RESUMO
OBJECTIVE: This study analyzed, using an umbrella review, existing systematic reviews on medications to prevent and control postoperative endodontic pain to guide professionals in choosing the most effective drug. MATERIALS AND METHODS: An electronic search in the PubMed (MEDLINE), LILACS, SciELO, EMBASE, Scopus, Web of Science, Cochrane Reviews, and Data Archiving and Networked Services (DANS) databases retrieved 17 systematic reviews. The study included only systematic reviews of clinical trials with or without meta-analyses evaluating effectiveness of medications in reducing pain after non-surgical endodontic treatment. RESULTS: The evidence showed that steroidal and non-steroidal anti-inflammatory drugs and opioids effectively controlled pain within six to 24 h. CONCLUSIONS: Dexamethasone, prednisolone, paracetamol, and mainly ibuprofen provided higher postoperative pain relief. The quality of evidence of the reviews ranged from very low to high, and the risk of bias from low to high, suggesting the need for well-designed clinical trials to provide confirmatory evidence. CLINICAL RELEVANCE: This review emphasizes the efficacy of developing protocols for pain control after endodontic therapy.
Assuntos
Dor Pós-Operatória , Tratamento do Canal Radicular , Humanos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Tratamento do Canal Radicular/métodos , Anti-Inflamatórios não Esteroides/uso terapêutico , Medição da Dor , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêuticoRESUMO
OBJECTIVES: Problematic use of opioids by older adults is associated with adverse effects and has become a public health crisis worldwide. Ageing-related disabilities in activities of daily living (ADL) could promote unnecessary use of opioids in this population. This study evaluates the association between ADL disability and opioid consumption in Brazilian older adults. STUDY DESIGN: Study design- cross-sectional secondary data analysis of the second wave of the Brazil Longitudinal Study of Ageing (ELSI-Brazil). METHODS: Data from the second wave of the Brazil Longitudinal Study of Ageing (ELSI-Brazil) were used. Older adults with chronic pain were included. ADL disability was measured using the Katz Index. The primary outcome was opioid consumption for chronic pain. The primary association was explored using logistic regression models adjusting for predetermined confounders. Sensitivity analyses evaluating model performance were done by calibrating and validating the model using randomly split equal sets. RESULTS: In those who reported presence of chronic pain (n = 2865), the prevalence of opioid use was 29% (95% CI:23.1%-35.6%). In adjusted models, participants with moderate and severe ADL disability had 1.6 (95% CI:1.13-2.32; P = 0.009) and 3.8 (95% CI: 1.80-7.90; P < 0.001) times higher odds of opioid consumption compared to no disability, respectively. Being female, alcohol consumption, higher pain intensity, history of dementia, fractures, and presence of ≥2 comorbidities were significantly associated with increased opioid use (P < 0.05). CONCLUSION: Nearly one-third of the Brazilian elderly population experiencing chronic pain reported using opioids. The functional decline during the process of ageing appears to be a risk factor for pain intolerance and opioid use. Multidisciplinary approaches to detect early ADL disabilities and improve mobility and access to assistive technologies need to be established to prevent opioid overuse and addiction in elderly populations.
Assuntos
Atividades Cotidianas , Analgésicos Opioides , Dor Crônica , Pessoas com Deficiência , Humanos , Brasil/epidemiologia , Feminino , Dor Crônica/tratamento farmacológico , Masculino , Idoso , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Pessoas com Deficiência/estatística & dados numéricos , Estudos Longitudinais , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
PURPOSE: Sex differences play a crucial role in understanding vulnerability to opioid addiction, yet there have been limited preclinical investigations of this effect during the transition from adolescence to adulthood. The present study compared the behaviors of male and female rodents in response to fentanyl treatment and targeted molecular correlates in the striatum and medial prefrontal cortex. MATERIALS AND METHODS: Thirty adolescent C57BL/6J mice underwent a 1-week fentanyl treatment with an escalating dose. In addition to evaluating locomotor activity and anxiety-related parameters, we also assessed naloxone-induced fentanyl acute withdrawal jumps. We employed real-time quantitative PCR (qPCR) to assess overall gene expression of dopaminergic receptors (Drd1, Drd2, Drd4 and Drd5) and the µ-opioid receptor Oprm1. The levels of epigenetic base modifications including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were assessed on CpG islands of relevant genes. RESULTS: Females had higher locomotor activity than males after chronic fentanyl treatment, and they exhibited higher fentanyl withdrawal jumping behavior induced by naloxone. Females also presented lower Drd4 gene expression and DNA methylation (5mC + 5hmC) in the striatum. We found that locomotor activity and fentanyl withdrawal jumps were negatively correlated with Drd4 methylation and gene expression in the striatum, respectively. CONCLUSIONS: The findings suggested that female mice displayed heightened sensitivity to the effects of fentanyl treatment during the transition from adolescence to adulthood. This effect may be associated with molecular alterations related to the Drd4 gene.
Assuntos
Fentanila , Camundongos Endogâmicos C57BL , Receptores Opioides mu , Caracteres Sexuais , Animais , Fentanila/farmacologia , Masculino , Feminino , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , Camundongos , Metilação de DNA/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , Naloxona/farmacologia , Comportamento Animal/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/genética , Síndrome de Abstinência a Substâncias/metabolismo , Epigênese Genética/efeitos dos fármacosRESUMO
This work focuses on the δ receptor (DOR), a G protein-coupled receptor (GPCR) belonging to the opioid receptor group. DOR is expressed in numerous tissues, particularly within the nervous system. Our study explores computationally the receptor's interactions with various ligands, including opiates and opioid peptides. It elucidates how these interactions influence the δ receptor response, relevant in a wide range of health and pathological processes. Thus, our investigation aims to explore the significance of DOR as an incoming drug target for pain relief and neurodegenerative diseases and as a source for novel opioid non-narcotic analgesic alternatives. We analyze the receptor's structural properties and interactions using Molecular Dynamics (MD) simulations and Gaussian-accelerated MD across different functional states. To thoroughly assess the primary differences in the structural and conformational ensembles across our different simulated systems, we initiated our study with 1 µs of conventional Molecular Dynamics. The strategy was chosen to encompass the full activation cycle of GPCRs, as activation processes typically occur within this microsecond range. Following the cMD, we extended our study with an additional 100 ns of Gaussian accelerated Molecular Dynamics (GaMD) to enhance the sampling of conformational states. This simulation approach allowed us to capture a comprehensive range of dynamic interactions and conformational changes that are crucial for GPCR activation as influenced by different ligands. Our study includes comparing agonist and antagonist complexes to uncover the collective patterns of their functional states, regarding activation, blocking, and inactivation of DOR, starting from experimental data. In addition, we also explored interactions between agonist and antagonist molecules from opiate and opioid classifications to establish robust structure-activity relationships. These interactions have been systematically quantified using a Quantitative Structure-Activity Relationships (QSAR) model. This research significantly contributes to our understanding of this significant pharmacological target, which is emerging as an attractive subject for drug development.
Assuntos
Simulação de Dinâmica Molecular , Receptores Opioides delta , Receptores Opioides delta/metabolismo , Receptores Opioides delta/química , Humanos , Ligantes , Analgésicos Opioides/farmacologia , Analgésicos Opioides/química , Ligação Proteica , Conformação ProteicaRESUMO
OBJECTIVES: Evaluate the effect of intravenous (IV) methadone versus intrathecal morphine (ITM) within an Enhanced Recovery After Cardiac Surgery (ERACS) pathway on postoperative pain and outcomes (length of hospital stay and postoperative complications) after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Two tertiary academic medical institutions within the same health system. PARTICIPANTS: Eligible 289 adult patients undergoing elective cardiac surgery with an enhanced recovery pathway from January 2020 through July 2021. INTERVENTIONS: Patients were administered ITM (0.25 mg) or IV methadone (0.1 mg/kg) if ITM was contraindicated. All patients were enrolled in an ERACS pathway using current Enhanced Recovery After Surgery society guidelines. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures included postoperative pain scores and opioid consumption measured as oral morphine equivalents. We analyzed patient demographics, procedural factors, intraoperative medications, and outcomes. Adjusted linear mixed models were fit to analyze associations between intervention and pain outcomes. ITM was associated with decrease in pain scores on postoperative day 0 after adjusting for clinical variables (average marginal effect, 0.49; 95% confidence interval, 0.002-0.977; p = 0.049). No difference in opioid consumption could be demonstrated between groups after adjusting for postoperative day and other variables of interest. CONCLUSIONS: ITM when compared with IV methadone was associated with a decrease in pain scores without any difference in opioid consumption after elective cardiac surgery. Methadone can be considered as a safe and effective alternative to ITM for ERACS protocols. Future large prospective studies are needed to validate this finding and further improve analgesia and safety.
Assuntos
Analgésicos Opioides , Procedimentos Cirúrgicos Cardíacos , Recuperação Pós-Cirúrgica Melhorada , Injeções Espinhais , Metadona , Morfina , Dor Pós-Operatória , Humanos , Estudos Retrospectivos , Metadona/administração & dosagem , Metadona/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Masculino , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Morfina/administração & dosagem , Morfina/uso terapêutico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Pessoa de Meia-Idade , Idoso , Administração Intravenosa , Estudos de Coortes , Resultado do Tratamento , Medição da Dor/métodosRESUMO
BACKGROUND: Emergence delirium remains a major postoperative concern for children undergoing surgery. Nalbuphine is a synthetic mixed agonist-antagonist opioid, which is believed to reduce the incidence of emergence delirium in children. The primary objective was to examine the effect of nalbuphine on emergence delirium in children undergoing surgery. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their starting dates until April 2023. Randomized Clinical Trials (RCT) and observational studies comparing nalbuphine and control in children undergoing surgery were included. RESULTS: Eight studies (n = 1466 patients) were eligible for inclusion of data analysis. Compared to the control, our pooled data showed that the nalbuphine group was associated with lower incidence of emergence delirium (RR = 0.38, 95% CI [0.30, 0.47], p < 0.001) and reduced postoperative pain scores (MD = -0.98, 95% CI [-1.92, -0.04], p = 0.04). CONCLUSIONS: This review showed the administration of nalbuphine is associated with significant decrease in the incidence of emergence delirium and postoperative pain scores among children undergoing surgery. However, due to limited sample size, high degree of heterogeneity and low level of evidence, future adequately powered trials are warranted to explore the efficacy of nalbuphine on emergence delirium among the pediatric population.
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Analgésicos Opioides , Delírio do Despertar , Nalbufina , Ensaios Clínicos Controlados Aleatórios como Assunto , Nalbufina/uso terapêutico , Nalbufina/administração & dosagem , Humanos , Criança , Delírio do Despertar/prevenção & controle , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , IncidênciaRESUMO
BACKGROUND: We assess trends in overdose mortality rates in Mexico from 1999 to 2019 and identify the states with the highest overdose mortality rates over time. METHODS: The analysis using mortality statistics examined deaths related to drug use. We estimated general overdose mortality rates at the national and state levels and calculated specific mortality rates associated with opioid and stimulant use using central rate estimation. We used joinpoint regression to analyse national and state-specific trends in overdose mortality from 1999 to 2019. FINDINGS: Nationally, the general overdose mortality rate increased annually by 10.49 % (p < 0.01, CI=11.4-18.9) from 2015 to 2019. The northern states of Baja California and Chihuahua were the states with the higher annual increases (18.6 %, p < 0.01, CI=4.2-29.6; and 15.6 %, p < 0.01, CI=12.9-19.7, respectively). By substance type, the national opioid-related mortality rate increased by 29.82 % per year from 2014 to 2019 (p < 0.01; CI=20.1-40.3), compared with an annual decrease of 11.43 % in the previous period (2005-2014) (p < 0.01; CI=-14.7- 8.0). Baja California was the state with the highest rise in opioid-related mortality from 2013 to 2019, with an annual increase of 15.84 % (p < 0.01; CI=1.4-32.3). Stimulant-related mortality increased by 21.79 % per year since 2013 (p < 0.01; CI=16.9-26.9), but it was not possible to calculate state-level trends. CONCLUSIONS: Drug-related mortality rates have increased in Mexico since 2015, particularly in the northern states of Baja California, Chihuahua, Sonora and Sinaloa. Improving harm reduction programmes and local surveillance of fatal and non-fatal overdoses is essential to address the silent escalation of overdose mortality.
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Overdose de Drogas , Humanos , México/epidemiologia , Overdose de Drogas/mortalidade , Overdose de Drogas/epidemiologia , Transtornos Relacionados ao Uso de Opioides/mortalidade , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Adulto , Masculino , Feminino , Analgésicos Opioides/intoxicação , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
BACKGROUND: Prior research has established the effectiveness of magnesium in relieving postoperative pain. This article aims to evaluate magnesium sulfate for perioperative analgesia in adults undergoing general abdominal surgery under general anesthesia. OBJECTIVE: The primary aim was to assess pain scores at 6 and 24 hours postoperatively in patients receiving magnesium sulfate vs. the control group. Secondary outcomes were postoperative opioid consumption, perioperative complications, and time to rescue analgesia. METHODS: A comprehensive database search identified studies comparing magnesium sulfate with control in adults undergoing general anesthesia for general abdominal surgery. Using random-effects models, data were presented as mean ± Standard Deviation (SD) or Odds Ratios (OR) with corresponding 95% Confidence Intervals (95% CI). A two-sided p-value < 0.05 was considered statistically significant. RESULTS: In total, 31 studies involving 1762 participants met the inclusion criteria. The magnesium group showed significantly lower postoperative pain scores at both early (within six hours) and late (up to 24 hours) time points compared to the control group. The early mean score was 3.1 ± 1.4 vs. 4.2 ± 2.3, and the late mean score was 2.3 ± 1.1 vs. 2.7 ± 1.5, resulting in an overall Mean Difference (MD) of -0.72; 95% CI -0.99, -0.44; p < 0.00001. The magnesium group was associated with lower rates of postoperative opioid consumption and shivering and had a longer time to first analgesia administration compared to the saline control group. CONCLUSION: Magnesium sulfate administration was linked to reduced postoperative pain and opioid consumption following general abdominal surgery.
Assuntos
Abdome , Analgésicos , Sulfato de Magnésio , Dor Pós-Operatória , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Sulfato de Magnésio/administração & dosagem , Abdome/cirurgia , Analgésicos/administração & dosagem , Anestesia Geral/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Assistência Perioperatória/métodosRESUMO
PURPOSE: To assess the effectiveness of bilateral superficial cervical plexus block (BSCPB) in treating post-thyroidectomy pain. METHODS: MEDLINE, Embase, Google Scholar, LILACS, and the Cochrane Central Register of Controlled Trials, were extensively searched. The search period extended from 1968 until December 2022. Randomized controlled trials comparing BSCPB to placebo, no block in patients with thyroidectomy for benign or malignant thyroid disease were included. Outcomes were pain in the first 24 h after surgery. Analgesic rescue, period before the first rescue dosage, and 24-h opioid usage were secondary outcomes. The RoB 2 instrument was used to evaluate the risk of bias. RESULTS: 34 of 354 studies were eligible. There were 2,519 patients. BSCPB reduced the intensity of pain postoperatively [SMD: - 1.17 (95% CI: - 1.54 to - 0.81)] and in the first 24 h [- 0.62 (95%: 0.91 to 0.33)]. A considerable delay for the first opioid dose, rescue analgesics, and postoperative opioid usage was also found. CONCLUSION: BSCPB's 24-h analgesic efficacy minimizes the requirement for rescue analgesia, postoperative opioid intake, and rescue analgesia start time. The choice of anesthetic and different application methods might affect its effectiveness.