Effects Of Morphine Research Articles

Loss of Astrocytic µ Opioid Receptors Exacerbates Aversion Associated with Morphine Withdrawal in Mice: Role of Mitochondrial Respiration.

Astrocytes express mu/µ opioid receptors, but the function of these receptors remains poorly understood. We evaluated the effects of astrocyte-restricted knockout of µ opioid receptors on reward- and aversion-associated behaviors in mice chronically exposed to morphine. Specifically, one of the floxed alleles of the Oprm1 gene encoding µ opioid receptor 1 was selectively deleted from brain astrocytes in Oprm1 inducible conditional knockout (icKO) mice. These mice did not exhibit changes in locomotor activity, anxiety, or novel object recognition, or in their responses to the acute analgesic effects of morphine. Oprm1 icKO mice displayed increased locomotor activity in response to acute morphine administration but unaltered locomotor sensitization. Oprm1 icKO mice showed normal morphine-induced conditioned place preference but exhibited stronger conditioned place aversion associated with naloxone-precipitated morphine withdrawal. Notably, elevated conditioned place aversion lasted up to 6 weeks in Oprm1 icKO mice. Astrocytes isolated from the brains of Oprm1 icKO mice had unchanged levels of glycolysis but had elevated oxidative phosphorylation. The basal augmentation of oxidative phosphorylation in Oprm1 icKO mice was further exacerbated by naloxone-precipitated withdrawal from morphine and, similar to that for conditioned place aversion, was still present 6 weeks later. Our findings suggest that µ opioid receptors in astrocytes are linked to oxidative phosphorylation and they contribute to long-term changes associated with opioid withdrawal.

Efficacy of a Vibrating Crib Mattress to Reduce Pharmacologic Treatment in Opioid-Exposed Newborns

Pharmacologic agents are often used to treat newborns with prenatal opioid exposure (POE) despite known adverse effects on neurodevelopment. Alternative nonpharmacological interventions are needed. To examine efficacy of a vibrating crib mattress for treating newborns with POE. In this dual-site randomized clinical trial, 208 term newborns with POE, enrolled from March 9, 2017, to March 10, 2020, were studied at their bedside throughout hospitalization. Half the cohort received treatment as usual (TAU) and half received standard care plus low-level stochastic (random) vibrotactile stimulation (SVS) using a uniquely constructed crib mattress with a 3-hour on-off cycle. Study initiated in the newborn unit where newborns were randomized to TAU or SVS within 48 hours of birth. All infants whose symptoms met clinical criteria for pharmacologic treatment received morphine in the neonatal intensive care unit per standard care. The a priori primary outcomes analyzed were pharmacotherapy (administration of morphine treatment [AMT], first-line medication at both study sites [number of infants treated], and cumulative morphine dose) and hospital length of stay. Intention-to-treat analysis was conducted. Analyses were performed on 181 newborns who completed hospitalization at the study sites (mean [SD] gestational age, 39.0 [1.2] weeks; mean [SD] birth weight, 3076 (489) g; 100 [55.2%] were female). Of the 181 analyzed infants, 121 (66.9%) were discharged without medication and 60 (33.1%) were transferred to the NICU for morphine treatment (31 [51.7%] TAU and 29 [48.3%] SVS). Treatment rate was not significantly different in the 2 groups: 35.6% (31 of 87 infants who received TAU) and 30.9% (29 of 94 infants who received SVS) (P = .60). Adjusting for site, sex, birth weight, opioid exposure, and feed type, infant duration on the vibrating mattress in the newborn unit was associated with reduction in AMT (adjusted odds ratio, 0.88 hours per day; 95% CI, 0.81-0.93 hours per day). This translated to a 50% relative reduction in AMT for infants who received SVS on average 6 hours per day. Among 32 infants transferred to the neonatal intensive care unit for morphine treatment who completed treatment within 3 weeks, those assigned to SVS finished treatment nearly twice as fast (hazard ratio, 1.96; 95% CI, 1.01-3.81), resulting in 3.18 fewer treatment days (95% CI, -0.47 to -0.04 days) and receiving a mean 1.76 mg/kg less morphine (95% CI, -3.02 to -0.50 mg/kg) than the TAU cohort. No effects of condition were observed among infants treated for more than 3 weeks (n = 28). The findings of this clinical trial suggest that SVS may serve as a complementary nonpharmacologic intervention for newborns with POE. Reducing pharmacotherapy with SVS has implications for reduced hospitalization stays and costs, and possibly improved infant outcomes given the known adverse effects of morphine on neurodevelopment. ClinicalTrials.gov Identifier: NCT02801331.

Effectiveness and safety of morphine administration for refractory dyspnoea among hospitalised patients with advanced heart failure: the Morphine-HF study

ObjectivesMorphine is effective in alleviating dyspnoea in patients with cancer. We aimed to investigate the effectiveness and safety of morphine administration for refractory dyspnoea in patients with advanced heart failure...

Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia.

Morphine is a drug used in chronic pain such as diabetic neuropathy, but the development of tolerance to its antinociceptive effect is an important clinical problem. Aspirin is an analgesic and antiapoptotic drug used in combination with morphine as an adjuvant in diabetic neuropathy. Our aim in this study was to investigate the effects of aspirin on morphine-induced neuronal apoptosis and analgesic tolerance in rats with diabetic neuropathy. The antinociceptive effects of aspirin (50mg/kg) and morphine (5mg/kg) were evaluated by thermal pain tests. Streptozotocin (65mg/kg) was injected intraperitoneally to induce diabetic neuropathy. To evaluate apoptosis, ELISA kits were used to measure caspase-3, Bax and Bcl-2 levels. Apoptotic cells were detected histologically by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. Study results indicate that prior administration of aspirin to diabetic rats significantly increased the antinociceptive efficacy of morphine compared to morphine alone. Thermal pain tests showed that aspirin significantly reduced morphine tolerance in rats with diabetic neuropathy. Biochemical analysis revealed that aspirin significantly decreased the levels of pro-apoptotic proteins, caspase-3 and Bax, while increasing the anti-apoptotic Bcl-2 in DRG neurons. Semiquantitative scoring demonstrated that aspirin provided a significant reduction in apoptotic cell counts in diabetic rats. In conclusion, these data suggested that aspirin attenuated morphine antinociceptive tolerance through anti-apoptotic activity in diabetic rat DRG neurons.

Effects of Post Trauma Morphine On Dorsal Horn Neuron Excitability: Studies using cFOS and RNAscope

Previous research has shown that a 5-day course of morphine enhances nociceptive sensitivity and allodynia when given 10 days after chronic constriction injury (CCI) as measured by the Von Frey test, a test where the hindpaw is poked with force (measured in grams) calibrated filament. This increased sensitivity to touch suggests that post trauma morphine makes second order sensory dorsal horn neurons more excitable. Therefore, it is hypothesized that during morphine enhanced allodynia, dorsal horn neurons will be more excitable to nociceptive stimulus. It was found that morphine enhanced allodynia causes more excitable neurons across a larger spatial range of the spinal cord, both rostral-caudal and dorsal-ventral along the dorsal horn. Mechanisms for the increased excitability of the dorsal horn are proposed and explored. These findings add to a robust literature which has detailed the paradoxical pain amplifying effects of morphine. Further, this study predicts that hyperexcitability of pain and touch pathways may occur as a clinically unintended side effect of morphine when administered to treat ongoing neuropathic pain. Lay Summary When working on the body, opioids take effect on various cells- including cells of the nervous system known as Glia. These glial cells produce various inflammatory responses that are typically known to decrease inflammation in the body. However, prior literature has revealed that following an activated state, these cells enter a “primed” form. If a second immunological activation occurs during this primed state, glial cells have been shown to release proteins that actually potentiate the state of pain. This study examines this hypothesis through the context of peripheral nerve injury (modeling injury, surgery, or trauma), followed by an administration of morphine. Using advanced imaging techniques, we are able to visualize exactly what modulators are inducing this potentiated pain response, as well as where in the nervous system these cells are found. Morphine has a potent effect on various aspects of the nervous system which may be alleviated by other treatment routes that focus specifically on the cell type and location that release the molecules that initiate the healing process. By unveiling the details of this mechanism, we can better understand how to treat patients following injury or surgery without inducing a higher pain response that can be caused by a short-term administration of morphine. To see the complete thesis, please visit https://scholar.colorado.edu/concern/undergraduate_honors_theses/0k225c53t.

Dexmedetomidina, un agonista de α2, incrementa el efecto analgésico de la morfina y reduce el desarrollo de tolerancia a la morfina suprimiendo el estrés oxidativo y la vía de señalización de TNF/IL-1 en ratas

BackgroundThe aim of the present study is to examine the possible effect de dexmedetomidine on the development of morphine tolerance in rats including nociception, morphine analgesia, apoptosis, oxidative stress, and tumour necrosis factor (TNF)/ interleukin-1 (IL-1) pathways. Materials and methodsIn this study, 36 Wistar Albino (225–245 g) rats were used. Animals were divided into 6 groups: saline (S), 20 mcg/kg dexmedetomidine (D), 5 mg/kg morphine (M), M + D, morphine tolerance (MT), and MT + D. The analgesic effect was measured with hot plate and tail-flick analgesia tests. After the analgesia tests, the dorsal root ganglia (DRG) tissues were excised. Oxidative stress parameters [total antioxidant status (TAS), total oxidant status (TOS)], TNF, IL-1 and apoptosis enzymes (Caspase-3, Caspase-9), were measured in DRG tissues. ResultsDexmedetomidine showed an antinociceptive effect when given alone (p < 0.05 to p < 0.001). In addition, dexmedetomidine increased the analgesic effect of morphine (p < 0.001), and also decreased the tolerance to morphine at a significant level (p < 0.01 to p < 0.001). Moreover, it decreased oxidative stress (p < 0.001) and TNF/IL-1 levels when given as an additional drug of single-dose morphine and morphine tolerance group (p < 0.001). Furthermore, dexmedetomidine decreased Caspase-3 and Caspase-9 levels after tolerance development (p < 0.001). ConclusiónDexmedetomidine has antinociceptive properties, and it increases the analgesic effect of morphine and also prevents tolerance development. These effects probably occur by the modulation of oxidative stress, inflammation and apoptosis.

Investigating the Co-administration of Ghrelin and Nicotine into the Medial Septum and Its Influencing on Morphine Amnestic Effect

Introduction: Evidence indicates that medial septum nicotinic receptors regulate cognitive processes. Ghrelin is a gut hormone that regulates energy homeostasis. Ghrelin is also produced in the brain and is involved in cognitive function. This study aims to evaluate the effects of medial septal administration of ghrelin on the amnestic effect of morphine in rats.In addition, the possible relationship between the medial septal ghrelin and acetylcholine nicotinic receptors on the amnestic effect of morphine is evaluated. Methods: The rats were implanted at the medial septum area and were microinjected with ghrelin and nicotinic receptor agents. The step-through type inhibitory avoidance apparatus was used for memory retrieval assessment. Results: The results showed that the administration of morphine after the training phase impaired memory consolidation. Post-training intra-septal injection of the same doses of either ghrelin or nicotine did not change memory performance; however, their co-application with morphine (significant dose: 7.5 mg/kg subcutaneous injection) increased the step-through latency and improved memory consolidation. Moreover, post-training co-application of low doses of the two agonists could not affect morphine-induced memory impairment. Conclusion: These results indicated no interaction between medial septal ghrelin and nicotinic receptors on the amnestic effect of morphine in rats.

Restoring the firing activity of ventral tegmental area neurons by lateral hypothalamic deep brain stimulation following morphine administration in rats

We have previously shown that high-frequency deep brain stimulation (DBS) of the lateral hypothalamus (LH) compromises morphine-induced addiction-like behavior in rats. The exact mechanism underlying this effect is not known. Here, we investigated the assumption that DBS in the LH influences the firing activity of neurons in the ventral tegmental area (VTA). To that end, male Wistar rats received morphine (5 mg/kg; s.c.) for three days and underwent extracellular single unit recording under general anesthesia one day later. During the recording, the rats received an intraoperative injection of morphine (5 mg/kg; s.c.) plus DBS in the LH (130 Hz pulse frequency, 150 μA amplitude, and 100 μs pulse width). One group of animals also received preoperative DBS after each morphine injection before the recording. The spiking frequency of VTA neurons was measured at three successive phases: (1) baseline (5–15 min); (2) DBS-on (morphine + DBS for 30 min); and (3) After-DBS (over 30 min after termination of DBS). Results showed that morphine suppressed the firing activity of a large population of non-DA neurons, whereas it activated most DA neurons. Intraoperative DBS reversed morphine suppression of non-DA firing, but did not alter the excitatory effect of morphine on DA neurons firing. With repeated preoperative application of DBS, non-DA neurons returned to the morphine-induced suppressive state, but DA neurons released from the excitatory effect of morphine. It is concluded that the development of morphine reward is associated with a hypoactivity of VTA non-DA neurons and a hyperactivity of DA neurons, and that DBS modulation of the spiking activity may contribute to the blockade of morphine addiction-like behavior.

Negative Impact of ST-Segment Elevation Myocardial Infarction and Morphine Dose on Ticagrelor Uptake and Pharmacodynamics: A Population PK/PD Analysis of Pooled Individual Participant Data.

Ticagrelor is widely used in patients with stable and acute coronary artery disease. Understanding the factors that influence its pharmacokinetics (PK) and pharmacodynamics (PD) could improve therapeutic outcomes. We therefore performed a pooled population PK/PD analysis using individual patient data from two studies. We focused on the impact of morphine administration and ST-segment elevation myocardial infarction (STEMI) on the risk of high platelet reactivity (HPR) and dyspnea. A parent-metabolite population PK/PD model was developed based on data from 63 STEMI, 50 non-STEMI, and 25 chronic coronary syndrome (CCS) patients. Simulations were then run to evaluate the risk of non-response and adverse events associated with the identified variability factors. The final PK model consisted of first-order absorption with transit compartments, distribution with two compartments for ticagrelor and one compartment for AR-C124910XX (active metabolite of ticagrelor), and linear elimination for both drugs. The final PK/PD model was an indirect turnover model with production inhibition. Morphine dose and STEMI, independently, had a significant negative effect on the absorption rate (reduction of log([Formula: see text]) by 0.21×morphine dose (mg) and by 2.37 in STEMI patients, both p<0.001), and the presence of STEMI significantly impacted both efficacy and potency (both p<0.001). The simulations run with the validated model showed a high rate of non-response in patients with those covariates (RR 1.19 for morphine, 4.11 for STEMI and 5.73 for morphine and STEMI, all three p<0.001). By increasing ticagrelor dosage, the negative morphine effect was reversible in patients without STEMI and just limited in patients with STEMI. The developed population PK/PD model confirmed the negative impact of morphine administration and presence of STEMI on ticagrelor PK and antiplatelet effect. Increasing ticagrelor doses seems effective in morphine users without STEMI, whereas the STEMI effect is not entirely reversible.

Repeated Administration of the Cannabinoid WIN Alters the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine.

Prior to the administration of morphine, the MAC was measured in both untreated rats (MAC (ISO)) and those treated with a cannabinoid (MAC (ISO + CANN)). The effects of morphine (MAC (ISO + MOR)) and dexmedetomidine (MAC (ISO + DEX)) on untreated rats and rats treated for 21 days with the cannabinoids (MAC (ISO + CANN + MOR)) and (MAC (ISO + CANN + DEX) were also studied. MAC (ISO) was 1.32 ± 0.06, and MAC (ISO + CANN) was 1.69 ± 0.09. MAC (ISO + MOR) was 0.97 ± 0.02 (26% less than MAC (ISO)). MAC (ISO + CANN + MOR) was 1.55 ± 0.08 (8% less than MAC (ISO + CANN)), MAC (ISO + DEX) was 0.68 ± 0.10 (48% less than MAC (ISO)), and MAC (ISO + CANN + DEX) was 0.67 ± 0.08 (60% less than MAC (ISO + CANN)). Medication with a cannabinoid for 21 days augmented the MAC of isoflurane. The sparing effect of morphine on isoflurane is lower in rats constantly medicated with a cannabinoid. The sparing effect of dexmedetomidine on the minimum alveolar concentration of isoflurane is greater in rats repeatedly medicated with a cannabinoid.

Morphine and dopamine: Low dose apomorphine can prevent both the induction and expression of morphine locomotor sensitization and conditioning

The disinhibition of dopamine neurons in the VTA by morphine is considered an important contributor to the reward potency of morphine. In this report, three experiments were conducted in which a low dose of apomorphine (0.05 mg/kg) was used as a pretreatment to reduce dopamine activity. Locomotor hyperactivity was used as the behavioral response to morphine (10.0 mg/kg). In the first experiment, five treatments with morphine induced the development of locomotor and conditioned hyperactivity that were prevented by apomorphine given 10 min prior to morphine. Apomorphine before either vehicle or morphine induced equivalent reductions in locomotion. In the second experiment, the apomorphine pretreatment was initiated after induction of a conditioned hyperactivity and apomorphine prevented the expression of the conditioning. To assess the effects of apomorphine on VTA and the nucleus accumbens, ERK measurements were carried out after the induction of locomotor and conditioned hyperactivity. Increased ERK activation was found and these effects were prevented by the apomorphine in both experiments. A third experiment was conducted to assess the effects of acute morphine on ERK before locomotor stimulation was induced by morphine. Acute morphine did not increase locomotion, but a robust ERK response was produced indicating that the morphine-induced ERK activation was not secondary to locomotor stimulation. ERK activation was again prevented by the apomorphine pretreatment. We suggest that contiguity between the ongoing behavioral activity and the morphine activation of the dopamine reward system incentivizes and potentiates the ongoing behavior generating equivalent behavioral sensitization and conditioned effects.

Analgesic effects of intrathecal morphine and bupivacaine during robotic-assisted surgery: A prospective randomized controlled study.

Limited data exist concerning the management of postoperative pain after robotic-assisted surgery. The present study was performed to investigate the efficacy of intrathecal morphine and bupivacaine to treat postoperative pain in adult women undergoing robot-assisted laparoscopic hysterectomy. The primary outcomes of this study were opioid consumption and pain scores during and after robotic surgery. 96 patients were prospectively enrolled and randomized to a nonspinal group (n = 48) and a spinal group (n = 48). The intrathecal regimen consisted of 100 μg morphine and 15 mg of bupivacaine. The numeric rating scale scores (NRS) were assessed every 15 min in the postoperative care unit (PACU) and pain was treated with iv fentanyl or morphine when NRS was above 5 and orally oxycodone when NRS was 3-5. Cumulative iv opioid-consumption and NRS scores were compared. Intrathecal morphine and bupivacaine resulted in a significantly lower cumulative total iv opioid (morphine equivalents) consumption (9.4 ± 3.9 vs. 22.8 ± 6.1 mg equivalents). Highest recorded NRS scores in the PACU were also significantly lower in the spinal group (2.0 ± 2.6 vs. 5.3 ± 3.2). Intrathecal morphine and bupivacaine to treat postoperative pain after robotic-assisted laparoscopic hysterectomy decrease total opioid consumption and NRS pain scores. This might be of great importance to diminish the rate of other serious disadvantages related to opioids.

HSP90 inhibition in the mouse spinal cord enhances opioid signaling by suppressing an AMPK-mediated negative feedback loop.

Opioids and other agonists of the μ-opioid receptor are effective at managing acute pain, but their chronic use can lead to tolerance that limits their efficacy. We previously reported that inhibiting the chaperone protein HSP90 in the spinal cords of mice promotes the antinociceptive effects of opioids in a manner that involved increased activation of the kinase ERK. Here, we found that the underlying mechanism involves the relief of a negative feedback loop mediated by the kinase AMPK. Intrathecal treatment of male and female mice with the HSP90 inhibitor 17-AAG decreased the abundance of the β1 subunit of AMPK in the spinal cord. The antinociceptive effects of 17-AAG with morphine were suppressed by intrathecal administration of AMPK activators and enhanced by an AMPK inhibitor. Opioid treatment increased the abundance of phosphorylated AMPK in the dorsal horn of the spinal cord, where it colocalized with a neuronal marker and the neuropeptide CGRP. Knocking down AMPK in CGRP-positive neurons enhanced the antinociceptive effects of morphine and demonstrated that AMPK mediated the signal transduction between HSP90 inhibition and ERK activation. These data suggest that AMPK mediates an opioid-induced negative feedback loop in CGRP neurons of the spinal cord and that this loop can be disabled by HSP90 inhibition to enhance the efficacy of opioids.

Efficacy of intrathecal morphine administration in pediatric patients undergoing selective dorsal rhizotomy.

The purpose of this study was to evaluate the effectiveness of intrathecal morphine following selective dorsal rhizotomy in pediatric patients previously diagnosed with cerebral palsy. This was a retrospective, cohort analysis over the course of four years. The analysis consisted of a treatment group which received intrathecal morphine (5 mcg/kg) injection and a control group that did not receive the injection prior to dural closure. All patients underwent multilevel laminectomies for selective dorsal rhizotomy at Akron Children's Hospital. The effectiveness of the treatment was measured by total dose of hydromorphone administered on patient-controlled analgesia (PCA), number of days on oral narcotics, and cumulative dose of oral narcotic. Of the analyzed 15 pediatric patients, seven patients received intrathecal morphine injection while the other eight did not receive the treatment prior to dural closure. There was a difference of 1135 mcg in total PCA dose between the study group (3243 mcg) and the control group (4378 mcg). The total PCA dose based on weight was lower in the study group (163 mcg/kg) than in the control group (171 mcg/kg). Based on these findings, the administration of intrathecal morphine clinically reduces the opiate need in the first 96 hours post-operatively.

Effect of single-shot intrathecal morphine versus continuous epidural analgesia on length of stay after gastrectomy for cancer: a retrospective cohort study.

Single-dose intrathecal opiates (ITO) could shorten the length of hospital stay compared to thoracic epidural analgesia (TEA). This study aimed to compare TEA with TIO in terms of length of hospital stay, pain control, and parenteral opioid consumption in patients undergoing gastrectomy for cancer. The patients who underwent gastrectomy for cancer in 2007-2018 at the CHU de Québec-Université Laval were included. The patients were grouped as TEA and intrathecal morphine (ITM). The primary outcome was the length of hospital of stay (LOS). The secondary outcomes were numeric rating scales (NRS) for pain and parenteral opioid consumption. A total of 79 patients were included. There were no differences in preoperative characteristics between the two groups (all P > 0.05). The median LOS was shorter in the ITM group than in the TEA group (median, 7.5 vs. 10days, P = 0.049). The opioids consumption at 12, 24, and 48h postoperatively was significantly lower in the TEA group at all time points. The NRS score for pain was lower in the TEA group than in the ITM group at all time points (all P < 0.05). Patients with ITM analgesia undergoing gastrectomy presented shorter LOS than those with TEA. ITM had an inferior pain control that did not have a clinical impact on recovery in the cohort studied. Given the limitations of this retrospective study, further trials are warranted.

Investigation of Inflammatory Effects of Morphine and Fentanyl on Early Wound Healing in Rats: an Experimental Study

Investigation of Inflammatory Effects of Morphine and Fentanyl on Early Wound Healing in Rats: an Experimental Study

EFFICACY OF INTRATHECAL MORPHINE AFTER LAPAROSCOPIC SURGERY FOR COLORECTAL CANCER AT CAN THO UNIVERSITY OF MEDICINE AND PHARMACY HOSPITAL

Background: There have been many studies in using intrathecal morphine order to reduce pain after obstetrics and gynecological surgeries, abdominal surgeries and orthopedic surgeries. These studies have shown that intrathecal morphine is very effective for pain relief after surgery. However, intrathecal morphine also has side effects especially in obstetric and gynecological surgeries such as pruritus, postoperative nausea and vomiting, and delayed respiratory depression. Although postoperative analgesia with intrathecal morphine has been widely used in obstetrics and gynecological surgeries, orthopedic surgeries, there have been very few studies on postoperative pain relief with intrathecal morphine for colorectal surgery. Laparoscopic colorectal surgery requires multimodal analgesia, so using intrathecal morphine to reduce postoperative pain in this surgery is essential in clinical practice. Therefore, studying the effectiveness of intrathecal morphine in this surgery is necessary, so we conducted this study. Objectives: To assess the effectiveness of analgesic and side effects of intrathecal morphine after laparoscopic colorectal surgery. Materials and Methods: This was a descriptive, cross-sectional study, including 63 patients undergoing laparoscopic colorectal cancer surgery with intrathecal morphine before general anesthesia. The degree of analgesia was assessed based on VAS. The postoperative side effects observed were postoperative nausea and vomiting, respiratory depression, and pruritus. Results: The analgesic effect at rest and on slight movement was 95.2%, and 88.9% respectively with VAS ≤ 3. The side effects were postoperative nausea and vomiting (6.3%), and pruritus (1.6%), both postoperative nausea and vomiting and pruritus (3.2%). In conclusion, 300µg intrathecal morphine showed a safe and positive analgesic effect for laparoscopic colorectal cancer surgery.

Intrathecal Morphine Injection for Postoperative Analgesia Following Gender-Affirming Pelvic Surgery: A Retrospective Case-Control Study.

Background Gender-affirming pelvic surgery (GAPS) can be associated with significant postoperative pelvic pain. Given the lack of available peripheral nerve blocks to the perineum, intrathecal morphine (ITM) injection could offer a potent analgesic modality for this patient population. No prior studies to date have been performed examining the analgesic effects of intrathecal morphine for these patients. Methods This retrospective case-control study aims to understand the postoperative analgesic effects of intrathecal morphine for these patients with a historical comparison group of patients who did not receive intrathecal morphine. Results Fourteen patients presented for gender-affirming pelvic surgery over an eight-month period at a single institution and were offered intrathecal morphine for postoperative analgesia. Their analgesic results were compared to a similar historical group of 13 patients who were not offered or declined intrathecal morphine. Conclusions Intrathecal morphine injection is a potent analgesic modality for patients presenting for gender-affirming pelvic surgery.

Heteroaromatic salvinorin A analogue (P-3 l) elicits antinociceptive and anxiolytic-like effects

Previous studies have attributed the prominent analgesic, hallucinogenic, sedative, and anxiolytic properties of Salvia divinorum to Salvinorin A. However, the overall pharmacological profile of this isolate limits its clinical applications. To address these limitations, our study evaluates the C(22)-fused-heteroaromatic analogue of salvinorin A [2-O-salvinorin B benzofuran-2-carboxylate] (P-3l) in mice nociception and anxiety models while assessing possible mechanism of action. In comparison with the control group, orally administered P-3l (1, 3, 10, and 30 mg/kg) attenuates acetic acid-induced abdominal writhing, formalin-induced hind paw licking, the thermal reaction to the hotplate, and/or aversive response in the elevated plus-maze, open field, and light-dark box; and potentiates the effect of morphine and diazepam at sub-effective doses (1.25 and 0.25 mg/kg, respectively) without eliciting significant alterations in relative organ weight, or haematological or biochemical parameters. The in vivo blockade of P-3 l effects by naloxone (non-selective opioid receptor antagonist), naloxonazine (antagonist of specific subtypes mu1 of μ-OR), and nor-binaltorphimine (selective ĸ-OR antagonist) supports initial results from binding assays and the interpretations made possible from computational modeling of the interactions of P-3 l with the opioid receptor subtypes. In addition to the opioidergic mechanism, the blockade of the P-3 l effect by flumazenil suggests benzodiazepine binding site involvement in its biological activities. These results support P-3 l potentially possessing clinical utility and substantiate the need for additional pharmacological characterization.

EFFECT OF THİAMİNE ON MORPHİNE ANALGESİA AND TOLERANCE İN RATS

Absract: The latest research have demonstrated that inflammation, oxidative stress and apoptosis plays a majör role in morphine analgesia and tolerance development. This search goals to examine the possible role of thiamine use on oxidative stress, inflammation and apoptosis in the development of morphine analgesia and morphine tolerance in rats. &#x0D; Methods: Thirty-six male Wistar rats were used in this study. The rats were severed into six groups: saline, 100 mg/kg thiamine, 5 mg/kg morphine, thiamine + morphine, morphine tolerance and thiamine + morphine tolerance. The resulting analgesic effect was measured by hot plate and tail movement analgesia tests. TAS and TOS, inflammation parameters, and apoptosis protein levels of the dorsal root ganglion tissues sample were measured using an ELISA kit. &#x0D; Results: When thiamine was given alone, it did not show anti-nociceptive effect (p&gt;0.05). In addition, thiamine enhanced the analgesic effect of morphine (p &lt; 0.05) and also significantly reduced tolerance to morphine (p &lt; 0.05). However, it reduced TOS when administered with a single dose of morphine and tolerance induction (p &lt; 0.05). In addition, thiamine reduced apoptosis protein levels after tolerance development (p &lt; 0.05). &#x0D; Conclusion: Consequently, these results may attain by reducing TOS, inflammation, and apoptosis.