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  1. Sawi W, Choy YC
    Middle East J Anaesthesiol, 2013 Feb;22(1):21-6.
    PMID: 23833846
    BACKGROUND: This was a double-blinded, prospective randomized controlled trial to compare the postoperative analgesia, side effects profile and overall satisfaction in patients who received intrathecal fentanyl with or without morphine for elective Caesarean.
    METHODS: Sixty ASA I and II parturients were randomized into two groups. Group I received intrathecal fentanyl with 0.1 mg morphine and Group II received intrathecal fentanyl only. Postoperatively, all patients were provided with oral analgesics. The degree of post-operative pain score was assessed by verbal pain score. The incidence of side effects was assessed every 4 hours for 24 hours, which included incidence of nausea, vomiting, pruritus, sedation and evidence of respiratory depression. Patient's overall satisfaction was also recorded.
    RESULTS: The verbal pain score was significantly lower in morphine group up to 20 hours postoperative period. The incidence of pruritus, nausea and vomiting were statistically significant up to 12 hours postoperative. There was no incidence of severe side effects in all the patients. There was significant difference between the morphine and no morphine group in terms of overall patient satisfaction.
    CONCLUSION: There was significant difference in terms of lower pain score, higher incidence of side effects with better patients' overall satisfaction in morphine group.
    Matched MeSH terms: Morphine/administration & dosage*
  2. Jamil MF, Subki MF, Lan TM, Majid MI, Adenan MI
    J Ethnopharmacol, 2013 Jun 21;148(1):135-43.
    PMID: 23608241 DOI: 10.1016/j.jep.2013.03.078
    ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Mitragynine is an indole alkaloid compound of Mitragyna speciosa (M. speciosa) Korth. (Rubiaceae). This plant is native to the southern regions of Thailand and northern regions of Malaysia and is frequently used to manage the withdrawal symptoms in both countries.

    AIM OF STUDY: To investigate the effect of mitragynine after chronic morphine treatment on cyclic AMP (cAMP) level and mRNA expression of mu-opioid receptor (MOR) in human neuroblastoma SK-N-SH cell.

    METHOD AND MATERIALS: Mitragynine was isolated from the Mitragyna speciosa plant using the acid-base extraction method. The cAMP level upon forskolin stimulation in the cells was determined using the Calbiochem(®) Direct Immunoassay Kit. The mRNA expression of the MOR was carried out using quantitative RT-PCR.

    RESULT: Cotreatment and pretreatment of morphine and mitragynine significantly reduced the production of cAMP level at a lower concentration of mitragynine while the higher concentration of this compound could lead to the development of tolerance and dependence as shown by the increase of the cAMP level production in foskolin stimulation. In MOR mRNA expression study, cotreatment of morphine with mitragynine significantly reduced the down-regulation of MOR mRNA expression as compared to morphine treatment only.

    CONCLUSION: These finding suggest that mitragynine could possibly avoid the tolerance and dependence on chronic morphine treatment by reducing the up-regulation of cAMP level as well as reducing the down-regulation of MOR at a lower concentration of mitragynine.

    Matched MeSH terms: Morphine/administration & dosage*
  3. Rahman NH, DeSilva T
    J Emerg Med, 2012 Dec;43(6):951-7.
    PMID: 23068783 DOI: 10.1016/j.jemermed.2012.02.069
    The use of patient-controlled analgesia (PCA) has been reported to provide effective pain relief, often resulting in less opioid consumption, and is associated with greater patient satisfaction when it is compared to other techniques of analgesia delivery.
    Matched MeSH terms: Morphine/administration & dosage*
  4. Siti Salmah G, Choy YC
    Med J Malaysia, 2009 Mar;64(1):71-4.
    PMID: 19852327 MyJurnal
    This was a prospective randomised, controlled, single-blind study done to determine the effect of intrathecal morphine 0.1 mg as compared with intrathecal fentanyl 25 microg in terms of analgesia and duration for postoperative pain relief after Caesarean section. Sixty ASA I or II parturients were randomised into two groups. Group 1 (n=33) received 1.8 ml of 0.5% hyperbaric bupivacaine combined with 0.1 mg morphine while Group 2 (n=27) received 1.8 ml of 0.5% hyperbaric bupivacaine combined with 25 microg fentanyl for spinal anaesthesia. Postoperatively, all patients were provided with patient controlled analgesia (PCA) morphine. Pain was assessed using visual analogue score (VAS) at 6, 12, 18 and 24 hours. Time to first demand of PCA morphine, cumulative PCA morphine requirement and opioid side effects were documented. The VAS for pain and the cumulative PCA morphine requirement were both significantly lower in Group 1 (p < 0.05) during the 24 hours study period. The time to first demand was also significantly longer in Group 1 (p < 0.05). Overall, there were no significant difference between the two groups in side effects, except for a high incidence of nausea and vomiting requiring treatment in Group B in the first six hours. In conclusion the addition of 0.1 mg morphine for spinal anaesthesia provided superior and longer postoperative analgesia after Caesarean section.
    Matched MeSH terms: Morphine/administration & dosage*
  5. Hadi MA, Kamaruljan HS, Saedah A, Abdullah NM
    Med J Malaysia, 2006 Dec;61(5):570-6.
    PMID: 17623958
    The success of major surgery depends partly on providing effective post-operative pain relief, which can be commonly achieved by morphine administration via patient- controlled analgesic (PCA) system. Alternatively, tramadol which is a weak opioid analgesic, can be used for post operative pain relief. The purpose of this study was to evaluate the effectiveness of intravenous PCA tramadol in comparison with PCA morphine in term of analgesic properties, sedation and side effects. A randomized, double-blinded study was conducted on 160 ASA I and II patients who underwent major operations. Eighty of them received a loading dose of intravenous morphine 0.1 mg/kg followed by PCA morphine bolus of 1 mg (1 mg/ml) as required, while the other 80 patients received a loading dose of 2.5 mg/kg of intravenous tramadol followed by PCA infusion of 10 mg (10 mg/ml) as required. Patients were monitored for pain, sedation and side effects as well as respiratory rate, nausea, vomiting, pruritus, blood pressure and pulse rate. Patients were evaluated 30 minutes, 4 hours, 24 hours and 48 hours post operation. There were no differences in the demographic data between the two groups (p > 0.05). The overall mean pain score in tramadol group was 0.70 +/- 0.60 as compared to 0.75 +/- 0.67 for morphine group. The mean pain score for tramadol and morphine groups at 30 minutes, 4 hours, 24 hours and 48 hours post operation were 1.32 +/- 0.79, 104 +/- 0.79, 0.35 +/- 0.48, 0.09 +/- 0.33 and 1.35 +/- 0.99, 1.14 +/- 0.81, 0.40 +/- 0.54, 0.10 +/- 0.34 respectively. The overall mean sedation score in tramadol and morphine group was 0.39 +/- 0.44 as compared to 0.35 +/- 0.43 for morphine group. The mean sedation score for tramadol and morphine group at 30 minutes, 4 hours, 24 hours and 48 hours post operation were 0.90 +/- 0.74, 0.56 +/- 0.59, 0.075 +/- 0.27, 0.025 +/- 0.16 and 0.84 +/- 0.70, 0.46 +/- 0.64, 0.08 +/- 0.27, 0.01 +/- 0.11 respectively. There was no significant difference in the overall mean pain and sedation score between the two groups as well as for each duration assessed (p > 0.05). There were also no significant differences between the two groups with regard to the blood pressure and heart rate. The incidence of nausea, vomiting and pruritus were the same in the two groups. This study indicates that PCA tramadol is as equally effective as PCA morphine control following major surgery. The incidences of sedation, nausea or pruritus were the same in the two groups.
    Matched MeSH terms: Morphine/administration & dosage
  6. Rao AS, Cardosa M, Inbasegaran K
    Anaesth Intensive Care, 2000 Feb;28(1):22-6.
    PMID: 10701031
    In a double-blind, placebo-controlled clinical trial (power of 80% to detect a 30% reduction in morphine consumption, P < 0.05), we have determined that the administration of two doses of intravenous ketoprofen 100 mg, one at the end of surgery and the second 12 hours postoperatively, was associated with a significant reduction in morphine consumption at eight (P = 0.028), 12 (P = 0.013) and 24 hours (P = 0.013) but not four hours (P = 0.065) postoperatively, as compared to placebo, when assessed by patient-controlled analgesia. There was no difference between the groups in pain scores or in the incidence of nausea and vomiting. One patient in the placebo group suffered from excessive sedation while one patient from the ketoprofen group suffered from transient oliguric renal failure. There were no other adverse effects. The results of this study show that ketoprofen does provide a morphine-sparing effect in the management of postoperative pain after abdominal surgery.
    Matched MeSH terms: Morphine/administration & dosage*
  7. Wan Mat WR, Yahya N, Izaham A, Abdul Rahman R, Abdul Manap N, Md Zain J
    Int J Risk Saf Med, 2014;26(2):57-60.
    PMID: 24902502 DOI: 10.3233/JRS-140611
    Acute pain service (APS) ensures provision of effective and safe postoperative pain relief. The following cases describe a potentially fatal error in managing patients who receive epidural analgesia postoperatively.
    Matched MeSH terms: Morphine/administration & dosage*
  8. Zakaria ZA, Safarul M, Valsala R, Sulaiman MR, Fatimah CA, Somchit MN, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2005 Jul;372(1):55-62.
    PMID: 16133487
    A series of preliminary studies was carried out to evaluate the antinociceptive (pain relief) activity of the aqueous extract of Corchorus olitorius L. leaves (COAE) and to determine the influence of temperature and opioid receptors on COAE activity using the abdominal constriction and hot plate tests in mice. COAE, at concentrations of 10, 25, 50, 75, and 100%, showed both peripheral and central antinociception that are non-concentration- and concentration-dependent respectively. The peripheral activity was clearly observed at a concentration of 25% and diminished at a concentration of 100%, while the central activity was observed at all the concentrations of COAE used. Furthermore, the insignificant results obtained indicated that this peripheral activity (at concentrations of 25 and 50%) was comparable to that of morphine (0.8 mg/kg). Pre-heating COAE at a temperature of 80 degrees C and 100 degrees C, or 60 degrees C and 80 degrees C was found to enhance its peripheral and central antinociception respectively. Pre-treatment with naloxone (10 mg/kg), a general opioid receptor antagonist, for 5 min, followed by COAE, was found to completely block its peripheral, but not central, antinociceptive activity. Based on this observation, we conclude that the antinociceptive activity exhibited by C. olitorius is enhanced by the increase in temperature and may be mediated peripherally, but not centrally, at least in part, via an opioid receptor.
    Matched MeSH terms: Morphine/administration & dosage
  9. Davoudi M, Vijeepallam K, Azizi H, Mirnajafi-Zadeh J, Semnanian S
    J Neural Transm (Vienna), 2019 11;126(11):1425-1435.
    PMID: 31493096 DOI: 10.1007/s00702-019-02064-2
    The locus coeruleus (LC) as a target of addictive drugs receives a dense projection of orexinergic fibres from the lateral hypothalamus (LH) and is accordingly a candidate site for the expression of the somatic aspects of morphine withdrawal. Recently it has been shown that the inhibitory synaptic currents of LC neurons decrease partly through orexin type 1 receptors in the context of naloxone-induced morphine withdrawal; however, its cellular mechanism remains unclear. In this study, whole-cell patch clamp recordings of LC neurons in brainstem slices were used to investigate the impact of protein kinase C (PKC) on GABAergic inhibitory post-synaptic currents (IPSCs) in the context of naloxone-induced morphine withdrawal. Male Wistar rats (P14-P21) received morphine (20 mg/kg, i.p.) daily for 7 consecutive days to induce morphine dependency. Our results showed that the application of PKC inhibitor (Go 6983; 1 µM) alone did not decrease the probability of GABA release in the LC neurons of the morphine-treated rats in the presence of naloxone. Although, Go 6983 reversed the reduction of the amplitude of evoked IPSCs (eIPSCs) and spontaneous IPSCs (sIPSCs) frequency induced by orexin-A but did not change the sIPSCs amplitude. These results indicate that the suppressive effect of orexin-A on IPSCs is probably reversed by PKC inhibitor in the LC neurons of morphine-treated rats in the context of naloxone withdrawal.
    Matched MeSH terms: Morphine/administration & dosage
  10. Tan EC, Lim Y, Teo YY, Goh R, Law HY, Sia AT
    J Pain, 2008 Sep;9(9):849-55.
    PMID: 18550441 DOI: 10.1016/j.jpain.2008.04.004
    There are reports suggesting that sensitivity to and tolerance of both clinical and experimental pain differ among ethnic groups. We examined self-rated pain score and morphine usage in 1034 women who underwent elective lower cesarian section (LSCS) for their deliveries. Data on pain scores and amount of total morphine use according to patient-controlled analgesia were collected every 4 hours. Overall, lowest pain scores were recorded 12 hours after surgery and highest at 24 hours. Morphine consumption was highest within the first 4 hours and lowest between 12 and 16 hours. There were statistically significant ethnic group differences in pain scores (P = 1.7 x 10(-7)) and morphine usage (P = 2.8 x 10(-15)) between ethnic groups, with Indians having the highest mean pain score and using the highest amount of morphine. The ethnic differences in pain score and morphine self-administration persisted after controlling for age, body mass index, and duration of operation.
    Matched MeSH terms: Morphine/administration & dosage
  11. Zin CS, Rahman NA, Ismail CR, Choy LW
    Pain Pract, 2017 07;17(6):774-781.
    PMID: 27676695 DOI: 10.1111/papr.12525
    BACKGROUND: There are currently limited data available on the patterns of opioid prescribing in Malaysia. This study investigated the patterns of opioid prescribing and characterized the dosing and duration of opioid use in patients with noncancer and cancer pain.
    METHODS: This retrospective, cross-sectional study was conducted at an outpatient hospital setting in Malaysia. All prescriptions for opioids (dihydrocodeine, fentanyl, morphine, and oxycodone) issued between January 2013 and December 2014 were examined. The number of prescriptions and patients, the distribution of mean daily dose, annual total days covered with opioids, and annual total opioid dose at the individual level were calculated and stratified by noncancer and cancer groups.
    RESULTS: A total of 1015 opioid prescriptions were prescribed for 347 patients from 2013 to 2014. Approximately 41.5% of patients (N = 144/347) and 58.5% (N = 203/347) were associated with noncancer and cancer diagnosis, respectively. Oxycodone (38.0%) was the highest prescribed primarily for the noncancer group. The majority of patients in both noncancer (74.3%) and cancer (60.4%) groups were receiving mean daily doses of < 50 mg morphine equivalents. The chronic use of opioids (> 90 days per year) was associated with 21.8% of patients in the noncancer group and 17.5% in the cancer group.
    CONCLUSIONS: The finding from this study showed that 41.5% of opioid users at an outpatient hospital setting in Malaysia received opioids for noncancer pain and 21.8% of these users were using opioids for longer than 90 days. The average daily dose in the majority of patients in both groups of noncancer and cancer was modest.
    Study site: outpatient clinic, hospital, Malaysia
    Matched MeSH terms: Morphine/administration & dosage
  12. Japarin RA, Yusoff NH, Hassan Z, Müller CP, Harun N
    Behav Brain Res, 2021 02 05;399:113021.
    PMID: 33227244 DOI: 10.1016/j.bbr.2020.113021
    Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine- or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.
    Matched MeSH terms: Morphine/administration & dosage
  13. Lee MT, Chen YH, Mackie K, Chiou LC
    J Pain, 2021 03;22(3):300-312.
    PMID: 33069869 DOI: 10.1016/j.jpain.2020.09.003
    Analgesic tolerance to opioids contributes to the opioid crisis by increasing the quantity of opioids prescribed and consumed. Thus, there is a need to develop non-opioid-based pain-relieving regimens as well as strategies to circumvent opioid tolerance. Previously, we revealed a non-opioid analgesic mechanism induced by median nerve electrostimulation at the overlaying PC6 (Neiguan) acupoint (MNS-PC6). Here, we further examined the efficacy of MNS-PC6 in morphine-tolerant mice with neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Daily treatments of MNS-PC6 (2 Hz, 2 mA), but not electrostimulation at a nonmedian nerve-innervated location, for a week post-CCI induction significantly suppressed established mechanical allodynia in CCI-mice in an orexin-1 (OX1) and cannabinoid-1 (CB1) receptor-dependent fashion. This antiallodynic effect induced by repeated MNS-PC6 was comparable to that induced by repeated gabapentin (50 mg/kg, i.p.) or single morphine (10 mg/kg, i.p.) treatments, but without tolerance, unlike repeated morphine-induced analgesia. Furthermore, single and repeated MNS-PC6 treatments remained fully effective in morphine-tolerant CCI-mice, also in an OX1 and CB1 receptor-dependent fashion. In CCI-mice receiving escalating doses of morphine for 21 days (10, 20 and 50 mg/kg), single and repeated MNS-PC6 treatments remained fully effective. Therefore, repeated MNS-PC6 treatments induce analgesia without tolerance, and retain efficacy in opioid-tolerant mice via a mechanism that involves OX1 and CB1 receptors. This study suggests that MNS-PC6 is an alternative pain management strategy that maybe useful for combatting the opioid epidemic, and opioid-tolerant patients receiving palliative care. PERSPECTIVE: Median nerve stimulation relieves neuropathic pain in mice without tolerance and retains efficacy even in mice with analgesic tolerance to escalating doses of morphine, via an opioid-independent, orexin-endocannabinoid-mediated mechanism. This study provides a proof of concept for utilizing peripheral nerve stimulating devices for pain management in opioid-tolerant patients.
    Matched MeSH terms: Morphine/administration & dosage
  14. Devi BC, Tang TS, Corbex M
    PMID: 16702132
    Effective cancer pain management is influenced by the attitudes and knowledge of treating physicians. A survey was conducted among the total population of government hospital doctors of Sarawak to study the barriers to cancer pain management. Two hundred and fifty-three respondents (83%) completed the survey. The study results highlight that knowledge about cancer pain management was low and barriers to morphine prescription were high. A majority of doctors were deterred from using morphine because of fear of addiction (36.5%) and respiratory depression (53.1%). Only 16.2% of the doctors chose the oral mode of administration to treat pain, furthermore 25% prescribed morphine on "PRN" basis. Doctors with undergraduate study in oncology consistently answered better suggesting that the situation can be improved by education. This study showed that barriers to morphine prescription and knowledge deficit amongst government doctors in Sarawak are strong but similar to those reported in western countries few years ago.
    Matched MeSH terms: Morphine/administration & dosage
  15. Zin CS, Chen LC, Knaggs RD
    Eur J Pain, 2014 Oct;18(9):1343-51.
    PMID: 24756859 DOI: 10.1002/j.1532-2149.2014.496.x
    BACKGROUND: This study evaluated the prescribing trends of four commonly prescribed strong opioids in primary care and explored utilization in non-cancer and cancer users.
    METHODS: This cross-sectional study was conducted from 2000 to 2010 using the UK Clinical Practice Research Datalink. Prescriptions of buprenorphine, fentanyl, morphine and oxycodone issued to adult patients were included in this study. Opioid prescriptions issued after patients had cancer medical codes were defined as cancer-related use; otherwise, they were considered non-cancer use. Annual number of prescriptions and patients, defined daily dose (DDD/1000 inhabitants/day) and oral morphine equivalent (OMEQ) dose were measured in repeat cross-sectional estimates.
    RESULTS: In total, there were 2,672,022 prescriptions (87.8% for non-cancer) of strong opioids for 178,692 users (59.9% female, 83.9% non-cancer, mean age 67.1 ± 17.0 years) during the study period. The mean annual (DDD/1000 inhabitants/day) was higher in the non-cancer group than in the cancer group for all four opioids; morphine (0.73 ± 0.28 vs. 0.12 ± 0.04), fentanyl (0.46 ± 0.29 vs. 0.06 ± 0.24), oxycodone (0.24 ± 0.19 vs. 0.038 ± 0.028) and buprenorphine (0.23 ± 0.15 vs. 0.008 ± 0.006). The highest proportion of patients were prescribed low opioid doses (OMEQ ≤ 50 mg/day) in both non-cancer (50.3%) and cancer (39.9%) groups, followed by the dose ranks of 51-100 mg/day (26.2% vs. 28.7%), 101-200 mg/day (15.1% vs. 19.2%) and >200 mg/day (8.25% vs. 12.1%).
    CONCLUSIONS: There has been a huge increase in strong opioid prescribing in the United Kingdom, with the majority of prescriptions for non-cancer pain. Morphine was the most frequently prescribed, but the utilization of oxycodone, buprenorphine and fentanyl increased markedly over time.
    Matched MeSH terms: Morphine/administration & dosage
  16. Abd Aziz N, Chue MC, Yong CY, Hassan Y, Awaisu A, Hassan J, et al.
    Int J Clin Pharm, 2011 Apr;33(2):150-4.
    PMID: 21744187 DOI: 10.1007/s11096-011-9480-7
    OBJECTIVE: To compare the efficacy of dexmedetomidine versus morphine as a sedative/analgesic among post-operative cardiac surgery patients.

    METHOD: A randomized controlled open-label study was performed at the cardiothoracic intensive care unit of Penang Hospital, Malaysia. A total of 28 patients who underwent cardiac surgeries were randomly assigned to receive either dexmedetomidine or morphine. Both groups were similar in terms of preoperative baseline characteristics. Efficacy measures included sedation scores and pain intensity and requirements for additional sedative/analgesic. Mean heart rate and arterial blood pressure were used as safety measures. Other measures were additional inotropes, extubation time and other concurrent medications.

    RESULTS: The mean dose of dexmedetomidine infused was 0.12 [SD 0.03] μg kg⁻¹ h⁻¹, while that of morphine was 13.2 [SD 5.84] μg kg⁻¹ h⁻¹. Dexmedetomidine group showed more benefits in sedation and pain levels, additional sedative/analgesic requirements, and extubation time. No significant differences between the two groups for the outcome measures, except heart rate, which was significantly lower in the dexmedetomidine group.

    CONCLUSION: This preliminary study suggests that dexmedetomidine was at least comparable to morphine in terms of efficacy and safety among cardiac surgery patients. Further studies with larger samples are recommended in order to determine the significant effects of the outcome measures.

    Matched MeSH terms: Morphine/administration & dosage*
  17. Fakurazi S, Rahman SA, Hidayat MT, Ithnin H, Moklas MA, Arulselvan P
    Molecules, 2013 Jan 04;18(1):666-81.
    PMID: 23292329 DOI: 10.3390/molecules18010666
    Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.
    Matched MeSH terms: Morphine/administration & dosage*
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