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
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
Objective To investigate the influence of dopamine （DA） and DA receptor＇s antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influen...Objective To investigate the influence of dopamine （DA） and DA receptor＇s antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influence of DA on the electric activity of the pain-excited neuron （PEN） in the caudate nucleus （Cd） of normal rats or morphinistic rats was recorded after the sciatic nerve was noxiously stimulated. Results DA shortened the average latency of the evoked discharge of PEN in the Cd of normal rats, indicating that DA could increase the activity of PEN and pain sensitivity in normal rats. This effect could be inhibited by Droperidol. DA increased the average latency of the evoked discharge of PEN in the Cd of morphinistic rats, indicating that DA could inhibit the activity of PEN and pain sensitivity in morphinistic rats. Conclusion The responses to painful stimulation were completely opposite between normal rats and morphinistic rats after the intracerebroventricular injection of DA.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
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
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
Objective To examine the effect of acetylcholine（ACh）on the electric activities of pain-excitation neurons （PEN）and pain-inhibitation neurons（PIN）in the hippocampal CA1 area of normal rats or morphinistic rats,a...Objective To examine the effect of acetylcholine（ACh）on the electric activities of pain-excitation neurons （PEN）and pain-inhibitation neurons（PIN）in the hippocampal CA1 area of normal rats or morphinistic rats,and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction.Methods The trains of electric impulses applied to sciatic nerve were set as noxious stimulation.The discharges of PEN and PIN in the CA l area were recorded extracellularly by glass microelectrode.We observed the influence of intracerebroventricular （i.c.v.）injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area.Results Noxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats.In normal rats,ACh decrease the pain-evoked discharge frequency of PEN,while increased the frequency of PIN.These effects reached the peak value at 4 min after injection of ACh.In morphinistic rats,ACh also inhibited the PEN electric activity and potentialized the PIN electric activity,but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine.Conclusion Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation.Morphine addiction attenuated the sensitivity of painrelated neurons to the noxious information.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.
基金Supported by the Key Research and Development Plan of Shandong Province(2018GGX106001)supported by the Natural Science Foundation of Shandong Province(ZR2017MEE066)Supported by the Science and Technology Plan of Shandong higher Education institutions(J16LB58)~~
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.
文摘Objective To investigate the influence of dopamine （DA） and DA receptor＇s antagonist on the transmission of noxious information in the central nervous system of normal rats or morphinistic rats. Methods The influence of DA on the electric activity of the pain-excited neuron （PEN） in the caudate nucleus （Cd） of normal rats or morphinistic rats was recorded after the sciatic nerve was noxiously stimulated. Results DA shortened the average latency of the evoked discharge of PEN in the Cd of normal rats, indicating that DA could increase the activity of PEN and pain sensitivity in normal rats. This effect could be inhibited by Droperidol. DA increased the average latency of the evoked discharge of PEN in the Cd of morphinistic rats, indicating that DA could inhibit the activity of PEN and pain sensitivity in morphinistic rats. Conclusion The responses to painful stimulation were completely opposite between normal rats and morphinistic rats after the intracerebroventricular injection of DA.
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）.
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.
基金the National Natural Science Foundation of China（No.30240058）.
文摘Objective To examine the effect of acetylcholine（ACh）on the electric activities of pain-excitation neurons （PEN）and pain-inhibitation neurons（PIN）in the hippocampal CA1 area of normal rats or morphinistic rats,and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction.Methods The trains of electric impulses applied to sciatic nerve were set as noxious stimulation.The discharges of PEN and PIN in the CA l area were recorded extracellularly by glass microelectrode.We observed the influence of intracerebroventricular （i.c.v.）injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area.Results Noxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats.In normal rats,ACh decrease the pain-evoked discharge frequency of PEN,while increased the frequency of PIN.These effects reached the peak value at 4 min after injection of ACh.In morphinistic rats,ACh also inhibited the PEN electric activity and potentialized the PIN electric activity,but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine.Conclusion Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation.Morphine addiction attenuated the sensitivity of painrelated neurons to the noxious information.
