AIM OF THE STUDY: To explore the antinociceptive (acute pain) and anti-neuropathic (chronic pain) activities of Lotus corniculatus leaves essential oil (LCEO) in addition to uncovering the possible mechanisms of antinociception.
MATERIALS AND METHODS: LCEO as well as the pure oleanolic acid (OA) compound, were assayed for their effects on acute (formalin induced paw licking test or FIPT) and chronic (cervical contusion injury models on the fifth cervical vertebra or CCS; 14-day intervals) pain. The possible involvements of NO-cGMP-K+ channel, TRPV, dopamine, cannabinoid, PPAR, adrenergic, and opioid mechanisms in the antinociceptive activity of LCEO have studied by formalin test. The levels of p53 and inflammatory markers were measured using a streptavidin biotin immune peroxidase complex and ELISA methods, respectively.
RESULTS: The LCEO and OA exerted antinociceptive activity in the first-phase of FIPT. Pretreatment with antagonists of TRPV1, dopamine D2, cannabinoid type1 and 2, and NO-cGMP-K+ channel blockers (glibenclamide, L-NAME and methylene blue) attenuated the antinociceptive effect of LCEO in FIPT. In addition, LCEO and OA meaningfully reduced hyperalgesia (days 6-14) and mechanical allodynia (days 2-14) in the CCS model. LCEO suppressed the apoptotic marker (p53) in CCS model and also ameliorated IL-2, TNF-α, and IL-1 in the spinal cord.
CONCLUSION: Finally, LCEO inhibited acute (possibly via the modulation of opioid, TRPV, dopamine, cannabinoid mechanisms as well as NO-cGMP-K+ channel) and chronic pain (via suppressing apoptotic and inflammatory markers) in male rats. The results also suggest that OA has analgesic activity against acute and chronic pain conditions.
METHODS: A comprehensive electronic literature search was carried out on research articles published between 1950 to July 2023 through major databases, such as Scopus, Web of Science, Google Scholar, PubMed, PsycINFO, EMBASE, Medline and Cochrane Library.
RESULTS: A total of 21 research articles were selected for review, which were comprised of sixteen animal studies, four human studies and one study on postmortem human brain samples. The selected studies revealed that alcohol, methamphetamine, cocaine, opioid and kratom exposures contributed to neuropsychiatric effects: such as decline in learning and memory function, executive dysfunction, alcohol, methamphetamine, opioid, and kratom dependence. These effects were associated with activation and persistent of ER stress and UPR with elevation of BiP and CHOP expression and the direction of ER stress is progressing towards the PERK-eIF2α-ATF4-CHOP pathway and neuronal apoptosis and neurodegeneration at various regions of the brain. In addition, regular kratom use in humans also contributed to elevation of p-JNK expression, denoting progress of ER stress towards the IRE1-ASK1-JNK-p-JNK pathway which was linked to kratom use disorder. However, treatment with certain compounds or biological agents could reverse the activation of ER stress.
CONCLUSIONS: The neuropsychiatric effects of alcohol, methamphetamine, cocaine, opioid and kratom use may be associated with persistent ER stress and UPR.
METHODS: From 2010 to 2014, men with HIV (N = 212) and opioid dependence before incarceration were enrolled in MMT within 6 months of release from Malaysia's largest prison and followed for 12-months post-release. As a prospective trial, allocation to MMT was at random and later by preference design (predictive nonetheless). MMT dosing was individually targeted to minimally achieve 80 mg/day. Time-to-event analyses were conducted to model linkage to MMT after release.
FINDINGS: Of the 212 participants allocated to MMT, 98 (46 %) were prescribed higher dosages (≥80 mg/day) before release. Linkage to MMT after release occurred in 77 (36 %) participants and significantly higher for those prescribed higher dosages (46% vs 28 %; p = 0.011). Factors associated with higher MMT dosages were being married, on antiretroviral therapy, longer incarceration periods, having higher levels of depression, and methadone preference compared to randomization. After controlling for other variables, being prescribed higher methadone dosage (aHR: 2.53, 95 %CI: 1.42-4.49) was the only independent predictor of linkage to methadone after release.
INTERPRETATION: Higher doses of methadone prescribed before release increased the likelihood of linkage to MMT after release. Methadone dosing should be introduced into international guidelines for treatment of opioid use disorder in prisons and further post-release benefits should be explored.
FUNDING: National Institute of Drug Abuse (NIDA).
OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023.
SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety.
AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.
METHODS: Patients (n = 94) scheduled for gynaecological laparotomy received i.v. fentanyl infusion (3 μg/kg/h) after induction of general anaesthesia. Post-operative fentanyl requirements were quantified by using a patient-controlled analgesia and the number of i.v. fentanyl rescue analgesia required were recorded. Pain control was assessed using visual analogue scores (VAS) and fentanyl's adverse effects were documented. CYP3A4*4, CYP3A4*5 and CYP3A4*18 alleles of cytochrome P450 3A4 were identified by polymerase chain reaction-restriction fragment length polymorphism. Differences in fentanyl requirements, VAS scores and adverse effects among the various genotypes were compared.
RESULTS AND DISCUSSION: No CYP3A4*4 and CYP3A4*5 alleles were detected. Eighty-nine patients (94·7%) were wild-type, five (5·3%) were heterozygous and none was homozygous. No significant difference was demonstrated between the genotype groups in terms of fentanyl consumption, pain control and adverse effects.
WHAT IS NEW AND CONCLUSION: CYP3A4*4 and CYP3A4*5 are rare in the Malaysian Malay population. Genetic polymorphism of CYP3A4*18 may not play an important role in influencing postoperative fentanyl requirements.
METHOD: Electronic literature search on PubMed was conducted using the following keywords: methylphenidate, cancer, carcinoma, oncology, oncological and tumour. We identified forty two relevant studies and publications on the use of methylphenidate in cancer patients to be included in this review.
RESULTS: Methylphenidate was found to have some evidence in reducing opioid-induced sedation, improving cognitive symptoms and reduction of fatigue in cancer patients. Nevertheless, the results were inconsistent due to variations in the study populations, study design and outcome measures, among others. There was minimal evidence on its use in treating depression. Otherwise, methylphenidate was generally well-tolerated by patients.
CONCLUSION: This review potentially supports the use of methylphenidate for opioid-induced sedation, cognitive decline and fatigue in cancer patients. Further placebo-controlled trials would help in strengthening the evidence for this treatment.
Materials and Methods: Data of five strong opioids consumption (morphine, oxycodone, fentanyl, pethidine, and methadone) between 2005 and 2014 from Malaysia, Singapore, Indonesia, Thailand, and Vietnam were extracted from the Pain and Policy Studies Group. Defined daily doses per 1000 inhabitants per day (DDD/1000 inhabitants/day) was used for calculating the annual amount of opioid use.
Results: The total consumption of five strong opioids was increased in all five Southeast Asian countries during a 10-year study period. Malaysia was recorded with the largest increase of the opioid consumption (993.18%), followed by Indonesia (530.34%), Vietnam (170.17%), Singapore (116.16%), and Thailand (104.66%). Malaysia also had the highest total strong opioid consumption (11.2 DDD/1000 inhabitants/day), primarily for methadone. Among the opioids used for pain management, fentanyl was primarily used in Malaysia and Singapore but the greatest increase in these two countries was for oxycodone. Fentanyl was also primarily used in Indonesia while morphine was predominantly used in Thailand and Vietnam.
Conclusion: Growing trends of strong opioids consumption in all five Southeast Asian countries demonstrated in this study may indicate improved access to opioid analgesics in these countries. Given the increasing trends, it is important to ensure that the utilization of opioids is according to the guideline to prevent the negative consequences of opioids particularly when used in chronic non-cancer pain.