Postoperative pain is an acute pain that appears due to the surgical act, reaching its maximum intensity in the first 24 - 48 hours after surgery. Postoperative pain control reduces possible postoperative complication...Postoperative pain is an acute pain that appears due to the surgical act, reaching its maximum intensity in the first 24 - 48 hours after surgery. Postoperative pain control reduces possible postoperative complications, as well as the patient’s stay in the medical institution. Objective: This study compared the effectiveness and side effects of oral transmucosal fentanyl citrate (OTFC) with IV morphine in the control of postoperative pain. Methods: Seventy-three patients (Fentanyl group: 27, morphine group: 46) were included. Changes in pain were evaluated with Visual Analog Scale (VAS) and Pain Relief Scale, Pain Intensity Differences (PID), Sum of Pain Intensity Differences (SPID), and Total Pain Relief (TOTPAR). At time zero, 15, 30, 45 min and 1, 2, 3, 4, 5 and 6 h. Results: The decrease in pain intensity measured by VAS was similar in both groups with no significant differences at any of the measurement points. Both products produced a significant increase in the Pain Relief scale, with no differences between groups at any of the measurement times. There were no differences between groups when comparing PID. Comparing SPID between groups, there were no differences at 15, 30 minutes, then there were significant differences in favor of the Fentanyl group up to 6 hours. Both products produced a significant increase in the TOPAR scale, with no differences between groups at any of the measurement times. The appearance of adverse effects was similar in both groups. Conclusions: Both products produced a significant reduction in the measures of pain intensity (VAS), increase of SPID, as well as a significant increase in the Pain Relief scale, a significant increase in the TOPAR scale, with no differences between the groups. The number of adverse effects was similar. The convenience of OTFC administration allows its administration without the special conditions needed for the administration of IV morphine.展开更多
OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Avail...OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target proteins of MT were retrieved from the GeneCards,PharmGkb,Therapeutic Target Database,DrugBank,and Online Mendelian Inheritance in Man databases.Information regarding MT and the drug targets was compared to obtain overlapping elements.This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram.Then,a“component-target”network diagram was constructed using screened drug components and target information,via Cytoscape(Institute for Systems Biology,Seattle,WA,USA).The database for annotation,visualization,and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses.Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.RESULTS:Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory,apoptosis,and nuclear factor kappa B(NF-κB)signaling pathways.Berberine(BBR),one of the main components of HLD,inhibited the development of MT in mice.BBR reduced cell viability while increasing B-cell lymphoma 2(Bcl-2)protein expression and decreasing CD86,NF-κB,Bax,and Caspase-3 protein expression in brain vascular 2(BV2)mcroglia cells treated with morphine.Additionally,BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.CONCLUSIONS:BBR,a key component of HLD,effectively suppressed microglial activation and neuroinflammation by regulating the NF-κB and apoptosis signaling pathways,thereby delaying MT.This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.展开更多
Objective: Postoperative pain (POP) following abdominal surgery can vary from a few hours to several days. This acute, unrelieved pain can become chronic, requiring patients to take analgesics on an almost daily basis...Objective: Postoperative pain (POP) following abdominal surgery can vary from a few hours to several days. This acute, unrelieved pain can become chronic, requiring patients to take analgesics on an almost daily basis for comfort. Analgesia using general opioids has many side effects and intrathecal morphine is a good alternative. This study was conducted to evaluate the efficacy of intrathecal morphine (ITM) versus conventional analgesia in the management of postoperative pain in colectomy performed by laparoscopic surgery. Methods: Cohort study conducted at the Hôpital Nord in Marseille, from 01 January to 31 July 2021 in patients aged at least 18 years undergoing anaesthesia for scheduled colectomy by laparoscopic surgery. The primary endpoint was postoperative pain intensity and the secondary endpoints were morphine consumption, treatment side effects and length of hospital stay. Statistical analysis was performed using XLSTAT software. Results: We included 193 patients: 131 in the control group (conventional analgesia) and 62 in the ITM group. We observed: a significant decrease in pain (assessed by numerical scale) in favour of the ITM group in the post-anaesthetic care room, i.e. 3 (±4) vs 1 (±2), p 0 and H2: 2 (±2) vs. 1 (±2);p Conclusion: These results suggest that intrathecal morphine (ITM) in laparoscopic colectomy provides effective postoperative analgesia with low morphine consumption, and a reduction in morphine side-effects compared with conventional analgesia.展开更多
Introduction: Ambulatory surgery requires effective analgesia with few side effects to allow a return home on the day of surgery. The aim of the study was to compare the efficacy of intrathecal morphine (Ram) and erec...Introduction: Ambulatory surgery requires effective analgesia with few side effects to allow a return home on the day of surgery. The aim of the study was to compare the efficacy of intrathecal morphine (Ram) and erector spinae plane block (ESP) in outpatient abdominal wall surgery. Methodology: Thirty-six patients were randomized into two groups. The ESP group (n = 23) benefited from the ESP block with bupivacaine 5% (20 ml) followed by spinal anesthesia with bupivacaine (7.5 mg) and sufenta (2.5 µg). The Ram group (n = 13) benefited from spinal anesthesia with bupivacaine (7.5 mg), sufenta (2.5 µg) and morphine (100 µg). The primary endpoint was whether or not to return home on the day of surgery. The secondary endpoint was the pain score by the visual analog scale (VAS) in the post-intervention monitoring room (SSPI). After 2 hours (H2) and one day (D1) after surgery, the morphine consumption in the immediate postoperative period (mg) and the undesirable effects. Results: Inguinal hernia surgery predominated (n = 30). No difference in age (45.05 vs 50.7;p = 0.4), ASA score (1.43 vs 1.53;p = 0.57). All patients (n = 36) returned home on the day of surgery. No difference in postoperative pain in SSPI (p = 0.6), 2 hours after surgery (p = 0.40) and the day after surgery (p = 0.6). Postoperative morphine consumption was identical (0.9 mg vs 0.2 mg, p = 0.2). There were 2 urinary retentions in the Ram group. Conclusion: The erector spinae plane block and intrathecal morphine are well tolerated and perfectly compatible with the requirements of outpatient abdominal wall surgery.展开更多
To examine whether there are sex differences in morphine dependence and its metabolism. Naloxone-precipitated withdrawal study was performed. Twenty rats were induced by naloxone 1 h after a single dose of morphine in...To examine whether there are sex differences in morphine dependence and its metabolism. Naloxone-precipitated withdrawal study was performed. Twenty rats were induced by naloxone 1 h after a single dose of morphine injection. The withdrawal syndromes were recorded and an HPLC-UV method was set up to quantify the plasma levels of morphine and morphine-3-glucuronide（M3G）. In the spontaneous withdrawal study, 97 rats were treated with progressive morphine for 28 d to develop physical dependence. The spontaneous withdrawal syndromes were recorded and plasma levels of morphine and M3G were determined after the last injection. No significant differences were observed in withdrawal syndrome of naloxone precipitating. More severe spontaneous withdrawal syndromes were produced by chronic morphine injection in male rats than in female rats（P0.05）. Higher maximum plasma concentration（Cmax） of morphine was measured in male rats than female rats, while female rats had higher Cmax of M3G than male rats in both acute and chronic morphine administration. Our results indicated that sex differences existed in withdrawal syndrome of morphine-dependent rats, and the pharmacokinetics of morphine showed sex difference by both acute and chronic administration. There might be a relationship between the severity of withdrawal syndrome and the plasma concentrations of morphine, M3G, and the ratio of morphine to M3G（M3G/MOR）.展开更多
The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg)...The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg) and immediate release tablets (IRMS, 20 mg). The plasma concentration of morphine was determined by GC MS. The pharmacokinetic parameters of controlled release tablets and immediate release tablets were calculated∶ C max was 19.38±3.80 and 21.27±6.21 ng/ml, t max was 2.36 ±0.37 h and 0.56±0.16 h, t 1/2β was 3.53±0.87 and 3.03±0.74 h, AUC was 145.15±17.65 and 93.08±16.65 ng/ml, respectively. The steady state plasma concentration of morphine sulphate in cancer patients after multiple doses was achieved, C max of CRMS and IRMS was 27.43±0.33 ng/ml and 22.68±0.16 ng/ml, C min of CRMS and IRMS was 19.45±1.44 ng/ml and 18.14±0.49 ng/ml, respectively.展开更多
To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug...To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulation was suspended for 5 d. On day 9, a challenge dose of morphine （10 mg/kg） was given and the locomotor activity was measured for 60 rain to confkrm the establishment of behavioral sensitization in mice. Moreover, 5-hydroxytryptophan （5-HTP）, a precursor of serotonin, at the doses of 20-80 mg/kg was given i.p. in combination with daily morphine treatment （induction）, during the morphine treatment suspension （transfer） or prior to the challenge dose of morphine （expression） and locomotor activity was measured on day 9 after the challenge dose of morphine. Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice. 5-HTP treatment selec- tively and dose-dependently blocked the induction, but not the transfer nor the expression of morphine induced behavioral sensitization. This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.展开更多
In the present study, the efficacy and safety of oxycodone and morphine in the treatment of cancer pain were compared in a meta-analysis with the goal of providing a reference for drug selection in clinical practice. ...In the present study, the efficacy and safety of oxycodone and morphine in the treatment of cancer pain were compared in a meta-analysis with the goal of providing a reference for drug selection in clinical practice. Electronic literature databases were searched for articles published through February 2015, including PubMed, MEDLINE, the Cochrane library, and Embase; and the China National Knowledge Intemet, VIP Databases and Wanfang Databases for studies published in Chinese. Only randomized controlled trials were selected. The primary outcome measures were efficacy and the incidence of adverse drug reactions （ADRs）. Data were extracted from the studies by two independent reviewers. A total of 15 studies containing 1338 patients were included in the analysis. The studies were divided into two subgroups according to different scoring methods. The pain relief efficacies of oxycodone and morphine were rated by the numerical rating scale （NRS） （risk ratio [RR]： 1.04; 95% confidence interval [CI]： 0.97-1.11）. Others were rated by the visual analog scale （VAS） （RR： 1.03; 95% CI： 0.97-1.10）. Five studies showed that pain intensity scores did not significantly differ between oxycodone and morphine treatments （standard mean difference [SMD] = 0.16, 95% CI： -0.01-0.33, P = 0.06）. Regarding ADRs, the incidence of constipation was lower in the oxycodone group （RR： 0.70; 95% CI： 0.58-0.85）. No statistical difference was observed among other ADRs. The efficacies of oxycodone and morphine were similar in treating cancer pain. However, the incidence of constipation was lower in patients treated with oxycodone.展开更多
Opiate dependence has become one of the most urgent problems of modernsociety. Opiate dependence involves physical and psychical dependence. Although many addicts can bedetoxified, the relapse ratio of 95% in 5 a demo...Opiate dependence has become one of the most urgent problems of modernsociety. Opiate dependence involves physical and psychical dependence. Although many addicts can bedetoxified, the relapse ratio of 95% in 5 a demonstrates that opiate psychical dependence is aproblem more troublesome. It has been reported that acute and chronic administration of L- NNA canmarkedly retard the development of tolerance to physical dependence on morphine, and suppress theabstinence syndromes precipitated by naloxone in opiate dependent rodents, and even reverse theexisting morphine tolerance. However, the effect of L-NNA on the positive reinforcement ofpsychically active substances and its possible mechanism have not yet been reported. In presentstudy, the effect of L- NNA en the psychical dependence induced by opiates was evaluated on thebasis of conditioned place preference.展开更多
This review provides a short account of carbohydrate derivatives of an important natural drug,morphine,along with their comparative efficacies as anesthetic agent.Sugar derivatives are found to have more prospect as a...This review provides a short account of carbohydrate derivatives of an important natural drug,morphine,along with their comparative efficacies as anesthetic agent.Sugar derivatives are found to have more prospect as anesthetic drug than morphine itself owing to their enhanced bioavailability.Synthetic schemes of these sugar derivatives and information on related patents are also included in this manuscript.展开更多
Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine ca...Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine can be explained in terms of pharmacodynamics and pharmacokinetics, genetic polymorphisms also play an important role. However, the genetic basis of different sensitivity and tolerance susceptibility to morphine remains ambiguous. Using 15 strains of inbred Genetic Diversity(GD) mice,a new resource with wide genetic and phenotypic variation, we demonstrated great variance in sensitivity to morphine analgesia and susceptibility to morphine tolerance between different GD strains. Among-i ndividual variance in response to morphine analgesia in the population can be modeled in GD mice. Two loci respectively may be associated with the among-i ndividual variance in morphine sensitivity and tolerance,confirming the role of genetic factors in among-i ndividual different responses to morphine. These results indicate that GD mice may be a potential tool for the identification of new biomarkers to improve the clinical administration of morphine.展开更多
The interaction of morphine and cholinergic system was shown in previous studies. In the present study, we investigated whether morphine would interact with the cholinergic antagonists, scopolamine and atropine in a Y...The interaction of morphine and cholinergic system was shown in previous studies. In the present study, we investigated whether morphine would interact with the cholinergic antagonists, scopolamine and atropine in a Y-maze spatial recognition memory. Pre-test treatments of morphine （5, 1.5, 0.5 mg/kg）, scopolamine （1, 0.1 mg/kg）, atropine （0.5, 0.1 mg/kg） were used in the experiments, relatively high or low doses were paired respectively as co-administration measures. The results showed that co-administration of morphine 0.Smg/kg ~ scopolamine 0.1 mg/kg and morphine 0.5 mg/kg ＋ atropine 0.1 mg/kg disturbed the inspective exploratory behavior （percent of arm duration） but not the inquisitive behavior （percent of arm visits） of the spatial memory retrieval, while the drugs didn＇t cause amnesia when single administered of the concerned low doses. Distinct interaction was found between scopolamine and morphine on increasing locomotor activity.展开更多
AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The eff...AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry.A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group,isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually.RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95±7.49 mmHg to 5.92±4.04 mmHg (P＜0.05) evidently after application of PTN. BPOS increased from 7.37±5.58mmHg to 16.60±13.87 mmHg, SOCA increased from 54.09±38.37 mmHg to 100.70±43.51 mmHg, SOF increased from 7.15±3.20 mmHg to 10.38±2.93 mmHg and CBDP increased 3.75±1.95 mmHg to 10.49±8.21 mmHg (P＜0.01)evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN,SOCA and SOF decreased separately from 100.64±44.99mmHg to 66.17±35.88 mmHg and from 10.70±2.76 mmHg to 9.04±1.71 mmHg (P＜0.05) markedly.CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant.展开更多
Nuclear factor kappa B（NF-κB） in the spinal cord is involved in pro-infl ammatory cytokine-mediated pain facilitation. However, the role of NF-κB activation in chronic morphine-induced analgesic tolerance and the ...Nuclear factor kappa B（NF-κB） in the spinal cord is involved in pro-infl ammatory cytokine-mediated pain facilitation. However, the role of NF-κB activation in chronic morphine-induced analgesic tolerance and the underlying mechanisms remain unclear. In the present study, we found that the level of phosphorylated NF-κB p65（p-p65） was increased in the dorsal horn of the lumbar 4–6 segments after intrathecal administration of morphine for 7 consecutive days, and the p-p65 was co-localized with neurons and astrocytes. The expression of TNF-α and IL-1β was also increased in the same area. In addition, pretreatment with pyrrolidinedithiocarbamate（PDTC） or SN50, inhibitors of NF-κB, prevented the development of morphine analgesic tolerance and alleviated morphine withdrawal-induced allodynia and hyperalgesia. The increase in TNF-α and IL-1β expression induced by chronic morphine exposure was also partially blocked by PDTC pretreatment. In another experiment, rats receiving PDTC or SN50 beginning on day 7 of morphine injection showed partial recovery of the anti-nociceptive effects of morphine and attenuation of the withdrawal-induced abnormal pain. Meanwhile, intrathecal pretreatment with lipopolysaccharide from Rhodobacter sphae-roides, an antagonist of toll-like receptor 4（TLR4）, blocked the activation of NF-κB, and prevented the development of morphine tolerance and withdrawal-induced abnormal pain. These data indicated that TLR4-mediated NF-κB activation in the spinal cord is involved in the development and maintenance of morphine analgesic tolerance and withdrawalinduced pain hypersensitivity.展开更多
Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place ...Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas. Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve acti-vation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.展开更多
OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and the antagonism of anticholinergic agents against morphine. METHODS: The action of these drugs on the sphincter of Oddi (SO) wa...OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and the antagonism of anticholinergic agents against morphine. METHODS: The action of these drugs on the sphincter of Oddi (SO) was evaluated by means of choledochofiberscopy manometry in 40 operated patients with T-tube. The patients were divided randomly into 4 groups: anisodamine, atropine, buscopan, and control. The following data were recorded: duodenal pressure (DP), basal pressure of the sphincter of Oddi (BPSO), contractive amplitude of the sphincter of Oddi (CASO), contractive frequency of the sphincter of Oddi (CFSO), contractive duration of the sphincter of Oddi (CDSO), and pressure of the common bile duct (PCBD). Both morphine and anticholinergic agents were given intramuscularly. RESULTS: After injection of 10 mg morphine, BPSO, CASO, CFSO, and PCBD increased significantly. After injection of 15 mg anisodamine or 0.75 mg atropine, CASO, BPSO declined obviously, and after injection of 20 mg buscopan, CASO, BPSO, CFSO declined obviously, but in anisodamine, atropine and buscopan groups, they differed insignificantly. CONCLUSIONS: The results illustrate that SO manometry via choledochofiberscopy is a new method for SO dynamic study. Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine and buscopan can antagonize the effect of morphine.展开更多
Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In...Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats(200-250 g) were used in 5 experimental groups: 1) non morphine treat rats(control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid(i.p., for 21 d); 3) morphine treated rats(10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression(P<0.01 and P<0.001, respectively) in brain VTA as well as serum level of BDNF(P<0.01) in comparison to control group. Treatment with 25 mg/kg crocin carotenoid caused a significant enhancement in BDNF and CREF gene expression(P<0.01 and P<0.05, respectively) and serum level of BDNF(P<0.01) in morphine-treated rats in comparison to morphine-treated group. Conclusions: Regarding to obtained results, crocin carotenoid can inhibit unfavorable effects of morphine on the neural system to some extent through enhancing BDNF and CREB gene expression in brain VTA and serum level of BDNF.展开更多
Summary： Morphine has been reported to suppress human immune response. We aimed to observe the effects of morphine, fentanyl and tramadol on NF- K B and IL-2 from both laboratory and clinical perspective. Jurkat cell...Summary： Morphine has been reported to suppress human immune response. We aimed to observe the effects of morphine, fentanyl and tramadol on NF- K B and IL-2 from both laboratory and clinical perspective. Jurkat cells were incubated with ten times clinically relevant concentrations of morphine, fentanyl and tramadol before being stimulated with PMA. NF- κB binding activity and IL-2 levels were measured, In the clinical study, 150 consenting patients were randomized into 3 groups according to the analgesics used in them, namely, group morphine （M）, group fentanyl （F） and group tramadol （T）. IL-2 was measured preoperatively and 1, 3 and 24 h after operation. Consequently, NF-κB activation was suppressed by morphine and fentanyl but not by tramadol. IL-2 was significantly decreased by morphine and fentanyl but not by tramadol in vitro. In the PCA patients, IL-2 was decreased in group M and increased in group F postoperatively. Whereas in group T, IL-2 was unchanged 1 h after operation but was significantly elevated 3 and 24 h after operation. Our results showed that the inhibition of morphine on IL-2 was most probably related to its suppression on NF-κB, Fentanyl had different effects on human immune response in vitro and in vivo. Tramadol may have immune enhancing effect.展开更多
AIM To study the antagonism of cholecystokinin octapeptide (CCK 8) against effect of morphine and its mechanism. METHODS The electrical and mechanical activities of rat duodenum in vitro were recorded simultan...AIM To study the antagonism of cholecystokinin octapeptide (CCK 8) against effect of morphine and its mechanism. METHODS The electrical and mechanical activities of rat duodenum in vitro were recorded simultaneously. RESULTS Acetylcholine (ACh) could increase the amplitude and the number of the spike potential (SPA and SPN) of rat duodenum in vitro , followed by the increase of the duodenal contraction amplitudes (CA), showing a positive correlation. Morphine, on the contrary, inhibited the potentiation of ACh, showing a negative correlation. CCK 8 could antagonize the effects of morphine, i.e. SPA and SPN were increased again, followed by the increase of CA. CCK A receptor antagonist Devazepide could reverse the antagonism of CCK 8 to the effect of morphine. CONCLUSION CCK 8 could antagonize the effect of morphine which inhibited the potentiation of ACh on the duodenal activities in vitro . The antagonistic effect of CCK 8 on morphine was mainly mediated by CCK A receptor.展开更多
Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to m...Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning. Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.展开更多
文摘Postoperative pain is an acute pain that appears due to the surgical act, reaching its maximum intensity in the first 24 - 48 hours after surgery. Postoperative pain control reduces possible postoperative complications, as well as the patient’s stay in the medical institution. Objective: This study compared the effectiveness and side effects of oral transmucosal fentanyl citrate (OTFC) with IV morphine in the control of postoperative pain. Methods: Seventy-three patients (Fentanyl group: 27, morphine group: 46) were included. Changes in pain were evaluated with Visual Analog Scale (VAS) and Pain Relief Scale, Pain Intensity Differences (PID), Sum of Pain Intensity Differences (SPID), and Total Pain Relief (TOTPAR). At time zero, 15, 30, 45 min and 1, 2, 3, 4, 5 and 6 h. Results: The decrease in pain intensity measured by VAS was similar in both groups with no significant differences at any of the measurement points. Both products produced a significant increase in the Pain Relief scale, with no differences between groups at any of the measurement times. There were no differences between groups when comparing PID. Comparing SPID between groups, there were no differences at 15, 30 minutes, then there were significant differences in favor of the Fentanyl group up to 6 hours. Both products produced a significant increase in the TOPAR scale, with no differences between groups at any of the measurement times. The appearance of adverse effects was similar in both groups. Conclusions: Both products produced a significant reduction in the measures of pain intensity (VAS), increase of SPID, as well as a significant increase in the Pain Relief scale, a significant increase in the TOPAR scale, with no differences between the groups. The number of adverse effects was similar. The convenience of OTFC administration allows its administration without the special conditions needed for the administration of IV morphine.
基金Natural Science Foundation-funded Project:Study on the Mechanism of Mechanical Stress Sensing Element Piezo Type Mechanosensitive Ion Channel Component 2 Interacting with Nuclear Receptor Subfamily 4 Group A Member 2 Mediating Traumatic Brain Injury(No.82172190)。
文摘OBJECTIVE:To investigate the mechanism underlying the effect of the Huanglian decoction(黄连汤,HLD)on morphine tolerance(MT),using network pharmacology,and to verify these mechanisms in vitro and in vivo.METHODS:Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target proteins of MT were retrieved from the GeneCards,PharmGkb,Therapeutic Target Database,DrugBank,and Online Mendelian Inheritance in Man databases.Information regarding MT and the drug targets was compared to obtain overlapping elements.This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram.Then,a“component-target”network diagram was constructed using screened drug components and target information,via Cytoscape(Institute for Systems Biology,Seattle,WA,USA).The database for annotation,visualization,and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses.Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.RESULTS:Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory,apoptosis,and nuclear factor kappa B(NF-κB)signaling pathways.Berberine(BBR),one of the main components of HLD,inhibited the development of MT in mice.BBR reduced cell viability while increasing B-cell lymphoma 2(Bcl-2)protein expression and decreasing CD86,NF-κB,Bax,and Caspase-3 protein expression in brain vascular 2(BV2)mcroglia cells treated with morphine.Additionally,BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.CONCLUSIONS:BBR,a key component of HLD,effectively suppressed microglial activation and neuroinflammation by regulating the NF-κB and apoptosis signaling pathways,thereby delaying MT.This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.
文摘Objective: Postoperative pain (POP) following abdominal surgery can vary from a few hours to several days. This acute, unrelieved pain can become chronic, requiring patients to take analgesics on an almost daily basis for comfort. Analgesia using general opioids has many side effects and intrathecal morphine is a good alternative. This study was conducted to evaluate the efficacy of intrathecal morphine (ITM) versus conventional analgesia in the management of postoperative pain in colectomy performed by laparoscopic surgery. Methods: Cohort study conducted at the Hôpital Nord in Marseille, from 01 January to 31 July 2021 in patients aged at least 18 years undergoing anaesthesia for scheduled colectomy by laparoscopic surgery. The primary endpoint was postoperative pain intensity and the secondary endpoints were morphine consumption, treatment side effects and length of hospital stay. Statistical analysis was performed using XLSTAT software. Results: We included 193 patients: 131 in the control group (conventional analgesia) and 62 in the ITM group. We observed: a significant decrease in pain (assessed by numerical scale) in favour of the ITM group in the post-anaesthetic care room, i.e. 3 (±4) vs 1 (±2), p 0 and H2: 2 (±2) vs. 1 (±2);p Conclusion: These results suggest that intrathecal morphine (ITM) in laparoscopic colectomy provides effective postoperative analgesia with low morphine consumption, and a reduction in morphine side-effects compared with conventional analgesia.
文摘Introduction: Ambulatory surgery requires effective analgesia with few side effects to allow a return home on the day of surgery. The aim of the study was to compare the efficacy of intrathecal morphine (Ram) and erector spinae plane block (ESP) in outpatient abdominal wall surgery. Methodology: Thirty-six patients were randomized into two groups. The ESP group (n = 23) benefited from the ESP block with bupivacaine 5% (20 ml) followed by spinal anesthesia with bupivacaine (7.5 mg) and sufenta (2.5 µg). The Ram group (n = 13) benefited from spinal anesthesia with bupivacaine (7.5 mg), sufenta (2.5 µg) and morphine (100 µg). The primary endpoint was whether or not to return home on the day of surgery. The secondary endpoint was the pain score by the visual analog scale (VAS) in the post-intervention monitoring room (SSPI). After 2 hours (H2) and one day (D1) after surgery, the morphine consumption in the immediate postoperative period (mg) and the undesirable effects. Results: Inguinal hernia surgery predominated (n = 30). No difference in age (45.05 vs 50.7;p = 0.4), ASA score (1.43 vs 1.53;p = 0.57). All patients (n = 36) returned home on the day of surgery. No difference in postoperative pain in SSPI (p = 0.6), 2 hours after surgery (p = 0.40) and the day after surgery (p = 0.6). Postoperative morphine consumption was identical (0.9 mg vs 0.2 mg, p = 0.2). There were 2 urinary retentions in the Ram group. Conclusion: The erector spinae plane block and intrathecal morphine are well tolerated and perfectly compatible with the requirements of outpatient abdominal wall surgery.
基金National Science and Technology Support Program of China(Grant No.2008BAI49B01)the National Basic Research Program of China(Grant No.2009CB522000)
文摘To examine whether there are sex differences in morphine dependence and its metabolism. Naloxone-precipitated withdrawal study was performed. Twenty rats were induced by naloxone 1 h after a single dose of morphine injection. The withdrawal syndromes were recorded and an HPLC-UV method was set up to quantify the plasma levels of morphine and morphine-3-glucuronide（M3G）. In the spontaneous withdrawal study, 97 rats were treated with progressive morphine for 28 d to develop physical dependence. The spontaneous withdrawal syndromes were recorded and plasma levels of morphine and M3G were determined after the last injection. No significant differences were observed in withdrawal syndrome of naloxone precipitating. More severe spontaneous withdrawal syndromes were produced by chronic morphine injection in male rats than in female rats（P0.05）. Higher maximum plasma concentration（Cmax） of morphine was measured in male rats than female rats, while female rats had higher Cmax of M3G than male rats in both acute and chronic morphine administration. Our results indicated that sex differences existed in withdrawal syndrome of morphine-dependent rats, and the pharmacokinetics of morphine showed sex difference by both acute and chronic administration. There might be a relationship between the severity of withdrawal syndrome and the plasma concentrations of morphine, M3G, and the ratio of morphine to M3G（M3G/MOR）.
文摘The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg) and immediate release tablets (IRMS, 20 mg). The plasma concentration of morphine was determined by GC MS. The pharmacokinetic parameters of controlled release tablets and immediate release tablets were calculated∶ C max was 19.38±3.80 and 21.27±6.21 ng/ml, t max was 2.36 ±0.37 h and 0.56±0.16 h, t 1/2β was 3.53±0.87 and 3.03±0.74 h, AUC was 145.15±17.65 and 93.08±16.65 ng/ml, respectively. The steady state plasma concentration of morphine sulphate in cancer patients after multiple doses was achieved, C max of CRMS and IRMS was 27.43±0.33 ng/ml and 22.68±0.16 ng/ml, C min of CRMS and IRMS was 19.45±1.44 ng/ml and 18.14±0.49 ng/ml, respectively.
基金National Natural Science Foundation of China (Grant No. 30570653)National Basic Research Program of China (Grant No. 2003CB515400)985 Program of China Ministry of Education
文摘To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulation was suspended for 5 d. On day 9, a challenge dose of morphine （10 mg/kg） was given and the locomotor activity was measured for 60 rain to confkrm the establishment of behavioral sensitization in mice. Moreover, 5-hydroxytryptophan （5-HTP）, a precursor of serotonin, at the doses of 20-80 mg/kg was given i.p. in combination with daily morphine treatment （induction）, during the morphine treatment suspension （transfer） or prior to the challenge dose of morphine （expression） and locomotor activity was measured on day 9 after the challenge dose of morphine. Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice. 5-HTP treatment selec- tively and dose-dependently blocked the induction, but not the transfer nor the expression of morphine induced behavioral sensitization. This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.
基金Evaluation of Safe and Rational Medication and Study and Application of Interventional Technology(Grant No.2013BAI06B04)
文摘In the present study, the efficacy and safety of oxycodone and morphine in the treatment of cancer pain were compared in a meta-analysis with the goal of providing a reference for drug selection in clinical practice. Electronic literature databases were searched for articles published through February 2015, including PubMed, MEDLINE, the Cochrane library, and Embase; and the China National Knowledge Intemet, VIP Databases and Wanfang Databases for studies published in Chinese. Only randomized controlled trials were selected. The primary outcome measures were efficacy and the incidence of adverse drug reactions （ADRs）. Data were extracted from the studies by two independent reviewers. A total of 15 studies containing 1338 patients were included in the analysis. The studies were divided into two subgroups according to different scoring methods. The pain relief efficacies of oxycodone and morphine were rated by the numerical rating scale （NRS） （risk ratio [RR]： 1.04; 95% confidence interval [CI]： 0.97-1.11）. Others were rated by the visual analog scale （VAS） （RR： 1.03; 95% CI： 0.97-1.10）. Five studies showed that pain intensity scores did not significantly differ between oxycodone and morphine treatments （standard mean difference [SMD] = 0.16, 95% CI： -0.01-0.33, P = 0.06）. Regarding ADRs, the incidence of constipation was lower in the oxycodone group （RR： 0.70; 95% CI： 0.58-0.85）. No statistical difference was observed among other ADRs. The efficacies of oxycodone and morphine were similar in treating cancer pain. However, the incidence of constipation was lower in patients treated with oxycodone.
基金ThisprojectwassupportedbyGrantofthePLALaboratoryforNewDrugEvaluation (No .96-0 2 )
文摘Opiate dependence has become one of the most urgent problems of modernsociety. Opiate dependence involves physical and psychical dependence. Although many addicts can bedetoxified, the relapse ratio of 95% in 5 a demonstrates that opiate psychical dependence is aproblem more troublesome. It has been reported that acute and chronic administration of L- NNA canmarkedly retard the development of tolerance to physical dependence on morphine, and suppress theabstinence syndromes precipitated by naloxone in opiate dependent rodents, and even reverse theexisting morphine tolerance. However, the effect of L-NNA on the positive reinforcement ofpsychically active substances and its possible mechanism have not yet been reported. In presentstudy, the effect of L- NNA en the psychical dependence induced by opiates was evaluated on thebasis of conditioned place preference.
文摘This review provides a short account of carbohydrate derivatives of an important natural drug,morphine,along with their comparative efficacies as anesthetic agent.Sugar derivatives are found to have more prospect as anesthetic drug than morphine itself owing to their enhanced bioavailability.Synthetic schemes of these sugar derivatives and information on related patents are also included in this manuscript.
基金supported by the National Key R&D Program of China (2017YFA0105204)National Natural Science Foundation of China (81873963)Fundamental Research Funds of Chinese Academy of Medical Sciences (2016ZX310044)。
文摘Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine can be explained in terms of pharmacodynamics and pharmacokinetics, genetic polymorphisms also play an important role. However, the genetic basis of different sensitivity and tolerance susceptibility to morphine remains ambiguous. Using 15 strains of inbred Genetic Diversity(GD) mice,a new resource with wide genetic and phenotypic variation, we demonstrated great variance in sensitivity to morphine analgesia and susceptibility to morphine tolerance between different GD strains. Among-i ndividual variance in response to morphine analgesia in the population can be modeled in GD mice. Two loci respectively may be associated with the among-i ndividual variance in morphine sensitivity and tolerance,confirming the role of genetic factors in among-i ndividual different responses to morphine. These results indicate that GD mice may be a potential tool for the identification of new biomarkers to improve the clinical administration of morphine.
基金National Natural Science Foundation of China(3077070030470553)~~
文摘The interaction of morphine and cholinergic system was shown in previous studies. In the present study, we investigated whether morphine would interact with the cholinergic antagonists, scopolamine and atropine in a Y-maze spatial recognition memory. Pre-test treatments of morphine （5, 1.5, 0.5 mg/kg）, scopolamine （1, 0.1 mg/kg）, atropine （0.5, 0.1 mg/kg） were used in the experiments, relatively high or low doses were paired respectively as co-administration measures. The results showed that co-administration of morphine 0.Smg/kg ~ scopolamine 0.1 mg/kg and morphine 0.5 mg/kg ＋ atropine 0.1 mg/kg disturbed the inspective exploratory behavior （percent of arm duration） but not the inquisitive behavior （percent of arm visits） of the spatial memory retrieval, while the drugs didn＇t cause amnesia when single administered of the concerned low doses. Distinct interaction was found between scopolamine and morphine on increasing locomotor activity.
文摘AIM: To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility.METHODS: The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry.A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group,isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually.RESULTS: BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95±7.49 mmHg to 5.92±4.04 mmHg (P＜0.05) evidently after application of PTN. BPOS increased from 7.37±5.58mmHg to 16.60±13.87 mmHg, SOCA increased from 54.09±38.37 mmHg to 100.70±43.51 mmHg, SOF increased from 7.15±3.20 mmHg to 10.38±2.93 mmHg and CBDP increased 3.75±1.95 mmHg to 10.49±8.21 mmHg (P＜0.01)evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN,SOCA and SOF decreased separately from 100.64±44.99mmHg to 66.17±35.88 mmHg and from 10.70±2.76 mmHg to 9.04±1.71 mmHg (P＜0.05) markedly.CONCLUSION: The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant.
基金supported by grants from the National Natural Science Foundation of China (31171070 and 81171060)
文摘Nuclear factor kappa B（NF-κB） in the spinal cord is involved in pro-infl ammatory cytokine-mediated pain facilitation. However, the role of NF-κB activation in chronic morphine-induced analgesic tolerance and the underlying mechanisms remain unclear. In the present study, we found that the level of phosphorylated NF-κB p65（p-p65） was increased in the dorsal horn of the lumbar 4–6 segments after intrathecal administration of morphine for 7 consecutive days, and the p-p65 was co-localized with neurons and astrocytes. The expression of TNF-α and IL-1β was also increased in the same area. In addition, pretreatment with pyrrolidinedithiocarbamate（PDTC） or SN50, inhibitors of NF-κB, prevented the development of morphine analgesic tolerance and alleviated morphine withdrawal-induced allodynia and hyperalgesia. The increase in TNF-α and IL-1β expression induced by chronic morphine exposure was also partially blocked by PDTC pretreatment. In another experiment, rats receiving PDTC or SN50 beginning on day 7 of morphine injection showed partial recovery of the anti-nociceptive effects of morphine and attenuation of the withdrawal-induced abnormal pain. Meanwhile, intrathecal pretreatment with lipopolysaccharide from Rhodobacter sphae-roides, an antagonist of toll-like receptor 4（TLR4）, blocked the activation of NF-κB, and prevented the development of morphine tolerance and withdrawal-induced abnormal pain. These data indicated that TLR4-mediated NF-κB activation in the spinal cord is involved in the development and maintenance of morphine analgesic tolerance and withdrawalinduced pain hypersensitivity.
文摘Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas. Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve acti-vation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.
文摘OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and the antagonism of anticholinergic agents against morphine. METHODS: The action of these drugs on the sphincter of Oddi (SO) was evaluated by means of choledochofiberscopy manometry in 40 operated patients with T-tube. The patients were divided randomly into 4 groups: anisodamine, atropine, buscopan, and control. The following data were recorded: duodenal pressure (DP), basal pressure of the sphincter of Oddi (BPSO), contractive amplitude of the sphincter of Oddi (CASO), contractive frequency of the sphincter of Oddi (CFSO), contractive duration of the sphincter of Oddi (CDSO), and pressure of the common bile duct (PCBD). Both morphine and anticholinergic agents were given intramuscularly. RESULTS: After injection of 10 mg morphine, BPSO, CASO, CFSO, and PCBD increased significantly. After injection of 15 mg anisodamine or 0.75 mg atropine, CASO, BPSO declined obviously, and after injection of 20 mg buscopan, CASO, BPSO, CFSO declined obviously, but in anisodamine, atropine and buscopan groups, they differed insignificantly. CONCLUSIONS: The results illustrate that SO manometry via choledochofiberscopy is a new method for SO dynamic study. Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine and buscopan can antagonize the effect of morphine.
基金supported by a grant from the Rafsanjan University of Medical Sciences(20/341/1395)
文摘Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats(200-250 g) were used in 5 experimental groups: 1) non morphine treat rats(control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid(i.p., for 21 d); 3) morphine treated rats(10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression(P<0.01 and P<0.001, respectively) in brain VTA as well as serum level of BDNF(P<0.01) in comparison to control group. Treatment with 25 mg/kg crocin carotenoid caused a significant enhancement in BDNF and CREF gene expression(P<0.01 and P<0.05, respectively) and serum level of BDNF(P<0.01) in morphine-treated rats in comparison to morphine-treated group. Conclusions: Regarding to obtained results, crocin carotenoid can inhibit unfavorable effects of morphine on the neural system to some extent through enhancing BDNF and CREB gene expression in brain VTA and serum level of BDNF.
文摘Summary： Morphine has been reported to suppress human immune response. We aimed to observe the effects of morphine, fentanyl and tramadol on NF- K B and IL-2 from both laboratory and clinical perspective. Jurkat cells were incubated with ten times clinically relevant concentrations of morphine, fentanyl and tramadol before being stimulated with PMA. NF- κB binding activity and IL-2 levels were measured, In the clinical study, 150 consenting patients were randomized into 3 groups according to the analgesics used in them, namely, group morphine （M）, group fentanyl （F） and group tramadol （T）. IL-2 was measured preoperatively and 1, 3 and 24 h after operation. Consequently, NF-κB activation was suppressed by morphine and fentanyl but not by tramadol. IL-2 was significantly decreased by morphine and fentanyl but not by tramadol in vitro. In the PCA patients, IL-2 was decreased in group M and increased in group F postoperatively. Whereas in group T, IL-2 was unchanged 1 h after operation but was significantly elevated 3 and 24 h after operation. Our results showed that the inhibition of morphine on IL-2 was most probably related to its suppression on NF-κB, Fentanyl had different effects on human immune response in vitro and in vivo. Tramadol may have immune enhancing effect.
文摘AIM To study the antagonism of cholecystokinin octapeptide (CCK 8) against effect of morphine and its mechanism. METHODS The electrical and mechanical activities of rat duodenum in vitro were recorded simultaneously. RESULTS Acetylcholine (ACh) could increase the amplitude and the number of the spike potential (SPA and SPN) of rat duodenum in vitro , followed by the increase of the duodenal contraction amplitudes (CA), showing a positive correlation. Morphine, on the contrary, inhibited the potentiation of ACh, showing a negative correlation. CCK 8 could antagonize the effects of morphine, i.e. SPA and SPN were increased again, followed by the increase of CA. CCK A receptor antagonist Devazepide could reverse the antagonism of CCK 8 to the effect of morphine. CONCLUSION CCK 8 could antagonize the effect of morphine which inhibited the potentiation of ACh on the duodenal activities in vitro . The antagonistic effect of CCK 8 on morphine was mainly mediated by CCK A receptor.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30470549）the National Basic Research Priorities Programme （973） of China （No.2006CBS00800）
文摘Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning. Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.
