Current Neuropharmacology最新文献

{"title":"Glymphatic System and Psychiatric Disorders: A Rapid Comprehensive Scoping Review","authors":"Tommaso Barlattani, Paolo Grandinetti, Alexsander Di Cintio, Alessio Montemagno, Roberta Testa, Chiara D’Amelio, Luigi Olivieri, Carmine Tomasetti, Alessandro Rossi, Francesca Pacitti, Domenico De Berardis","doi":"10.2174/1570159x22666240130091235","DOIUrl":"https://doi.org/10.2174/1570159x22666240130091235","url":null,"abstract":"Background: Since discovering the glymphatic system, there has been a looming interest in exploring its relationship with psychiatric disorders. Recently, increasing evidence suggests an involvement of the glymphatic system in the pathophysiology of psychiatric disorders. However, clear data are still lacking. In this context, this rapid comprehensive PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) scoping review aims to identify and analyze current evidence about the relation between the glymphatic system and psychiatric disorders. Methods: We conducted a comprehensive review of the literature and then proceeded to discuss the findings narratively. Tables were then constructed and articles were sorted according to authors, year, title, location of study, sample size, psychiatric disorder, the aim of the study, principal findings, implications. Results: Twenty papers were identified as eligible, among which 2 articles on Schizophrenia, 1 on Autism Spectrum Disorders, 2 on Depression, 1 on Depression and Trauma-related Disorders, 1 on Depression and Anxiety, 2 on Anxiety and Sleep Disorders, 8 on Sleep Disorders, 2 on Alcohol use disorder and 1 on Cocaine Use Disorder. Conclusion: This review suggests a correlation between the glymphatic system and several psychiatric disorders: Schizophrenia, Depression, Anxiety Disorders, Sleep Disorders, Alcohol Use Disorder, Cocaine Use Disorder, Trauma-Related Disorders, and Autism Spectrum Disorders. Impairment of the glymphatic system could play a role in Trauma-Related Disorders, Alcohol Use Disorders, Cocaine Use Disorders, Sleep Disorders, Depression, and Autism Spectrum Disorders. It is important to implement research on this topic and adopt standardized markers and radio diagnostic tools.","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":"4 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141063536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Translational Future of Stress Neurobiology and Psychosis Vulnerability: A Review of the Evidence.","authors":"Alexis E Cullen, Javier Labad, Dominic Oliver, Adam Al-Diwani, Amedeo Minichino, Paolo Fusar-Poli","doi":"10.2174/1570159X21666230322145049","DOIUrl":"10.2174/1570159X21666230322145049","url":null,"abstract":"<p><p>Psychosocial stress is a well-established risk factor for psychosis, yet the neurobiological mechanisms underlying this relationship have yet to be fully elucidated. Much of the research in this field has investigated hypothalamic-pituitary-adrenal (HPA) axis function and immuno-inflammatory processes among individuals with established psychotic disorders. However, as such studies are limited in their ability to provide knowledge that can be used to develop preventative interventions, it is important to shift the focus to individuals with increased vulnerability for psychosis (i.e., high-risk groups). In the present article, we provide an overview of the current methods for identifying individuals at high-risk for psychosis and review the psychosocial stressors that have been most consistently associated with psychosis risk. We then describe a network of interacting physiological systems that are hypothesised to mediate the relationship between psychosocial stress and the manifestation of psychotic illness and critically review evidence that abnormalities within these systems characterise highrisk populations. We found that studies of high-risk groups have yielded highly variable findings, likely due to (i) the heterogeneity both within and across high-risk samples, (ii) the diversity of psychosocial stressors implicated in psychosis, and (iii) that most studies examine single markers of isolated neurobiological systems. We propose that to move the field forward, we require well-designed, largescale translational studies that integrate multi-domain, putative stress-related biomarkers to determine their prognostic value in high-risk samples. We advocate that such investigations are highly warranted, given that psychosocial stress is undoubtedly a relevant risk factor for psychotic disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"350-377"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9156740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetics of Fear, Anxiety and Stress - Focus on Histone Modifications.","authors":"Marco A Ell, Miriam A Schiele, Nicola Iovino, Katharina Domschke","doi":"10.2174/1570159X21666230322154158","DOIUrl":"10.2174/1570159X21666230322154158","url":null,"abstract":"<p><p>Fear-, anxiety- and stress-related disorders are among the most frequent mental disorders. Given substantial rates of insufficient treatment response and often a chronic course, a better understanding of the pathomechanisms of fear-, anxiety- and stress-related disorders is urgently warranted. Epigenetic mechanisms such as histone modifications - positioned at the interface between the biological and the environmental level in the complex pathogenesis of mental disorders - might be highly informative in this context. The current state of knowledge on histone modifications, chromatin-related pharmacology and animal models modified for genes involved in the histone-related epigenetic machinery will be reviewed with respect to fear-, anxiety- and stress-related states. Relevant studies, published until 30th June 2022, were identified using a multi-step systematic literature search of the Pub- Med and Web of Science databases. Animal studies point towards histone modifications (e.g., H3K4me3, H3K9me1/2/3, H3K27me2/3, H3K9ac, H3K14ac and H4K5ac) to be dynamically and mostly brain region-, task- and time-dependently altered on a genome-wide level or gene-specifically (<i>e.g., Bdnf</i>) in models of fear conditioning, retrieval and extinction, acute and (sub-)chronic stress. Singular and underpowered studies on histone modifications in human fear-, anxiety- or stress-related phenotypes are currently restricted to the phenotype of PTSD. Provided consistent validation in human phenotypes, epigenetic biomarkers might ultimately inform indicated preventive interventions as well as personalized treatment approaches, and could inspire future innovative pharmacological treatment options targeting the epigenetic machinery improving treatment response in fear-, anxiety- and stressrelated disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"843-865"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9156742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Exercise to Redynamize Interoception in Substance use Disorders.","authors":"Damien Brevers, Joël Billieux, Philippe de Timary, Olivier Desmedt, Pierre Maurage, José Cesar Perales, Samuel Suárez-Suárez, Antoine Bechara","doi":"10.2174/1570159X21666230314143803","DOIUrl":"10.2174/1570159X21666230314143803","url":null,"abstract":"<p><p>Physical exercise is considered a promising medication-free and cost-effective adjunct treatment for substance use disorders (SUD). Nevertheless, evidence regarding the effectiveness of these interventions is currently limited, thereby signaling the need to better understand the mechanisms underlying their impact on SUD, in order to reframe and optimize them. Here we advance that physical exercise could be re-conceptualized as an \"interoception booster\", namely as a way to help people with SUD to better decode and interpret bodily-related signals associated with transient states of homeostatic imbalances that usually trigger consumption. We first discuss how mismatches between current and desired bodily states influence the formation of reward-seeking states in SUD, in light of the insular cortex brain networks. Next, we detail effort perception during physical exercise and discuss how it can be used as a relevant framework for re-dynamizing interoception in SUD. We conclude by providing perspectives and methodological considerations for applying the proposed approach to mixed-design neurocognitive research on SUD.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1047-1063"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9111625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabotropic Glutamate Receptors Type 3 and 5 Feature the \"NeuroTransmitter-type\" of Glioblastoma: A Bioinformatic Approach.","authors":"Matteo Caridi, Marika Alborghetti, Valeria Pellicelli, Rosamaria Orlando, Francesco Ernesto Pontieri, Giuseppe Battaglia, Antonietta Arcella","doi":"10.2174/1570159X22666240320112926","DOIUrl":"10.2174/1570159X22666240320112926","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) represents an aggressive and common tumor of the central nervous system. The prognosis of GBM is poor, and despite a refined genetic and molecular characterization, pharmacological treatment is largely suboptimal.</p><p><strong>Objective: </strong>Contribute to defining a therapeutic line in GBM targeting the mGlu3 receptor in line with the principles of precision medicine.</p><p><strong>Methods: </strong>Here, we performed a computational analysis focused on the expression of type 3 and 5 metabotropic glutamate receptor subtypes (mGlu3 and mGlu5, respectively) in high- and low-grade gliomas.</p><p><strong>Results: </strong>The analysis allowed the identification of a particular high-grade glioma type, characterized by a high expression level of both receptor subtypes and by other markers of excitatory and inhibitory neurotransmission. This so-called neurotransmitter-GBM (NT-GBM) also shows a distinct immunological, metabolic, and vascularization gene signature.</p><p><strong>Conclusion: </strong>Our findings might lay the groundwork for a targeted therapy to be specifically applied to this putative novel type of GBM.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1923-1939"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Metalloproteinases in Diabetes-associated Mild Cognitive Impairment.","authors":"Vitoria Mattos Pereira, Suyasha Pradhanang, Jonathan F Prather, Sreejayan Nair","doi":"10.2174/1570159X22666240517090855","DOIUrl":"10.2174/1570159X22666240517090855","url":null,"abstract":"<p><p>Diabetes has been linked to an increased risk of mild cognitive impairment (MCI), a condition characterized by a subtle cognitive decline that may precede the development of dementia. The underlying mechanisms connecting diabetes and MCI involve complex interactions between metabolic dysregulation, inflammation, and neurodegeneration. A critical mechanism implicated in diabetes and MCI is the activation of inflammatory pathways. Chronic low-grade inflammation, as observed in diabetes, can lead to the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and interferon-gamma (IFNγ), each of which can exacerbate neuroinflammation and contribute to cognitive decline. A crucial enzyme involved in regulating inflammation is ADAM17, a disintegrin, and metalloproteinase, which can cleave and release TNF-α from its membrane-bound precursor and cause it to become activated. These processes, in turn, activate additional inflammation-related pathways, such as AKT, NF-κB, NLP3, MAPK, and JAK-STAT pathways. Recent research has provided novel insights into the role of ADAM17 in diabetes and neurodegenerative diseases. ADAM17 is upregulated in both diabetes and Alzheimer's disease, suggesting a shared mechanism and implicating inflammation as a possible contributor to much broader forms of pathology and pointing to a possible link between inflammation and the emergence of MCI. This review provides an overview of the different roles of ADAM17 in diabetes-associated mild cognitive impairment diseases. It identifies mechanistic connections through which ADAM17 and associated pathways may influence the emergence of mild cognitive impairment.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"58-74"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Lithium Treatment Alters NMDA and AMPA Receptor Synaptic Availability and Dendritic Spine Organization in the Rat Hippocampus.","authors":"Lucia Caffino, Giorgia Targa, Anne Stephanie Mallien, Francesca Mottarlini, Beatrice Rizzi, Judith R Homberg, Peter Gass, Fabio Fumagalli","doi":"10.2174/1570159X21666230913144420","DOIUrl":"10.2174/1570159X21666230913144420","url":null,"abstract":"<p><strong>Background: </strong>The mechanisms underlying the action of lithium (LiCl) in bipolar disorder (BD) are still far from being completely understood. Previous evidence has revealed that BD is characterized by glutamate hyperexcitability, suggesting that LiCl may act, at least partially, by toning down glutamatergic signaling abnormalities.</p><p><strong>Objective: </strong>In this study, taking advantage of western blot and confocal microscopy, we used a combination of integrative molecular and morphological approaches in rats exposed to repeated administration of LiCl at a therapeutic dose (between 0.6 and 1.2 mmol/l) and sacrificed at two different time points, i.e., 24 hours and 7 days after the last exposure.</p><p><strong>Results: </strong>We report that repeated LiCl treatment activates multiple, parallel, but also converging forms of compensatory neuroplasticity related to glutamatergic signaling. More specifically, LiCl promoted a wave of neuroplasticity in the hippocampus, involving the synaptic recruitment of GluN2A-containing NMDA receptors, GluA1-containing AMPA receptors, and the neurotrophin BDNF that are indicative of a more plastic spine. The latter is evidenced by morphological analyses showing changes in dendritic spine morphology, such as increased length and head diameter of such spines. These changes may counteract the potentially negative extra-synaptic movements of GluN2B-containing NMDA receptors as well as the increase in the formation of GluA2-lacking Ca²⁺-permeable AMPA receptors.</p><p><strong>Conclusion: </strong>Our findings highlight a previously unknown cohesive picture of the glutamatergic implications of LiCl action that persist long after the end of its administration, revealing for the first time a profound and persistent reorganization of the glutamatergic postsynaptic density receptor composition and structure.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"2045-2058"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensory Reinforced Corticostriatal Plasticity.","authors":"Nicolas Vautrelle, Véronique Coizet, Mariana Leriche, Lionel Dahan, Jan M Schulz, Yan-Feng Zhang, Abdelhafid Zeghbib, Paul G Overton, Enrico Bracci, Peter Redgrave, John N J Reynolds","doi":"10.2174/1570159X21666230801110359","DOIUrl":"10.2174/1570159X21666230801110359","url":null,"abstract":"<p><strong>Background: </strong>Regional changes in corticostriatal transmission induced by phasic dopaminergic signals are an essential feature of the neural network responsible for instrumental reinforcement during discovery of an action. However, the timing of signals that are thought to contribute to the induction of corticostriatal plasticity is difficult to reconcile within the framework of behavioural reinforcement learning, because the reinforcer is normally delayed relative to the selection and execution of causally-related actions.</p><p><strong>Objective: </strong>While recent studies have started to address the relevance of delayed reinforcement signals and their impact on corticostriatal processing, our objective was to establish a model in which a sensory reinforcer triggers appropriately delayed reinforcement signals relayed to the striatum via intact neuronal pathways and to investigate the effects on corticostriatal plasticity.</p><p><strong>Methods: </strong>We measured corticostriatal plasticity with electrophysiological recordings using a light flash as a natural sensory reinforcer, and pharmacological manipulations were applied in an <i>in vivo</i> anesthetized rat model preparation.</p><p><strong>Results: </strong>We demonstrate that the spiking of striatal neurons evoked by single-pulse stimulation of the motor cortex can be potentiated by a natural sensory reinforcer, operating through intact afferent pathways, with signal timing approximating that required for behavioural reinforcement. The pharmacological blockade of dopamine receptors attenuated the observed potentiation of corticostriatal neurotransmission.</p><p><strong>Conclusion: </strong>This novel <i>in vivo</i> model of corticostriatal plasticity offers a behaviourally relevant framework to address the physiological, anatomical, cellular, and molecular bases of instrumental reinforcement learning.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1513-1527"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10302418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional MRI Techniques Suggesting that the Stress System Interacts with Three Large Scale Core Brain Networks to Help Coordinate the Adaptive Response: A Systematic Review.","authors":"George Paltoglou, Charikleia Stefanaki, George P Chrousos","doi":"10.2174/1570159X21666230801151718","DOIUrl":"10.2174/1570159X21666230801151718","url":null,"abstract":"<p><strong>Objective: </strong>Synthesis of functional MRI (fMRI) and functional connectivity (FC) analysis data on human stress system (SS) function, as it relates to the dynamic function of the Salience (SN), Default Mode (DMN) and Central Executive (CEN) networks.</p><p><strong>Methods: </strong>Systematic search of Medline, Scopus, Clinical Trials.gov, and Google Scholar databases of studies published prior to September 2022 resulted in 28 full-text articles included for qualitative synthesis.</p><p><strong>Results: </strong>Acute stress changes the states of intra-/inter- neural network FCs and activities from those of resting, low arousal state in the SN, DMN and CEN, during which intra- and inter-network FCs and activities of all three networks are low. SS activation is positively linked to the activity of the SN and negatively to that of the DMN, while, in parallel, it is associated with an initial decrease and a subsequent increase of the intra- network FC and activity of the CEN. The FC between the DMN and the CEN increases, while those between the SN and the CEN decrease, allowing time for frontal lobe strategy input and \"proper\" CEN activity and task decision. SN activation is linked to sensory hypersensitivity, \"impaired\" memory, and a switch from serial to parallel processing, while trait mindfulness is associated with FC changes promoting CEN activity and producing a \"task-ready state\".</p><p><strong>Conclusion: </strong>SS activation is tightly connected to that of the SN, with stress hormones likely potentiating the intra-network FC of the latter, attenuating that of the DMN, and causing a biphasic suppression- to-activation response of the CEN, all adaptive changes favoring proper decisions and survival.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"976-989"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9958854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Cav2.3 (R-type) Calcium Channel in Pain and Analgesia: A Scoping Review.","authors":"Marcella de Amorim Ferreira, Juliano Ferreira","doi":"10.2174/1570159X21666230811102700","DOIUrl":"10.2174/1570159X21666230811102700","url":null,"abstract":"<p><strong>Background: </strong>Voltage-gated calcium channels (VGCCs) play an important role in pain development and maintenance. As Cav2.2 and Cav3.2 channels have been identified as potential drug targets for analgesics, the participation of Cav2.3 (that gives rise to R-type calcium currents) in pain and analgesia remains incompletely understood.</p><p><strong>Objective: </strong>Identify the participation of Cav2.3 in pain and analgesia.</p><p><strong>Methods: </strong>To map research in this area as well as to identify any existing gaps in knowledge on the potential role of Cav2.3 in pain signalling, we conducted this scoping review. We searched PubMed and SCOPUS databases, and 40 articles were included in this study. Besides, we organized the studies into 5 types of categories within the broader context of the role of Cav2.3 in pain and analgesia.</p><p><strong>Results: </strong>Some studies revealed the expression of Cav2.3 in pain pathways, especially in nociceptive neurons at the sensory ganglia. Other studies demonstrated that Cav2.3-mediated currents could be inhibited by analgesic/antinociceptive drugs either indirectly or directly. Some articles indicated that Cav2.3 modulates nociceptive transmission, especially at the pre-synaptic level at spinal sites. There are studies using different rodent pain models and approaches to reduce Cav2.3 activity or expression and mostly demonstrated a pro-nociceptive role of Cav2.3, despite some contradictory findings and deficiencies in the description of study design quality. There are three studies that reported the association of single-nucleotide polymorphisms in the Cav2.3 gene (CACNA1E) with postoperative pain and opioid consumption as well as with the prevalence of migraine in patients.</p><p><strong>Conclusion: </strong>Cav2.3 is a target for some analgesic drugs and has a pro-nociceptive role in pain.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1909-1922"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}