flick test in rats were designed. Experiments were carried out at two-dose levels, that is, therapeutically equivalent dose (TED) and TED × 2. Animals were divided into three groups (six animals in each group), first group serving as a control group, second and third group labeled as test drug group. Test drug at both the doses significantly decreased the writhing syndrome in comparison to control the group. In comparison to control the group, incidences of formalin-induced paw licking were reduced in test drug groups in both early and late phases of pain. In tail flick response, threshold was significantly increased in both test drug groups at every time intervals. Study showed that stem bark of T. arjuna possesses analgesic activity in all experimental models.

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.

Clinical Evaluation of a Novel Technology for Oral Patient-Controlled Analgesia, the PCoA® Acute Device, for Hospitalized Patients with Postoperative Pain, in Pilot Feasibility Study

PubMed Central

Wirz, Stefan; Conrad, Stefan; Schimo, Kai; Hoffmann, Eva

2017-01-01

Background Acute postoperative pain delays recovery and increases morbidity and mortality. Traditional administration of postoperative analgesics by nurses is often inefficient. The present study evaluated the safety, efficacy, and usability of a novel, patient-controlled analgesic dispenser, the PCoA Acute. Methods A controlled pilot study was conducted at three medical centers. Patients scheduled for elective surgery were enrolled into two groups, both taking oral analgesics: a control group (n = 43), opioids dispensed by nurses, and a test group (n = 27), opioids dispensed via the PCoA Acute. Pill intake data were recorded. Pain ratings at rest and during movement were surveyed. Results No severe adverse events were recorded. Average pill intake time was reduced from 8 : 58 minutes in the control group to 1 : 17 minutes in the test group (P value < 0.05). The test group took 67% more pills than the control group, indicating enhanced compliance. Pain scores were significantly lower for patients in the test group (P value < 0.05). Over 90% of PCoA Acute users were satisfied with its use. Conclusions The study confirmed that PCoA Acute is safe and effective. It is well accepted by patients and medical staff. Its use can optimize pain medication administration. PMID:29093632

Effects of over-the-counter analgesic use on reproductive hormones and ovulation in healthy, premenopausal women

PubMed Central

Matyas, R.A.; Mumford, S.L.; Schliep, K.C.; Ahrens, K.A.; Sjaarda, L.A.; Perkins, N.J.; Filiberto, A.C.; Mattison, D.; Zarek, S.M.; Wactawski-Wende, J.; Schisterman, E.F.

2015-01-01

STUDY QUESTION Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women? SUMMARY ANSWER Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders. WHAT IS KNOWN ALREADY Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear. STUDY DESIGN, SIZE, DURATION The BioCycle Study was a prospective, observational cohort study (2005–2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles. PARTICIPANTS, SETTING, METHODS Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo. MAIN RESULTS AND THE ROLE OF CHANCE During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for ‘healthy’ cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, −1.6–32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH. LIMITATIONS, REASONS FOR CAUTION Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women. WIDER IMPLICATIONS OF THE FINDINGS The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function. STUDY FUNDING/COMPETING INTERESTS This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose. PMID:25954035

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.

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

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.

Anti-Nociceptive Effects of Elcatonin Injection for Postmenopausal Women with Back Pain: A Randomized Controlled Trial

PubMed Central

Ikegami, Shota; Kamimura, Mikio; Uchiyama, Shigeharu; Nakagawa, Hiroyuki; Hashidate, Hiroyuki; Takahara, Kenji; Takahashi, Jun; Kato, Hiroyuki

2010-01-01

Background: Eel calcitonin (elcatonin) injection is widely used for elderly patients suffering from somatic pain in Japan. However, there have been few reports on the analgesic effects of elcatonin injection. The purpose of this study was to examine the analgesic effects of elcatonin injection in postmenopausal women with lower back pain. Methods: This study was designed as a double-blind, randomized, placebo-controlled study. Thirty-six women aged ≥50 years with acute lower back pain participated in this study. They were randomly divided into two treatment groups according to whether they received a placebo or a weekly trigger point injection of elcatonin (20 units). They were observed for 5 weeks and the extent of pain at motion and at rest according to the visual analog scale (VAS) was evaluated. The mean VAS scores for the elcatonin group were then compared with those of the placebo group. Results: There were no statistically significant differences in the mean VAS scores for pain at rest between the two groups during the 5-week treatment course. However, the mean VAS scores for motion pain in the elcatonin group were significantly lower than those in the placebo group at the third, fifth and sixth weeks. Conclusions: Elcatonin injection (20 units) significantly relieved motion pain in the lower back in postmenopausal women after three weeks of treatment. This analgesic effect continued for the subsequent 3 weeks. PMID:20448810

Effects of Interscalene Nerve Block for Postoperative Pain Management in Patients after Shoulder Surgery.

PubMed

Chen, Hsiu-Pin; Shen, Shih-Jyun; Tsai, Hsin-I; Kao, Sheng-Chin; Yu, Huang-Ping

2015-01-01

Shoulder surgery can produce severe postoperative pain and movement limitations. Evidence has shown that regional nerve block is an effective management for postoperative shoulder pain. The purpose of this study was to investigate the postoperative analgesic effect of intravenous patient-controlled analgesia (PCA) combined with interscalene nerve block in comparison to PCA alone after shoulder surgery. In this study, 103 patients receiving PCA combined with interscalene nerve block (PCAIB) and 48 patients receiving PCA alone after shoulder surgery were included. Patients' characteristics, preoperative shoulder score and range of motion, surgical and anesthetic condition in addition to visual analog scale (VAS) pain score, postoperative PCA consumption, and adverse outcomes were evaluated. The results showed that PCA combined with interscalene nerve block (PCAIB) group required less volume of analgesics than PCA alone group in 24 hours (57.76 ± 23.29 mL versus 87.29 ± 33.73 mL, p < 0.001) and 48 hours (114.86 ± 40.97 mL versus 183.63 ± 44.83 mL, p < 0.001) postoperatively. The incidence of dizziness in PCAIB group was significantly lower than PCA group (resp., 1.9% and 14.6%, p = 0.005). VAS, nausea, and vomiting were less in group PCAIB, but in the absence of significant statistical correlation. Interscalene nerve block is effective postoperatively in reducing the demand for PCA analgesics and decreasing opioids-induced adverse events following shoulder surgery.

Lidocaine/ketorolac-loaded biodegradable nanofibrous anti-adhesive membranes that offer sustained pain relief for surgical wounds.

PubMed

Kao, Ching-Wei; Lee, Demei; Wu, Min-Hsuan; Chen, Jan-Kan; He, Hong-Lin; Liu, Shih-Jung

2017-01-01

The aim of this study was to develop and evaluate the effectiveness of biodegradable nanofibrous lidocaine/ketorolac-loaded anti-adhesion membranes to sustainably release analgesics on abdominal surgical wounds. The analgesic-eluting membranes with two polymer-to-drug ratios (6:1 and 4:1) were produced via an electrospinning technique. A high-performance liquid chromatography (HPLC) assay was employed to characterize the in vivo and in vitro release behaviors of the pharmaceuticals from the membranes. It was found that all biodegradable anti-adhesion nanofibers released effective concentrations of lidocaine and ketorolac for over 20 days post surgery. In addition, a transverse laparotomy was setup in a rat model for an in vivo assessment of activity of postoperative recovery. No tissue adhesion was observed at 2 weeks post surgery, demonstrating the potential anti-adhesion capability of the drug-eluting nanofibrous membrane. The postoperative activities were recorded for two groups of rats as follows: rats that did not have any membrane implanted (group A) and rats that had the analgesic-eluting membrane implanted (group B). Rats in group B exhibited faster recovery times than those in group A with regard to postoperative activities, confirming the pain relief effectiveness of the lidocaine- and ketorolac-loaded nanofibrous membranes. The experimental results suggested that the anti-adhesion nanofibrous membranes with sustainable elution of lidocaine and ketorolac are adequately effective and durable for the purposes of postoperative pain relief in rats.

Lidocaine/ketorolac-loaded biodegradable nanofibrous anti-adhesive membranes that offer sustained pain relief for surgical wounds

PubMed Central

Kao, Ching-Wei; Lee, Demei; Wu, Min-Hsuan; Chen, Jan-Kan; He, Hong-Lin; Liu, Shih-Jung

2017-01-01

The aim of this study was to develop and evaluate the effectiveness of biodegradable nanofibrous lidocaine/ketorolac-loaded anti-adhesion membranes to sustainably release analgesics on abdominal surgical wounds. The analgesic-eluting membranes with two polymer-to-drug ratios (6:1 and 4:1) were produced via an electrospinning technique. A high-performance liquid chromatography (HPLC) assay was employed to characterize the in vivo and in vitro release behaviors of the pharmaceuticals from the membranes. It was found that all biodegradable anti-adhesion nanofibers released effective concentrations of lidocaine and ketorolac for over 20 days post surgery. In addition, a transverse laparotomy was setup in a rat model for an in vivo assessment of activity of postoperative recovery. No tissue adhesion was observed at 2 weeks post surgery, demonstrating the potential anti-adhesion capability of the drug-eluting nanofibrous membrane. The postoperative activities were recorded for two groups of rats as follows: rats that did not have any membrane implanted (group A) and rats that had the analgesic-eluting membrane implanted (group B). Rats in group B exhibited faster recovery times than those in group A with regard to postoperative activities, confirming the pain relief effectiveness of the lidocaine- and ketorolac-loaded nanofibrous membranes. The experimental results suggested that the anti-adhesion nanofibrous membranes with sustainable elution of lidocaine and ketorolac are adequately effective and durable for the purposes of postoperative pain relief in rats. PMID:28860755

Analgesic Effect of Botulinum Toxin A in Myofascial Pain Syndrome Patients Previously Treated with Local Infiltration of Anesthetic and Steroids.

PubMed

Cartagena-Sevilla, Joaquín; García-Fernández, María R; Vicente-Villena, Juan P

2016-12-01

The purpose of this study was to evaluate the analgesic effect of botulinum toxin A (BoNTA) injections in patients with myofascial pain syndrome (MPS) who were previously treated with the local infiltration of anesthetic and steroids (LIAS). The study included a retrospective phase and a longitudinal open-label prospective phase, which were conducted on consecutive patients with MPS previously treated with the local infiltration of anesthetic (levobupivacaíne 0.25%) and steroids (triamcinolone 40 mg). Eligible patients were treated with a single intramuscular injection of BoNTA (Botox; Allergan, Inc., Irvine, CA). The treatment efficacy was determined according to the degree of pain relief obtained. Eighty-two patients met the inclusion/exclusion criteria and were included in the study. Successful results were obtained for 32 (39.0%) and 30 (36.6%) patients, during treatment with BoNTA and LIAS, respectively. The mean (standard deviation) length of the analgesic effect was significantly longer with BoNTA (29.6 [SD = 17.7] weeks) than with LIAS (8.5 [SD = 6.4] weeks), P <.0001. As regards the side effects, 19 (23.2%) patients reported transient soreness at the injection site for 2 to 3 days with BoNTA. The MPS patients previously treated with a local infiltration of anesthetic and steroids who then received a single injection of BoNTA experienced significantly reduced pain for a relatively long time.

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.

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.

Anti-inflammatory and analgesic activities of solvent fractions of the leaves of Moringa stenopetala Bak. (Moringaceae) in mice models.

PubMed

Tamrat, Yohannes; Nedi, Teshome; Assefa, Solomon; Teklehaymanot, Tilahun; Shibeshi, Workineh

2017-09-29

Many people still experience pain and inflammation regardless of the available drugs for treatments. In addition, the available drugs have many side effects, which necessitated a quest for new drugs from several sources in which medicinal plants are the major one. This study evaluated the analgesic and anti- inflammatory activity of the solvent fractions of Moringa stenopetala in rodent models of pain and inflammation. Successive soxhlet and maceration were used as methods of extractions using solvents of increasing polarity; chloroform, methanol and water. Swiss albino mice models were used in radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema to assess the analgesic and anti-inflammatory activities. The test groups received different doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the three fractions (chloroform, methanol and aqueous). The positive control groups received morphine (20 mg/kg) or aspirin (100 mg/kg or 150 mg/kg) based on the respective models. The negative control groups received the 10 ml/kg of vehicles (distilled water or 2% Tween 80). In all models, the chloroform fraction had protections only at a dose of 400 mg/kg. However, the methanol and aqueous fraction at all doses have shown significant central and peripheral analgesic activities with a comparable result to the standards. The aqueous and methanol fractions significantly reduced carrageenan induced inflammation in a dose dependent manner, in which the highest reduction of inflammation was observed in aqueous fraction at 400 mg/kg. This study provided evidence on the traditionally claimed uses of the plant in pain and inflammatory diseases, and Moringa stenopetala could be potential source for development of new analgesic and anti-inflammatory drugs.

Comparison of the post-operative analgesic effect of paravertebral block, pectoral nerve block and local infiltration in patients undergoing modified radical mastectomy: A randomised double-blind trial

PubMed Central

Syal, Kartik; Chandel, Ankita

2017-01-01

Background and Aims: Paravertebral block, pectoral nerve (Pecs) block and wound infiltration are three modalities for post-operative analgesia following breast surgery. This study compares the analgesic efficacy of these techniques for post-operative analgesia. Methods: Sixty-five patients with American Society of Anesthesiologists’ physical status 1 or 2 undergoing modified radical mastectomy with axillary dissection were recruited for the study. All patients received 21 mL 0.5% bupivacaine with adrenaline in the technique which was performed at the end of the surgery prior to extubation. Patients in Group 1 (local anaesthetic [LA], n = 22) received infiltration at the incision site after surgery, Group 2 patients (paravertebral block [PVB], n = 22) received ultrasound-guided ipsilateral paravertebral block while Group 3 patients [PECT] (n = 21) received ultrasound-guided ipsilateral Pecs blocks I and II. Patients were evaluated for pain scores at 0, 2, 4, 6, 12 and 24 h, duration of post-operative analgesia and rescue analgesic doses required. Non-normally distributed data were analysed using the Kruskal-Wallis test and Analysis of variance for normal distribution. Results: The post-operative visual analogue scale scores were lower in PVB group compared with others at 0, 2, 4, 12 and 24 h (P < 0.05). Mean duration of analgesia was significantly prolonged in PVB group (P < 0.001) with lesser rescue analgesic consumption up to 24 h. Conclusion: Ultrasound-guided paravertebral block reduces post-operative pain scores, prolongs the duration of analgesia and decreases demands for rescue analgesics in the first 24 h of post-operative period compared to ultrasound-guided Pecs block and local infiltration block. PMID:28890559

Comparison of the post-operative analgesic effect of paravertebral block, pectoral nerve block and local infiltration in patients undergoing modified radical mastectomy: A randomised double-blind trial.

PubMed

Syal, Kartik; Chandel, Ankita

2017-08-01

Paravertebral block, pectoral nerve (Pecs) block and wound infiltration are three modalities for post-operative analgesia following breast surgery. This study compares the analgesic efficacy of these techniques for post-operative analgesia. Sixty-five patients with American Society of Anesthesiologists' physical status 1 or 2 undergoing modified radical mastectomy with axillary dissection were recruited for the study. All patients received 21 mL 0.5% bupivacaine with adrenaline in the technique which was performed at the end of the surgery prior to extubation. Patients in Group 1 (local anaesthetic [LA], n = 22) received infiltration at the incision site after surgery, Group 2 patients (paravertebral block [PVB], n = 22) received ultrasound-guided ipsilateral paravertebral block while Group 3 patients [PECT] ( n = 21) received ultrasound-guided ipsilateral Pecs blocks I and II. Patients were evaluated for pain scores at 0, 2, 4, 6, 12 and 24 h, duration of post-operative analgesia and rescue analgesic doses required. Non-normally distributed data were analysed using the Kruskal-Wallis test and Analysis of variance for normal distribution. The post-operative visual analogue scale scores were lower in PVB group compared with others at 0, 2, 4, 12 and 24 h ( P < 0.05). Mean duration of analgesia was significantly prolonged in PVB group ( P < 0.001) with lesser rescue analgesic consumption up to 24 h. Ultrasound-guided paravertebral block reduces post-operative pain scores, prolongs the duration of analgesia and decreases demands for rescue analgesics in the first 24 h of post-operative period compared to ultrasound-guided Pecs block and local infiltration block.

The Role of the Tamsulosin in the Medical Expulsion Therapy for Distal Ureteral Stones

PubMed Central

Nuraj, Petrit; Hyseni, Nexhmi

2017-01-01

Background: This research aims to evaluate the role of tamsulosin in the medical expulsion therapy for distal ureteral stones, including her effects in stone expulsion time, expulsion rates, stone size, pain episodes and analgesic dosage usage. Material and methods: The 104 patients with distal ureteral calculi were examined, with the size of the stones 4-10 mm. They were randomly divided into two groups: study group (n=52), received tamsulosin 0.4 mg in morning, for 28 days, analgesic (diclofenac 75 mg), high fluid intake and Control group (n=52) received analgesic (diclofenac 75 mg), high fluid intake. Results: There is no significant difference between groups, based on sex (P=0.835) and age (P=0.987). Average size of the stones was 6.5 mm (SD ± 1.6 mm), with no significant difference (P=0.996). Stone expulsion rate is 90.4% in the study group and 71.2% from the control group, with statistical significance (P=0.023). The average time of the expulsion of stones in the study group was 9.6 days (SD ± 7.1 days), control group 13.7 days (SD ± 7.3 days), with statistical significance, (P=0.034). Average dose of analgesics in the study group was 63.7 mg (SD ± 45.2 mg), control group is 109.2 (SD ± 53.3), with statistical significance (P=0.019). Conclusion: Our study reveals that tamsulosin is efficient for the treatment of distal ureteral stones. Tamsulosin decrease the number of ureteral colic episodes, by acting as a spasmolytic, increase and hasten stone expulsion rates, reduce days of stone expulsion, decrease analgesic dose usage. PMID:28790547

Efficacy of Ketamine in Improving Pain after Tonsillectomy in Children: Meta-Analysis

PubMed Central

Cho, Hye Kyung; Kim, Kyu Won; Jeong, Yeon Min; Lee, Ho Seok; Lee, Yeon Ji; Hwang, Se Hwan

2014-01-01

Background and objectives The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children. Subjects and Methods Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0–24 hours after leaving the operation room were included in the analysis. Results The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics. Conclusion Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study. PMID:24979227

Pharmacological action of choline and aspirin coadministration on acute inflammatory pain.

PubMed

Yong-Ping, Shi; Jin-Da, Wang; Ru-Huan, Wang; Xiang-Di, Zhao; Hai-Tao, Yu; Hai, Wang

2011-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain but undesirable side effects limit their clinical usefulness. Choline is a α7 nicotinic receptor agonist that has antinociceptive effects in a variety of pain models. Drug combination is a strategy in the management of pain to reduce side effects. The aim of the study was to evaluate the nature of the interaction between choline and aspirin in two distinct inflammatory pain models. The analgesic mechanism of choline was also investigated. In the writhing test, intravenous administration of choline or aspirin showed dose-dependent antinociceptive activity, and isobolographic analysis revealed a synergistic nature of the interaction between choline and aspirin. More importantly, coadministration choline with aspirin could significantly shorten the antinociceptive latency of aspirin and prolong the antinociceptive duration of aspirin in the writhing test. In the carrageenan test, single administration of choline or aspirin significantly attenuated carrageenan-induced thermal hyperalgesia in a dose-dependent relationship. Coadministration of non-analgesic doses of aspirin with choline significantly suppressed the thermal hyperalgesia, with a longer duration efficacy. Furthermore, we found that α7 nicotinic, muscarinic, and opioid-receptors are involved in the antinociceptive effect of choline in the writhing test and the antinociceptive effect produced by systemically administered choline may be via a peripheral mechanism. In conclusion, coadministration of choline and aspirin holds promise for development as a safe analgesic drug combination for inflammatory pain, with a higher potency and longer duration than either aspirin or choline alone. Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

[Postoperative pain management by intravenous patient-controlled analgesia in patients undergoing upper abdominal gastrointestinal surgery].

PubMed

Kajiyama, Seiji; Niihata, Tomoko; Sugimoto, Yuki; Kawamoto, Masashi

2012-10-01

We conducted a retrospective study to evaluate the effectiveness of intravenous patient-controlled analgesia (IVPCA) in the early postoperative period after upper abdominal gastrointestinal surgery. We also evaluated the postoperative effects of intraoperative analgesic dosage in patients after this surgery. A total of 59 adult patients classified as ASA 1-3 were allocated to one of two groups: Group A, 23 patients who requested IVPCA more than 50 times, and Group B, 36 patients with fewer than 50 requests. IVPCA was induced using morphine 1 mg x ml(-1) without a base dose. The bolus dose was 1 ml and the lock-out time was 5 min. There was no significant difference between the two groups in the total intraoperative remifentanil dosage/body weight/surgical duration, predicted effect-site concentration of fentanyl during extubation, and utilization of flurbiprofen. The doses of morphine were significantly higher, and the visual analogue scale scores for pain at rest and during movement tended to be lower in group A than in group B. The results of this study suggest that the effects of intraoperative analgesics may not be significant. Patients who had received the above mentioned anesthetic regimen intraoperatively also required full postoperative analgesia as well.

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.

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.

[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.

[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.

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.

Assessing the impact of the extended-release/long-acting opioid an-algesics risk evaluation and mitigation strategies on opioid prescrip-tion volume.

PubMed

Divino, Victoria; Cepeda, M Soledad; Coplan, Paul; Maziere, Jean-Yves; Yuan, Yingli; Wade, Rolin L

The Food and Drug Administration approved the extended-release/long-acting (ER/LA) opioid analgesics risk evaluation and mitigation strategies (REMS) in July 2012 to educate healthcare providers and patients about safe and appropriate opioid analgesic use. The authors evaluated the impact of the REMS on ER/LA opioid analgesic utilization, overall and stratified by patient characteristics and prescriber type associated with greater expected need for analgesia. Retrospective repeated cross-sectional study. QuintilesIMS's National Prescription Audit™ and LifeLink™ patient-level longitudinal prescription databases measured prescription volumes, projected to national estimates. Changes were assessed in ER/LA opioid analgesic prescriptions dispensed from the 2-year pre-REMS implementation (July 2010 to June 2012) to the 18-month post-REMS implementation (July 2013 to December 2014) periods (with 12-month transitional implementation period in between). Average quarterly ER/LA opioid prescription volume significantly decreased by 4.3 percent from Preimple-mentation to the Active Period (5.58 vs 5.34 million, p < 0.001). Differences in prescription volume change were observed between age, gender, and payer types. Prescription volume either significantly decreased or remained stable from Preimplementation to the Active Period among most provider specialties evaluated. The largest volume decreases were observed for dentists (-48.5 percent) and emergency medicine specialists (-25.5 percent) (both p < 0.001). The largest increases were observed for nurse practitioners (+33.7 percent) and physician assistants (+31.2 percent; both p < 0.001), whose overall prescribing of nonopioid medications also increased. A significant decrease in dispensed ER/LA opioid prescriptions was observed following REMS implementation compared to Preimplementation. The impact on volume varied by patient characteristics and prescriber specialty. The REMS program, in conjunction with other healthcare policies and initiatives, likely influenced these observations.

Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway

PubMed Central

De, Soumita; Maroo, Niteeka; Saha, Piu; Hazra, Samik; Chatterjee, Mitali

2013-01-01

Objectives: The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action. Materials and Methods: Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA) and generation of reactive oxygen species (ROS) was measured by flow cytometry using 2’,7’-dichlorodihydrofluorescein diacetate. Results: PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001). In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01. Conclusions: The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration. PMID:24130383

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.

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.

Effect of near-infrared rays on female menstrual pain in Korea.

PubMed

Lee, Jin-Min; Kim, Kye-Ha

2017-09-01

Most Korean women who experience menstrual pain have reported taking pain medicine and making use of complementary alternative therapies. However, because some interventions may cause side effects, more effective pain-relieving measures need to be identified. This study using a non-equivalent group design, evaluated the effects of near-infrared rays on dysmenorrhea among Korean women. The experimental group wore a near-infrared ray abdominal belt for the duration of one menstrual cycle until the end of the menstrual period, while the control group used hot packs. The level of menstrual pain, menstrual pain duration, and pain medicine use were measured. The menstrual pain, average menstrual pain duration, and use of analgesics were reduced in the near-infrared rays group. The results of this study indicate that the near-infrared ray LED belt was effective in reducing menstrual pain, menstrual pain duration compared to the use of analgesics in Korean women with dysmenorrhea. Therefore, near-infrared rays may be used to relieve menstrual pain and improve the quality of life of women with dysmenorrhea in Korea. © 2017 John Wiley & Sons Australia, Ltd.

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.

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.

Prospective double-blind clinical trial evaluating the effectiveness of Bromelain in the third molar extraction postoperative period

PubMed Central

de la Barrera-Núñez, María C.; Yáñez-Vico, Rosa M.; Batista-Cruzado, Antonio; Heurtebise-Saavedra, Jean M.; Castillo-de Oyagüe, Raquel

2014-01-01

Objectives: To evaluate the anti-inflammatory and analgesic effect of Bromelain (pineapple extract) administered orally in the postoperative after extraction of impacted lower molars. Study Design: This is a prospective, placebo-controlled, unicentric, double-blind study; the sample size was 34 patients. The pre and postoperative outcomes, evaluated on the third (D3) and eighth day (D8), included inflamtion, pain and oral aperture, as well as the need for analgesics. One group received bromelain 150mg per day for three days and 100mg on days 4 to 7. The other group received placebo in the same dosage. All outcomes werrecorded quantitatively and analyzed with the Mann-Whitney U test for independent samples. Results: Although there were no statistically significant differences between the treatment groups, a trend towards less inflammation and improved oral aperture was observed in the group that received bromelain, compared to the group that received placebo. This trend can be attributed completely to random reasons, since there is no statistical difference in the results. Conclusions: Further studies are necessary to analyze different administration patterns and doses of bromelain for the use in the postoperative of impacted third molars. Key words:Tooth extraction, third molar, postoperative period, bromeline, clinical study. PMID:24316697

Ethnopharmacological investigation of the aerial part of Phragmites karka (Poaceae).

PubMed

Sultan, Ramiz Ahmed; Kabir, Mohammad Shah Hafez; Uddin, Mir Muhammad Nasir; Uddin, Mohi; Mahmud, Zobaer Al; Raihan, Sheikh Zahir; Qais, Nazmul

2017-05-01

In this ethnopharmacological study, methanolic extract of the aerial plant parts of Phragmites karka (Family: Poaceae) and its petroleum ether and carbon tetrachloride fractions were investigated for bioactivities in Swiss-albino mice, namely, analgesic, central nervous system (CNS) depressant, hypoglycemic, and antidiarrheal activity. The cold methanolic extract of the aerial plant parts of Phragmites karka (MEPK) was first prepared, and it was then further fractionated as petroleum ether (PEFMEPK) and carbon tetrachloride (CTFMEPK) fractions. Analgesic activity was performed employing acidic acid-induced writhing test, central analgesic effect by radiant heat tail-flick method. CNS depressant activity was evaluated by phenobarbitone-induced sleeping time test. Hypoglycemic activity was tested by glucose tolerance test (GTT). Antidiarrheal activity was evaluated by castor oil-induced diarrhea method. For all in vivo tests, doses of 200 and 400 mg/kg body weight were used. In the mice model, the MEPK, PEFMEPK, and CTFMEPK fractions showed significant peripheral analgesic activity at a dose of 400 mg/kg body weight with percentage of inhibition of acetic acid-induced writhing 77.67 (p<0.001), 33.50 (p<0.001), and 40.29 (p<0.001), respectively, compared to the standard dichlofenac (60.68%, p<0.001) group. The hypoglycemic properties of MEPK, PEFMEPK, and CTFMEPK extracts were evaluated in normoglycemic mice where the reduction of blood glucose level after 30 min of glucose load were 69.85%, 78.91%, and 72.73%, respectively, and for standard glibenclamide, the reduction was 72.85%. All results were significant (p<0.05). In the case of the CNS depressant activity by phenobarbitone-induced sleeping time test, the crude ME significantly reduced sleep latency by 57.14% and increased the duration of sleep by 63.29% compared to the control, which were comparable to that of standard diazepam (65.71% and 77.62%, respectively). Among all the extract and fractions, methanolic extract showed the maximum antidiarrheal effect. The methanolic extract at 200 mg/kg dose induced a significant decrease in the total number of defecation in 4 h (69.05% of inhibition, p<0.001) and at 400 mg/kg dose showed 76.19% of inhibition (p<0.001). In light of the available literature, these findings represent the first experimental investigation of biological activities of P. karka in the perspective of their traditional use.

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.

The effect of local/topical analgesics on incisional pain in a pig model.

PubMed

Castel, David; Sabbag, Itai; Meilin, Sigal

2017-01-01

Interest in the development of new topical/local drug administration for blocking pain at peripheral sites, with maximum drug activity and minimal systemic effects, is on the rise. In the review article by Kopsky and Stahl, four critical barriers in the process of research and development of topical analgesics were indicated. The active pharmaceutical ingredient (API) and the formulation are among the major challenges. The road to the development of such drugs passes through preclinical studies. These studies, if planned correctly, should serve as guidance for choosing the right API and formulation. Although rodent models for pain continue to provide valuable data on the mechanisms driving pain, their use in developing topical and localized treatment approaches is limited for technical (intraplate injection area is small) as well as mechanical reasons (non-similarity to human skin and innervation). It has been previously shown that pigs are comparable to humans in ways that make them a better choice for evaluating topical and local analgesics. The aim of this study was to summarize several experiments that used pigs for testing postoperative pain in an incisional pain model (skin incision [SI] and skin and muscle incision [SMI]). At the end of the surgery, the animals were treated with different doses of bupivacaine solution (Marcaine ® ), bupivacaine liposomal formulation (Exparel ® ) or ropivacaine solution (Naropin). Von Frey testing demonstrated a decrease in the animals' sensitivity to mechanical stimulation expressed as an increase in the withdrawal force following local treatment. These changes reflect the clinical condition in the level as well as in the duration of the response. These data indicate a good resemblance between pig and human skin and suggest that use of these animals in the preclinical phase of developing topical analgesics can, to some extent, release the bottleneck.

Basil, tea tree and clove essential oils as analgesics and anaesthetics in Amphiprion clarkii (Bennett, 1830).

PubMed

Correia, A M; Pedrazzani, A S; Mendonça, R C; Massucatto, A; Ozório, R A; Tsuzuki, M Y

2017-11-27

In this study were evaluated the anaesthesia and analgesic effects of clove Eugenia caryophyllata, tea tree Melaleuca alternifolia and basil Ocimum basilicum essential oils (EO) during handling of yellowtail clownfish Amphiprion clarkii. Juveniles (3.70 ± 0.75 cm and 1.03 ± 0.50 g; mean ± standard deviation) were submitted to concentrations of 40, 50, 60, 70 and 80 µl L-1 of clove, 150, 200, 250, 300 and 350 µl L-1 of basil and 200, 300, 400, 500 and 600 µl L-1 of tea tree oils (n=10/concentration), previously defined in pilot tests. Individually and only once, fish from each treatment were placed in a glass recipient containing 1 L of seawater at a temperature of 25 °C, salinity of 35 g L-1 and the specific concentration of diluted EO (stock solution). Control (only seawater) and blank (seawater and ethanol at the highest concentration used to dilute the oils) treatments were also conducted. After reaching the stage of surgical anaesthesia, fish were submitted to biometry and a sensibility test. After that, they were transferred to clean seawater for anaesthesia recovery. The times of induction needed to reach each anaesthesia stage and anaesthesia recovery were recorded. Animals were observed for 72 hours after the procedures. All the EO provoked anaesthesia and analgesic effects in A. clarkii, but basil oil is not recommended because it caused involuntary muscle contractions and mortality in 100% and 12% of fish, respectively. The lower concentrations that promote suitable induction and recovery times are 50 µl L-1 of clove oil and 500 µl L-1 of tea tree oil. However, due to its complementary high analgesic efficiency, clove oil is recommended as the ideal anaesthetic for A. clarkii.

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

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.

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.

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

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

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.

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.

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.

[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.

Evaluation of the Effect of Reflexology on Pain Control and Analgesic Consumption After Appendectomy.

PubMed

Khorsand, Ali; Tadayonfar, Moosa Al-Reza; Badiee, Shapour; Aghaee, Monavar Afzal; Azizi, Hoda; Baghani, Sara

2015-12-01

Appendicitis is the most common cause of severe abdominal pain in the world, and the associated postsurgical pain, as occurs with other surgical procedures, is one of the most common problems. Today, there is a growing tendency toward nondrug methods and alternative medicine to reduce the adverse effects of drugs. Reflexology involves applying pressure on certain areas of the palms, feet, and ears in order to reduce stress and pain in certain areas of the body. The aim of this study was to determine the effect of reflexology massage on pain relief after appendectomy. This clinical trial was conducted at the surgical emergency unit of Imam Reza Hospital of Mashhad, Iran, in 2013. Pain intensity and analgesic consumption were compared between 105 patients before and immediately, 1 hour, 6 hours, and 24 hours after the intervention in three groups of intervention, control, and placebo. Patients in all three groups received analgesics, as required. The experimental group received pressure on a defined area of the right foot for about 10 minutes and the Shen Men point of the ear for 1 minute. This pressure in the placebo group was applied on the left foot and the left earlobe. Patients in the control group received routine care only. The results were evaluated at a 95% confidence level, and data were analyzed using SPSS software version 12 (SPSS, Inc., Chicago, IL). At the beginning of the study, the mean pain intensity in different groups according to analysis of variance was not significantly different (p = 0.439); however, there was a notable difference in pain intensity between the intervention and other groups after reflexology therapy. In addition, methadone consumption was significantly lower in the reflexology group than in the other two groups (p ≤ 0.001). Reflexology is effective for reducing pain after appendectomy surgery.

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.

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

Effects of combined general-epidural anesthesia and total intravenous anesthesia on cellular immunity and prognosis in patients with non‑small cell lung cancer: A comparative study.

PubMed

Xu, Qiang; Shi, Nian-Jun; Zhang, Hao; Zhu, Yan-Mei

2017-10-01

The aim of the present study was to investigate the effects of combined general‑epidural anesthesia (CGEA) and total intravenous anesthesia (TIVA) on cellular immunity and prognosis in patients with non‑small cell lung cancer (NSCLC) in a Chinese population. One‑hundred and twenty NSCLC patients were randomly divided into a TIVA group (n=60) and a CGEA group (n=60) using a random number table. All patients underwent video‑assisted thoracoscopic surgery for radical resection. Blood pressure (BP) and peripheral oxygen saturation (SpO2) were measured. Post‑operative analgesic effects were evaluated with a visual analog scale pain score. Flow cytometry was applied to measure T lymphocyte subsets [cluster of differentiation (CD)3+, CD4+, CD8+ and CD4+/CD8+] and natural killer cell CD56+. A 3‑year follow‑up was conducted to observe the prognosis. The analgesic effects of CGEA were identified to be better than those of TIVA. Compared with the TIVA group, the CGEA group demonstrated a shorter time of spontaneous breathing recovery, eyes opening, and extubation, lower heart rate, blood pressure and mean arterial pressure, and higher SpO2. At 24 and 48 h after surgery, CD3+, CD4+, CD4+/CD8+ and CD56+ in the CGEA group were higher than those in the TIVA group. At 72 h after surgery, CD3+, CD4+, CD4+/CD8+ in the CGEA group were higher than those in the TIVA group. These results indicate that CGEA and TIVA effected cellular immunity, and CGEA had a reduced effect on cellular immunity and improved postoperative analgesic effects.

Influence of low-level laser therapy on the healing of human bone maxillofacial defects: A systematic review.

PubMed

Santinoni, Carolina Dos Santos; Oliveira, Hiskell Francine Fernandes; Batista, Victor Eduardo de Souza; Lemos, Cleidiel Aparecido Araujo; Verri, Fellippo Ramos

2017-04-01

This systematic review evaluates the effectiveness of low-level laser therapy (LLLT) to enhance maxillofacial area bone repair. A comprehensive search of studies published up to February 2017 and listed in PubMed/MEDLINE, Scopus, and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The 15 selected studies evaluated a total of 374 patients (mean age, 28.5years) who were treated with LLLT. Gallium-arsenide (GaAs) and gallium aluminium arsenide (GaAlAs) were the most commonly used devices, and LLLT parameters varied greatly. Wavelengths varied from 500 to 1000nm. Tooth extraction, distraction osteogenesis, maxillary expansion, periodontal defects, orthodontic movement and maxillary cystic defects were evaluated. From the 15 selected studies, six evaluated bone repair (primary outcomes). Of these, four studies showed improvement in bone formation after using LLLT, two demonstrated improved results for only one follow up period, and one showed no additional benefits. The other 9 studies evaluated secondary parameters related to healing (secondary outcomes) in the maxillofacial area after applying LLLT, including anti-inflammatory, analgesic, and healing accelerator effects, and quality of life related to oral health. There were no adverse or negative effects of LLLT reported. Within the limitation of this review, a possible improvement in bone density can be found when LLLT is applied postoperatively in maxillofacial bony defects. LLLT also seems to promote anti-inflammatory and analgesic effects and accelerate healing, as well as enhance quality of life related to oral health. However, LLLT use protocols need to be standardized before more specific conclusions can be drawn about this subject. Copyright © 2017 Elsevier B.V. All rights reserved.

Design, synthesis and biological screening of some pyridinylpyrazole and pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic, antipyretic and antimicrobial agents.

PubMed

El-Hawash, Soad A M; Soliman, Raafat; Youssef, Amal M; Ragab, Hanan M A; Elzahhar, Perihan A S; El-Ashmawey, Ibrahim M; Abdel Wahab, Abeer E; Shaat, Iman A

2014-05-01

A series of substituted pyridinylpyrazole (or isoxazole) derivatives were synthesized and evaluated for their anti-inflammatory (AI) activity using formalin-induced paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The analgesic activity of the same compounds was evaluated using rat-tail withdrawal technique. Their antipyretic activity was also evaluated. The results revealed that compounds 4a,b, 6a, 8a, 14c and 15a exhibited significant AI and analgesic activities. Compounds 5a, 6a and 8a displayed good antipyretic activity. Compounds 14c and 15a showed good COX-2 inhibitory activity and weak inhibition of COX-1. Additionally, the most active compounds were shown to have a large safety margin (ALD50 >300-400 mg / Kg) and minimal ulcerogenic potentialities when administered orally at a dose of 300 mg/Kg. Docking studies for 14c and 15a with COX-2 showed good binding profile. Antimicrobial evaluation proved that most of the compounds exhibited distinctive activity against the gram negative bacteria, P. aeruginosa and E coli.

A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

PubMed Central

Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

2016-01-01

The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

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

[Economic analysis of parecoxib in the management of postsurgical pain in gynecology].

PubMed

Muciño-Ortega, Emilio; Galindo-Suárez, Rosa María; Díaz-Ponce, Humberto; Walter-Tordecillas, Miguel Angel

2012-11-01

Poorly managed postoperative pain has a negative impact in healing patients and costs of care. A model to estimate economic and health consequences of parecoxib 40 mg and morphine 12 mg regarding ketorolac 30 mg, on the management of postoperative pain in gynecologic laparotomy surgery from the perspective of the Mexican Social Security Institute (IMSS) was developed. A systematic review to identify the proportion of patients that rated their analgesic treatment as "excellent" or "good" in the Patient Global Evaluation of Study Medication, 12 hours after administration of the analgesic (responders), was performed. The patients who rated "fair" or "poor" their treatment were administered additional 4 mg of morphine. Costs in the model correspond to the acquisition costs of analgesics in which the institution would incur. The proportion and cost per responder were: morphine: 14.44% and $192.79, ketorolac: 32.44% and $34.82, parecoxib: 35.51% and $121.25.Treatment with morphine was more expensive and less effective than both, ketorolac and parecoxib, while the cost per additional percent point of responders with parecoxib (compared to ketorolac) was $28.15. For the management of postoperative pain, ketorolac and parecoxib are more effective and less expensive than morphine, additionally parecoxib would be an alternative for patients with contraindication to ketorolac use. The management of postoperative pain with parecoxib is more effective and, in the context of IMSS, less expensive than morphine, also constitutes an alternative with a reasonable incremental cost compared to ketorolac.

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.

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.

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

[Survey on patients' impression of and degree of satisfaction to epidural anesthesia].

PubMed

Doudou, Yoriko; Saeki, Hiroshi; Morimoto, Yasuhiro; Matsumoto, Mishiya; Sakabe, Takefumi

2007-10-01

[corrected] Epidural analgesia is one of the methods to relieve pain after the operation. In general, patient-controlled epidural analgesia (PCEA) is efficient in providing high patient's satisfaction. However, it is not clear whether the patients are really satisfied with this analgesic technique in our hospital. Therefore, we studied this issue in 70 patients who had received elective surgery and epidural analgesia postoperatively. We used questionnaires to investigate patients' impression of and degree of satisfaction to, epidural analgesia. We interviewed patients before operation and, 1 and 7 days after operation. We also evaluated PCEA usage, analgesic usage and side effects of epidural analgesia during the postoperative period. Preoperatively 80% of the patients had an anticipation of adequate analgesia with epidural analgesia. Although 54% of the patients had anxiety/fear during the epidural puncture, postoperative analgesia met their expectation in 86% of the patients. PCEA was used only in limited number of patients. The limited use of PCEA may be caused by inadequate information given to the patients. Therefore, it is necessary to give more easily understandable information to the patients about this analgesic procedure for better patients' acceptance, comfort and satisfaction.

A Randomized Controlled Trial Examining the Effect of the Addition of the Mandibular Block to Cervical Plexus Block for Carotid Endarterectomy.

PubMed

Kavrut Ozturk, Nilgun; Kavakli, Ali Sait; Sagdic, Kadir; Inanoglu, Kerem; Umot Ayoglu, Raif

2018-04-01

Although the cervical plexus block generally provides adequate analgesia for carotid endarterectomy, pain caused by metal retractors on the inferior surface of the mandible is not prevented by the cervical block. Different pain relief methods can be performed for patients who experience discomfort in these areas. In this study, the authors evaluated the effect of mandibular block in addition to cervical plexus block on pain scores in carotid endarterectomy. A prospective, randomized, controlled trial. Training and research hospital. Patients who underwent a carotid endarterectomy. Patients scheduled for carotid endarterectomy under cervical plexus block were randomized into 2 groups: group 1 (those who did not receive a mandibular block) and group 2 (those who received a mandibular block). The main purpose of the study was to evaluate the mandibular block in addition to cervical plexus block in terms of intraoperative pain scores. Intraoperative visual analog scale scores were significantly higher in group 1 (p = 0.001). The amounts of supplemental 1% lidocaine and intraoperative intravenous analgesic used were significantly higher in group 1 (p = 0.001 and p = 0.035, respectively). Patient satisfaction scores were significantly lower in group 1 (p = 0.044). The amount of postoperative analgesic used, time to first analgesic requirement, postoperative visual analog scale scores, and surgeon satisfaction scores were similar in both groups. There was no significant difference between the groups with respect to complications. No major neurologic deficits or perioperative mortality were observed. Mandibular block in addition to cervical plexus block provides better intraoperative pain control and greater patient satisfaction than cervical plexus block alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Preemptive Analgesic Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Postoperative Pain: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Eidy, Mohammad; Fazel, Mohammad Reza; Janzamini, Monir; Haji Rezaei, Mostafa; Moravveji, Ali Reza

2016-04-01

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological analgesic method used to control different types of pain. The aim of this study was to evaluate the effects of preoperative TENS on post inguinal hernia repair pain. This randomized, double-blind, placebo-controlled clinical trial was performed on 66 male patients with unilateral inguinal hernias who were admitted to the Shahid Beheshti hospital in Kashan, Iran, from April to October 2014. Participants were selected using a convenience sampling method and were assigned to intervention (n = 33) and control (n = 33) groups using permuted-block randomization. Patients in the intervention group were treated with TENS 1 hour before surgery, while the placebo was administered to patients in the control group. All of the patients underwent inguinal hernia repair by the Lichtenstein method, and pain intensity was evaluated at 2, 4, 6, and 12 hours after surgery using a visual analogue scale. Additionally, the amounts of analgesic administered by pump were calculated and compared between the two groups. The mean estimated postoperative pain intensity was 6.21 ± 1.63 in the intervention group and 5.45 ± 1.82 in the control group (P = 0.08). In the intervention group pain intensity at 2 and 4 hours after surgery were 3.54 ± 1.48 and 5.12 ± 1.41 (P < 0.001), respectively. In the control group these values were 4.0±1.5 and 4.76 ± 1.39 (P = 0.04), respectively. No significant differences were observed in mean pain intensities at 6 and 12 hours. TENS can reduce postoperative pain in the early hours after inguinal hernia repair surgery.

Preemptive Analgesic Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Postoperative Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Eidy, Mohammad; Fazel, Mohammad Reza; Janzamini, Monir; Haji Rezaei, Mostafa; Moravveji, Ali Reza

2016-01-01

Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological analgesic method used to control different types of pain. Objectives The aim of this study was to evaluate the effects of preoperative TENS on post inguinal hernia repair pain. Patients and Methods This randomized, double-blind, placebo-controlled clinical trial was performed on 66 male patients with unilateral inguinal hernias who were admitted to the Shahid Beheshti hospital in Kashan, Iran, from April to October 2014. Participants were selected using a convenience sampling method and were assigned to intervention (n = 33) and control (n = 33) groups using permuted-block randomization. Patients in the intervention group were treated with TENS 1 hour before surgery, while the placebo was administered to patients in the control group. All of the patients underwent inguinal hernia repair by the Lichtenstein method, and pain intensity was evaluated at 2, 4, 6, and 12 hours after surgery using a visual analogue scale. Additionally, the amounts of analgesic administered by pump were calculated and compared between the two groups. Results The mean estimated postoperative pain intensity was 6.21 ± 1.63 in the intervention group and 5.45 ± 1.82 in the control group (P = 0.08). In the intervention group pain intensity at 2 and 4 hours after surgery were 3.54 ± 1.48 and 5.12 ± 1.41 (P < 0.001), respectively. In the control group these values were 4.0±1.5 and 4.76 ± 1.39 (P = 0.04), respectively. No significant differences were observed in mean pain intensities at 6 and 12 hours. Conclusions TENS can reduce postoperative pain in the early hours after inguinal hernia repair surgery. PMID:27275401

Unmasking the Effect of Analgesics on Endodontic Diagnosis Using a Novel Bite Force Sensor Device: A Prospective, Randomized Clinical Trial.

PubMed

Kishnani, Sushil; Saha, Suparna Ganguly; Bhardwaj, Anuj; Dubey, Sandeep; Saha, Mainak; Kala, Shubham; Jain, Sohini; Narwani, Shweta

2016-10-01

A definitive diagnosis is of primary importance before initiating any endodontic treatment; yet, there are occasions when the dental professional is unable to accurately reproduce the patient's chief complaint, as it can pose a dilemma and may require consideration of multiple variables in order to reach an accurate diagnosis. So to overcome this problem, a methodical approach in providing endodontic treatment should be implemented which includes diagnosis, definitive dental treatment and adjunctive drug therapy, known as the "3D" strategy. The purpose of this study was to evaluate the possible "masking" effect of these analgesics on endodontic diagnosis using a novel bite force sensor device. A total of 90 patients with endodontic pain were selected and they were given either a placebo or 400 mg ibuprofen (brufen) or 50mg diclofenac sodium (voveron). Both patients and operators were completely blinded to the drugs administered. Bite force tolerance values were noted before and one hour after administration of medication using the self designed bite force sensor. The pre- and post-bite force tolerance values were tabulated for both contralateral and affected tooth. For the affected tooth, there was statistically significant difference between pre- and post-bite force tolerance values in Group I (i.e., ibuprofen) and Group II (i.e., diclofenac sodium) (p<0.05) with no significant difference observed in Group III (placebo). The easily available over the counter self administered analgesics in addition to providing symptomatic relief to patients suffering from symptomatic apical periodontitis may also cloud the definitive diagnosis of the clinician, thus jeopardising the treatment plan. The self designed bite force sensor was effective in arriving at a definitive diagnosis in teeth with chronic irreversible pulpitis with symptomatic apical periodontitis, where the allodynia has been camouflaged by the use of analgesics like ibuprofen and diclofenac sodium.

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

PubMed Central

Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

2015-01-01

Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

[Effectiveness and safety of oxcarbazepine in chronic neuropathic pain: a study of 40 cases].

PubMed

Fenollosa-Vázquez, P; Canós-Verdecho, M A; Núñez-Cornejo, C; Pallarés-Delgado, J

Neuropathic pain (NP) often fails to respond to the commonly established analgesic treatment. This fact, together with the existence of side effects, has led to the need to evaluate the analgesic effectiveness of antiepileptic drugs, which, as in the case of oxcarbazepine (OXC), are a valid alternative. The aim of this study was to evaluate the effectiveness and safety of OXC in patients suffering from chronic NP. We conducted a prospective, open study involving a series of 40 patients diagnosed with a long history of NP, which was previously resistant to different kinds of treatment with anticonvulsants, non-steroidal anti-inflammatory (NSAI) drugs, opiates and adjuncts. Patients were treated with OXC and they were evaluated in both the basal (prior to treatment) and final visits (after treatment) by means of the visual analogue scale (VAS), SF-McGill questionnaire and the Lattinen test. The patient's general impression of the result was also obtained. The statistical analysis was performed by calculating the "effect size", by computing Cohen's d. Treatment with OXC diminishes different symptomatic variations of this pain, but especially so in the case of lancinating discharges (d = 0.87, important effect) and burning pain (d = 0.60, moderate-important effect), although the allodynia (d = 0.48, moderate effect) also improved with treatment. In the opinion of the patients themselves, response to treatment was good or very good in 50% of cases. The chief side effects observed were dizziness, drowsiness and abdominal upsets. OXC can be seen as a therapeutic alternative to be taken very much into account in patients with NP having different aetiologies; it has a good benefit-risk ratio and is a form of treatment that is well accepted by patients.

[Nursing intervention and evaluation of postoperative pain in preschool children with cleft lip and palate].

PubMed

Gong, Caixia; Yan, Miao; Jiang, Fei; Chen, Zehua; Long, Yuan; Chen, Lixian; Zheng, Qian; Shi, Bing

2014-06-01

This study aimed to observe the postoperative pain rate and degree of pain in preschool children with cleft lip and palate, and investigate the effect of nursing intervention on pain relief. A total of 120 hospitalized cases of three- to seven-year-old preschool children with cleft lip and palate were selected from May to October 2011. The subjects were randomly divided into the control group and experimental groups 1, 2, and 3. The control group used conventional nursing methods, experimental group 1 used analgesic drug treatment, experimental group 2 used psychological nursing interventions, and experimental group 3 used both psychological nursing intervention and analgesic drug treatment. After 6, 12, 24, and 48 h, pain self-assessment, pain parent-assessment, and pain nurse-assessment were calculated for the four groups using the pain assessment forms, and their ratings were compared. The postoperative pain rates of the four groups ranged from 50.0% to 73.3%. The difference among the four groups was statistically significant (P < 0.001). The differences among the control group and experimental groups 1 and 2 were not statistically significant (P = 0.871), whereas the differences among experimental group 3 and the other groups were statistically significant (P < 0.001). Postoperative pain in preschool children with cleft lip and palate is common. Psychological nursing intervention with analgesic treatment is effective in relieving postoperative pain.

Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics.

PubMed

Trang, Tuan; Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W; Gutstein, Howard; Cahill, Catherine M

2015-10-14

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. 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. Copyright © 2015 the authors 0270-6474/15/3513879-10$15.00/0.

Spinal α2-adrenergic and muscarinic receptors and the NO release cascade mediate supraspinally produced effectiveness of gabapentin at decreasing mechanical hypersensitivity in mice after partial nerve injury

PubMed Central

Takasu, Keiko; Honda, Motoko; Ono, Hideki; Tanabe, Mitsuo

2006-01-01

After partial nerve injury, the central analgesic effect of systemically administered gabapentin is mediated by both supraspinal and spinal actions. We further evaluate the mechanisms related to the supraspinally mediated analgesic actions of gabapentin involving the descending noradrenergic system. Intracerebroventricularly (i.c.v.) administered gabapentin (100 μg) decreased thermal and mechanical hypersensitivity in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. These effects were abolished by intrathecal (i.t.) injection of either yohimbine (3 μg) or idazoxan (3 μg), α2-adrenergic receptor antagonists. Pretreatment with atropine (0.3 mg kg−1, i.p. or 0.1 μg, i.t.), a muscarinic receptor antagonist, completely suppressed the effect of i.c.v.-injected gabapentin on mechanical hypersensitivity, whereas its effect on thermal hypersensitivity remained unchanged. Similar effects were obtained with pirenzepine (0.1 μg, i.t.), a selective M1-muscarinic receptor antagonist, but not with methoctramine (0.1 and 0.3 μg, i.t.), a selective M2-muscarinic receptor antagonist. The cholinesterase inhibitor neostigmine (0.3 ng, i.t.) potentiated only the analgesic effect of i.c.v. gabapentin on mechanical hypersensitivity, confirming spinal acetylcholine release downstream of the supraspinal action of gabapentin. Moreover, the effect of i.c.v. gabapentin on mechanical but not thermal hypersensitivity was reduced by i.t. injection of L-NAME (3 μg) or L-NMMA (10 μg), both of which are nitric oxide (NO) synthase inhibitors. Systemically administered naloxone (10 mg kg−1, i.p.), an opioid receptor antagonist, failed to suppress the analgesic actions of i.c.v. gabapentin, indicating that opioid receptors are not involved in activation of the descending noradrenergic system by gabapentin. Thus, the supraspinally mediated effect of gabapentin on mechanical hypersensitivity involves activation of spinal α2-adrenergic receptors followed by muscarinic receptors (most likely M1) and the NO cascade. In contrast, the effect of supraspinal gabapentin on thermal hypersensitivity is independent of the spinal cholinergic–NO system. PMID:16582934

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

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.

Inhibitory effects of eugenol on putative nociceptive response in spinal cord preparation isolated from neonatal rats.

PubMed

Yagura, Saki; Onimaru, Hiroshi; Kanzaki, Koji; Izumizaki, Masahiko

2018-06-01

Eugenol is contained in several plants including clove and is thought to exert an analgesic effect. It has been suggested that the slow ventral root potential induced by ipsilateral dorsal root stimulation in the isolated (typically lumbar) spinal cord of newborn rats reflects the nociceptive response, and this in vitro experimental model is useful to assess the actions of analgesics. To further elucidate neuronal mechanisms of eugenol-induced analgesia, we examined the effects of extracellularly applied eugenol on the nociceptive spinal reflex response. To evaluate the effects of eugenol on putative nociceptive responses, the ipsilateral fifth lumbar (L5) dorsal root was stimulated using a glass suction electrode, and the induced reflex responses were recorded from the L5 and twelfth thoracic (Th12) ventral roots in spinal cord preparations (Th10-L5) from newborn rats (postnatal day 0-3). We found that eugenol (0.25-1.0 mM) caused dose-dependent attenuation of the reflex response and also depressed spontaneous ventral root activity. We also found that the slow ventral root potential was further divided into two components: initial and late components. A lower concentration of eugenol selectively depressed the late component. The inhibitory effects by 1.0 mM eugenol were not reversed by 10 µM capsazepine (TRPV1 antagonist) or 40 µM HC-030031 (TRPA1 antagonist). The depressive effect of eugenol on the reflex response was also confirmed by optical recordings using voltage-sensitive dye. Our report provides additional evidence on the basic neuronal mechanisms of eugenol to support its clinical use as a potential analgesic treatment.

Analgesic and anticonvulsant effects of extracts from the leaves of Kalanchoe crenata (Andrews) Haworth (Crassulaceae).

PubMed

Nguelefack, T B; Nana, P; Atsamo, A D; Dimo, T; Watcho, P; Dongmo, A B; Tapondjou, L A; Njamen, D; Wansi, S L; Kamanyi, A

2006-06-15

Kalanchoe crenata Andr. (Crassulaceae) is a fleshy herbaceous plant used in the African traditional medicine as remedies against otitis, headache, inflammations, convulsions and general debility. In the present work, the analgesic effects of methylene chloride/methanol (1:1) (CH(2)Cl(2)/CH(3)OH) extract and its hexane, methylene chloride (CH(2)Cl(2)), ethyl acetate, n-butanol fractions and aqueous residue have been evaluated using acetic acid, formalin and pressure test. The anticonvulsant effects of the CH(2)Cl(2)/CH(3)OH extract were also investigated on seizures induced by pentylenetetrazol (PTZ 70 mg/kg), strychnine sulphate (STN 2.5 mg/kg) and thiosemicarbazide (TSC 50 mg/kg). CH(2)Cl(2)/CH(3)OH extract and its fractions, administered orally at the doses of 150 and 300 mg/kg, exhibited protective effect of at least 30% on the pain induced by acetic acid. The CH(2)Cl(2) fraction at 300 mg/kg showed a maximal effect of 78.49%. The CH(2)Cl(2)/CH(3)OH extract and its CH(2)Cl(2) fraction at the doses of 150 and 300 mg/kg significantly reduced the first phase of pain induced by formalin while the second phase was completely inhibited. The CH(2)Cl(2) fraction produced more than 45% reduction in the sensitivity to pain induced by pressure. The CH(2)Cl(2)/CH(3)OH extract of Kalanchoe crenata significantly increased the latency period in seizures induced by PTZ and significantly reduced the duration of seizures induced by the three convulsant agents. The extract protected 20% of animals against death in seizures induced by TSC and STN. These results suggest a peripheral and central analgesic activities as well as an anticonvulsant effect of the leaves of Kalanchoe crenata.

Comparison of Continuous Femoral Nerve Block with and Without Combined Sciatic Nerve Block after Total Hip Arthroplasty: A Prospective Randomized Study.

PubMed

Nishio, Shoji; Fukunishi, Shigeo; Fukui, Tomokazu; Fujihara, Yuki; Okahisa, Shohei; Takeda, Yu; Yoshiya, Shinichi

2017-06-23

In association with the growing interests in pain management, several modalities to control postoperative pain have been proposed and examined for the efficacy in the recent studies. Various modes of peripheral nerve block have been proposed and the effectiveness and safety have been examined for each of those techniques. We have described our clinical experiences, showing that continuous femoral nerve block could provide a satisfactory analgesic effect after total hip arthroplasty (THA) procedure. In this study, we compared the effectiveness and safety of continuous femoral nerve block with and without sciatic nerve blockade on pain control after THA. Forty patients scheduled for THA were included in the study and randomly divided into 2 groups. Postoperative analgesic measure was continuous femoral nerve block alone, while the identical regimen of continuous femoral nerve block was combined with sciatic nerve block. The amount of postoperative pain was evaluated in the immediate postoperative period, 6 hours, and 12 hours after surgery. Moreover, postoperative complications as well as requirement of supplemental analgesics during the initial 12 hours after surgery were reviewed in the patient record. The obtained study results showed that the supplemental sciatic nerve blockade provided no significant effect on arrival at the postoperative recovery room, while the NRS pain score was significantly reduced by the combined application of sciatic nerve blockade at 6 and 12 hours after surgery. In the investigation of postoperative analgesiarelated complications, no major complication was encountered without significant difference in complication rate between the groups.

Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial

PubMed Central

Ayatollahi, Vida; Behdad, Shekoufeh; Hatami, Maryam; Moshtaghiun, Hossein; Baghianimoghadam, Behnam

2012-01-01

Aim To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects. Methods The double-blind randomized clinical trial was performed on 126 patients aged 5-12 years who had been scheduled for elective tonsillectomy. The patients were randomly divided into 3 groups to receive either ketamine, tramadol, or placebo. They had American Society of Anesthesiologists physical status class I and II. All patients underwent the same method of anesthesia and surgical procedure. The three groups did not differ according to their age, sex, and duration of anesthesia and surgery. Post operative pain was evaluated using CHEOPS score. Other parameters such as the time to the first request for analgesic, hemodynamic elements, sedation score, nausea, vomiting, and hallucination were also assessed during 12 hours after surgery. Results Tramadol group had significantly lower pain scores (P = 0.005), significantly longer time to the first request for analgesic (P = 0.001), significantly shorter time to the beginning of liquid regimen (P = 0.001), and lower hemodynamic parameters such as blood pressure (P = 0.001) and heart rate (P = 0.001) than other two groups. Ketamine group had significantly greater presence of hallucinations and negative behavior than tramadol and placebo groups. The groups did not differ significantly in the presence of nausea and vomiting. Conclusion Preoperative peritonsillar infiltration of tramadol can decrease post-tonsillectomy pain, analgesic consumption, and the time to recovery without significant side effects. Registration No: IRCT201103255764N2 PMID:22522994

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

PubMed

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

2015-06-01

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

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.

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

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.

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

Cocrystal of Ibuprofen⁻Nicotinamide: Solid-State Characterization and In Vivo Analgesic Activity Evaluation.

PubMed

Yuliandra, Yori; Zaini, Erizal; Syofyan, Syofyan; Pratiwi, Wenny; Putri, Lidiya Novita; Pratiwi, Yuti Sahra; Arifin, Helmi

2018-06-04

Ibuprofen is classified as a BCS class II drug which has low solubility and high permeability. We conducted the formation of the cocrystalline phase of ibuprofen with coformer nicotinamide to increase its solubility. The purpose of this study was to characterize the solid state of cocrystalline phase of ibuprofen-nicotinamide, determine the solubility, and evaluate its in vivo analgesic activity. The cocrystal of ibuprofen-nicotinamide was prepared by a slow evaporation method. The solid-state characterization was conducted by powder X-ray diffraction (PXRD) analysis, differential thermal analysis (DTA), and scanning electron microscopy (SEM). To investigate the in vivo analgesic activity, 28 male Swiss-Webster mice were injected with acetic acid 0.5% following oral administration of intact ibuprofen, physical mixture, and its cocrystalline phase with nicotinamide (equivalent to 26 mg/kg ibuprofen). The number of writhes was counted, and pain inhibition was calculated. All data were analyzed with one-way ANOVA followed by Duncan's Multiple Range Test (95% confidence interval). The results revealed that a new cocrystalline phase was successfully formed. The solubility testing showed that the cocrystal formation enhanced the solubility significantly as compared with the physical mixture and intact ibuprofen. A significant increase in the analgesic activity of cocrystal ibuprofen-nicotinamide was also confirmed.

Lost but making progress—Where will new analgesic drugs come from?

PubMed Central

Borsook, David; Hargreaves, Richard; Bountra, Chas; Porreca, Frank

2015-01-01

There is a critical need for effective new pharmacotherapies for pain. The paucity of new drugs successfully reaching the clinic calls for a reassessment of current analgesic drug discovery approaches. Many points early in the discovery process present significant hurdles, making it critical to exploit advances in pain neurobiology to increase the probability of success. In this review, we highlight approaches that are being pursued vigorously by the pain community for drug discovery, including innovative preclinical pain models, insights from genetics, mechanistic phenotyping of pain patients, development of biomarkers, and emerging insights into chronic pain as a disorder of both the periphery and the brain. Collaborative efforts between pharmaceutical, academic, and public entities to advance research in these areas promise to de-risk potential targets, stimulate investment, and speed evaluation and development of better pain therapies. PMID:25122640

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.

Antinociceptive effects of nalbuphine hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; KuKanich, Butch; Keuler, Nicholas S; Klauer, Julia M; Paul-Murphy, Joanne R

2011-06-01

To evaluate the antinociceptive effects and duration of action of nalbuphine HCl administered IM on thermal thresholds in Hispaniolan Amazon parrots (Amazona ventralis). 14 healthy adult Hispaniolan Amazon parrots of unknown sex. 3 doses of nalbuphine (12.5, 25, and 50 mg/kg, IM) and saline (0.9% NaCl) solution (control treatment) were evaluated in a blinded complete crossover experimental design by use of foot withdrawal threshold to a noxious thermal stimulus. Baseline data on thermal threshold were generated 1 hour before administration of nalbuphine or saline solution; thermal threshold measurements were obtained 0.5, 1.5, 3, and 6 hours after administration. Nalbuphine administered IM at 12.5 mg/kg significantly increased the thermal threshold (mean change, 2.4°C), compared with results for the control treatment, and significantly changed thermal threshold for up to 3 hours, compared with baseline results (mean change, 2.6° to 3.8°C). Higher doses of nalbuphine did not significantly change thermal thresholds, compared with results for the control treatment, but had a significant effect, compared with baseline results, for up to 3 and 1.5 hours after administration, respectively. Nalbuphine administered IM at 12.5 mg/kg significantly increased the foot withdrawal threshold to a thermal noxious stimulus in Hispaniolan Amazon parrots. Higher doses of nalbuphine did not result in significantly increased thermal thresholds or a longer duration of action and would be expected to result in less analgesic effect than lower doses. Further studies are needed to fully evaluate the analgesic effects of nalbuphine in psittacine species.

Attitudes and concerns of Canadian animal health technologists toward postoperative pain management in dogs and cats.

PubMed

Dohoo, S E; Dohoo, I R

1998-08-01

Three hundred and twenty-two Canadian animal health technologists (AHTs) were surveyed to determine their attitudes toward postoperative pain management in dogs and cats following 6 surgical procedures, their concerns regarding the use of opioid analgesics, and their role within veterinary practices with respect to postoperative pain control. Two hundred and sixty-four (82%) returned the questionnaire. Pain perception was defined as the average of pain rankings for dogs and cats (on a scale of 1 to 10) following abdominal surgery, or the value for dogs or cats if the AHT worked with only 1 of the 2 species. Maximum concern about the risks associated with the postoperative use of morphine or oxymorphone was defined as the highest rating assigned to any of the 6 risks evaluated in either dogs or cats. Animal health technologists reported significantly higher pain perception scores than did veterinarians who completed a similar survey 2 years previously. Higher pain perception scores were associated with decreased satisfaction with the adequacy of analgesic therapy in their practice, higher pain control goals, and attendance at continuing education within the previous 12 months. The majority of AHTs (55%) agreed that one or more risks associated with the use of morphine or oxymorphone outweighed the benefits. The 3 issues that were perceived to pose the greatest risk were respiratory depression, bradycardia, and sedation and excitement, for dogs and cats, respectively. Most AHTs (68%) considered their knowledge related to the recognition and control of pain to be adequate, compared with 24% of veterinarians who responded to a similar previous survey. As for veterinarians, experience gained while in practice was ranked as the most important source of knowledge, while the technical program attended was ranked as least important. Over 88% of the AHTs provided nursing care during the postoperative period, monitored animals for side effects of postoperative analgesic therapy, informed veterinarians when animals were in pain, recommended analgesic therapy when they believed it was warranted, reported that animals received analgesics when they believed it was warranted, administered analgesics under the instruction of a veterinarian, and believed they were part of a team working to provide adequate postoperative pain control.

A Comparison of Three Different Volumes of Levobupivacaine for Caudal Block in Children Undergoing Orchidopexy and Inguinal Hernia Repair

PubMed Central

Marjanovic, Vesna; Budic, Ivana; Stevic, Marija; Simic, Dusica

2017-01-01

Objective 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. Subjects and Methods 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. Results 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. Conclusion 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. PMID:28437787

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

PubMed

Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

2016-05-04

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] μmol/kg) greater than dopamine (190 [181-203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Changes in pain and concurrent pain medication use following compounded topical analgesic treatment for chronic pain: 3- and 6-month follow-up results from the prospective, observational Optimizing Patient Experience and Response to Topical Analgesics study

PubMed Central

Gudin, Jeffrey A; Brennan, Michael J; Harris, E Dennis; Hurwitz, Peter L; Dietze, Derek T; Strader, James D

2017-01-01

Background Opioids and other controlled substances prescribed for chronic pain are associated with abuse, addiction, and death, prompting national initiatives to identify safe and effective pain management strategies including topical analgesics. Methods This prospective, observational study evaluated changes from baseline in overall mean severity and interference scores on the Brief Pain Inventory scale and the use of concurrent pain medications at 3- and 6-month follow-up assessments in chronic pain patients treated with topical analgesics. Changes in pain severity and interference and medication usage were compared between treated patients and unmatched and matched controls. Results The unmatched intervention group (unmatched-IG) included 631 patients who completed baseline and 3-month follow-up surveys (3-month unmatched-IG) and 158 who completed baseline and 6-month follow-up assessments (6-month unmatched-IG). Baseline and 3-month follow-up data were provided by 76 unmatched controls and 76 matched controls (3-month unmatched-CG and matched-CG), and 51 unmatched and 36 matched patients completed baseline and 6-month follow-up surveys (6-month unmatched-CG and matched-CG). Baseline demographic characteristics and mean pain severity and interference scores were similar between groups. There were statistically significant decreases from baseline in mean pain severity and interference scores within the 3- and 6-month unmatched-IG (all P<0.001). Significantly greater decreases in the mean change from baseline in pain severity and interference scores were evident for the 3- and 6-month unmatched-IG versus unmatched-CG (all P<0.001), with similar results when the 3- and 6-month matched-IG and matched-CG were compared. A higher percentage of the 3- and 6-month unmatched-IG and matched-IG de-escalated use of concurrent pain medications (all P<0.001), while significantly higher percentages of the unmatched-CG and matched-CG escalated medication use. Side effects were reported by <1% of the unmatched-IG. Conclusion Topical analgesics appear to be effective and safe for the treatment of chronic pain, with randomized controlled trials needed to confirm these findings. PMID:29042810

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

Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble carriers: phase equilibria, solid-state characterisation and in-vivo/pharmacodynamic evaluation.

PubMed

Abdelkader, Hamdy; Abdallah, Ossama Y; Salem, Hesham; Alani, Adam W G; Alany, Raid G

2014-10-01

The solid-state interactions of fused mixtures nimesulide (ND) with polyethylene glycol (PEG) 4000, urea or mannitol were studied through constructing thaw-melt phase equilibrium diagrams. The solid-state characteristics were investigated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Various types of interactions were identified such as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND-urea and complete solid immiscibility of ND with mannitol. The effects of carrier concentrations on the equilibrium solubility and in-vitro dissolution characteristics were studied. Linear increases (R(2)  > 0.99) in the aqueous solubility of ND in various concentrations of PEG 4000 and urea were obtained, whereas mannitol did not exhibit any effect on the solubility of ND. Similar trends were obtained with the dissolution efficiency of the fused mixtures of ND with PEG 4000 and urea compared with the corresponding physical mixtures and untreated drug. The analgesic effects of untreated ND and the selected formulations were investigated by evaluating the drug's ability to inhibit the acetic acid-induced writhing response. The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug. © 2014 Royal Pharmaceutical Society.

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.

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

Nitrous Oxide During Labor: Maternal Satisfaction Does Not Depend Exclusively on Analgesic Effectiveness.

PubMed

Richardson, Michael G; Lopez, Brandon M; Baysinger, Curtis L; Shotwell, Matthew S; Chestnut, David H

2017-02-01

Evidence on the analgesic effectiveness of nitrous oxide for labor pain is limited. Even fewer studies have looked at patient satisfaction. Although nitrous oxide appears less effective than neuraxial analgesia, it is unclear whether labor analgesic effectiveness is the most important factor in patient satisfaction. We sought to compare the relationship between analgesic effectiveness and patient satisfaction with analgesia in women who delivered vaginally using nitrous oxide, neuraxial analgesia (epidural or combined spinal-epidural [CSE]), or both (neuraxial after a trial of nitrous oxide). A standardized survey was recorded on the first postpartum day for all women who received anesthetic care for labor and delivery. Data were queried for women who delivered vaginally with nitrous oxide and/or neuraxial labor analgesia over a 34-month period in 2011 to 2014. Parturients with complete data for analgesia quality and patient satisfaction were included. Analgesia and satisfaction scores were grouped into 8 to 10 high, 5 to 7 intermediate, and 0 to 4 low. These scores were compared with the use of ordinal logistic regression across 3 groups: nitrous oxide alone, epidural or CSE alone, or nitrous oxide followed by neuraxial (epidural or CSE) analgesia. A total of 6507 women received anesthesia care and delivered vaginally. Complete data were available for 6242 (96%) women; 5261 (81%) chose neuraxial analgesia and 1246 (19%) chose nitrous oxide. Of the latter, 753 (60%) went on to deliver with nitrous oxide alone, and 493 (40%) switched to neuraxial analgesia. Most parturients who received neuraxial analgesia (>90%) reported high analgesic effectiveness. Those who used nitrous oxide alone experienced variable analgesic effectiveness, with only one-half reporting high effectiveness. Among all women who reported poor analgesia effectiveness (0-4; n = 257), those who received nitrous oxide alone were more likely to report high satisfaction (8-10) than women who received epidural analgesia alone (OR 2.5; 95% CI 1.4-4.5; P = .002). Women who reported moderate analgesia (5-7) and received nitrous oxide only were more likely to report high satisfaction compared with the other groups. Among women who reported a high level of analgesic effectiveness, satisfaction with anesthesia was high and not different among groups. Patients who received nitrous oxide alone were as likely to express satisfaction with anesthesia care as those who received neuraxial analgesia, even though they were less likely to report excellent analgesia. Although pain relief contributes to the satisfaction with labor analgesia care, our results suggest that analgesia is not the only contributor to maternal satisfaction.

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.

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.

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.

Time Dependent Antinociceptive Effects of Morphine and Tramadol in the Hot Plate Test: Using Different Methods of Drug Administration in Female Rats

PubMed Central

Gholami, Morteza; Saboory, Ehsan; Mehraban, Sogol; Niakani, Afsaneh; Banihabib, Nafiseh; Azad, Mohamad-Reza; Fereidoni, Javid

2015-01-01

Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There was a significant correlation between the day, drug, group, and their interaction (P<0.001). At 1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0.001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0.001). At the 15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life. PMID:25561936

The research gap in chronic paediatric pain: A systematic review of randomised controlled trials.

PubMed

Boulkedid, R; Abdou, A Y; Desselas, E; Monégat, M; de Leeuw, T G; Avez-Couturier, J; Dugue, S; Mareau, C; Charron, B; Alberti, C; Kaguelidou, F

2018-02-01

Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases. © 2017 European Pain Federation - EFIC®.

Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation

PubMed Central

Abou el Ela, Amal El Sayeh F.; Hassan, Maha A.; El- Maraghy, Dalia A.

2013-01-01

The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet. PMID:25161380

Foot massage: effectiveness on postoperative pain in breast surgery patients.

PubMed

Ucuzal, Meral; Kanan, Nevin

2014-06-01

The aim of this study was to determine the effect of foot massage on pain after breast surgery, and provide guidance for nurses in nonpharmacologic interventions for pain relief. This was a quasiexperimental study with a total of 70 patients who had undergone breast surgery (35 in the experimental group and 35 in the control group). Patients in the control group received only analgesic treatment, whereas those in the experimental group received foot massage in addition to analgesic treatment. Patients received the first dose of analgesics during surgery. As soon as patients came from the operating room, they were evaluated for pain severity. Patients whose pain severity scored ≥4 according to the Short-Form McGill Pain Questionnaire were accepted into the study. In the experimental group, pain and vital signs (arterial blood pressure, pulse, and respiration) were evaluated before foot massage at the time patients complained about pain (time 0) and then 5, 30, 60, 90, and 120 minutes after foot massage. In the control group, pain and vital signs were also evaluated when the patients complained about pain (time 0) and again at 5, 30, 60, 90, and 120 minutes, in sync with the times when foot massage was completed in the experimental group. A patient information form was used to collect descriptive characteristics data of the patients, and the Short-Form McGill Pain Questionnaire was used to determine pain severity. Data were analyzed for frequencies, mean, standard deviation, chi-square, Student t, Pillai trace, and Bonferroni test. The results of the statistical analyses showed that patients in the experimental group experienced significantly less pain (p ≤ .001). Especially notable, patients in the experimental group showed a decrease in all vital signs 5 minutes after foot massage, but patients in the control group showed increases in vital signs except for heart rate at 5 minutes. The data obtained showed that foot massage in breast surgery patients was effective in postoperative pain management. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Endomorphin-2 analogs with C-terminal esterification produce potent systemic antinociception with reduced tolerance and gastrointestinal side effects.

PubMed

Wang, Chang-Lin; Qiu, Ting-Ting; Yang, Dai-Jun; Yuan, Bi-Yu; Han, Feng-Tong; Li, Li; Gu, Ning

2017-04-01

C-terminal esterification of opioid peptides may change their opioid activities due to the modified physicochemical properties. In the present study, the pharmacological activities of C-terminal esterified endomorphin-2 (EM-2) analogs 1-3 were characterized by in vitro metabolic stability and octanol/buffer distribution assays. Also, the antinociceptive profiles in the radiant heat paw withdrawal test and related side effects of these analogs were determined. Our results showed that all three analogs significantly increased the metabolic stability and lipophilicity. Moreover, analogs 1-3 displayed potent antinociceptive activities after intracerebroventricular (i.c.v.) administration. Analogs 1 and 3 exhibited about 2-fold higher antinociception than EM-2, and differential opioid mechanisms were involved. In addition, EM-2 at 50 μmol/kg failed to produce any significant antinociceptive activity after subcutaneous (s.c.) administration, whereas equimolar dose of analogs 1-3 produced significant analgesic effects. Analog 3 showed the highest antinociceptive activity after systemic administration, which was consistent with its in vitro stability and lipophilicity. We further evaluated the antinociceptive tolerance of analogs 1-3. In acute tolerance test, analogs 1-3 shifted the dose-response curves rightward by only 1.4-3.2 fold as determined by tolerance ratio, whereas EM-2 by 5.6-fold, demonstrating reduced antinociceptive tolerance. Also, analogs 1 and 2 decreased chronic antinociceptive tolerance by central and peripheral administration of drugs. In particular, analogs 3 displayed insignificant chronic antinociceptive tolerance. Furthermore, analogs 1-3 were less prone to induce gastrointestinal side effects at analgesic doses. The present investigation gave the evidence that C-terminal esterified modifications of EM-2 will facilitate the development of novel opioid analgesics with reduced side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-term use of minimal footwear on pain, self-reported function, analgesic intake, and joint loading in elderly women with knee osteoarthritis: A randomized controlled trial.

PubMed

Trombini-Souza, Francis; Matias, Alessandra B; Yokota, Mariane; Butugan, Marco K; Goldenstein-Schainberg, Claudia; Fuller, Ricardo; Sacco, Isabel C N

2015-12-01

Efforts have been made to retard the progressive debilitating pain and joint dysfunction in patients with knee osteoarthritis. We aimed to evaluate the therapeutic effect of a low-cost minimalist footwear on pain, function, clinical and gait-biomechanical aspects of elderly women with knee osteoarthritis. Throughout a randomized, parallel and controlled clinical trial, fifty-six patients with medial knee osteoarthritis were randomly allocated to an intervention (n=28) or control group (n=28), and assessed at baseline and after three and six months. The intervention involved wearing Moleca(®) footwear for at least 6h/day, 7 days/week, over 6 months. The pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index was the primary outcome. The secondary outcomes were the other subscales, Lequesne score, distance walked in 6 min, knee oedema and effusion, knee adduction moment and paracetamol intake. Intention-to-treat analysis was performed using two-way casewise ANOVA (< .05) and Cohen's d coefficient. Intervention group showed improvement in pain (effect size: 1.41, p<.001), function (effect size: 1.22, p=.001), stiffness (effect size: 0.76, p=.001), Lequesne score (effect size: 1.07, p<.001), and reduction by 21.8% in the knee adduction moment impulse (p=.017) during gait wearing Moleca(®). The analgesic intake was lower in the intervention group. The long-term use of Moleca(®) footwear relieves pain, improves self-reported function, reduces the knee loading while wearing Moleca(®), refrains the increase of analgesic intake in elderly women with knee osteoarthritis and can be considered as a conservative mechanical treatment option. ClinicalTrials.gov (NCT01342458). Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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

Antinociceptive properties of physalins from Physalis angulata.

PubMed

Lima, Milena da Silva; Evangelista, Afrânio Ferreira; Santos, Gisele Graça Leite Dos; Ribeiro, Ivone Maria; Tomassini, Therezinha Coelho Barbosa; Pereira Soares, Milena Botelho; Villarreal, Cristiane Flora

2014-11-26

Pain is the most common reason a patient sees a physician. Nevertheless, the use of typical painkillers is not completely effective in controlling all pain syndromes; therefore further attempts have been made to develop improved analgesic drugs. The present study was undertaken to evaluate the antinociceptive properties of physalins B (1), D (2), F (3), and G (4) isolated from Physalis angulata in inflammatory and centrally mediated pain tests in mice. Systemic pretreatment with 1-4 produced dose-related antinociceptive effects on the writhing and formalin tests, traditional screening tools for the assessment of analgesic drugs. On the other hand, only 3 inhibited inflammatory parameters such as hyperalgesia, edema, and local production of TNF-α following induction with complete Freund's adjuvant. Treatment with 1, 3, and 4 produced an antinociceptive effect on the tail flick test, suggesting a centrally mediated antinociception. Reinforcing this idea, 2-4 enhanced the mice latency reaction time during the hot plate test. Mice treated with physalins did not demonstrate motor performance alterations. These results suggest that 1-4 present antinociceptive properties associated with central, but not anti-inflammatory, events and indicate a new pharmacological property of physalins.

Opioids in people with cancer-related pain

PubMed Central

2008-01-01

Introduction Up to 80% of people with cancer experience pain at some time during their illness, and most will need opioid analgesics. This review assesses how different opioid analgesics compare, in terms of both pain control and adverse effects, in people with cancer. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: what are the effects of opioids in treating cancer-related pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 22 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: codeine, dihydrocodeine, transdermal fentanyl, hydromorphone, methadone, morphine, oxycodone, and tramadol. PMID:19445735

Emergency department management of pain and anxiety related to orthopedic fracture care: a guide to analgesic techniques and procedural sedation in children.

PubMed

Kennedy, Robert M; Luhmann, Jan D; Luhmann, Scott J

2004-01-01

Orthopedic fractures and joint dislocations are among the most painful pediatric emergencies. Safe and effective management of fracture-related pain and anxiety in the emergency department reduces patient distress during initial evaluation and often allows definitive management of the fracture. No consensus exists on which pharmacologic regimens for procedural sedation/analgesia are safest and most effective. For some children, control of fracture pain is the primary goal, whereas for others, relief from anxiety is an additionally important objective. Furthermore, strategies for the management of fracture pain may vary by fracture location and patient characteristics; thus, no single regimen is likely to provide the best means of analgesia and anxiolysis for all patients. Effective analgesia can be provided by local or regional anesthesia, such as hematoma, Bier, or nerve blocks. Alternatively, induction of deep sedation with analgesic agents such as ketamine or fentanyl, often combined with sedative-anxiolytic agents such as midazolam, may be used to manage distress associated with fracture reduction. A combination of local anesthesia with moderate sedation, for example nitrous oxide, is another attractive option.

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.

Effect of Oral Administration of Bromelain on Postoperative Discomfort After Third Molar Surgery.

PubMed

Ghensi, Paolo; Cucchi, Alessandro; Creminelli, Luca; Tomasi, Cristiano; Zavan, Barbara; Maiorana, Carlo

2017-03-01

The purpose of this prospective randomized controlled clinical trial was to evaluate the effect of oral administration of bromelain on discomfort after mandibular third molar surgery. Eighty-four consecutive patients requiring surgical removal of a single mandibular impacted third molar under local anesthesia were randomly assigned to receiving no drug (control group, Group A), postoperative 40 mg bromelain every 6 hours for 6 days (Group B), preoperative 4 mg dexamethasone sodium phosphate as a submucosal injection (Group C), and preoperative 4 mg dexamethasone sodium phosphate as a submucosal injection plus postoperative 40 mg bromelain every 6 hours for 6 days (Group D). Standardized surgical and analgesic protocols were adopted. Maximum interincisal distance and facial contours were measured at baseline and on postoperative days 2 and 7. Pain was measured objectively by counting the number of analgesic tablets required. Patient perception of the severity of symptoms was assessed with a follow-up questionnaire (PoSSe scale). On postoperative day 2, there was a statistically significant reduction in facial edema in both Groups C and D compared with the control group, but no statistically significant differences were observed between Group B and the control group. At evaluation on postoperative day 7, Group D showed a statistically significant reduction in postoperative swelling compared with the control group. The combined use of bromelain and dexamethasone (Group D) induced a statistically significant reduction in the total number of analgesic tablets taken after surgery compared with the control group. The treatment groups had a limited, nonsignificant effect on trismus when compared with the control group. Bromelain used singly showed moderate anti-inflammatory efficacy, reducing postoperative swelling, albeit not to any significant extent compared with no drug administration. The combined use of bromelain and dexamethasone sodium phosphate yielded the best results in terms of control of postoperative discomfort.

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

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,…

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.

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.

"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.

Gabapentin Inhibits Protein Kinase C Epsilon Translocation in Cultured Sensory Neurons with Additive Effects When Coapplied with Paracetamol (Acetaminophen).

PubMed

Vellani, Vittorio; Giacomoni, Chiara

2017-01-01

Gabapentin is a well-established anticonvulsant drug which is also effective for the treatment of neuropathic pain. Although the exact mechanism leading to relief of allodynia and hyperalgesia caused by neuropathy is not known, the blocking effect of gabapentin on voltage-dependent calcium channels has been proposed to be involved. In order to further evaluate its analgesic mechanisms, we tested the efficacy of gabapentin on protein kinase C epsilon (PKC ε ) translocation in cultured peripheral neurons isolated from rat dorsal root ganglia (DRGs). We found that gabapentin significantly reduced PKC ε translocation induced by the pronociceptive peptides bradykinin and prokineticin 2, involved in both inflammatory and chronic pain. We recently showed that paracetamol (acetaminophen), a very commonly used analgesic drug, also produces inhibition of PKC ε . We tested the effect of the combined use of paracetamol and gabapentin, and we found that the inhibition of translocation adds up. Our study provides a novel mechanism of action for gabapentin in sensory neurons and suggests a mechanism of action for the combined use of paracetamol and gabapentin, which has recently been shown to be effective, with a cumulative behavior, in the control of postoperative pain in human patients.

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.

Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues--Observations in two patients with acromegaly and severe headache.

PubMed

Marina, Djordje; Burman, Pia; Klose, Marianne; Casar-Borota, Olivera; Luque, Raúl M; Castaño, Justo P; Feldt-Rasmussen, Ulla

2015-10-01

Somatotropinomas have unique "fingerprints" of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a common complaint in acromegaly and considered a clinical marker of disease activity. SSAs are reported to have an own analgesic effect, but the sst involved are unknown. We investigated sst expression in two acromegalic patients with severe headache and no biochemical effects of octreotide, but a good response to pasireotide. We searched the literature for determinants of biochemical and analgesic effects of SSAs in somatotropinomas. Case 1 had no biochemical or analgesic effects of octreotide, a semi-selective SSA, but a rapid and significant effect of pasireotide, a pan-SSA. Case 2 demonstrated discordance between analgesic and biochemical effects of octreotide, in that headache disappeared, but without biochemical improvement. In contrast, pasireotide normalized insulin-like growth factor 1. Both adenomas were sparsely granulated and had strong membranous expressions of sst2a in 50-75% and sst5 in 75-100% of tumor cells. The truncated sst5 variant TMD4 (sst5TMD4) showed expression in 20-57% of tumor cells. A poor biochemical response to octreotide may be associated with tumor expression of a truncated sst5 variant, despite abundant sst2a expression, suggesting an influence from variant sst5 on common sst signaling pathways. Furthermore, unrelated analgesic and biochemical effects of SSAs supported a complex pathogenesis of acromegaly-associated headache. Finally, assessment of truncated sst5 in addition to full length sst could be important for a choice of postoperative SSA treatment in somatotropinomas. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

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

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.

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.

PHYTOCHEMICAL SCREENING, ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF PENTANISIA PRUNELLOIDES FROM THE EASTERN CAPE PROVINCE, SOUTH AFRICA.

PubMed

Mathews, Miya Gugulethu; Ajayi, Oyemitan Idris; Opeoluwa, Oyedeji Oyehan; Oluwatobi, Oluwafemi Samuel; Benedicta N, Nkeh-Chungag; Phindile, Songca Sandile; Oyedeji; Omowumi, Adebola

2016-01-01

Pentanisia prunelloides is a medicinal plant widely used to remedy various ailments including infections, fever and rheumatism in Eastern Cape Province of South Africa. There is scanty report on the phytochemical and biological properties of the plant; hence various solvent extracts of the dried plant materials were phytochemically screened, and its aqueous extract evaluated for acute toxicity effect, analgesic and antiinflammatory properties in rodents. Different extracts of both leaf and rhizome were obtained separately with ethanol, methanol and water. Portions of the filtrate were used for qualitative screening of secondary metabolites and remaining portions were concentrated and dried. Dried grounded leaf and rhizome of the plant were also used for quantitative screening for some major components. The aqueous extract of the leaf and rhizome were used for acute toxicity (LD 50 ) test, antiinflammatory and analgesic activities in rodents. The qualitative phytochemical screening showed the presence of several phytoconstituents with saponins, flavonoids and alkaloids constituting highest constituents in the leaf and rhizome. The LD50: of the aqueous extracts (from leaf or rhizome) was found to be ≥5000 mg/kg orally. The leaf and rhizome aqueous extract (250-500 mg/kg) significantly (p<0.01) reduced egg albumin-induced paw oedema and paw licking in mice induced by formalin, signifying antinociceptive and antiinflammatory activities respectively. It is concluded that the leaf and rhizome of P. prunelloides are rich in various phytochemicals which could be associated with their medicinal uses. The aqueous leaf and rhizome extracts are similarly non-toxic orally, showed antiinflammatory and analgesic potentials thus rationalizing its use in folkloric medicine.

Local treatment of tendinopathies and myofascial pain syndromes with the 5-HT3 receptor antagonist tropisetron.

PubMed

Müller, W; Stratz, T

2004-01-01

The use of local tropisetron injections improved the treatment of tendinopathies considerably, with the effect being comparable to the topical application of local anaesthetics combined with depot corticosteroids. On the other hand, local injection of prilocaine alone exerted a shorter and weaker effect on the condition. After it had been proven that systemic application of the 5-HT3 receptor antagonist tropisetron exerts an analgesic effect on musculoskeletal pain in fibromyalgia, we investigated the efficacy of the substance in tendinopathies and myofascial pain syndromes. Local injections of tropisetron as a treatment for trigger points in myofascial pain syndrome also brought about rapid and prolonged relief in the majority of cases. The analgesic effect was far superior to the action of local anaesthetics. The present findings indicate that the analgesic action of the 5-HT3 receptor antagonist tropisetron sets in rapidly and lasts for a long time. Various mechanisms are under discussion to explain the long duration of the effect. Tropisetron not only has an analgesic but probably also an antiphlogistic effect which can be attributed to the inhibited release of substance P and other neuropeptides from the nociceptors and the blocked release of phlogistic substances from macrophages, monocytes etc.

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

PubMed

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

2012-12-01

Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p < 0.05), while exposure to the non resonant random EMFs exerted no effects. Additionally, naloxone administration inhibited the analgesic effects of the NMR spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

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.

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, 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

Validation of a Preclinical Spinal Safety Model: Effects of Intrathecal Morphine in the Neonatal Rat

PubMed Central

Westin, B. David; Walker, Suellen M.; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L.

2010-01-01

Background Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long term function following intrathecal morphine in the neonatal rat. Methods Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P)3, 10 and 21. The relationship between injectate volume and segmental spread was assessed post mortem and by in-vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 minutes following intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis and glial response were evaluated 1 and 7 days following P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Results Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally-mediated analgesia at all ages with lower dose requirements in younger pups. High dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. Conclusions The therapeutic ratio for intrathecal morphine (toxic dose / antinociceptive dose) was at least 300 at P3, and at least 20 at P21 (latter doses limited by side effects). This data provides relative efficacy and safety data for comparison with other analgesic preparations and contributes supporting evidence for the validity of this preclinical neonatal safety model. PMID:20526189

Validation of a preclinical spinal safety model: effects of intrathecal morphine in the neonatal rat.

PubMed

Westin, B David; Walker, Suellen M; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L

2010-07-01

Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationship between injectate volume and segmental spread was assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 min after intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relative efficacy and safety for comparison with other analgesic preparations and contribute supporting evidence for the validity of this preclinical neonatal safety model.

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

Evaluation of analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease.

PubMed

Stathopoulou, Thaleia-Rengina; Kouki, Maria; Pypendop, Bruno H; Johnston, Atholl; Papadimitriou, Serafeim; Pelligand, Ludovic

2017-09-01

Objectives The objective of this study was to evaluate the analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease. Methods Six adult client-owned cats with chronic gingivostomatitis (weighing 5.1 ± 1.1 kg) were recruited for a randomised, prospective, blinded, saline-controlled, crossover study. Pain scores, dental examination, stomatitis score and buccal pH measurement were conducted on day 1 under sedation in all cats. On day 2, animals were randomised into two groups and administered one of the two treatments buccally (group A received buprenorphine 0.02 mg/kg and group B received 0.9% saline) and vice versa on day 3. Pain scores and food consumption were measured at 30, 90 and 360 mins after the administration of buprenorphine. Blood samples were taken at the same time and plasma buprenorphine concentration was measured by liquid chromatography-mass spectrometry. Data were statistically analysed as non-parametric and the level of significance was set as P <0.05. Results There were no major side effects after buprenorphine administration. Buccal pH values ranged between 8.5 and 9.1 and the stomatitis disease activity index between 10 and 22 (17.8 ± 4.5) with the scale ranging from 0-30. The maximum buprenorphine plasma concentration (14.8 ng/ml) was observed 30 mins after administration and there was low inter-individual variability. There was a significant difference between baseline pain scores compared with pain scores after buprenorphine ( P <0.05 ) and between the saline and buprenorphine group at 30 mins ( P = 0.04) and 90 mins ( P = 0.04). There was also a significant effect of the stomatitis index on the pain score. Regarding the pharmacokinetic parameters, cats with stomatitis showed lower bioavailability and shorter absorption half-life after buccal administration of buprenorphine compared with normal cats in previous studies. Conclusions and relevance Buccal administration of buprenorphine in cats with gingivostomatitis produces an analgesic effect and low inter-individual variability in plasma concentration, and it can be incorporated in their multimodal analgesia plan.