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- Gene Expression Profile of Calcium/Calmodulin-Dependent Protein Kinase IIα in Rat's Hippocampus during Morphine Withdrawal. [Journal Article]
- Basic Clin Neurosci 2013; 4(2):146-52.
Calcium/calmodulin-dependent protein kinase II (CaMKII) which is highly expressed in the hippocampus is known to play a pivotal role in reward-related memories and morphine dependence.In the present study, repeated morphine injections once daily for 7 days was done to induce morphine tolerance in male Wistar rats, after which gene expression profile of α-isoform of CaMKII (CaMKIIα) in the hippocampus was evaluated upon discontinuation of morphine injection over 21 days of morphine withdrawal. Control groups received saline for 7 consecutive days. For gene expression study, rats' brains were removed and the hippocampus was dissected in separate groups on days 1, 3, 7, 14, and 21 since discontinuation of of morphine injection. A semi-quantitative RT-PCR method was used to evaluate the gene expression profile.Tolerance to morphine was verified by a significant decrease in morphine analgesia in a hotplate test on day 8 (one day after the final repeated morphine injections). Results showed that gene expression of CaMKIIα at mRNA level on day 1, 3, 7, 14 and 21 of morphine withdrawal was significantly altered as compared to the saline control group. Post hoc Tukey's test revealed a significantly enhanced CaMKIIα gene expression on day 14.It can be concluded that CaMKIIα gene expression during repeated injections of morphine is increased and this increase continues up to 14 days of withdrawal then settles at a new set point. Therefore, the strong morphine reward-related memory in morphine abstinent animals may, at least partly be attributed to, the up-regulation of CaMKIIα in the hippocampus over 14 days of morphine withdrawal.
- Evaluating the effects of oral morphine on embryonic development of cerebellum in wistar rats. [Journal Article]
- Basic Clin Neurosci 2013; 4(2):130-5.
In the present research, the effect of morphine consumption during pregnancy on the development of the embryo's spinal cord was studied in Wistar rat.250-300 g) were mated with males. The test group received morphine (0.01 mg/ml) in their drinking water. Pregnant rats were later killed with chloroform on the 12th, 13th and 14th days of pregnancy, and the embryos were taken out surgically. The embryos were fixed in formalin 10% for 2 weeks. Then, the weight of fixed embryos was calculated by a scale. In addition, several animals' sizes including fronto-posterior and lateral length were measured by a caliper. Tissue processing, sectioning and hematoxylin and eosin (H&E) staining were applied for the embryos. The sections were examined for spinal cord development by light microscope and MOTIC software. Significant decrease was observed in the fronto-posterior and lateral length and the weight of the embryos in the test groups. The thickness of the white matter layer decreased on the 12th, 13th and 14th embryonic days. The thickness of the spine's grey layer was also less than the control group, on the same days. Increase in the length of the ependimal duct observed as well. Number of grey substance cells decreased compared to the control group within the same days. Meanwhile, thickness of the germinal layer reduced in comparison to the control group on the mentioned days. In conclusion, morphine consumption during pregnancy causes defects in growth and completion of the spinal cord.
- Evaluation of the analgesic effect of subcutaneous methadone after cesarean section. [Journal Article]
- Adv Biomed Res 2014.:197.
Inadequate pain control has a significant role in maternal and neonatal health in early post-partum period which interferes with breastfeeding and has a negative influence on child normal growth. The aim of this study is evaluation of subcutaneous methadone effectiveness on post-operative pain control.Double blind randomized prospective clinical trial involving 60 term pregnancy patients through 2008 to 2009 Undergo cesarean.Prime gravid candidate of elective cesarean and spinal anesthesia class 1 or 2. Known case of drug allergy and methadone interaction, addiction, uncontrolled medical disease excluded. Case group injected 10 mg of subcutaneous methadone in the site of incision before final suture. Morphine was a pain reliever in follow up examination. Data include mean of pain, nausea and vomiting, MAP, etc., collected and analyzed by independent-T test and Man Whitney test.Although mean usage of morphine between groups was not significant statistically but the mean pain severity (P value < 0.05) and mean satisfactory (P value = 0.02) was statistically significant between groups. Other parameters were not statistically significant.We suggest subcutaneous methadone as a safe pain reliever in post cesarean section patients.
- Pharmacognosy: Science of natural products in drug discovery. [Journal Article]
- Bioimpacts 2014; 4(3):109-10.
Pharmacognosy deals with the natural drugs obtained from organisms such as most plants, microbes, and animals. Up to date, many important drugs including morphine, atropine, galanthamine, etc. have originated from natural sources which continue to be good model molecules in drug discovery. Traditional medicine is also a part of pharmacognosy and most of the third world countries still depend on the use of herbal medicines. Consequently, pharmacognosy always keeps its popularity in pharmaceutical sciences and plays a critical role in drug discovery.
- ATP-sensitive Potassium Channels and L-type Calcium Channels are Involved in Morphine-induced Hyperalgesia after Nociceptive Sensitization in Mice. [Journal Article]
- Basic Clin Neurosci 2014; 5(3):191-8.
We investigated the role of ATP-sensitive potassium channels and L-type calcium channels in morphine-induced hyperalgesia after nociceptive sensitization.We used a hotplate apparatus to assess pain behavior in male NMRI mice. Nociceptive sensitization was induced by three days injection of morphine and five days of drug free. On day 9 of the schedule, pain behavior test was performed for evaluating the effects of morphine by itself and along with nimodipine, a blocker of L-type calcium channels and diazoxide, an opener of ATP-sensitive potassium channels. All drugs were injected through an intraperitoneal route.The results showed that morphine (7.5, 10 and 15 mg/kg) induced analgesia in normal mice, which was prevented by naloxone (1 mg/kg). After nociceptive sensitization, analgesic effect of morphine (10 and 15 mg/kg) was significantly decreased in sensitized mice. The results showed that nimodipine (2.5, 5, 10 and 20 mg/kg) had no significant effect on pain behavior test in either normal or sensitized mice. However, nimodipine (20 mg/ kg) along with morphine (10 and 15 mg/kg) caused more decrease in morphine analgesia in sensitized mice. Furthermore, diazoxide by itself (0.25, 1, 5 and 20 mg/kg) had also no significant effect on pain behavior in both normal and sensitized mice, but at dose of 20 mg/kg along with morphine (10 and 15 mg/kg) decreased analgesic effect of morphine in sensitized mice.It can be concluded that potassium and calcium channels have some roles in decrease of analgesic effect of morphine after nociceptive sensitization induced by pretreatment of morphine.
- Effects of Hydroalcoholic Extract of Tanacetum Sonbolii (Asteraceae) on Pain-related Behaviors during Formalin Test in Mice. [Journal Article]
- Basic Clin Neurosci 2014; 5(2):162-8.
Tanacetum sonbolii (Asteraceae) is an endemic species in Iran. In the present study, we examined the effects of Tanacetum sonbolii hydroalcoholic extract on the formalin test in mice.126 Swiss albino mice weighing 230-280g were used as subjects. The formalin test was performed on two control groups (marked as intact and saline groups; n = 6 in each group) and an experimental group. In all groups, the formalin test was recorded for 60 min after administration of extract and drugs in mice.The results showed that Tanacetum sonbolii (150 and 300 mg/kg) produced significant antinociception in phase 2. In addition, different doses of Tanacetum sonbolii extract (600, 900 and 1200 mg/kg) also induced antinociceptive effects in phase1 and phase 2. On the other hand, morphine could induce antinociception in a dose-dependent manner. Diclofenac (10 mg/kg) failed to affect the pain scores compared to Tanacetum sonbolii (300 mg/kg) group.It seems that administration of hydroalcoholic extract of Tanacetum sonbolii has the potential to relieve pain through both central and peripheral mechanisms in persistent inflammatory nociception.
- Programmable intrathecal pumps for the management of chronic pain: recommendations for improved efficiency. [Journal Article, Review]
- J Pain Res 2014.:571-7.
The management of chronic pain can be very challenging. Often, physicians employ intrathecal (IT) drug delivery systems as a last resort to relieve intractable pain. The system consists of an implantable pump that stores and delivers medication through a catheter to the IT space. Programmability is achieved by positioning an external devise over the implanted pump to change the mode of drug delivery. The innovations in programmable IT drug delivery systems are expanding more rapidly than ever before. Unfortunately, the rapid expansion is accompanied by a lack of prospective randomized trials examining these new options. In an effort to improve results and reduce side effects, publications by experts or expert consensus panels provide guidance for the community. The purpose of this article is to provide a summary of high interest topics in recent publications.
- Effects of opioids on human serotonin transporters. [JOURNAL ARTICLE]
- Naunyn Schmiedebergs Arch Pharmacol 2014 Oct 22.
The serotonin (5-hydroxtryptamine, 5-HT) system plays a role in analgesia and emesis. The aim of this study was to test whether opioids or ketamine inhibit the human 5-HT transporter and whether this increases free plasma 5-HT concentrations. HEK293 cells, stably transfected with the human 5-HT transporter cDNA, were incubated with morphine, hydromorphone, fentanyl, alfentanil, pethidine (meperidine), tramadol, ketamine, and the reference substance citalopram (specific 5-HT transporter inhibitor). The uptake of [(3)H]5-HT was measured by liquid scintillation counting. In a second series of experiments, study drugs were incubated with plasma of ten healthy blood donors and change of 5-HT plasma-concentrations were measured (ELISA). The end point was the inhibition of the 5-HT transporter by different analgesics either in HEK293 cells or in human platelets ex vivo. Tramadol, pethidine, and ketamine suppressed [(3)H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230 μM, respectively. These drugs also prevented 5-HT uptake in platelets with an increase in free plasma 5-HT. Free 5-HT concentrations in human plasma were increased by citalopram 1 μM, tramadol 20 μM, pethidine 30 μM, and ketamine 100 μM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p < 0.005). No change in both experimental settings was observed for the other opioids. Tramadol and pethidine inhibited the 5-HT transporter in HEK293 cells and platelets. This inhibition may contribute to serotonergic effects when these opioids are given in combination, e.g., with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors.
- [Clinical significance of ropivacaine local infiltration for postoperative analgesia after total laparoscopic radical gastrectomy in elderly patients]. [English Abstract, Journal Article]
- Zhonghua Yi Xue Za Zhi 2014 Jul 22; 94(28):2188-92.
To explore the analgesic effects and postoperative recovery of ropivacaine incision infiltration in elderly patients after total laparoscopic radical gastrectomy.The clinical data were obtained prospectively from 61 elderly patients ( ≥ 65y) undergoing traditional total laparoscopic radical gastrectomy under standard general anesthesia at our department during January 2012 and September 2013. After surgery, they were randomly double-blindly divided into 3 groups: local infiltration of ropivacaine group (0.5% ropivacaine incision infiltration, 40 ml, n = 22), local infiltration of sodium chloride group (0.9% sodium chloride injection incision infiltration, 40 ml, n = 20) and control group (no analgesic, n = 19). The intensity of postoperative pain was evaluated by numeric rating scale (NRS). And 10 mg of morphine was administered intramuscularly as rescue medication when NRS exceeded 4.NRS, cases on remedy analgesia and associated side effects were observed and recorded after 6 h postoperatively. A comparative study was made for postoperative first ambulation time, intestinal function recovery time, complication incidence, postoperative hospital stay and medical expenses among three groups.Significant postoperative difference existed in NRS at 6, 12, 24, 48 h among ropivacaine, sodium and control groups respectively (6 h: 2.65 ± 0.25 vs 5.47 ± 0.12 vs 5.63 ± 0.27, 12 h: 2.42 ± 0.34 vs 5.82 ± 0.63 vs 5.67 ± 0.49, 24 h: 2.27 ± 0.83 vs 3.95 ± 0.51 vs 3.84 ± 0.60, 48 h: 2.05 ± 0.90 vs 3.75 ± 0.72 vs 3.74 ± 0.56, P < 0.05) . The patients with ropivacaine local infiltration had a lower rate of remedy analgesia than those with sodium chloride injection incision infiltration or without analgesic (both P < 0.05). There was no obvious adverse effect of ropivacaine infiltration at 48 h postoperatively. Both postoperative first ambulation and peristalsis recovery time were shorter (P < 0.05) in ropivacaine group ((53 ± 9) and (80 ± 6) h) than sodium group ((91 ± 11) and (105 ± 9) h) and control group ((93 ± 11) and (109 ± 10) h) . Meanwhile, ropivacaine group had significance decreased postoperative hospital stay and medical expenses than that in local infiltration of sodium group and control group ((10.2 ± 1.3) vs (12.6 ± 1.3), (12.9 ± 1.6) days, (57 000 ± 5 000) vs (63 000 ± 6 000), (65 000 ± 6 000) yuan) (all P < 0.05). Occurrence of complications significantly differed among three groups (local infiltration of ropivacaine group 9.10% (2/22), local infiltration of sodium chloride group 25.00% (5/20) and control group 21.05% (4/19), P < 0.05).Ropivacaine infiltration may reduce postoperative pain after total laparoscopic radical gastrectomy, enable faster recovery and provide an alternative analgesia in elderly patients.
- Simultaneous determination of the content of isoquinoline alkaloids in Dicranostigma leptopodum (Maxim) Fedde and the effective fractionation of the alkaloids by high-performance liquid chromatography with diode array detection. [JOURNAL ARTICLE]
- J Sep Sci 2014 Oct 20.
A simple and efficient method was developed for the simultaneous determination of eight isoquinoline alkaloids in methanol extracts of Dicranostigma leptopodum (Maxim) Fedde and the effective fractionation of the alkaloids of D. leptopodum by high-performance liquid chromatography with diode array detection. The chromatographic conditions were optimized on a SinoChrom ODS-BP column to obtain a good separation of the four types of alkaloid analytes, including two aporphines (isocorydine, corydine), two protopines (protopine and allocryptopine), a morphine (sinoacutine), and three quaternary protoberberine alkaloids (berberrubine, 5-hydroxycoptisine, and berberine). The separation of these alkaloids was significantly affected by the composition of the mobile phase, and particularly by its pH value. Acetonitrile (A) and 0.2% phosphoric acid solution adjusted to pH 6.32 with triethylamine (B) were selected as the mobile phase with a gradient elution. With this method, a new quaternary protoberberine alkaloid was isolated and the two structural isomers (isocorydine and corydine) were baseline separated. The appropriate harvest period for D.leptopodum was also recommended based on our analysis. The method for the effective fraction of the alkaloids of D.leptopodum was optimized under this method with regards to the varying significant pharmacological activities of the alkaloids. This article is protected by copyright. All rights reserved.