Effects of Thymbra spicata extract and Thymol on morphine withdrawal syndrome in mice (insights to the liver function, antioxidant, and behavioral responses).

Safe chemicals for drug withdrawal can be extracted from natural sources. This study investigates the effects of clonidine and Thymbra spicata extract (TSE) on mice suffering from morphine withdrawal syndrome. Thymol, which is the active constituent in TSE, was also tested. A total of 90 mice were divided into nine groups. Group 1 was the control group, while Group 2 was given only morphine, and Group 3 received morphine and 0.2 mg/kg of clonidine. Groups 4-6 were given morphine along with 100, 200, and 300 mg/kg of TSE, respectively. Groups 7-9 received morphine plus 30, 60, and 90 mg/kg of Thymol, respectively, for 7 days. An oral naloxone challenge of 3 mg/kg was used to induce withdrawal syndrome in all groups. Improvement of liver enzyme levels (aspartate aminotransferase, alkaline phosphatase, and alanine transaminase) (p < .01) and behavioral responses (frequencies of jumping, frequencies of two-legged standing, Straub tail reaction) (p < .01) were significantly observed in the groups receiving TSE and Thymol (Groups 4-9) compared to Group 2. Additionally, antioxidant activity in these groups was improved compared to Group 2. Nitric oxide significantly decreased in Groups 4 and 6 compared to Groups 2 and 3 (p < .01). Superoxide dismutase increased dramatically in Groups 5, 8, and 9 compared to Groups 2 and 3 (p < .01). Groups 5-9 were significantly different from Group 2 in terms of malondialdehyde levels (p < .01). Certain doses of TSE and Thymol were found to alleviate the narcotics withdrawal symptoms. This similar effect to clonidine can pave the way for their administration in humans.

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis.

Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects. METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23. RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05). CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

Effect of repeated intraperitoneal injections of different concentrations of oxycodone on immune function in mice.

Background: The effect of oxycodone as an opioid receptor agonist on immune function is still controversial. In this study, we investigated the possible effects of oxycodone on immune function in mice and its possible mechanisms of action. Methods: By repeated intraperitoneal injections of 25 mg/kg morphine and 5 mg/kg, 20 mg/kg, and 60 mg/kg oxycodone, we assessed possible changes in the number of splenic lymphocytes and inflammatory cytokines in the serum of mice. CD4+ T cells and CD8+ T cells were sorted from the spleen to observe whether the expression levels of opioid receptors and downstream signals were altered. Results: Repeated administration of oxycodone at a dose above 20 mg/kg resulted in significant weight loss. Repeated administration of oxycodone exhibits significant dose-dependent reduction in CD4+ T cells, with little effect on CD8+ T cells and little effect on inflammatory cytokine levels. Low- and intermediate-dose oxycodone increased the mRNA expression level of MOR, KOR, and DOR to varying degrees. Moreover, oxycodone increases the mRNA expression levels of the TLR4 signaling pathway to varying degrees. Conclusion: Repeated intraperitoneal injection of oxycodone induces immunosuppression in mice.

Peripheral nerve blocks for analgesia following cesarean delivery A narrative review.

Spinal and epidural blocks are commonly employed for pain relief during and following cesarean section. Intrathecal morphine (ITM) has been the gold standard for the same for many years. In recent times, many peripheral nerve blocks (PNBs) have been tried for postoperative analgesia following cesarean delivery (PACD). This article has reviewed the common PNBs used for PACD. The role of PNBs along with ITM has been studied and the current best strategy for PACD has also been explored. Currently, Ilio-inguinal nerve and anterior transversus abdominis plane block in conjunction with intrathecal morphine have been found to be the most effective strategy, providing lower rest pain at 6 hours as compared to ITM alone. In patients not receiving intrathecal morphine, recommended PNBs are lateral transversus abdominis plane block, single shot local anesthetic wound infiltration, or continuous wound infiltration with catheter below rectus fascia. PNBs are recommended for PACD. They have an opioid-sparing effect and are devoid of adverse effects associated with central neuraxial blocks such as hypotension, bradycardia, and urine retention. However, caution must be observed with PNBs for possible local anesthetic toxicity due to the large volumes of drug required.

Parental Exposure to Morphine Before Conception Decreases Morphine and Cocaine-Induced Locomotor Sensitization in Male Offspring.

Repeated exposure to abused drugs leads to reorganizing synaptic connections in the brain, playing a pivotal role in the relapse process. Additionally, recent research has highlighted the impact of parental drug exposure before gestation on subsequent generations. This study aimed to explore the influence of parental morphine exposure 10 days prior to pregnancy on drug-induced locomotor sensitization. Adult male and female Wistar rats were categorized into morphine-exposed and control groups. Ten days after their last treatment, they were mated, and their male offspring underwent morphine, methamphetamine, cocaine, and nicotine-induced locomotor sensitization tests. The results indicated increased locomotor activity in both groups after drug exposure, although the changes were attenuated in morphine and cocaine sensitization among the offspring of morphine-exposed parents (MEPs). Western blotting analysis revealed altered levels of D2 dopamine receptors (D2DRs) in the prefrontal cortex and nucleus accumbens of the offspring from MEPs. Remarkably, despite not having direct in utero drug exposure, these offspring exhibited molecular alterations affecting morphine and cocaine-induced sensitization. The diminished sensitization to morphine and cocaine suggested the development of a tolerance phenotype in these offspring. The changes in D2DR levels in the brain might play a role in these adaptations.

Alkaloid Accumulation and Distribution within the Capsules of Two Opium Poppy (Papaver somniferum L.) Varieties.

The goal of this study was to clarify the role of capsule size and morphology in the alkaloid yield of poppy. In 2023, two industrial varieties from large-scale cultivation were investigated. Three classes of capsule size (large, medium, and small) and four organelles (wall, placenta, disc, and thalamus) of the seedless capsule were studied for their mass proportions and alkaloid contents. In 'Meara', large capsules had 41% lower total alkaloid levels than smaller ones. In 'Morgana', there was no difference in total alkaloids between size groups, but large capsules had higher contents of codeine and thebaine. Among the four organelles, the wall represented the largest mass in both varieties (60-67%), while the disc and the thalamus gave the lowest proportions (below 9%). In the variety 'Meara', the highest alkaloid contents appeared in the wall (2.69% d.w.), followed by the placenta, and the other two parts. 'Morgana' accumulated the highest alkaloid content (3.72% d.w.) in the placenta. Morphine follows the trend of the total content, while codeine and thebaine may differ. Accurate information on the accumulation of alkaloids in the generative organs may contribute to increasing effectiveness in target-oriented breeding and optimization of cultivation with an appropriate choice of variety.

A novel strategy to elicit enduring anti-morphine immunity and relief from addiction by targeting Acr1 protein nano vaccine through TLR-2 to dendritic cells.

Morphine addiction poses a significant challenge to global healthcare. Current opioid substitution therapies, such as buprenorphine, naloxone and methadone are effective but often lead to dependence. Thus, exploring alternative treatments for opioid addiction is crucial. We have developed a novel vaccine that presents morphine and Pam3Cys (a TLR-2 agonist) on the surface of Acr1 nanoparticles. This vaccine has self-adjuvant properties and targets TLR-2 receptors on antigen-presenting cells, particularly dendritic cells. Our vaccination strategy promotes the proliferation and differentiation of morphine-specific B-cells and Acr1-reactive CD4 T-cells. Additionally, the vaccine elicited the production of high-affinity anti-morphine antibodies, effectively eliminating morphine from the bloodstream and brain in mice. It also reduced the expression of addiction-associated µ-opioid receptor and dopamine genes. The significant increase in memory CD4 T-cells and B-cells indicates the vaccine's ability to induce long-lasting immunity against morphine. This vaccine holds promise as a prophylactic measure against morphine addiction.

Effects of A1 Milk, A2 Milk and the Opioid-like Peptide ß-Casomorphin-7 on the Proliferation of Human Peripheral Blood Mononuclear Cells.

Special attention is given to cow's milk and its variants, with ongoing discussions about health-related impacts primarily focusing on the A1 variant in contrast to the A2 variant. The difference between these variants lies in a single amino acid alteration at position 67 of ß-casein. This alteration is presumed to make the A1 variant more susceptible to enzymatic breakdown during milk digestion, leading to an increased release of the peptide ß-casomorphin-7 (BCM-7). BCM-7 is hypothesized to interact with µ-opioid receptors on immune cells in humans. Although BCM-7 has demonstrated both immunosuppressive and inflammatory effects, its direct impact on the immune system remains unclear. Thus, we examined the influence of A1 and A2 milk on Concanavalin A (ConA)-stimulated human peripheral blood mononuclear cells (PBMCs), as well as the effect of experimentally digested A1 and A2 milk, containing different amounts of free BCM-7 from ß-casein cleavage. Additionally, we evaluated the effects of pure BCM-7 on the proliferation of ConA-stimulated PBMCs and purified CD4+ T cells. Milk fundamentally inhibited PBMC proliferation, independent of the ß-casein variant. In contrast, experimentally digested milk of both variants and pure BCM-7 showed no influence on the proliferation of PBMCs or isolated CD4+ T cells. Our results indicate that milk exerts an anti-inflammatory effect on PBMCs, regardless of the A1 or A2 ß-casein variant, which is nullified after in vitro digestion. Consequently, we deem BCM-7 unsuitable as a biomarker for food-induced inflammation.

Protective effect of dexmedetomidine against delayed bone healing caused by morphine via PI3K/Akt mediated Nrf2 antioxidant defense system.

Background: As a class of analgesics, opioids are frequently used to treat both acute and chronic moderate to severe pain. Patients frequently receive opioid painkillers after orthopedic accidents or surgeries. Evidence suggests that opioid drug users have a 55.1% higher risk of fracture and poor bone repair than non-users of opioid drugs. The key pathogenic alterations in the incidence and progression of poor bone repair are over apoptosis and aging of osteoblasts due to the stress caused by oxidation. Dexmedetomidine (Dex) has been proven to protect against a variety of degenerative illnesses by reducing oxidative stress. However, nothing is known about how it affects bone repair. Methods: PI3K/Akt/Nrf2 pathway was detected by immunofluorescence and Western blot. SOD, CAT, JC-1, dihydroethidium and mitosox were used in the Oxidative Stress. Micro-CT, H&E and Masson's staining, immunohistochemically were performed to evaluate the therapeutic effects of DEX on calvarial defects in the morphine-induced rat model. Results: We found that morphine-induced an imbalance in the metabolism and catabolism of primary rat Osteoblasts. However, these conditions could be inhibited by DEX treatment. In the meantime, DEX induced the expression of Nrf2-regulated antioxidant enzymes such as NQO1, HO-1, GCLm, GCLc, and TrxR1. DEX-mediated Nrf2 activation is linked to the PI3K/Akt signaling system. Furthermore, it has been established that intravenous DEX enhanced the growth of bone healing in a model of a surgically produced rat cranial lesion. Conclusion: This is the first description of the unique DEX mechanism acting as a Nrf2 activator against morphine-mediated oxidative harm, raising the possibility that the substance may be used to prevent bone defects.

Evaluation of Postoperative Efficacy and Safety of Celecoxib in Children Hospitalized After Adenotonsillectomy.

OBJECTIVE: The choice of optimal analgesia following an adenotonsillectomy is a clinical issue because of the risk of respiratory depression and bleeding. The objective of this study was to assess the effect of celecoxib on opioid use and pain scores in children hospitalized after adenotonsillectomy and to document its adverse effects. METHODS: This retrospective study was conducted in a tertiary care pediatric hospital. We compared a group of subjects aged 1 to 17 years who were prescribed celecoxib and opioids between January 2017 and June 2020 following an adenotonsillectomy during a 3-day or less hospitalization to a group of matched controls for sex, age, and length of stay who were prescribed opioids. RESULTS: A total of 228 patients were identified (76 in the celecoxib + opioids group, 152 in the control group). Opioid use, in oral morphine equivalent daily dose, was lower in the celecoxib + opioids group at 0 to 24 hours of hospitalization (0.15 vs 0.20 mg/kg/day, p = 0.05). Initiating celecoxib within 24 hours of surgery (n = 60) significantly reduced opioid requirement for up to 48 hours compared with controls (0-24 hours: 0.12 vs 0.20 mg/kg/day, p = 0.002; 25-48 hours: 0.02 vs 0.09 mg/kg/day, p = 0.001). A shorter length of stay was observed for patients receiving celecoxib + opioids during the first 24-hour post--operative period (27 vs 32 hours, p = 0.01). With celecoxib use, no significant change in pain scores and occurrence of adverse effects including bleeding was found. CONCLUSIONS: Using celecoxib early after an adenotonsillectomy has reduced both opioid use and duration of hospital stay without increasing adverse effects or bleeding.

Regional anesthesia is safe for use in intramedullary nailing of low-energy tibial shaft fractures.

PURPOSE: The purpose was to compare perioperative outcomes of patients who underwent general or regional anesthesia for intramedullary (IM) nailing of tibial shaft fractures (TSFs). METHODS: Retrospective chart review was performed on a consecutive series of low-energy TSF patients who presented to a single academic medical center and a level 1 trauma center who underwent operative repair with a reamed IM nail. Collected information included demographics, injury information, anesthesia type (general or regional i.e. peripheral nerve block), intra-operative opiate consumption (converted to morphine milliequivalents [MME], and post-operative pain visual-analog scale [VAS] pain scores. Patients were divided into 3 groups based on the type of anesthesia received and univariate analysis was performed to compare the 3 groups. RESULTS: Seventy-six patients were included, with an average age of 44.47±16.0 years. There were 38 (50 %) who were administered general anesthesia and 38 (50 %) who were administered regional anesthesia in the form of a peripheral nerve block. There were no differences between the groups with respect to demographics, medical co-morbidities, rate of open fractures or AO/OTA fracture classification. Regional anesthesia patients received less intra-operative MME than general anesthesia patients (17.57±10.6, 28.96±13.8, p < 0.001). Patients who received regional anesthesia also spent less time in the operating room, received less MME on post-operative day 1, and ambulated further on post-operative day 1, however none of these differences were statistically significant. There were no cases of missed post-operative compartment syndrome or complications related to the administration of the peripheral nerve block. CONCLUSIONS: Regional anesthesia in TSF surgery received less intra-operative opioid requirements, without any untoward effects. LEVEL OF EVIDENCE: Therapeutic Level III.

Meperidine compared to morphine for rigors associated with monoclonal antibody-related infusion reactions.

INTRODUCTION: Infusion reactions, characterized by symptoms such as rigors, fever, and hypotension, are common adverse events that occur during monoclonal antibody (MAB) therapy. The treatment of rigors often involves opioids, most commonly meperidine, despite limited evidence supporting use in the setting of MAB infusions. This study aims to compare the efficacy and safety of intravenous (IV) meperidine and morphine is treatment of MAB-related rigors, filling a significant gap in the literature. METHODS: This was a single-center, retrospective cohort study which reviewed patients either inpatient or within outpatient infusion centers from January 2015 to January 2024. Patients receiving IV 2 mg morphine or 25 mg meperidine for MAB-related rigors were included. The primary outcome was defined as the number of opioid doses required for rigors ablation. Secondary outcomes included rates of naloxone administration and documented sedation. RESULTS: A total of 1251 administration events were screened, of which 127 and 26 rigor events were in the meperidine and morphine cohorts, respectively, were included. A majority of both cohorts required only one dose of either agent for rigors ablation with <20% of either cohort requiring 2 or more doses (p = 0.539). Low rates of sedation were observed in both groups. CONCLUSION: Both meperidine and morphine effectively manage MAB-related rigors within minimal safety concerns. These findings suggest that morphine is a suitable alternative to meperidine for this indication, which may influence future formulary decision, provide alternatives for drug shortage, and optimize supportive care for patients undergoing MAB therapy.

Raha syrup attenuates the morphine withdrawal-induced locomotor sensitisation by increasing the cerebrospinal fluid serotonin in rats receiving the opium tincture maintenance treatment.

Morphine withdrawal increases locomotor sensitisation, relapse and impair regulation of serotonin system. We evaluated the effectiveness of Raha syrup on the cerebrospinal fluid (CSF) serotonin levels following locomotor sensitisation in morphine-withdrawn rats receiving the opium tincture (OT). Morphine withdrawal rats gavaged daily with OT and Raha syrup (for 30 days) and then challenged with morphine and evaluated for locomotor activity and CSF serotonin levels before morphine challenge and 2 weeks after cessation of treatment. Raha syrup attenuated locomotor activity, increased the CSF serotonin after morphine challenge, and continued 2 weeks after cessation of treatment in rats receiving OT. Whereas, rats receiving OT alone after morphine challenge exhibited a relative decrease in locomotor activity, without changing CSF serotonin. Raha syrup attenuated locomotor sensitisation in morphine-withdrawn rats receiving OT probably by increasing serotonin. Therefore, administration of Raha syrup along with OT may benefit to treatment relapse in addicts receiving OT maintenance treatment.

Adolescent nicotine exposure promotes adulthood opioid consumption that persists despite adverse consequences and increases the density of insular perineuronal nets.

Adolescence marks a sensitive period for neurodevelopment wherein exposure to drugs of abuse may disrupt maturation and induce persistent changes in neurophysiology which may exacerbate the risk for developing substance use disorders in adulthood. Adolescent nicotine exposure (ANE) enhances motivation to obtain drugs of abuse, particularly opioids, and increases vulnerability for the development of opioid use disorder (OUD). Here, we characterized ANE effects on learning about the adverse consequences of opioid consumption in adulthood in the absence of further nicotine administration. First, we show that ANE engenders punishment resistant fentanyl self-administration in a heterogenous seeking-taking chain schedule of reinforcement at least at the tested dose of fentanyl (0.75 µg/kg). We found that ANE rats consumed significantly more fentanyl and contingent foot shock punishment was less efficacious in limiting fentanyl seeking in ANE rats, relative to nicotine-naïve controls. Next, we demonstrated that ANE limits learning about the deleterious consequences of acute opioid intoxication in adulthood. In a combined conditioned taste avoidance and place preference paradigm we found that ANE resulted in significant reductions in the strength of morphine-induced CTA, and a simultaneous enhancement of CPP at a higher dose that was less capable of driving reinforcement in naïve controls. Finally, we examined the expression of perineuronal nets (PNNs) within insular cortex (IC) and found ANE rats to have increased density of PNNs across the anterior IC and significantly more parvalbumin-labeled IC cells relative to naïve controls. Together, these data lay the framework for a mechanistic explanation of the extreme comorbidity between nicotine use and development of OUDs.

Morphine synovial fluid concentrations after intravenous regional limb perfusion in horses during standing sedation.

BACKGROUND: Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb. OBJECTIVES: The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin. STUDY DESIGN: Randomised cross-over in vivo experiment. METHODS: Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout period between treatments. Synovial fluid was collected from the radiocarpal joint (RCJ) at 10, 20, 30, 120, 240, 480, 720 and 1440 min after IVRLP. The tourniquet was removed after the 30-min sample was collected. Synovial concentrations of morphine and major metabolites were measured using liquid chromatography-tandem mass spectrometry. Amikacin concentrations were quantified by a fluorescence polarisation immunoassay. RESULTS: Measurable concentrations of morphine were apparent in the RCJ of all horses. Median CMAX of morphine in the M group was 4753.1 (2115.7-14 934.5) ng/mL and 4477 (3434.3-7363) ng/mL in the MA group (p = 0.5). Median CMAX of synovial amikacin was 322.6 (157.5-1371.6 µg/mL). MAIN LIMITATIONS: Limitations include small sample size. Investigators were not blinded to the treatments and a third treatment group where amikacin alone was administered via IVRLP to the study population was not included. CONCLUSIONS: IVRLP using morphine is a feasible technique and synovial morphine concentrations were measurable following IVRLP and were not affected when used concurrently with amikacin. Administration of morphine via IVRLP may be beneficial as an analgesic technique for orthopaedic conditions of the distal limb while limiting potential serious systemic side-effects.

Nalbuphine versus morphine: an adjuvant to spinal anesthesia for controlling pain after total knee arthroplasty: a propensity score-matched analysis.

BACKGROUND: Nalbuphine, a synthetic k-agonist and µ-antagonist, provides efficient pain relief while reducing opioid-related adverse effects. This study aims to compare the efficacy of intrathecal nalbuphine (ITN) with intrathecal morphine (ITM) for post-TKA pain. METHODS: A retrospective cohort analysis of 131 patients who underwent TKA with spinal anesthesia (SA), a single shot of adductor canal block, and periarticular injections was conducted. The patients were divided into 2 groups, Group N received 0.8 mg nalbuphine, and Group M received 0.2 mg morphine as an adjuvant to SA. Propensity-score matching was employed to compare the visual analog scales (VAS) of postoperative pain intensity, cumulative morphine use (CMU), maximum knee flexion angle, straight leg raise (SLR) ability, incidence of postoperative nausea and vomiting (PONV), and length of hospital stay (LHS). RESULTS: The mean VAS of group M were significantly lower than group N at 6, 12, 18, and 24 h (P < 0.01). Group M had lower CMU than group N at 24 h (P < 0.01) and 48 h (P < 0.01), while there was no significant difference between groups in terms of knee flexion angle and SLR at any time point. Additionally, 29.3 and 57.9% of patients in group N and M experienced PONV, respectively (p = 0.04), and group N had significantly shorter LHS compared to group M (P < 0.001). CONCLUSION: Although, intrathecal morphine (ITM) still provides better pain control particularly in the first 24 h, patients who received intrathecal nalbuphine (ITN) had significantly fewer incidence of PONV, and shorter LHS.

Effects of Acetic Acid and Morphine in Shore Crabs, Carcinus maenas: Implications for the Possibility of Pain in Decapods.

Noxious chemicals, coupled with morphine treatment, are often used in studies on pain in vertebrates. Here we show that injection of morphine caused several behavioural changes in the crab, Carcinus maenas, including reduced pressing against the sides of the enclosure and more rubbing and picking at the mouth parts and, at least for a short time, more defensive displays. Subsequent injection of acetic acid into one rear leg caused rubbing of the injected leg and the injected leg was held vertically off the ground. These activities directed at or involving the specific leg are consistent with previous observations of directed behaviour following noxious stimuli and are consistent with the idea that decapods experience pain. Further, acetic acid but not injection of water induced autotomy of the injected leg in these animals. Because autotomy is temporally associated with directed behaviour, it is possible that the autotomy is a pain-related response. Acetic acid is clearly a noxious substance when applied to decapods. However, morphine had no effect on the activities associated with acetic acid injection and thus there is no evidence for an analgesic effect. Further, the injection of acetic acid did not interfere with behavioural effects of morphine. The activities directed towards the site of injection are like those observed with injection, or with external application, of various noxious substances and the present study adds to a growing body of knowledge about possible pain in decapods.

A systematic review of morphine equivalent conversions in plastic surgery: Current methods and future directions.

INTRODUCTION: Protocols surrounding opioid reduction have become commonplace in plastic surgery to improve peri-operative outcomes. Within such protocols, opioid requirement is a frequently analyzed outcome. Though often examined, there is no literature standard conversion for morphine milligram equivalents (MME) at present, leading to questionable external validity. We hypothesized significant heterogeneity in MME reporting would exist within plastic surgery literature. METHODS: Following the PRISMA guidelines, the authors conducted a systematic review of 16 journals. Clinical studies focused on opioid reduction within plastic surgery were identified. Primary outcomes included reporting of morphine equivalents (ME) delivery (IV/oral), operative ME, inpatient ME, outpatient ME, timeline, and method of calculation. RESULTS: Among the 101 studies analyzed, 73% reported opioid requirements in the form of ME. Among those that used ME, 3% reported IV ME, 41% reported oral, 32% reported both, and 25% gave no indication of either. Operative ME were reported in 19% of studies. Furthermore, 54% of studies reported inpatient ME whereas 32% of studies reported outpatient ME. Only 19% reported the number of days opioids were consumed postoperatively. Moreover, 27% of the studies reported the actual method of ME conversion, with 17 unique methods described. Only 8 studies (8%) reported using the Center for Disease Control and Prevention guidelines for ME conversion. CONCLUSION: There is significant variability among the reported ME conversion methodology within plastic surgery literature. Highlighting these discrepancies is an essential step in creating and implementing a single, standard method to mitigate opioid morbidity in plastic surgery and to optimize enhanced recovery protocols.