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Pain Jul 2021This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and... (Meta-Analysis)
Meta-Analysis
This narrative review represents an output from the International Association for the Study of Pain's global task force on the use of cannabis, cannabinoids, and cannabis-based medicines for pain management, informed by our companion systematic review and meta-analysis of preclinical studies in this area. Our aims in this review are (1) to describe the value of studying cannabinoids and endogenous cannabinoid (endocannabinoid) system modulators in preclinical/animal models of pain; (2) to discuss both pain-related efficacy and additional pain-relevant effects (adverse and beneficial) of cannabinoids and endocannabinoid system modulators as they pertain to animal models of pathological or injury-related persistent pain; and (3) to identify important directions for future research. In service of these goals, this review (1) provides an overview of the endocannabinoid system and the pharmacology of cannabinoids and endocannabinoid system modulators, with specific relevance to animal models of pathological or injury-related persistent pain; (2) describes pharmacokinetics of cannabinoids in rodents and humans; and (3) highlights differences and discrepancies between preclinical and clinical studies in this area. Preclinical (rodent) models have advanced our understanding of the underlying sites and mechanisms of action of cannabinoids and the endocannabinoid system in suppressing nociceptive signaling and behaviors. We conclude that substantial evidence from animal models supports the contention that cannabinoids and endocannabinoid system modulators hold considerable promise for analgesic drug development, although the challenge of translating this knowledge into clinically useful medicines is not to be underestimated.
Topics: Animals; Cannabinoid Receptor Modulators; Cannabinoids; Cannabis; Endocannabinoids; Pain; Pain Management; Receptors, Cannabinoid
PubMed: 33729211
DOI: 10.1097/j.pain.0000000000002268 -
Journal of Endocrinological... Nov 2023The clinical significance of metabolic syndrome (MetS) versus its single components in erectile dysfunction (ED) is conflicting. Thus, the purpose is to analyze the... (Review)
Review
PURPOSE
The clinical significance of metabolic syndrome (MetS) versus its single components in erectile dysfunction (ED) is conflicting. Thus, the purpose is to analyze the available evidence on the relationship between MetS-along with its components-and ED.
METHODS
All prospective and retrospective observational studies reporting information on ED and MetS were included. In addition, we here reanalyzed preclinical and clinical data obtained from a previously published animal model of MetS and from a consecutive series of more than 2697 men (mean age: 52.7 ± 12), respectively.
RESULTS
Data derived from this meta-analysis showed that MetS was associated with an up to fourfold increased risk of ED when either unadjusted or adjusted data were considered. Meta-regression analysis, performed using unadjusted statistics, showed that the MetS-related risk of ED was closely associated with all the MetS components. These associations were confirmed when unadjusted analyses from clinical models were considered. However, fully adjusted data showed that MetS-associated ED was more often due to morbidities included (or not) in the algorithm than to the MetS diagnostic category itself. MetS is also associated with low testosterone, but its contribution to MetS-associated ED-as derived from preclinical and clinical models-although independent, is marginal.
CONCLUSIONS
The results of our analysis suggest that MetS is a useless diagnostic category for studying ED. However, treating the individual MetS components is important, because they play a pivotal role in determining ED.
PubMed: 37515706
DOI: 10.1007/s40618-023-02136-x -
The Journal of Surgical Research Dec 2023Heart transplantation is the treatment of choice for end-stage heart failure. There is a mismatch between the number of donor hearts available and the number of patients... (Review)
Review
INTRODUCTION
Heart transplantation is the treatment of choice for end-stage heart failure. There is a mismatch between the number of donor hearts available and the number of patients awaiting transplantation. Expanding the donor pool is critically important. The use of hearts donated following circulatory death is one approach to increasing the number of available donor hearts.
MATERIALS AND METHODS
A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines utilizing Pubmed/MEDLINE and Embase. Articles including adult human studies and preclinical animal studies of heart transplantation following donation after circulatory death were included. Studies of pediatric populations or including organs other than heart were excluded.
RESULTS
Clinical experience and preclinical studies are reviewed. Clinical experience with direct procurement, normothermic regional perfusion, and machine perfusion are included. Preclinical studies addressing organ function assessment and enhancement of performance of marginal organs through preischemic, procurement, preservation, and reperfusion maneuvers are included. Articles addressing the ethical considerations of thoracic transplantation following circulatory death are also reviewed.
CONCLUSIONS
Heart transplantation utilizing organs procured following circulatory death is a promising method to increase the donor pool and offer life-saving transplantation to patients on the waitlist living with end-stage heart failure. There is robust ongoing preclinical and clinical research to optimize this technique and improve organ yield. There are also ongoing ethical considerations that must be addressed by consensus before wide adoption of this approach.
PubMed: 37657140
DOI: 10.1016/j.jss.2023.07.050 -
The Annals of Pharmacotherapy Feb 2023The objective of this systematic review is to summarize in vitro, preclinical, and human data related to omadacycline and infection (CDI). (Review)
Review
OBJECTIVE
The objective of this systematic review is to summarize in vitro, preclinical, and human data related to omadacycline and infection (CDI).
DATA SOURCES
PubMed and Google Scholar were searched for "omadacycline" AND ("" OR "" OR "") for any studies published before February 15, 2022. The US Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) was searched for omadacycline (for reports including "" or "CDI" or "gastrointestinal infection"). The publications list publicly available at Paratek Pharmaceuticals, Inc. Web site was reviewed.
STUDY SELECTION AND DATA EXTRACTION
Publications presenting primary data on omadacycline and published in English were included.
DATA SYNTHESIS
Preclinical and clinical evidence was extracted from 14 studies. No case reports in indexed literature and no reports on FDA AERS were found. Omadacycline has potent in vitro activity against many clinical strains and diverse ribotypes. In phase 3 studies, there were no reports of CDI in patients who received omadacycline for either community-acquired bacterial pneumonia or acute bacterial skin and skin structure infection.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Omadacycline should be considered a low-risk antibiotic regarding its propensity to cause CDI.
CONCLUSIONS
Reducing the burden of CDI on patients and the health care system should be a priority. Patients with appropriate indications who are at heightened risk of CDI may be suitable candidates for omadacycline therapy. In these patients, omadacycline may be preferable to antibiotics with a high CDI risk.
Topics: Humans; Clostridioides; Anti-Bacterial Agents; Clostridium Infections; Clostridioides difficile; Bacteria; Community-Acquired Infections
PubMed: 35656828
DOI: 10.1177/10600280221089007 -
Pharmacological Reviews Jan 2022A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies... (Review)
Review
A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration, and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones' role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women.The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and not a priori designed to detect sex differences. Additionally, imaging studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving but not cue- or cocaine-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or opioids in rodent models. SIGNIFICANCE STATEMENT: This systematic review summarizes clinical and preclinical studies on sex differences in psychostimulant and opioid craving and relapse. Results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. Results of preclinical studies reviewed provide evidence for sex differences in reinstatement and incubation of cocaine seeking but not for reinstatement or incubation of methamphetamine or opioid seeking.
Topics: Analgesics, Opioid; Animals; Cocaine; Cocaine-Related Disorders; Craving; Extinction, Psychological; Female; Humans; Male; Recurrence; Self Administration; Sex Characteristics
PubMed: 34987089
DOI: 10.1124/pharmrev.121.000367 -
Eating and Weight Disorders : EWD Feb 2023Recent studies have reported a gut microbiota imbalance or dysbiosis associated with anorexia nervosa (AN), which has prompted an appraisal of its aetiological role, and... (Review)
Review
PURPOSE
Recent studies have reported a gut microbiota imbalance or dysbiosis associated with anorexia nervosa (AN), which has prompted an appraisal of its aetiological role, and the reformulation of AN as a metabo-psychiatric disorder. Thus, the aim of this paper was to critically review the current scientific findings regarding the role of microbiota in anorexia nervosa.
METHODS
A systematic study of peer-reviewed literature published in four databases between 2009 and 2022 was conducted according to PRISMA guidelines. Both human and animal studies were included.
RESULTS
A total of 18 studies were included. In animal models, both the preclinical and clinical findings were inconsistent regarding microbiota composition, faecal metabolite concentrations, and the effects of human faecal microbiota transplants.
CONCLUSION
The methodological limitations, lack of standardisation, and conceptual ambiguity hinder the analysis of microbiota as a key explanatory factor for AN.
LEVEL OF EVIDENCE
Level I, systematic review.
Topics: Animals; Humans; Anorexia Nervosa; Microbiota; Gastrointestinal Microbiome; Feces
PubMed: 36752887
DOI: 10.1007/s40519-023-01529-4 -
Headache May 2023To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology. (Review)
Review
OBJECTIVE
To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology.
BACKGROUND
The features of migraine attacks, including characteristics, duration, frequency, and prevalence, are sex-dependent with variability across a lifetime, indicating the involvement of the hypothalamus-pituitary-gonadal axis. Prolactin is a key regulator of this axis, and a new line of evidence implicates prolactin signaling in sex-related differences in pain perception.
METHODS
In this systematic review, we searched PubMed and EMBASE for the terms prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain, and trigeminal pain pathway to find preclinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.
RESULTS
Of a total of 15 preclinical articles selected, 11 were both ex vivo and in vivo, 3 were ex vivo, and 1 was an in vivo study. The main findings were that prolactin receptors are distributed in the trigeminal pain pathway, and prolactin induced migraine-like behavior in rodents. Moreover, prolactin signaling has a crucial role in calcitonin gene-related peptide (CGRP) release, a key molecule in migraine pathogenesis, and prolactin gene deletion attenuated CGRP-induced migraine-like behavior.
CONCLUSION
Preclinical data indicate a key role of prolactin and its receptors in mechanisms causing migraine. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify the influences of prolactin in migraine-attack initiation.
Topics: Humans; Calcitonin Gene-Related Peptide; Headache; Migraine Disorders; Pain; Prolactin; Animals; Mice; Rats
PubMed: 36752584
DOI: 10.1111/head.14412 -
Brain Sciences Feb 2020Intracranial aneurysms (IA) are characterized by weakened cerebral vessel walls that may lead to rupture and subarachnoid hemorrhage. The mechanisms behind their... (Review)
Review
Intracranial aneurysms (IA) are characterized by weakened cerebral vessel walls that may lead to rupture and subarachnoid hemorrhage. The mechanisms behind their formation and progression are yet unclear and warrant preclinical studies. This systematic review aims to provide a comprehensive, systematic overview of available animal models for the study of IA pathobiology. We conducted a systematic literature search using the PubMed database to identify preclinical studies employing IA animal models. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies were reviewed and categorized according to the experimental animal and aneurysm model. Of 4266 returned results, 3930 articles were excluded based on the title and/or abstract and further articles after screening the full text, leaving 123 studies for detailed analysis. A total of 20 different models were found in rats (nine), mice (five), rabbits (four), and dogs (two). Rat models constituted the most frequently employed intracranial experimental aneurysm model (79 studies), followed by mice (31 studies), rabbits (12 studies), and two studies in dogs. The most common techniques to induce cerebral aneurysms were surgical ligation of the common carotid artery with subsequent induction of hypertension by ligation of the renal arteries, followed by elastase-induced creation of IAs in combination with corticosterone- or angiotensin-induced hypertension. This review provides a comprehensive summary of the multitude of available IA models to study various aspects of aneurysm formation, growth, and rupture. It will serve as a useful reference for researchers by facilitating the selection of the most appropriate model and technique to answer their scientific question.
PubMed: 32120907
DOI: 10.3390/brainsci10030134 -
Pharmaceuticals (Basel, Switzerland) Dec 2022The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively... (Review)
Review
The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively evaluated. The aim of this study was to systematically summarize the available knowledge on this topic according to PRISMA guidelines. Data from preclinical and clinical studies were analyzed, considering the safety and efficacy of ASA in the treatment of MD and the correlation of inflammatory parameters with the effect of ASA treatment. Twenty-one studies were included. Both preclinical and clinical studies found evidence indicating the safety and efficacy of low-dose ASA in the treatment of all types of affective episodes in MD. Observational studies have indicated a reduced risk of all types of affective episodes in chronic low-dose ASA users (HR 0.92, 95% CI: 0.88, 0.95, p < 0.0001). An association between ASA response and inflammatory parameters was found in preclinical studies, but this was not confirmed in clinical trials. Further long-term clinical trials evaluating the safety and efficacy of ASA in recurrent MD, as well as assessing the linkage of ASA treatment with inflammatory phenotype and cytokines, are required. There is also a need for preclinical studies to understand the exact mechanism of action of ASA in MD.
PubMed: 36678565
DOI: 10.3390/ph16010067 -
Cells Nov 2023There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past... (Review)
Review
There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.
Topics: Humans; Heart Ventricles; Epigenesis, Genetic; Ventricular Dysfunction, Right; Myocardium; Ventricular Function, Right
PubMed: 38067121
DOI: 10.3390/cells12232693