opioid

This study aimed to assess the dose-dependent effect of DADLE and to explore its relationship with the TRAF6/NF-κB/NLRP3 pathway.

After 45 min of ischemia, reperfusion was sustained for 24 hr in mice to establish the myocardial infarction model. DADLE was administered at doses of 0.25, 0.5, or 1 mg/kg to this model. TTC-Evans Blue double staining, HE staining, and Masson staining were conducted to evaluate myocardial injury. TUNEL staining was used to detect apoptosis. Western blotting and immunofluorescence staining were applied to measure levels of TRAF6, NF-κB p65, NLRP3, caspase-1, pro-caspase-1, and ASC. ELISA assays were used to assess TNF-α and IL-1β levels. 

DADLE at all three doses lessened the infarcted area compared with the PBS control. DADLE at 0.5 mg/kg was more efficacious than 0.25 and 1 mg/kg in reducing the infarcted size, pathological scores, and fibrosis. DADLE effectively reduced the number of apoptotic cells as shown by the TUNEL assay. Levels of TRAF6, NF-κB p65, ASC, NLRP3, caspase-1, and pro-caspase-1 proteins were increased after ischemia-reperfusion (I/R) but were reversed by DADLE. Immunofluorescence staining results for NF-κB and NLRP3 demonstrated similar changes. ELISA assays showed that TNF-α and IL-1β concentrations were increased in the model and reversed by DADLE. 

DADLE can significantly ameliorate myocardia ischemia-reperfusion injury (MIRI), with the dosage of 0.5 mg/kg presenting the greatest benefit. DADLE may exert its protective effects by activating the TRAF6/NF-κB/NLRP3 signaling pathway.

Methadone maintenance treatment (MMT) causes important clinical problems, such as oxidative stress (OS) and inflammation. Zinc (Zn) has antioxidant and anti-inflammatory effects and regulates gene expression.

This study investigated the effects of Zn administration on the metabolic, OS, and expression of nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), and interleukin 10 genes in heroin patients undergoing MMT.

This clinical trial was conducted on 45 patients under MMT who received 30 mg/d of Zn (n=23) or placebo (n=22). Fasting blood samples were collected at baseline and 12 weeks after the intervention to quantify metabolic parameters, OS, and gene expression.

Zn levels were significantly elevated in the intervention group compared to the placebo group. Further, consuming Zn could significantly improve high-density lipoprotein levels, insulin, homeostasis model assessment-estimated insulin resistance, and OS. Anxiety significantly decreased after 12 weeks of intervention. Finally, Zn up-regulated Nrf2 gene expression in patients under MMT.

The results indicated that Zn administration could improve metabolic factors and gene expression in patients undergoing MMT

The purpose is to evaluate the correlation between patient-reported satisfaction measures and opioid prescribing practices of hand surgeons.

This retrospective study evaluated the opioid prescription practices of 19 fellowship-trained hand surgeons at a single practice, over a 12-month period. The total number of opioid prescriptions sent, opioid prescriptions per surgery, average total morphine milligram equivalents (MME) prescribed per patient and the average MME per prescription were determined. The correlation coefficients were calculated for the total opioid prescriptions and the likelihood to recommend a physician, the overall service impression and the impression of physician empathy.

5,089 patient satisfaction surveys were completed.  Pearson’s correlation demonstrated the “likelihood to recommend a surgeon” exhibited a moderate negative correlation with the total number of opioid prescriptions and the average MME per prescription (R=-0.38, R2=0.142, and R=-0.30, R2=0.089) respectively. Overall service impression exhibited a moderate negative correlation with total opioid prescriptions and average MME per prescription (R=-0.39, R2=0.142, and R=-0.30, R2=0.088), respectively. Perception of physician empathy exhibited a very weak negative correlation with total opioid prescriptions and weak correlation with average MME per prescription (R=-0.06, R2=0.004 and R=-0.29, R2=0.087), respectively. There were no statistically significant differences.

This study demonstrated that measures of patient satisfaction did not correlate with opioid prescriptions.

Context: 

Nicotine has been investigated in prior studies for its analgesic effects and its impact on postoperative nausea and vomiting (PONV), yet results have been inconsistent.

This systematic review and narrative synthesis evaluates the effects of perioperative nicotine administration on postoperative pain control and PONV in patients undergoing general anesthesia.

A systematic literature review was conducted, and findings were summarized narratively. Comprehensive searches were performed in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar for studies published between 2004 and 2023, using a PICO-based approach. The PICO criteria included: Patients undergoing general anesthesia, perioperative nicotine as the intervention, placebo or no nicotine as the comparator, and pain scores as the primary outcome. The Mendeley application was utilized to eliminate duplicate data. Title, abstract, and full-text screenings were independently conducted by all authors using the online review platform Rayyan. Final data were individually extracted into Excel spreadsheets. The risk of bias in the included studies was assessed with the Cochrane Risk of Bias 2 (RoB 2) tool.

Eleven studies encompassing 753 participants (384 receiving nicotine, 369 controls) were included. Of these, 514 were female and 239 were male, all having undergone different surgical procedures and receiving nicotine via various methods and dosage forms. The majority of participants were nonsmokers. Primary outcomes across the studies predominantly involved postoperative pain scores, while secondary outcomes included the incidence of PONV, antiemetic requirements, and opioid consumption. No additional analyses were performed due to heterogeneity among the included studies.

Although perioperative nicotine administration demonstrated reductions in postoperative pain, nausea, vomiting, and opioid consumption in some studies, the effect of nicotine on PONV was inconsistent. Variability in patient populations, dosage forms, and dosages complicates the formulation of definitive clinical recommendations. Overall, perioperative nicotine shows promise for improving postoperative pain management, but its impact on PONV requires careful consideration. Nicotine administration has been investigated as an analgesic adjunct and as a strategy for preventing PONV. This systematic review aimed to determine the effect of perioperative nicotine administration on postoperative pain and PONV.

The epidemiology of drug poisoning is an essential field of study in public health research that explores the many aspects of this urgent problem. Accidental poisoning is the third most common cause of death and the fifth most common reason for hospital visits in several developing countries. Pharmaceutical poisoning is the second most common cause of hospital admissions and deaths in Iran, where unintentional poisoning remains a serious health concern. This research aims to thoroughly investigate all aspects of drug poisoning cases using epidemiological analysis. This study analyzed the records of 701 consecutive patients at Shiraz Faghihi hospital Medical Emergency Center in Iran between April 1 and September 30, 2022. Poisoning diagnosis was determined based on reports and documents. Data were collected from patient medical records and analyzed using SPSS software, with a significance level set at P < 0.05. The chi-square test was used to compare the means of drug-posing variables and demographic variables. This study reviewed 701 cases, with an average age of 35.02 ± 16.104 (P < 0.001), 45.8% of whom had education levels higher than high school (P = 0.012). The majority (66.6%) had no psychiatric history (P < 0.001), and 55.6% had no history of addiction (P < 0.001). The predominant poisoning agent was opium (48.9%), followed by benzodiazepine poisoning (40.2%). About 10% were attributed to other causes. A mortality rate of 3.4% was observed, and 96.6% of the cases survived. The study underscores the crucial importance of addressing drug usage for both prevention and therapy. Additionally, the revelation that medicines often serve as the primary source of toxicity, particularly in developing countries, emphasizes the high accessibility and potential hazards associated with these medications.

It is known that both major abdominal surgeries and opioids used for postoperative pain management affect postoperative cognitive functions. The aim of this study is to investigate the effectiveness of thoracoabdominal nerve block through the perichondral approach (TAPA block) compared to conventional methods in preventing postoperative pain, reducing opioid consumption and saving cognitive functions in major abdominal surgeries.  

Ninety patients who undergo major abdominal surgery were included in this observational study. Preoperative cognitive functions of the patients were evaluated via the Mini-Mental State Examination test (MMSE). Ultrasound guided TAPA block was applied to the patients in the TAPA group. IV morphine was administered to patients who could not undergo TAPA. All patients received intravenous Patient-Controlled Analgesia devices (PCA) with morphine. Pain assessment was documented with the numeric rating scale (NRS) at postoperative hours 1, 2, 6, 12, 24. Opioid consumption in the postoperative 24-hour period was recorded. MMSE was performed preoperatively, after recovery, and on postoperative days 1and 3.  

Demographic data, operation durations, pre-, intra-, and postoperative body temperatures, and preoperative MMSE scores of both groups were similar. Total opioid consumption, recovery times, and all postoperative NRS values in the TAPA group were significantly lower. There was no difference between groups in terms of cognitive functions on the postoperative immediate, 1st, and 3rd days.  

In major abdominal surgery, TAPA Block reduced opioid consumption, provided early recovery, and provided effective pain management. However, TAPA block did not make any difference in terms of cognitive function.

Post-induction positioning influences the onset speed of the sensory block by affecting anesthetic distribution. Techniques such as using opioids and extending recovery stays aim to enhance this process.

This study aimed to evaluate the impact of transitioning patients from a sitting to a lateral position immediately after the induction of 0.5% hyperbaric bupivacaine spinal anesthesia on postoperative pain and opioid consumption.

In this prospective, randomized clinical trial, patients scheduled for percutaneous nephrolithotomy (PCNL) under spinal anesthesia at Shahid Labafinejad Hospital in 2023 were divided into intervention (lateral position) and control (supine position) groups. Blood pressure, mean arterial pressure (MAP), and heart rate were recorded upon entering recovery, then every 10 minutes up to 60 minutes, and every 15 minutes up to 120 minutes post-operation. Pain levels were assessed using the Visual Analogue Scale (VAS) at specified intervals. Patient satisfaction with analgesia quality was also evaluated.

The study included 35 patients in the lateral group and 34 in the supine group. Pain levels significantly differed between the groups over time (P = 0.0001). The lateral group had a longer analgesia duration (28.8 ± 10.0 minutes vs. 22.9 ± 2.9 minutes, P = 0.105) and lower total narcotic consumption (21.7 ± 5.8 mg vs. 30.4 ± 10.2 mg, P = 0.012). Mean arterial pressure changes showed no significant difference (P = 0.061). Patient satisfaction was significantly higher in the lateral group (P = 0.0001).

Transitioning from the sitting to lateral position post-induction with hyperbaric bupivacaine enhances hemodynamic stability, improves drug distribution in the cerebrospinal fluid (CSF), and enhances sensory block quality. This approach increases postoperative analgesia duration, reduces opioid use and related complications, and decreases the duration of surgery.

Postoperative pain poses a high risk of psychological and physical trauma to surgical patients. Magnesium sulfate (MgSO₄) is inexpensive, safe, and has been used in many anesthesia procedures to evaluate its role in reducing perioperative pain and opioid consumption.

A comprehensive search was conducted across several databases, including Google Scholar, Cochrane, and PubMed, up to 2024. The study included trials that used magnesium alone or in combination perioperatively.

Our search included clinical trials, totaling 29 articles. Eighteen of them examined magnesium alone compared with various analgesics or placebo in clinical studies, which may help reduce postoperative pain and opioid consumption. The effectiveness of magnesium alone was assessed in various surgical procedures, using different doses of magnesium sulfate and various methods of administration. Eleven articles examined magnesium as an additive to show its effectiveness in combination with conventional anesthetics and analgesics.

Magnesium has been compared with many anesthetics and analgesics, both alone and in combination, showing remarkable efficacy in relieving pain during surgery and reducing opioid consumption. Many studies found that intraperitoneal magnesium sulfate had significantly greater efficacy than intravenous administration. A dose of 30–50 mg/kg of magnesium sulfate, followed by a maintenance dose of 6–12 mg/kg/h, is recommended and was found to be effective and safe in many trials.

Cirrhosis is a significant public health concern, causing approximately 790,000 deaths annually. Despite the possibility of adverse effects from analgesics, which can be fatal and preventable, guidelines for their use in this setting do not exist, and there is a lack of research in this field. Thus, this review aims to summarize and analyze published data on different opioids in patients with liver cirrhosis to provide possible evidence-based guidelines for the safe use of opioids. Both compensated and decompensated patients should avoid NSAIDs. Because of the risk of hepatic encephalopathy, opioids must be avoided or used sparingly at low and infrequent doses. A long-term follow-up is required for toxicity, adverse effects, and complications of all pain relievers.

Opioids can lead to mood disorders, anxiety, depression, and cognitive impairment. Valproic acid (VPA) has neuroprotective effects that can prevent neural degeneration. This study aims to examine the impact of VPA on learning, social interaction, and depression in mice dependent on morphine.

Subjects were divided into four groups and received injections of saline, VPA, morphine, or a combination of VPA and morphine for eight days. Behavioral tests were conducted on day 8, and then administration of VPA and morphine was stopped, leading to spontaneous withdrawal syndrome. Behavioral tests were repeated on day 11, and histological analysis was performed on the hippocampus.

The preference index (PI%) decreased in the novel object recognition test in the VPA and morphine sulfate (MOR) groups compared to the control (CTL) group in the chronic phase. The concomitant administration of VPA and morphine caused an increase in social interaction criteria in both the chronic and withdrawal phases. The decrease in immobility time in the VPA and MOR + VPA groups compared to the CTL group in the withdrawal phase was not statistically significant in the tail suspension test (TST). In Nissl staining, the combination of MOR + VPA led to a significant decrease in the DC/All cell ratio compared to the individual MOR and VPA groups (P < 0.05).

VPA may improve social relationships and depression indices during morphine withdrawal. VPA may potentially mitigate the cellular changes in the CA1 of the hippocampus induced by morphine.

Regarding the probable effectiveness of adding fluoxetine to a medical regimen of opioid treatment, the present study aimed to compare the effect of naltrexone with or without fluoxetine to prevent relapse to opioid addiction.

In this cross-sectional study in 2016, 93 people with an opium addiction who were detoxified in Imam Reza Hospital in Mashhad, Iran, were selected using a purposeful sampling method. They were randomly divided into two groups (naltrexone and naltrexone + fluoxetine). The morphine urine test was performed at the end of the 1st month, 2nd month, 3rd month, 4th month, and more than 4 months after detoxification. The data were analyzed through descriptive statistics, Fisher's exact test, Pearson chi-square, Independent samples t-test, Mann-Whitney test, and SPSS software.

Finally, 73 patients (39 patients in the naltrexone group and 34 patients in the naltrexone + fluoxetine group) were evaluated. The two groups had no significant demographic variable differences except marital status. The findings showed no significant difference in the relapse rate between the two groups, although a lower rate of relapse was seen in the naltrexone + fluoxetine group than in the naltrexone group (P= 0.563). At the same time, the naltrexone + fluoxetine group had more positive morphine urine tests in the early months than the naltrexone group significantly (P= 0.040).

The present study showed that adding fluoxetine to naltrexone reduces the relapse rate, while it is associated with a shorter duration of retention than the naltrexone group.

Perioperative pain management can improve surgery results and patient outcomes. Moreover, multimodal methods for pain control have been advised so this study was conducted to assess the beneficial impact of preoperative ultrasound-guided femoral nerve blocks in hip replacement surgery.

This study is a double-blinded clinical trial including 60 individuals who were candidates for joint replacement surgery. The intervention group (n = 30) received a femoral nerve block prior to general anesthesia.

 After surgery, patients received morphine, Apotel, and morphine + Apotel, all of which were administered at lower doses in the intervention group (femoral nerve block) than in the control group. Pain intensity in first hour (P= 0.01), 4 hours (P= 0.003), 8 hours (P= 0.01), 12 hours (P= 0.001), and 24 hours (P= 0.01) after surgery and average pain 4 hours (P= 0.01), 8 hours (P = 0.01), 12 hours (P = 0.02), and 24 hours (P= 0.01) after surgery was significantly less in the intervention group (femoral nerve block) than in the control group.

The findings of our investigation demonstrated the efficacy of ultrasound-guided femoral nerve blocks in the improvement of pain control following hip replacement surgery.

Pain is an unpleasant experience and a subjective term that is associated with tissue damage. Cancer patients experience pain for a myriad of reasons, from disease related to treatment causes and unrelated to both of these categories.
Opioids are the mainstay in the treatment of moderate to severe cancer pain. Progressive opioid dose increases can cause opioid-induced hyperalgesia (OIH).
OIH has no definite management, here we present a 47-year-old cancer patient with OIH and her management.

The diversity of the portfolio of pharmaceutical and non-pharmacological services is an undeniable necessity; however, we must remember that the thinking of harm reduction should govern this process. If we only pay attention to the variety of drugs and their different forms, eventually the noble goal of harm reduction will suffer. In an article that Pedersen et al. prepared about the slow-release form of buprenorphine, there are structural and content problems that will be addressed in this article. This article criticizes the rapid change in the provision of harm reduction services and discusses the impact of structural changes in the provision of services and the location of service provision.

Regarding the unpleasant pain sensation and the public’s desire to use traditional herbs, the present study aimed to assess the analgesic and anti-inflammatory effect of Chenopodium botrys L. The present research was divided into two main sections to assess the analgesic and anti-inflammatory effect of Chenopodium botrys L. in male mice. To investigate the analgesic effect of Chenopodium botrys L., thirty-six male mice were randomly classified into six groups vehicle (receiving normal saline), experimental groups received morphine (a well-known opioid, 1 mg/kg), hydroalcoholic extracts of Chenopodium botrys L. (30, 100, and 300 mg/kg), and naloxone (opioid receptor antagonist) with the highest dose of Chenopodium botrys L. concurrently for one week. Thirty mice were divided into five groups to receive normal saline, various doses of extract (30, 100, and 300 mg/kg), and dexamethasone (a well-known anti-inflammatory drug, 10 mg/kg) to assess the anti-inflammatory effect of Chenopodium botrys L. In both sections, after the last doses of the treatment, the animals got ready for behavioral study related to pain. Overall, the highest doses of Chenopodium botrys L. demonstrated much better results than other doses, which were comparable to opioids and dexamethasone, a well-known analgesic and anti-inflammatory medicines, respectively. Regarding present findings, the Chenopodium botrys L. plant can be a new candidate as an analgesic agent, which needs more investigation in the search and pharmaceutical development.