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Cureus Jul 2022Recent evidence links melatonin hormone and its receptor to the etiology and behavioral manifestation of addiction. The role of exogenous melatonin in addiction... (Review)
Review
Recent evidence links melatonin hormone and its receptor to the etiology and behavioral manifestation of addiction. The role of exogenous melatonin in addiction treatment is still inconsistent and unclear. The present study aimed to review the literature on randomized clinical trials that evaluated the role of melatonin supplementation, compared to placebo, in the treatment of various substance addictions. The literature searches of relevant articles published in the English language in MEDLINE and Google Scholar databases were performed from inception up to May 2021. We included only randomized clinical trials investigating the effect of melatonin treatment, compared to placebo, on substance addiction-related parameters. Non-randomized clinical trials, observation studies, and animal studies were excluded. The risk of bias-2 was used to assess the quality of the studies. Of 537 articles, 12 randomized control trials (RCT) met our inclusion criteria. Studies have been conducted on substances of addiction including benzodiazepine (BZD), alcohol, nicotine, and opioids. Our results indicated that melatonin treatment had mixed results in improving sleep quality and was not found beneficial in BDZ cessation/discontinuation rate among patients with BDZ dependence. Sleep quality and mental health had improved by melatonin supplements in opioid addiction. In nicotine addiction, melatonin treatment showed effectiveness only on mood changes but not in performance tests. In patients with alcohol use disorder (AUD), melatonin treatment did not show any improvement in sleep quality. We found that the use of exogenous melatonin in substance addiction has mixed results which do not provide sufficient evidence, relative to randomized clinical trials, to establish its role.
PubMed: 35967139
DOI: 10.7759/cureus.26764 -
PloS One 2015Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The... (Review)
Review
Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double-blind studies using 'inhibitory' or 'sensitizing', physiological test paradigms in healthy human subjects. The databases PubMed and Embase were searched according to predefined criteria. Out of a total of 2,142 records, 63 studies (1,477 subjects [male/female ratio = 1.5]) were considered relevant. Twenty-five studies utilized 'inhibitory' test paradigms (ITP) and 38 studies utilized 'sensitizing' test paradigms (STP). The ITP-studies were characterized as conditioning modulation models (22 studies) and repetitive transcranial magnetic stimulation models (rTMS; 3 studies), and, the STP-studies as secondary hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and rTMS. In the remaining 14 conditioning modulation studies either absence of effects or ambiguous effects by MOR-antagonists, were observed. In the STP-studies, no effect of the opioid-blockade could be demonstrated in 5 out of 6 secondary hyperalgesia studies. The direction of MOR-antagonist dependent effects upon pain ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect, presumably mediated by an EOS-dependent mechanisms of analgesia and hyperalgesia.
Topics: Analgesia; Analgesics, Opioid; Animals; Female; Humans; Male; Narcotic Antagonists; Pain Management; Randomized Controlled Trials as Topic
PubMed: 26029906
DOI: 10.1371/journal.pone.0125887 -
The Cochrane Database of Systematic... Jul 2014Several surveys over the past few years have demonstrated that postoperative pain in children is not treated appropriately. One pharmacological treatment option in a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several surveys over the past few years have demonstrated that postoperative pain in children is not treated appropriately. One pharmacological treatment option in a multimodal approach for postoperative pain treatment is the systemic administration of opioids. However, opioids are rarely used for postoperative pain treatment in children due to fear of adverse events. One long-standing opioid for systemic use is nalbuphine, a kappa-receptor agonist and µ-receptor antagonist. The efficacy of nalbuphine is believed to be similar to morphine. Increased dosing might result in a ceiling effect, and thus less analgesia than expected. In addition, there might be a lower risk for opioid-induced side effects (nausea, vomiting) and severe adverse events (respiratory depression) due to the antagonistic effect of the µ-receptor. Nalbuphine may be an useful opioid for postoperative use in children, but exact efficacy (e.g. compared to other commonly used opioids) has not been determined yet.
OBJECTIVES
To assess the efficacy and adverse events of nalbuphine for acute postoperative pain treatment in children undergoing surgery.
SEARCH METHODS
We systematically searched the following databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7), MEDLINE via Pubmed (January 1966 to July 2013) and EMBASE via Ovid (January 1947 to July 2013). We did not impose any restrictions regarding language or publication date. We checked all reference lists of retrieved articles for additional references.
SELECTION CRITERIA
All randomised controlled trials (RCTs) investigating nalbuphine compared with placebo or other opioids were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently scanned the retrieved articles and made a decision regarding inclusion or exclusion of studies for this review. The same authors also performed the data extraction and the assessment of risk of bias.
MAIN RESULTS
Ten RCTs including 658 patients were finally included in this systematic review. Five trials compared nalbuphine with placebo. Data from one out of five studies for the outcome moderate/severe pain following nalbuphine compared to placebo gave a risk ratio (RR) 1 hour postoperatively (postop) of 0.1 (95% confidence interval (CI) 0.01 to 0.71; low quality evidence) and a RR 2 hours postop of 0.14 (95% CI 0.02 to 1.06; low quality evidence). The estimated RR based on data from a single study indicated that nalbuphine reduced the requirement for analgesia two hours postop (RR 0.47; 95% CI 0.27 to 0.84; low quality evidence). Two included trials compared nalbuphine with morphine and showed a nonsignificant lower or comparable RR for moderate/severe pain at 1 hour postop (RR 0.84; 95% CI 0.12 to 5.74; low quality evidence), and 2 hours postop (RR 1.09; 95% CI 0.59 to 2.01; low quality evidence) for nalbuphine versus morphine. Four trials compared nalbuphine with tramadol for postoperative pain; data from one trial (per outcome) revealed a lower but nonsignificant RR for the need of additional rescue analgesics in children receiving nalbuphine (RR 2 hours postop 0.75; 95% CI 0.39 to 1.43; low quality evidence) (RR 12 hours postop 0.33; 95% CI 0.04 to 2.77; low quality evidence). One out of three trials comparing nalbuphine with pethidine demonstrated that the RR was not significantly lower following nalbuphine administration compared to pethidine (RR 2 hours postop 1.07; 95% CI 0.52 to 2.23; low quality evidence) (RR 24 hours postop 1.13; 95% CI 0.52 to 2.44; very low quality evidence). The most common adverse event was postoperative nausea and vomiting (PONV). Only one included trial reported that the RR for PONV in the postoperative care unit (PACU) was not significantly higher following nalbuphine compared to placebo (RR 1.00; 95% CI 0.16 to 6.42; low quality evidence) nor to morphine (RR 1.33; 95% CI 0.64 to 2.77; low quality evidence).
AUTHORS' CONCLUSIONS
Because the overall quality of available evidence was low, this systematic review could not definitively show that the analgesic efficacy of nalbuphine is superior compared to placebo. Furthermore, due to the lack of significant results the comparison with other common opioids is also unclear. The same holds true for the evidence focusing on adverse events following nalbuphine compared to placebo or other opioid administration. The evidence is limited, because studies did not report conclusively all important postoperative pain outcomes (e.g. number of patients with the need for rescue analgesia, postoperative pain scores). Thus, a quantitative analysis was not possible for many major aspects (e.g. rescue analgesia, pain scores) and heterogeneity could not be further explored.
Topics: Adolescent; Analgesics, Opioid; Child; Child, Preschool; Humans; Meperidine; Morphine; Nalbuphine; Pain, Postoperative; Randomized Controlled Trials as Topic; Tramadol; Young Adult
PubMed: 25079857
DOI: 10.1002/14651858.CD009583.pub2 -
Advances in Nutrition (Bethesda, Md.) Sep 2017This is the first systematic review, to our knowledge, of published studies investigating the gastrointestinal effects of A1-type bovine β-casein (A1) compared with... (Review)
Review
This is the first systematic review, to our knowledge, of published studies investigating the gastrointestinal effects of A1-type bovine β-casein (A1) compared with A2-type bovine β-casein (A2). The review is relevant to nutrition practice given the increasing availability and promotion in a range of countries of dairy products free of A1 for both infant and adult nutrition. In vitro and in vivo studies (all species) were included. In vivo studies were limited to oral consumption. Inclusion criteria encompassed all English-language primary research studies, but not reviews, involving milk, fresh-milk products, β-casein, and β-casomorphins published through 12 April 2017. Studies involving cheese and fermented milk products were excluded. Only studies with a specific gastrointestinal focus were included. However, inclusion was not delimited by specific gastrointestinal outcome nor by a specific mechanism. Inclusion criteria were satisfied by 39 studies. In vivo consumption of A1 relative to A2 delays intestinal transit in rodents via an opioid-mediated mechanism. Rodent models also link consumption of A1 to the initiation of inflammatory response markers plus enhanced Toll-like receptor expression relative to both A2 and nonmilk controls. Although most rodent responses are confirmed as opioid-mediated, there is evidence that dipeptidyl peptidase 4 stimulation in the jejunum of rodents is via a nonopioid mechanism. In humans, there is evidence from a limited number of studies that A1 consumption is also associated with delayed intestinal transit (1 clinical study) and looser stool consistency (2 clinical studies). In addition, digestive discomfort is correlated with inflammatory markers in humans for A1 but not A2. Further research is required in humans to investigate the digestive function effects of A1 relative to A2 in different populations and dietary settings.
Topics: Animals; Biomarkers; Caseins; Diet; Dipeptidyl Peptidase 4; Disease Models, Animal; Endorphins; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 28916574
DOI: 10.3945/an.116.013953 -
A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism.European Journal of Nuclear Medicine... Nov 2016To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism. (Review)
Review
PURPOSE
To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism.
METHODS
MEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded.
RESULTS
Seventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABA receptors in PSP, MSA, and CBS patients were included in this review. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques to distinguish between parkinsonian syndromes. Microglial activation has been found in all forms of atypical parkinsonism and reflects the known distribution of neuropathologic changes in these disorders. Opioid receptors are decreased in the striatum of PSP and MSA patients. Subcortical cholinergic dysfunction was more severe in MSA and PSP than Parkinson's disease patients although no significant changes in cortical cholinergic receptors were seen in PSP with cognitive impairment. GABA receptors were decreased in metabolically affected cortical and subcortical regions in PSP patients.
CONCLUSIONS
PET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments.
Topics: Biomarkers; Biomedical Research; Evidence-Based Medicine; Humans; Molecular Imaging; Nerve Tissue Proteins; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 27470326
DOI: 10.1007/s00259-016-3464-8 -
BMC Musculoskeletal Disorders Dec 2016The aim of the present study was to provide an overview of the literature addressing the role of genetic factors and biomarkers predicting pain recovery in newly... (Review)
Review
BACKGROUND
The aim of the present study was to provide an overview of the literature addressing the role of genetic factors and biomarkers predicting pain recovery in newly diagnosed lumbar radicular pain (LRP) patients.
METHODS
The search was performed in Medline OVID, Embase, PsycInfo and Web of Science (2004 to 2015). Only prospective studies of patients with LRP addressing the role of genetic factors (genetic susceptibility) and pain biomarkers (proteins in serum) were included. Two independent reviewers extracted the data and assessed methodological quality.
RESULTS
The search identified 880 citations of which 15 fulfilled the inclusion criteria. Five genetic variants; i.e., OPRM1 rs1799971 G allele, COMT rs4680 G allele, MMP1 rs1799750 2G allele, IL1α rs1800587 T allele, IL1RN rs2234677 A allele, were associated with reduced recovery of LRP. Three biomarkers; i.e., TNFα, IL6 and IFNα, were associated with persistent LRP.
CONCLUSION
The present results indicate that several genetic factors and biomarkers may predict slow recovery in LRP. Still, there is a need for replication of the findings. A stricter use of nomenclature is also highly necessary.
TRIAL REGISTRATION
The review is registered PROSPERO 20 of November 2015. Registration number is CRD42015029125 .
Topics: Alleles; Biomarkers; Catechol O-Methyltransferase; Disabled Persons; Genetic Predisposition to Disease; Humans; Interferon-alpha; Interleukin 1 Receptor Antagonist Protein; Interleukin-1alpha; Interleukin-6; Low Back Pain; Lumbosacral Region; Matrix Metalloproteinase 1; Polymorphism, Single Nucleotide; Prevalence; Receptors, Opioid, mu; Sciatica; Tumor Necrosis Factor-alpha
PubMed: 27964712
DOI: 10.1186/s12891-016-1356-5 -
British Journal of Anaesthesia Jun 2019Opioid-induced hyperalgesia (OIH) is well documented in preclinical studies, but findings of clinical studies are less consistent. The objective was to undertake a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Opioid-induced hyperalgesia (OIH) is well documented in preclinical studies, but findings of clinical studies are less consistent. The objective was to undertake a systematic review and meta-analysis of studies examining evidence for OIH in humans after opioid exposure.
METHODS
Systematic electronic searches utilised six research databases (Embase, Medline, PubMed, CINAHL Plus, Web of Science, and OpenGrey). Manual 'grey' literature searches were also undertaken. The Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework was used to develop search strategies, and findings are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Data synthesis and subgroup analyses were undertaken using a random effects model (DerSimonian-Laird method).
RESULTS
A total of 6167 articles were identified. After abstract and full-text reviews, 26 articles (involving 2706 participants) were included in the review. There was evidence of OIH, assessed by pain tolerance, in response to noxious thermal (hot and cold) stimuli, but not electrical stimuli. There was no evidence of OIH when assessing pain detection thresholds. OIH was more evident in patients with opioid use disorder than in patients with pain, and in patient groups treated with N-methyl-d-aspartate receptor antagonists (primarily evidenced in methadone-maintained populations).
CONCLUSIONS
OIH was evident in patients after chronic opioid exposure, but findings were dependent upon pain modality and assessment measures. Further studies should consider evaluating both pain threshold and pain tolerance across a range of modalities to ensure assessment validity. Significant subgroup findings suggest that potential confounders of pain judgements, such as illicit substance use, affective characteristics, or coping styles, should be rigorously controlled in future studies.
Topics: Analgesics, Opioid; Chronic Pain; Drug Administration Schedule; Humans; Hyperalgesia; Pain Measurement; Pain Threshold
PubMed: 30915985
DOI: 10.1016/j.bja.2018.09.019 -
Medicine Aug 2021Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB).
METHODS
We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796.
RESULTS
After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05).
CONCLUSIONS
This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.
Topics: Adjuvants, Anesthesia; Adrenergic alpha-2 Receptor Agonists; Anesthesia, Local; Dexamethasone; Dexmedetomidine; Glucocorticoids; Humans; Nerve Block; Peripheral Nerves; Randomized Controlled Trials as Topic
PubMed: 34449500
DOI: 10.1097/MD.0000000000027064 -
Frontiers in Pharmacology 2020Pain is considered an unpleasant sensory and emotional experience, being considered as one of the most important causes of human suffering. Computational chemistry...
INTRODUCTION
Pain is considered an unpleasant sensory and emotional experience, being considered as one of the most important causes of human suffering. Computational chemistry associated with bioinformatics has stood out in the process of developing new drugs, through natural products, to manage this condition.
OBJECTIVE
To analyze, through literature data, recent molecular coupling studies on the antinociceptive activity of essential oils and monoterpenes.
DATA SOURCE
Systematic search of the literature considering the years of publications between 2005 and December 2019, in the electronic databases PubMed and .
ELIGIBILITY CRITERIA
Were considered as criteria of 1) Biological activity: non-clinical effects of an OE and/or monoterpenes on antinociceptive activity based on animal models and analysis, 2) studies with plant material: chemically characterized essential oils and/or their constituents isolated, 3) clinical and non-clinical studies with analysis to assess antinociceptive activity, 4) articles published in English. Exclusion criteria were literature review, report or case series, meta-analysis, theses, dissertations, and book chapter.
RESULTS
Of 16,006 articles, 16 articles fulfilled all the criteria. All selected studies were non-clinical. The most prominent plant families used were Asteraceae, Euphorbiaceae, Verbenaceae, Lamiaceae, and Lauraceae. Among the phytochemicals studied were α-Terpineol, 3-(5-substituted-1,3,4-oxadiazol-2-yl)-N'-[2-oxo-1,2-dihydro-3H-indol-3-ylidene] propane hydrazide, β-cyclodextrin complexed with citronellal, (-)-α-bisabolol, β-cyclodextrin complexed with farnesol, and p-Cymene. The softwares used for docking studies were Molegro Virtual Docker, SybylX, Vlife MDS, AutoDock Vina, Hex Protein Docking, and AutoDock 4.2 in PyRx 0.9. The molecular targets/complexes used were Nitric Oxide Synthase, COX-2, GluR2-S1S2, TRPV1, β-CD complex, CaV, CaV, CaV, and CaV, 5-HT receptor, delta receptor, kappa receptor, and MU (μ) receptor, alpha adrenergic, opioid, and serotonergic receptors, muscarinic receptors and GABA opioid and serotonin receptors, 5-HT and M receptors. Many of the covered studies used molecular coupling to investigate the mechanism of action of various compounds, as well as molecular dynamics to investigate the stability of protein-ligand complexes.
CONCLUSIONS
The studies revealed that through the advancement of more robust computational techniques that complement the experimental studies, they may allow some notes on the identification of a new candidate molecule for therapeutic use.
PubMed: 32547391
DOI: 10.3389/fphar.2020.00777 -
Genes Jul 2023Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how...
BACKGROUND
Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field.
METHODS
Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing.
RESULTS
We identified three original studies. In one study, the authors observed that six (5.9%) patients with functional seizures carried pathogenic/likely pathogenic variants. In another study, the authors observed that, in functional seizures, there was a significant correlation with genes that are over-represented in adrenergic, serotonergic, oxytocin, opioid, and GABA receptor signaling pathways. In the third study, the authors observed that patients with functional seizures, as well as patients with depression, had significantly different genotypes in single nucleotide polymorphisms compared with controls.
CONCLUSION
Future genetic investigations of patients with functional seizures would increase our understanding of the pathophysiological and neurobiological problems underlying this common neuropsychological stress-associated condition.
Topics: Humans; Analgesics, Opioid; Cognition; DNA Copy Number Variations; Genotype; Seizures
PubMed: 37628589
DOI: 10.3390/genes14081537