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1.
Medicine (Baltimore) ; 99(33): e21670, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872033

RESUMO

BACKGROUND: Total knee arthroplasty (TKA) is an established and successful surgical procedure which is the major treatment for degenerative knee joint diseases. A novel technique to address posterior knee joint pain is the infiltration of local anesthetic between the interspace between the popliteal artery and capsule of the knee (IPACK). The goal of this randomized clinical trial was to assess the efficacy and safety of adding IPACK to adductor canal block (ACB) after TKA. METHODS: This was a prospectively randomized trial that investigated the effectiveness and safety of the IPACK after TKA. Approval from Clinical Studies Ethical Committee in Qilu Hospital of Shandong University was obtained. The inclusion criteria were adult patients undergoing primary unilateral TKA and American Society of Anesthesiologists grade 1 or 2 with normal cognitive function. The patients were randomized to 1 of 2 treatment options: ACB-alone group and ACB + IPACK group. The primary outcome was the total morphine consumption during postoperative 24 hours. Secondary outcomes included postoperative pain score, time to first and total dosage of rescue morphine in postoperative 48 hours, early and late postoperative period (from postoperative day 0-3 months follow-up) performance-based test (Timed-Up and Go test, and quadriceps strength). Postoperative nausea and vomiting, length of hospital stay, patient satisfaction, and other adverse events were also evaluated. RESULTS: It was hypothesized that when combined with a control group, the IPACK block would result in a lower morphine consumption and pain score after TKA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5765).


Assuntos
Artroplastia do Joelho/métodos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Analgésicos Opioides/administração & dosagem , Anestésicos Locais/administração & dosagem , Humanos , Morfina/administração & dosagem , Artéria Poplítea , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego
3.
Medicine (Baltimore) ; 99(34): e21816, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846821

RESUMO

BACKGROUND: Due to the soft tissue injury and large amount of bone destruction involved, undesirable postoperative pain remains a challenge for both patients and surgeons after unicompartmental knee replacement (UKR). However, there are no studies comparing the effectiveness of oral and intravenous acetaminophen as part of a standard multimodal perioperative pain regimen after UKR. Thus, this prospective randomized study was conducted to compare pain control outcomes with postoperative oral versus intravenous acetaminophen use in adults undergoing UKR. METHODS: The institutional review board of the Traditional Chinese Medicine- western Medicine Hospital of Cangzhou approved the study protocol. This blinded and randomized study was carried out in accordance with the principles of the Helsinki Declaration. We included patients who were scheduled for UKR with an American Society of Anesthesiologists status of I to III, who were mentally competent, and who were able to give consent for enrolment in the study. Patients were randomly assigned on a 1:1 basis to receive either intravenous acetaminophen or oral acetaminophen. We ensured that the patients, care providers, and outcome assessors were blinded to the group assignment during the study period. Primary outcomes were postoperative pain at rest and during motion (knee flexion of 45°) measured using a visual analog scale score. Secondary outcomes included morphine consumption at 24, 48, and 72 hours after surgery, length of hospital stay, range of motion, daily ambulation distance, and adverse events occurrence. All statistical analyses were performed using SPSS 25.0. Differences associated with a P value of <.05 were considered statistically significant. RESULTS: It was hypothesized that patients receiving intravenous acetaminophen would exhibit similar postoperative outcomes compared with patients receiving oral acetaminophen. TRIAL REGISTRATION: This study was registered in Research Registry (researchregistry5825).


Assuntos
Acetaminofen/administração & dosagem , Artroplastia do Joelho/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/efeitos adversos , Administração Intravenosa , Administração Oral , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Humanos , Articulação do Joelho/fisiopatologia , Tempo de Internação , Morfina/uso terapêutico , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Projetos de Pesquisa , Caminhada
4.
Life Sci ; 257: 118048, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622946

RESUMO

AIMS: Naldemedine is a peripherally acting µ-opioid receptor antagonists (PAMORAs) indicated for the treatment of opioid-induced constipation (OIC). We investigated the preventive effect of naldemedine on morphine-induced nausea and vomiting in ferrets and conducted a pharmacokinetic/pharmacodynamic (PK/PD) analysis. MAIN METHODS: The antiemetic effect of naldemedine was evaluated as the frequency and time of retching (rhythmic abdominal contractile motion) and vomiting (throwing up vomit or similar reactions) caused by morphine in ferrets. After a single oral administration of naldemedine to ferrets, the plasma concentrations of naldemedine and morphine were measured by liquid chromatography-tandem mass spectrometry. KEY FINDINGS: Naldemedine showed a potent and dose-dependent anti-emetic effects against morphine-induced emetic responses, for up to 6 h. The dose of naldemedine that produced half the maximal effect (ED50) value for anti-emetic effect of naldemedine in the morphine-treated ferrets was 0.033 mg/kg. The PK/PD analysis revealed that the antiemetic effect was related to the plasma naldemedine concentration, with a half maximal effective concentration that produces half the maximal effect (EC50) of 3.51 ng/mL. The plasma concentration producing an antiemetic effect was almost 200-fold lower than that inducing an anti-analgesic effect in rats. SIGNIFICANCE: Naldemedine showed potent inhibition of morphine-induced vomiting for up to 6 h after dosing. These data suggest that naldemedine possesses antiemetic properties and could be effective against opioid-induced nausea and vomiting (OINV).


Assuntos
Naltrexona/análogos & derivados , Náusea/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Animais , Constipação Intestinal/induzido quimicamente , Furões , Masculino , Morfina/efeitos adversos , Naltrexona/metabolismo , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Receptores Opioides mu/antagonistas & inibidores , Vômito/induzido quimicamente
5.
Harefuah ; 159(6): 423-428, 2020 Jun.
Artigo em Hebraico | MEDLINE | ID: mdl-32583645

RESUMO

BACKGROUND: Spinal morphine provides the optimal treatment for post-cesarean analgesia, despite frequent nausea and vomiting. We investigated the incidence of nausea and vomiting 24 hours after cesarean delivery in women receiving intrathecal morphine 100 µcg and intravenous prophylactic dexamethasone and ondansetron. METHODS: In a prospective, observational, Institutional Review Board (IRB) approved study of women undergoing cesarean delivery according to a standardized anesthetic protocol, the subjects were approached preoperatively and underwent standardized interviews regarding prior anesthesia experience and history of postoperative nausea and vomiting. In the post anesthesia care unit and 24 hours postoperatively, the women were interviewed regarding the incidence of nausea and vomiting, Women with and without nausea at 24 hours were compared for potential associated risk factors. RESULTS: Among 201 women recruited, 29 (14.5%) had nausea and 7 (3.5%) vomited in the postoperative care unit. During the first 24 hours, 36 (17.9%) had experienced nausea and 19 (9.5%) had vomited when interviewed at the 24-hours postoperatively. Women who had nausea 24 hours postoperatively were more likely to have nausea in the post anesthesia care unit than women without nausea during 24 hours after cesarean delivery (41.7% versus 1.2%, p<0.001). We did not find preoperative risk factors for postoperative nausea and vomiting. CONCLUSIONS: We report that almost 20% of the women managed with prophylactic dual therapy of ondansetron and dexamethasone had nausea during the 24 hours after administration of low dose intrathecal morphine. Our findings suggested that women who experience nausea or vomiting in the immediate postoperative period are at increased risk of nausea and vomiting in the 24-hour postoperative period.


Assuntos
Analgésicos Opioides/uso terapêutico , Morfina/uso terapêutico , Náusea e Vômito Pós-Operatórios , Antieméticos , Cesárea , Método Duplo-Cego , Feminino , Humanos , Injeções Espinhais , Gravidez , Estudos Prospectivos
6.
S D Med ; 73(5): 198-201, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32579798

RESUMO

INTRODUCTION: Medical use and overuse of opioids have become an increasing problem over the past several decades. Postoperative pain control is the strongest indication for the use of opioid analgesics. Previous studies have demonstrated benefit from complementary and alternative therapy (CAT) for postoperative pain relief. A prior study conducted by Riswold et al. found that a unit staff training session on CAT improved patient experiences postoperatively following total joint replacement. The study was limited in that it did not examine if there were any changes in opioid usage following this intervention. METHODS: This study is a continuation of the Riswold et al. study on CAT training intervention. In July 2017, a four-hour staff training session on alternative comfort measures and pain medication administration took place. Opioid administration data was extracted from the PYXIS software for all patients who had received more than three opioid administrations across their hospital stay in the three months prior to CAT training and the three months post-training. Opioid administrations were converted to total oral morphine equivalents. The pre- and post-intervention groups were compared using independent sample t-tests using SPSS software. RESULTS: Statistically significant reduction of total oral morphine equivalents occurred following CAT training intervention (p=.034, CI 2.76, 69.81). Average oral morphine equivalents per day (p=0.023, CI 1.26, 16.57) and per administration (p=0.00048, CI 0.64, 2.25) also were significantly reduced following the CAT training intervention. CONCLUSION: This study strengthens the findings of prior studies, showing that CAT can improve patient satisfaction while also reducing overall opioid burden for post-surgical patients.


Assuntos
Analgésicos Opioides , Terapias Complementares , Transtornos Relacionados ao Uso de Opioides , Manejo da Dor , Humanos , Morfina , Dor Pós-Operatória/terapia
9.
Gan To Kagaku Ryoho ; 47(5): 797-800, 2020 May.
Artigo em Japonês | MEDLINE | ID: mdl-32408322

RESUMO

Cancer pain was observed in 131 of 160 patients with advanced cancer living at home. Oxycodone or morphine was administered to patients suffering from cancer pain or fentanyl transdermal patch was switched to morphine. Subsequently, 70 patients were found to have alleviation of symptoms such as nausea/vomiting, dyspnea, abdominal fullness, general fatigue, cough, and urinary urgency in addition to pain. Pain was defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage by the International Association for the Study of Pain. This definition of pain is cited in a lot of books. However, the author was unable to intervene with detailed reports of unpleasant sensations associated with tissue damage. Therefore, here the author reports about an unpleasant sensation caused by tissue damage of cancer that was alleviated by oxycodone or morphine.


Assuntos
Dor do Câncer/tratamento farmacológico , Neoplasias , Administração Cutânea , Analgésicos Opioides , Fentanila , Humanos , Morfina , Oxicodona , Dor
10.
Rev Med Suisse ; 16(694): 1022-1025, 2020 May 20.
Artigo em Francês | MEDLINE | ID: mdl-32432418

RESUMO

New technologic devices are presented: insulin pumps and continuous glucose monitoring (CGM) devices as well as morphine pumps to help general practitioners to deal different intensive situations. Insulin pumps and CGM devices are revolutionary for the management of diabetes. However, their use requires strong patient involvement, the opposite of automated diabetes management. Morphine pumps are a great help when patients in end-of-life stage cannot swallow oral morphine anymore. This article summarizes the main principles of use of these technological devices, common problems and situations at risk primary care practice.


Assuntos
Automonitorização da Glicemia/métodos , Glicemia/análise , Medicina de Família e Comunidade/métodos , Morfina/administração & dosagem , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Humanos , Morfina/uso terapêutico
11.
Can J Surg ; 63(3): E250-E253, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32386476

RESUMO

Background: Postoperative opioid analgesia may cause respiratory depression. We assessed whether following total hip arthroplasty, placebo-adjusted reductions in morphine consumption at 48 hours with parecoxib (47.0%), propacetamol (35.1%) or parecoxib plus propacetamol (67.9%) translated into a reduction in hypoxemic events. Methods: This was a post hoc analysis of a randomized, placebo-controlled, noninferiority study. Patients were randomly assigned to receive intravenous parecoxib (40 mg twice daily), propacetamol (2 g 4 times daily), parecoxib plus propacetamol (40 mg twice daily + 2 g 4 times daily) or placebo. Dose, date and time of morphine administration via patient-controlled analgesia were monitored throughout the study. In patients not receiving supplemental oxygen, peripheral blood oxygenation was assessed continuously for 48 hours after surgery. Hypoxemia was defined as peripheral oxygen saturation less than 90%. The times and oximeter readings of hypoxemic events were recorded. Pearson correlation coefficient was used to assess for correlations between cumulative morphine consumption at 48 hours and mean number of hypoxemic events. Results: A significantly smaller proportion of patients who received the combined treatment with parecoxib and propacetamol had hypoxemia versus placebo (2.8% v. 13.2%, p < 0.05), and the mean number of hypoxemic events was significantly smaller for parecoxib (0.12), propacetamol (0.06) and parecoxib plus propacetamol (0.03) versus placebo (0.36; all p < 0.05). There was no correlation between the reduction in cumulative morphine consumption at 48 hours and the mean number of hypoxemic events in any treatment group (all p > 0.1). Conclusion: Following total hip arthroplasty, a greater than 70% reduction in morphine consumption may be necessary to translate into a corresponding reduction in hypoxemic events.


Assuntos
Acetaminofen/análogos & derivados , Analgesia Controlada pelo Paciente/métodos , Artroplastia de Quadril/efeitos adversos , Hipóxia/epidemiologia , Isoxazóis/administração & dosagem , Morfina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/administração & dosagem , Adulto , Idoso , Analgésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Hipóxia/prevenção & controle , Incidência , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Suíça/epidemiologia , Resultado do Tratamento
12.
Nat Commun ; 11(1): 2611, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457298

RESUMO

Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system. However, how opioid impacts the immune system is still barely characterized systematically. In order to understand the immune modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evokes widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide. Furthermore, scRNA-seq reveals the same phenomenon after a short in vitro morphine treatment. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program. Our results suggest that further characterization of the immune modulatory effects of opioid is critical to ensure the safety of clinical opioids.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Transtornos Relacionados ao Uso de Opioides/imunologia , Viroses/imunologia , Adulto , Antivirais/farmacologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interferons/farmacologia , Leucócitos Mononucleares , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Morfina/farmacologia , Análise de Célula Única , Adulto Jovem
15.
Am J Emerg Med ; 38(7): 1470-1474, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32349890

RESUMO

INTRODUCTION: The choice of intravenous paracetamol or morphine for the pain control of renal colic remains controversial. We conduct a systematic review and meta-analysis to compare the analgesic efficacy and safety of intravenous paracetamol with morphine for renal colic pain. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2019 for randomized controlled trials (RCTs) assessing the analgesic efficacy and safety of intravenous paracetamol versus morphine for renal colic pain. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs are included in the meta-analysis. Intravenous paracetamol can lead to significantly lower pain scores at 30 min (standard mean difference (Std. MD) = -0.40; 95% confidence interval (CI) = -0.68 to -0.12; P = 0.005) and incidence of dizziness (risk ratio (RR) = 0.06; 95% CI = 0.01 to 0.48; P = 0.007) than morphine for renal colic pain. There is no statistical difference of pain scores at 15 min (Std. MD = -0.80; 95% CI = -1.84 to 0.24; P = 0.13), analgesic rescue (RR = 0.73; 95% CI = 0.45 to 1.19; P = 0.21), the incidence of adverse events (RR = 0.60; 95% CI = 0.35 to 1.03; P = 0.06), nausea or vomiting (RR = 0.61; 95% CI = 0.20 to 1.87; P = 0.38) between two groups. CONCLUSIONS: Intravenous paracetamol may result in lower pain scores at 30 min than morphine for renal colic pain, and more studies should be conducted to compare their analgesic efficacy.


Assuntos
Acetaminofen/uso terapêutico , Morfina/uso terapêutico , Cólica Renal/tratamento farmacológico , Administração Intravenosa , Analgésicos não Entorpecentes/uso terapêutico , Analgésicos Opioides/uso terapêutico , Tontura/induzido quimicamente , Humanos , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Bratisl Lek Listy ; 121(4): 263-270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32356440

RESUMO

Bone marrow mesenchymal stem cells (BM-MSC) have recently been predicted to have a major therapeutic potential due to secretion of soluble factors and the release of cytokines and growth factors, which could mediate the cellular communication to induce cell differentiation/maturity. The aim of the present study was to determine the effect of mBM condition medium on morphine-induced cell death in PC12, U87, AGS and MCF-7 cell lines. The condition media were harvested as mBM soup (mBM soup 24 and mBM soup 48h, respectively). To investigate the effect of mBM soup on cell lines, morphological changes were studied with an inverted microscope, the viability of cells was determined with trypan blue staining and MTT assay, the type of cell death was determined using Hoescht / PI staining, and NO secretion analysis. Viability assay showed that mBM soup (24 and 48 h) in time-dependent manner increased cell viability (pndings suggest that mBM soup can enhance the proliferation and growth of cell lines and can suppress cell death induced by morphine (Fig. 8, Ref. 59). Text in PDF www.elis.sk. Keywords: morphine, BM-MSC soup, cell viability, cell death, NO.


Assuntos
Células da Medula Óssea/química , Meios de Cultivo Condicionados/farmacologia , Células-Tronco Mesenquimais/química , Morfina/farmacologia , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Humanos , Células MCF-7 , Células PC12 , Ratos
17.
Bratisl Lek Listy ; 121(4): 271-277, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32356441

RESUMO

AIM: The present study was undertaken to evaluate the effects of different concentrations of morphine in chronic manner on neuroglial differentiation in PC12 cells. METHODS: PC12 cells were cultured in RPMI 1640 culture medium including 0.02 % bovine serum albumin together with different concentrations of morphine for 12 days. Cytotoxicity was performed by lactate dehydrogenase assay. Cell death was performed by PI/Hoechst staining assay. Neuroglial differentiation was performed by Nestin, Tuj-1, MAP-2, S-100 and GFAP Immunocytochemistry assay. RESULTS: Data showed that morphine either at low or high concentration activated opioid  receptors, which  resulted in a decrease of cytotoxicity and cell death and induction of Nestin, Tuj-1, MAP-2, Neurofilament-M (NF-M), GFAP and S-100 protein expression as compared in treated cells  with the control (untreated cells) (p<005). CONCLUSION: It can be concluded that low concentrations of morphine in chronic manner stimulate the neuroglial-like differentiation by activating protein expression and survival-promoting signaling in PC12 cells with opioid receptor-dependent mechanism (Fig. 8, Ref. 36). Text in PDF www.elis.sk.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Morfina/farmacologia , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Animais , Morte Celular , Células PC12 , Ratos
18.
Life Sci ; 251: 117604, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32243929

RESUMO

AIMS: Opioids (i.e. morphine) were found to induce triple negative breast cancer (TNBC) metastasis while nonsteroidal anti-inflammatory drugs (i.e. ketolorac) were associated with decreased metastasis in TNBC. These contradictory findings demand clarification on the effect of postoperative morphine and ketorolac on TNBC metastasis. MATERIALS AND METHODS: TNBC xenograft mice were established using MDA-MB-231 cells. When tumors reached ~100 mm3, the primary tumor was resected. Mice were then randomly assigned to four groups (n = 14): (i) saline, (ii) morphine (10 mg kg-1) (iii) morphine + ketorolac (10 mg kg-1 of morphine and 20 mg kg-1 of ketorolac) (iv) ketorolac (20 mg kg-1); administrated for three consecutive days after resection. Three weeks after resection, the number of lung metastases was measured. Microvessel density, thrombospondin-1 (TSP-1) and c-Myc expression in recurrent tumors were determined. To elucidate the above phenomenon in vitro, MDA-MB-231 cells were treated according to the regiment above; with or without supplementation of an AKT inhibitor to determine the activation of PI3K/AKT/c-Myc pathway. KEY FINDINGS: In mice, morphine promoted TNBC metastasis and angiogenesis, decreased TSP-1 expression and increased c-Myc expression, while co-administration of ketorolac significantly reversed the phenotypes above (p < .05). Mechanistically, morphine inhibited TSP-1 secretion by activating PI3K/AKT/c-Myc pathway (p < .05), while ketorolac promoted TSP-1 secretion (p < .05) by suppressing PI3K/AKT/c-Myc pathway. SIGNIFICANCE: Our study indicated that morphine enhanced TNBC metastasis and angiogenesis while ketorolac suppressed this effect. Mechanistically, this may be related to the enhancement of TSP-1 synthesis after ketorolac administration which further de-activated PI3K/AKT/c-Myc pathway.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cetorolaco/farmacologia , Morfina/toxicidade , Neovascularização Patológica/prevenção & controle , Neoplasias de Mama Triplo Negativas/terapia , Analgésicos Opioides/toxicidade , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica/prevenção & controle , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Drugs Today (Barc) ; 56(4): 269-286, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32309822

RESUMO

Oliceridine is a next-generation investigational intravenous opioid that is a G protein-selective agonist at the µ-opioid receptor. The G protein selectivity of this compound results in potent analgesia with substantially reduced recruitment of ß-arrestin, a signaling pathway associated with opioid-related adverse events. In randomized, placebo- and active-controlled clinical studies, use of oliceridine for the management of moderate to severe acute pain provided potent analgesic effect superior to that observed with placebo, with lower incidence of adverse events, including respiratory events and gastrointestinal events of nausea and vomiting, compared with morphine. Here, we provide a review of the preclinical and clinical data of intravenous oliceridine, a selective agonist, which has the potential to offer a wider therapeutic window than conventional opioids.


Assuntos
Dor Aguda/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Compostos de Espiro/uso terapêutico , Tiofenos/uso terapêutico , Proteínas de Ligação ao GTP/agonistas , Humanos , Morfina , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Opioides mu
20.
Sheng Li Xue Bao ; 72(2): 255-261, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32328620

RESUMO

Preclinical studies suggest that the GABAB receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABAB receptor agonist, is the only specific GABAB receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABAB receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 µL/side or 0.12 nmol/0.2 µL/side), rather than vehicle or BLF (0.01 nmol/0.2 µL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABAB receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.


Assuntos
Baclofeno/administração & dosagem , Condicionamento Clássico , Morfina , Núcleo Accumbens/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides , Animais , Agonistas dos Receptores de GABA-B/administração & dosagem , Locomoção , Masculino , Memória , Camundongos , Camundongos Endogâmicos C57BL , Recompensa
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