Neuropharmacology最新文献_第3页

GPR88 impairs the signaling of kappa opioid receptors in a heterologous system and in primary striatal neurons.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-28 DOI: 10.1016/j.neuropharm.2024.110242

Rafael Rivas-Santisteban, Jaume Lillo, Claudia Garrigós, Gemma Navarro, Rafael Franco

{"title":"GPR88 impairs the signaling of kappa opioid receptors in a heterologous system and in primary striatal neurons.","authors":"Rafael Rivas-Santisteban, Jaume Lillo, Claudia Garrigós, Gemma Navarro, Rafael Franco","doi":"10.1016/j.neuropharm.2024.110242","DOIUrl":"10.1016/j.neuropharm.2024.110242","url":null,"abstract":"The physiological role of GPR88, an orphan G protein-coupled receptor (GPCR) predominantly expressed in the striatum, remains unclear, despite its altered expression in parkinsonian animal models. GPR88 is known to interact with other GPCRs. Specifically, GPR88 expression inhibits signaling mediated by the μ-opioid receptor in cells coexpressing both receptors. The effect of GPR88 on the kappa-opioid receptor (KOR) is less understood. In this study, we examine the interaction between GPR88 and KOR, and the impact of GPR88 expression on KOR-mediated signaling in heterologous cells and primary striatal neurons. Bioluminescence resonance energy transfer and proximity ligation assays revealed an interaction between GPR88 and KOR. Functional assays showed that GPR88 antagonized the effects of U69,593, a selective KOR agonist, on forskolin-stimulated cAMP levels, β-arrestin-2 recruitment, and phosphorylation of extracellular signal-regulated kinases (ERK1/2) in HEK-293T cells coexpressing both receptors. In primary striatal neurons, GPR88 and KOR complexes were observed, with KOR activation effects enhanced when GPR88 expression was suppressed using RNA interference. These results suggest that GPR88 and KOR are coexpressed in striatal neurons, where GPR88 inhibits KOR activation. Notably, the GPR88-KOR heteromer was more prevalent in dopamine D1-receptor-containing neurons of the direct pathway of the basal ganglia. Given the roles of KORs in dopamine release, motor function regulation, and pain and reward perception, the GPR88-KOR interaction warrants further investigation in the context of neuropathic pain, Parkinson's disease, and neuropsychiatric disorders.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110242"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755549","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}

引用次数: 0

Modeling of Parkinson's disease by intrastriatal administration of streptozotocin.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-01 Epub Date: 2024-12-04 DOI: 10.1016/j.neuropharm.2024.110246

Jelena Osmanovic Barilar, Vito Papic, Vladimir Farkas, Ivana Rubic, Patrik Meglic, Robert Bagaric, Ana Babic Perhoc, Davor Virag, Jan Homolak, Melita Salkovic-Petrisic, Ana Knezovic

{"title":"Modeling of Parkinson's disease by intrastriatal administration of streptozotocin.","authors":"Jelena Osmanovic Barilar, Vito Papic, Vladimir Farkas, Ivana Rubic, Patrik Meglic, Robert Bagaric, Ana Babic Perhoc, Davor Virag, Jan Homolak, Melita Salkovic-Petrisic, Ana Knezovic","doi":"10.1016/j.neuropharm.2024.110246","DOIUrl":"10.1016/j.neuropharm.2024.110246","url":null,"abstract":"Parkinson's disease (PD) is a highly heterogeneous and therefore a possible cause of translation failure of drugs from animal testing to human treatments can be because existing models cannot replicate the entire spectrum of PD features. One of the theories of the origin of neurodegenerative diseases assumes metabolic dysfunction as a common fundamental thread of disease development. Intracerebroventricular administration of streptozotocin induces insulin resistance in the brain (Alzheimer's disease animal model). The aim of this project is to examine whether metabolic dysfunction caused by direct application of streptozotocin to brain region affected in PD (striatum) can induce characteristic PD symptoms. Adult male Wistar rats were given streptozotocin bilaterally or unilaterally in striatum. PET scan, cognitive, behavioural and motoric functions were tested one month after administration. Metabolite and protein analysis was done by untargeted metabolomics, ELISA and Western blot. Rats administered bilaterally showed motoric deficit, cognitive deficit of spatial learning and memory, fear conditioned and recognition memory, and anxiety-like behaviour, accompanied by impaired brain glucose uptake and metabolism. The results provide first evidence that bilateral intrastriatal administration of streptozotocin (particularly lower dose) can cause development of the hallmark PD symptoms. As metabolic dysfunction is increasingly associated with PD, an animal model with hypermetabolism in the early-on could be a better PD model for testing diverse therapeutics and the results could be better translated to humans. Further characterization is needed for understanding possible underlying mechanism and development of a new animal model for unique PD endophenotype expressing motoric, cognitive and metabolic symptomatology.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"265 ","pages":"110246"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792019","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}

引用次数: 0

A selective small-molecule agonist of G protein-gated inwardly-rectifying potassium channels reduces epileptiform activity in mouse models of tumor-associated and provoked seizures.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-01 Epub Date: 2024-12-09 DOI: 10.1016/j.neuropharm.2024.110259

Robert A Rifkin, Xiaoping Wu, Brianna Pereira, Brian Ja Gill, Edward M Merricks, Andrew J Michalak, Alexander R Goldberg, Nelson Humala, Athanassios Dovas, Ganesha Rai, Guy M McKhann, Paul A Slesinger, Peter Canoll, Catherine Schevon

{"title":"A selective small-molecule agonist of G protein-gated inwardly-rectifying potassium channels reduces epileptiform activity in mouse models of tumor-associated and provoked seizures.","authors":"Robert A Rifkin, Xiaoping Wu, Brianna Pereira, Brian Ja Gill, Edward M Merricks, Andrew J Michalak, Alexander R Goldberg, Nelson Humala, Athanassios Dovas, Ganesha Rai, Guy M McKhann, Paul A Slesinger, Peter Canoll, Catherine Schevon","doi":"10.1016/j.neuropharm.2024.110259","DOIUrl":"10.1016/j.neuropharm.2024.110259","url":null,"abstract":"Tumor associated epilepsy is a common and debilitating co-morbidity of brain tumors, for which inadequate treatments are available. Additionally, animal models suggest a potential link between seizures and tumor progression. Our group has previously described a mouse model of diffusely infiltrating glioma and associated chronic epilepsy. G protein-gated inwardly rectifying potassium (GIRK) channels are important regulators of neuronal excitability, but their development as a target of antiseizure medications has been hampered by cross-reactivity with GIRK channels in the heart. Recently GiGA1, a novel GIRK agonist that is highly selective for brain tissue, was developed and shown to have antiseizure properties in an acute chemoconvulsant model. Here, we test GiGA1 ex vivo in our established mouse model of tumor associated epilepsy, demonstrating that a highly selective, small-molecule GIRK agonist can reduce seizure-like activity in the peritumoral region, where neurons and glioma cells interact and from which focal seizures arise.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110259"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813711","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}

引用次数: 0

Subanesthetic propofol alleviates chronic stress-induced anxiety by enhancing VTADA neurons' activity. 亚麻醉状态下的异丙酚可通过增强 VTADA 神经元的活性来缓解慢性压力诱发的焦虑。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-03-01 Epub Date: 2024-12-13 DOI: 10.1016/j.neuropharm.2024.110264

Shaolei Jiang, Dengyun Ge, Bo Song, Xiaofei Deng, Zhongdong Liu, Jian He, Jing Sun, Zhi Zhu, Zhiqiang Meng, Yingjie Zhu

{"title":"Subanesthetic propofol alleviates chronic stress-induced anxiety by enhancing VTADA neurons' activity.","authors":"Shaolei Jiang, Dengyun Ge, Bo Song, Xiaofei Deng, Zhongdong Liu, Jian He, Jing Sun, Zhi Zhu, Zhiqiang Meng, Yingjie Zhu","doi":"10.1016/j.neuropharm.2024.110264","DOIUrl":"10.1016/j.neuropharm.2024.110264","url":null,"abstract":"Anxiety, a common mental disorder, imposes significant clinical and economic burdens. Previous studies indicate that propofol has anxiolytic effects at anesthetic doses. However, the risks associated with general anesthesia limit its application in anxiety treatment. The feasibility of using subanesthetic doses of propofol to alleviate chronic stress-induced anxiety and the underlying neural mechanisms remain unknown. Here, we found that subanesthetic dose (20 mg/kg and 40 mg/kg) of propofol alleviated anxiety-like behaviors induced by chronic unpredictable mild stress (CUMS) in mice, and the anxiolytic effects were maintained for at least 6 h. In vivo calcium imaging study showed that propofol significantly enhanced Ca2+ signals in ventral tegmental area dopaminergic (VTADA) neurons. Whole-cell patch-clamp recordings confirmed that subanesthetic propofol increased the excitability of VTADA neurons while inhibiting VTA GABAergic (VTAGABA) neurons. Propofol suppressed spontaneous inhibitory postsynaptic currents (sIPSCs) in VTADA neurons, accompanied by a decline in the ability of GABAergic neurons to transmit inhibitory signals. These findings suggests that a subanesthetic dose of propofol enhances the excitability of VTADA neurons through disinhibition, demonstrating its potential for the treatment of CUMS-associated anxiety-like behaviors.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110264"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829530","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}

引用次数: 0

Cholesterol metabolites modulate ionotropic P2X4 and P2X7 receptor current in microglia cells.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-01-02 DOI: 10.1016/j.neuropharm.2024.110294

Michele Barraco, Eva Kudova, Claudio Bucolo, Lucia Ciranna, Maria Angela Sortino, Mariangela Chisari

{"title":"Cholesterol metabolites modulate ionotropic P2X4 and P2X7 receptor current in microglia cells.","authors":"Michele Barraco, Eva Kudova, Claudio Bucolo, Lucia Ciranna, Maria Angela Sortino, Mariangela Chisari","doi":"10.1016/j.neuropharm.2024.110294","DOIUrl":"https://doi.org/10.1016/j.neuropharm.2024.110294","url":null,"abstract":"The central nervous system is a well-known steroidogenic tissue producing, among others, cholesterol metabolites such as neuroactive steroids, oxysterols and steroid hormones. It is well known that these endogenous molecules affect several receptor classes, including ionotropic GABAergic and NMDA glutamatergic receptors in neurons. It has been shown that also ionotropic purinergic (P2X) receptors are cholesterol metabolites' targets. Among P2X receptors, purinergic P2X4 and P2X7 receptors are expressed in microglia, the innate immune cells involved in the brain inflammatory response. In this study, we explore the ionotropic purinergic receptors modulation by cholesterol metabolites in microglia. Patch-clamp experiments were performed in BV2 cells, a murine microglia cell line, to evaluate effects of cholesterol metabolites using micro- and nanomolar concentrations. About P2X4 receptor, we found that testosterone butyrate (20 μM and 200 nM) and allopregnanolone (10 μM and 100 nM) both potentiated its current, while neither 25-hydroxycholesterol (10 μM and 100 nM) nor 17β-estradiol (1 μM) showed any effects. On the other hand, P2X7 receptor current was potentiated by allopregnanolone (10 μM) and 25-hydroxycholesterol (10 μM and 100 nM). Taken together, our data show that modulation of either P2X4 and P2X7 current is affected differently by cholesterol metabolites, suggesting a structure-activity relationship among these players. Identifying the possible link between purinergic transmission, microglia and cholesterol metabolites will allow to define new targets for drug development to treat neuroinflammation.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110294"},"PeriodicalIF":4.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927702","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}

引用次数: 0

Microglial activation and neuroinflammation in acute and chronic cognitive deficits in sepsis.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-31 DOI: 10.1016/j.neuropharm.2024.110285

Paul Denver, Colm Cunningham

{"title":"Microglial activation and neuroinflammation in acute and chronic cognitive deficits in sepsis.","authors":"Paul Denver, Colm Cunningham","doi":"10.1016/j.neuropharm.2024.110285","DOIUrl":"https://doi.org/10.1016/j.neuropharm.2024.110285","url":null,"abstract":"Sepsis is characterised by dysregulated immune responses to infection, leading to multi-organ dysfunction and high rates of mortality. With increasing survival rates in recent years long-term neurological and psychiatric consequences have become more apparent in survivors. Many patients develop sepsis associated encephalopathy (SAE) which encompasses the profound but usually transient neuropsychiatric syndrome delirium but also new brain injury that emerges in the months and years post-sepsis. It now clear that systemic inflammatory signals reach the brain during sepsis and that very significant neuroinflammation ensues. The major brain resident immune cell population, the microglia, has been implicated in acute and chronic cognitive dysfunction in animal models of sepsis based on a growing number of studies using bacterial endotoxin and in polymicrobial sepsis models such as cecal ligation and puncture. The current review explores the effects of sepsis on the brain, focussing on how systemic insults translate to microglial activation and neuroinflammation and how this disrupts neuronal function and integrity. We examine what has been demonstrated specifically with respect to microglial activation, revealing robust evidence for a role for neuroinflammation in sepsis-induced brain sequelae but less clear information on the extent of the specific microglial contribution to this, arising from findings using global knockout mice, non-selective drugs and treatments that equally target peripheral and central compartments. There is, nonetheless, clear evidence that microglia do become activated and do contribute to brain consequences of sepsis thus arguing for improved understanding of these neuroinflammatory processes toward the prevention and treatment of sepsis-induced brain dysfunction.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110285"},"PeriodicalIF":4.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922398","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}

引用次数: 0

A term as Editor-in-Chief of Neuropharmacology: Ups and downs and highs and lows.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-30 DOI: 10.1016/j.neuropharm.2024.110270

Bruno G Frenguelli

引用次数: 0

Clozapine and rapamycin reverse behavioral abnormalities in an animal model of autoimmune schizophrenia.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-27 DOI: 10.1016/j.neuropharm.2024.110286

Duilin Liu, Caiyun Zhu, Hui Wei

{"title":"Clozapine and rapamycin reverse behavioral abnormalities in an animal model of autoimmune schizophrenia.","authors":"Duilin Liu, Caiyun Zhu, Hui Wei","doi":"10.1016/j.neuropharm.2024.110286","DOIUrl":"10.1016/j.neuropharm.2024.110286","url":null,"abstract":"Objective: Autoantibody-associated psychosis represents a distinct disease subgroup of patients with schizophrenia with a suspected autoimmune origin. Although preliminary studies have suggested adjunctive drug treatment strategies targeting the immune system, further validation of these findings is warranted. Autoantibodies against SFT2D2 have been identified in patients with schizophrenia. ApoE-/- mice immunized with SFT2D2-peptides can be used as a model for testing immunotherapy in this subgroup of patients. We used the atypical antipsychotic drug clozapine and immunosuppressant rapamycin to test their effects in this mouse model.Methods: The mice were evaluated for cognitive and schizophrenia-like behaviors. Following behavioral testing, brain samples were collected for analyzing specific pathological changes and dendritic spine formation.Results: Clozapine and rapamycin reversed impaired pre-pulse inhibition, motor impairment, and improved cognitive ability in ApoE -/- mice exposed to anti-SFT2D2 immunoglobulin G. Immunohistochemical assays revealed that both clozapine and rapamycin significantly reduced activated microglial infiltration and restored neuronal dendritic spine density.Conclusions: Our study results suggested that clozapine and rapamycin possess therapeutic benefits for managing autoimmune psychosis and provide mechanistic insights into immunotherapies involving immunosuppressive agents.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110286"},"PeriodicalIF":4.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902851","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}

引用次数: 0

Angiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-26 DOI: 10.1016/j.neuropharm.2024.110279

K Mińczuk, E Schlicker, A Krzyżewska, B Malinowska

{"title":"Angiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors.","authors":"K Mińczuk, E Schlicker, A Krzyżewska, B Malinowska","doi":"10.1016/j.neuropharm.2024.110279","DOIUrl":"10.1016/j.neuropharm.2024.110279","url":null,"abstract":"Although angiotensin 1-7 (Ang 1-7) and its role as a part of the \"protective\" axis of the renin-angiotensin system are well described in the literature, the mechanisms of its angiotensin II-like pressor and tachycardic effects following its acute central administration are not fully understood. It was the aim of the present study to examine which receptors contribute to the aforementioned cardiovascular effects. Ang 1-7 and antagonists for glutamate, GABA, vasopressin, thromboxane A2 (TP), α1-adrenergic, and P2X purinoceptors or modulators of oxidative stress were injected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anesthetized male Wistar rats. Acute injection of Ang 1-7 into the PVN increased blood pressure (BP) by about 15 mmHg and heart rate (HR) by about 14 beats/min. After preinjection with bicuculline (GABAA receptor antagonist), CNQX + D-AP5 (AMPA/kainate and NMDA receptor antagonists) and SQ29548 (TP receptor antagonist) the BP and HR reactions to Ang 1-7 were attenuated or abolished. The vasopressin V1A and V1B receptor antagonists conivaptan and nelivaptan, and the NADPH oxidase inhibitor apocynin even reversed the pressor and tachycardic effects of Ang 1-7. Antagonists of P2X (PPADS) and α1-adrenergic receptors (prazosin), the free radical scavenger tempol and the superoxide dismutase inhibitor DETC did not modify the cardiovascular effects of Ang 1-7. The (Mas receptor-related) rise in BP and HR evoked by Ang 1-7 administered to the rat PVN is linked to glutamate, vasopressin, GABAA and thromboxane receptors, and to oxidative stress, but does not seem to involve α1-adrenergic or P2X receptors.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110279"},"PeriodicalIF":4.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896344","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}

引用次数: 0

Curcumin analog C16 attenuates bone cancer pain induced by MADB 106 breast cancer cells in female rats and inhibits the CREB/NLGN2 signaling axis by targeting CaMKⅠα.

IF 4.6 2区医学

Neuropharmacology Pub Date : 2024-12-25 DOI: 10.1016/j.neuropharm.2024.110284

Liping Chen, Chaobo Ni, Dashan Lu, Shuyao Zhang, Yuhua Li, Dongjie Wang, Bohan Hua, Huadong Ni, Longsheng Xu, Ming Yao

{"title":"Curcumin analog C16 attenuates bone cancer pain induced by MADB 106 breast cancer cells in female rats and inhibits the CREB/NLGN2 signaling axis by targeting CaMKⅠα.","authors":"Liping Chen, Chaobo Ni, Dashan Lu, Shuyao Zhang, Yuhua Li, Dongjie Wang, Bohan Hua, Huadong Ni, Longsheng Xu, Ming Yao","doi":"10.1016/j.neuropharm.2024.110284","DOIUrl":"10.1016/j.neuropharm.2024.110284","url":null,"abstract":"Bone cancer pain (BCP) is one of the most severe complications faced by patients with cancer; however, current pharmacological options are limited. Curcumin has been demonstrated to possess anti-inflammatory and analgesic properties; however, our preliminary research found that the analgesic efficiency of curcumin is not high in BCP. Consequently, curcumin analogs have emerged as a significant focus of our research. This study aimed to systematically investigate the analgesic effects of C16 in rats with BCP induced by MADB 106 breast cancer cells (MADB 106-induced BCP) and elucidate the underlying molecular mechanisms. A range of experimental methods, including kinase profiling, transcriptome sequencing, behavioral tests, immunofluorescence, and biochemical analyses, were employed to comprehensively assess the role of C16 in the MADB 106-induced BCP model. The results indicated that C16 significantly alleviated bone cancer pain induced by Luciferin-MADB 106 cells (10^6 cells) in a dose-dependent manner. Importantly, kinase profiling and validation experiments identified CaMKIα in spinal dorsal horn neurons as the primary target of C16's analgesic effect on MADB 106-induced BCP. Continuous intrathecal administration of C16 markedly suppressed the expression of CREB and P-CREB and reduced the expression of neuroligin 2 in the spinal cords of BCP rats, thereby clarifying the mechanism of action of C16 in alleviating MADB 106-induced BCP. These findings suggest that C16 possesses significant therapeutic potential for mitigating MADB 106-induced BCP nociceptive hypersensitivity, providing a foundation for the future development of novel drugs targeting MADB 106-induced BCP.","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":" ","pages":"110284"},"PeriodicalIF":4.6,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896347","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}

引用次数: 0