Canadian journal of physiology and pharmacology最新文献_第9页

Myosin inhibitors for the treatment of obstructive hypertrophic cardiomyopathy: a Canadian perspective on a first-in-class therapy. 肌球蛋白抑制剂治疗梗阻性肥厚性心肌病：加拿大一流治疗的观点。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0124

Wesley Lau, Saif Dababneh, Kevin Ong, Darwin Yeung, Shubhayan Sanatani, Thomas M Roston

{"title":"Myosin inhibitors for the treatment of obstructive hypertrophic cardiomyopathy: a Canadian perspective on a first-in-class therapy.","authors":"Wesley Lau, Saif Dababneh, Kevin Ong, Darwin Yeung, Shubhayan Sanatani, Thomas M Roston","doi":"10.1139/cjpp-2025-0124","DOIUrl":"10.1139/cjpp-2025-0124","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is a relatively common heritable cardiac condition (∼1 in 500), which poses significant morbidity and mortality. Severe symptoms are often from dynamic left ventricular outflow tract (LVOT) obstruction which may result in dyspnea, chest pain, fatigue, and (pre)syncope. This obstructive phenotype is present in more than half of cases. Traditional pharmacological therapies used to treat symptomatic LVOT obstruction are ineffective in many patients thereby necessitating septal reduction therapy in the form of alcohol septal ablation or surgical myectomy. In recent years, the demand for improved HCM treatment without surgical intervention has led to the development of a new class of drugs called cardiac myosin inhibitors. Mavacamten represents the first-in-class cardiac myosin inhibitor, which is now approved in Canada, available for special authorization cost coverage in most provinces, and is increasingly being prescribed in both specialized HCM programs and general cardiology clinics. As such, many general cardiologists, internists, and family physicians will need to be familiar with these agents. This review on the myosin inhibitors, particularly mavacamten, provides a perspective for more general cardiovascular providers by summarizing the key mechanisms, clinical trials, expected outcomes, and potential impacts on the Canadian healthcare system.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Early treatment with pyridostigmine alleviates the isoprenaline-induced model of heart failure with preserved ejection fraction (HFpEF) in rats. 早期应用吡哆斯的明治疗可减轻大鼠保留射血分数（HFpEF）心力衰竭。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0245

Sonja T Marinković, Tanja Šobot, Žana M Maksimović, Ðorđe Ðukanović, Snežana Uletilović, Nebojša Mandić-Kovačević, Sanja Jovičić, Milka Matičić, Milica Gajić Bojić, Aneta Stojmenovski, Anđela Bojanić, Dragana Lončar-Stojiljković, Ranko Škrbić, Miloš P Stojiljković

{"title":"Early treatment with pyridostigmine alleviates the isoprenaline-induced model of heart failure with preserved ejection fraction (HFpEF) in rats.","authors":"Sonja T Marinković, Tanja Šobot, Žana M Maksimović, Ðorđe Ðukanović, Snežana Uletilović, Nebojša Mandić-Kovačević, Sanja Jovičić, Milka Matičić, Milica Gajić Bojić, Aneta Stojmenovski, Anđela Bojanić, Dragana Lončar-Stojiljković, Ranko Škrbić, Miloš P Stojiljković","doi":"10.1139/cjpp-2025-0245","DOIUrl":"10.1139/cjpp-2025-0245","url":null,"abstract":"Acetylcholinesterase (AChE) inhibitors constitute a large and chemically diverse group of compounds that inhibit the enzyme AChE. Some of these compounds that are used to treat Alzheimer's disease have been reported to have favourable cardiovascular effects, i.e., a 35% reduction of the risk for cardiovascular disease. There has been a growing interest in AchE inhibitors as a potential therapeutic approach for cardiovascular diseases, especially heart failure (HF), since they correct the autonomic imbalance, a key component in the development of heart failure. In the present study, HF was induced in male Wistar albino rats using an isoprenaline model (85 mg/kg/day s.c. for 2 days, followed by 3 weeks of HF development) of heart failure with preserved ejection fraction. Afterwards, rats were treated with pyridostigmine (20 mg/kg/day in tap water for 14 days), while the controls received no treatment. Electrocardiographic and echosonographic measurements were obtained, and samples were taken for antioxidative status measurement and histopathological analysis. Administration of pyridostigmine resulted in preservation of cardiac contractile function (↑ EF), coupled with a decrease in chamber wall thinning (↑ PWDd, ↑ PWDs) and dilatation progression (↓ LVIDd, ↓ LVIDs). Additionally, histopathological findings showed significantly reduced tissue damage score and attenuation of cardiac fibrosis development, indicating the cardioprotective potential of pyridostigmine when used as treatment for the early stages of heart failure; however, further investigations are needed to fully investigate the interplay between the several proposed mechanisms through which AChE inhibitors express their protective effects.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Caenorhabditis elegans as a model to explore the genetic underpinnings of human pain-related processes: cannabinoid and opioid neuropharmacology as an example. 秀丽隐杆线虫作为一个模型来探索人类疼痛相关过程的遗传基础：大麻素和阿片神经药理学为例。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0303

Graeme F Ernest-Hoar, Mia E Simmons, Catrina M Loucks

{"title":"Caenorhabditis elegans as a model to explore the genetic underpinnings of human pain-related processes: cannabinoid and opioid neuropharmacology as an example.","authors":"Graeme F Ernest-Hoar, Mia E Simmons, Catrina M Loucks","doi":"10.1139/cjpp-2025-0303","DOIUrl":"10.1139/cjpp-2025-0303","url":null,"abstract":"Caenorhabditis elegans has many traits that make it a valuable model for human neurobiology, including the study of pain-related processes. In particular, its genetic tractability can help uncover novel genetic factors involved in pain-related signal transduction. This can be beneficial for studying pain medications, such as cannabinoids and opioids. Here, we review how the pain-related impacts of cannabinoids/opioids have been assessed using behavioural assays (e.g., measuring feeding, locomotion, and nociception). Reviewed studies identified genetic factors responsible for both cannabinoid (e.g., endocannabinoid receptor npr-19) and opioid (e.g., opioid receptor npr-17) signalling, which were in turn used to characterize neurotransmission (e.g., monoaminergic, neuropeptidergic, and Hedgehog signalling) and complex modulators (e.g., TRP channels involved in cannabinoid signalling) contributing to cannabinoid/opioid signalling. Additionally, studies using these models were able to discover novel genetic components, including frpr-13 (orthologous to human GRP139), involved in opioid sensitivity, and ptr-25 (orthologous to human PTCHD1), involved in opioid tolerance. The pathways highlighted in this review represent clear paths for further investigation of the genetic mechanisms underlying individual differences in pain sensitivity, pain relief, and drug tolerance. Overall, this review demonstrates the value of C. elegans as a model for uncovering the genetic underpinnings of pain and its management.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The impact of different energy sources on redox balance during endometriotic cyst laparoscopy. 子宫内膜异位囊肿腹腔镜手术中不同能量来源对氧化还原平衡的影响。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0198

Igor Gogic, Vladimir Jakovljevic, Marina Nikolic, Sasa Raicevic, Aleksandra Stojanovic

{"title":"The impact of different energy sources on redox balance during endometriotic cyst laparoscopy.","authors":"Igor Gogic, Vladimir Jakovljevic, Marina Nikolic, Sasa Raicevic, Aleksandra Stojanovic","doi":"10.1139/cjpp-2025-0198","DOIUrl":"10.1139/cjpp-2025-0198","url":null,"abstract":"The aim of the study was to follow the impact of cystectomy and compare bipolar and laser electrocoagulation on prooxidative stress biomarkers and antioxidative capacity. A total of 60 women with diagnosed endometriosis were included in the study and divided in two groups according to laparoscopy treatment with different energy sources for electrocoagulation. Prooxidative parameters (superoxide anion radical (O2-), nitrites (NO2-), hydrogen peroxide (H2O2), index of lipid peroxidation measured as thiobarbituric acid reactive substances) and antioxidative defence system parameters (reduced glutathione (GSH), activity of superoxide dismutase (SOD), and activity of catalase (CAT)) were determined spectrophotometrically before and after the surgery. The value of H2O2 was decreased in group treated with biporal electrocoagulation, while the value of GSH was increased in both groups. The value of O2- was significantly decreased in the group treated with laser, while SOD activity was increased in the same group. Both methods had a similar effect on index of lipid peroxidase and reduced glutathione, but when it comes to the decreasing of harmful superoxide anion radical and increasing of SOD activity, laser electrocoagulation showed better outcome. The role of oxidative stress in both understanding the pathogenesis of this disease and as a potential therapeutic target is certainly of great importance.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Glucagon-like peptide 1 receptor agonists: anti-inflammatory effects in cardiovascular diseases. 胰高血糖素样肽1受体激动剂：在心血管疾病中的抗炎作用。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0021

Zorislava Bajic, Tanja Sobot, Miloš P Stojiljković, Dragan M Djuric, Ranko Škrbić

{"title":"Glucagon-like peptide 1 receptor agonists: anti-inflammatory effects in cardiovascular diseases.","authors":"Zorislava Bajic, Tanja Sobot, Miloš P Stojiljković, Dragan M Djuric, Ranko Škrbić","doi":"10.1139/cjpp-2026-0021","DOIUrl":"10.1139/cjpp-2026-0021","url":null,"abstract":"The potential therapeutic applications of glucagon-like peptide-1 (GLP-1) have led to the development of GLP-1 receptor agonists (GLP-1RAs), which replicate GLP-1's effects. The primary use of GLP-1RAs is the management of type 2 diabetes (T2DM) by stimulation of insulin secretion. In addition to its metabolic functions, GLP-1 exhibits significant anti-inflammatory effects through various molecular pathways, utilizing both direct and indirect mechanisms. Experimental studies have revealed that GLP-1RAs modulate multiple inflammatory pathways, including cytokine production, oxidative stress, glucotoxicity, lipotoxicity, and immune cell recruitment across multiple organs. They interact with their receptors on immune cells, thereby reducing the production of inflammatory cytokines and decreasing the infiltration of immune cells into tissues. There is considerable overlap among the pathways activated by GLP-1R in cardiovascular tissue, which can lead to anti-apoptotic, antioxidative, and anti-inflammatory effects. Clinical studies have confirmed the anti-inflammatory effects of GLP-1RAs in conditions such as acute myocardial infarction, left ventricular dysfunction, coronary artery disease, and ST-segment elevation myocardial infarction. Notably, GLP-1RAs are included in the European Society of Cardiology guidelines for managing cardiovascular disease in patients with T2DM.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The influence of histamine and antihistamines on microglial regulation and neuroinflammation. 组胺和抗组胺药对小胶质调节和神经炎症的影响。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0317

Marcus Pehar, Jan Westhoff, Dagmar Fischer, Marianna Kulka

{"title":"The influence of histamine and antihistamines on microglial regulation and neuroinflammation.","authors":"Marcus Pehar, Jan Westhoff, Dagmar Fischer, Marianna Kulka","doi":"10.1139/cjpp-2025-0317","DOIUrl":"10.1139/cjpp-2025-0317","url":null,"abstract":"Despite extensive characterisation of immune responses across peripheral organs, the immunological landscape of the central nervous system (CNS) remains incompletely defined. Among the resident immune cell populations in the brain, mast cells and microglia have emerged as key modulators of neuroinflammatory processes. Research has increasingly also shown that these cells contribute to fundamental homeostatic functions, including regulation of sleep, affective states, and energy balance. These cells engage in complex bidirectional communication, mediated in part by the biogenic amine histamine. Although histamine was first identified over a century ago, its multifaceted roles in CNS homeostasis, immune surveillance, and neuropathophysiology remain poorly delineated. This review examines the biosynthesis, receptor-mediated signalling, and functional consequences of histaminergic activity within the brain, with a particular focus on microglial dynamics. We discuss crosstalk between mast cells and microglia via histamine signalling pathways, and the potential implications of this interaction in the etiology of neurodevelopmental disorders. Furthermore, we evaluate the emerging evidence on the capacity of centrally acting antihistamines, especially those capable of penetrating the blood-brain barrier, to modulate microglial phenotypes. Collectively, these insights underscore the urgent need for deeper mechanistic studies to elucidate histamine's role in CNS immunophysiology.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-20"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Acitretin negatively regulates osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. 阿维黄素负向调控大鼠骨髓间充质干细胞成骨分化：类维甲酸对骨分化的影响。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0266

Oğuzhan Ekin Efe, Ekin Efe, Selda Emre Aydingöz, Ahmet Çevik Tufan

{"title":"Acitretin negatively regulates osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells.","authors":"Oğuzhan Ekin Efe, Ekin Efe, Selda Emre Aydingöz, Ahmet Çevik Tufan","doi":"10.1139/cjpp-2025-0266","DOIUrl":"10.1139/cjpp-2025-0266","url":null,"abstract":"Acitretin, a widely used second-generation retinoid, has diverse systemic effects, yet its influence on osteogenic processes remains unclear. This study investigated the effects of acitretin on in vitro osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMD-MSCs). BMD-MSCs were isolated from femur and tibia of six male Wistar rats (200-250 g, 4-6 weeks). At Passage 3, cells exhibited spindle-shaped morphology, expressed mesenchymal markers (CD90, CD44, CD29, CD54, and CD106), and lacked hematopoietic marker CD45. Multipotency was confirmed by adipogenic, chondrogenic, and osteogenic differentiation assays. Cells were then exposed to acitretin (10, 100, and 1000 µg/L) or vehicle (dimethyl sulfoxide, DMSO), and osteogenic differentiation was assessed at day 14 by Alizarin Red-S staining and semiquantitative RT-PCR analysis of collagen I alpha 2, osteonectin, and osteopontin expression. High-dose acitretin (1000 µg/L) significantly inhibited osteogenic differentiation, independent of DMSO, while lower concentrations showed no marked effect. These findings demonstrate that acitretin suppresses osteogenic differentiation of BMD-MSCs under in vitro conditions, suggesting potential implications for bone metabolism in patients receiving retinoid therapy. Further studies should focus on elucidating the mechanism of this effect, determining the frequency of skeletal system-related side effects in patients using retinoids, and determining the conditions of use of acitretin in high-risk patients.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Potassium depolarized rat uterus in response to oxytocin and its structural analogues: kinetic analysis. 钾去极化大鼠子宫对催产素及其结构类似物的反应：动力学分析。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0104

Vladimir Pliska, Denis J Crankshaw

{"title":"Potassium depolarized rat uterus in response to oxytocin and its structural analogues: kinetic analysis.","authors":"Vladimir Pliska, Denis J Crankshaw","doi":"10.1139/cjpp-2025-0104","DOIUrl":"10.1139/cjpp-2025-0104","url":null,"abstract":"The subject of this communication is the kinetic analysis of dynamic processes in the myometrium of rats in a depolarized state, with a focus on their biomechanics and possible implications in obstetrics. Depolarization was achieved by increasing the concentration of K+ in the organ bath. It is attended by a fast transient increase in muscle tension and the slower establishment of a new resting state in which the phasic component of contractile activity is suppressed. The myometrium remains stimulable by oxytocin and its structural analogues. Time-tonic response profiles indicate participation of several superimposed, time-dependent exponential components whose rate constants reflect transport and distribution routes regulating the intracellular calcium concentration. The initial rapid rise in tension is followed by a slower change to a steady-state level. Its interruption by oil immersion is followed by an exponential tension decline which allows the determination of the affinity constants of OXT peptides in the depolarized state. The average potency ratio polarized-to-depolarized myometrium assessed for 11 OXT peptides is 9.14. There was no evidence of ligand bias between the two states. Kinetic analysis of the response profiles shows a satisfactory consistency with the reported changes in calcium sensitization and transport processes following OXT stimulation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Exploring the causal relationship between inflammatory cytokines and diabetic foot ulcer: a bidirectional Mendelian randomization and clinical validation study. 探讨炎症细胞因子与糖尿病足溃疡之间的因果关系：一项双向孟德尔随机化和临床验证研究。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0320

Jianyi Liu, Hao Tan, Yan Liu, Zhentan Lu, Weibing Zhong, Zehao Niu

{"title":"Exploring the causal relationship between inflammatory cytokines and diabetic foot ulcer: a bidirectional Mendelian randomization and clinical validation study.","authors":"Jianyi Liu, Hao Tan, Yan Liu, Zhentan Lu, Weibing Zhong, Zehao Niu","doi":"10.1139/cjpp-2025-0320","DOIUrl":"10.1139/cjpp-2025-0320","url":null,"abstract":"Diabetic foot ulcers (DFU) are a major complication of diabetes, often driven by chronic inflammation. The role of specific inflammatory cytokines in DFU development is unclear due to challenges in observational studies. This study used a two-sample, bidirectional Mendelian randomization (MR) approach to assess the causal effects of 41 circulating inflammatory cytokines on DFU risk. Instrumental variables were selected based on genome-wide significance and linkage disequilibrium criteria. The primary analysis was inverse-variance weighted, with validation through enzyme-linked immunosorbent assay and real-time PCR in DFU patients and controls. Genetically predicted levels of CTACK (CCL27) and MIG (CXCL9) were linked to reduced DFU risk, with odds ratios of 0.538 for CTACK and 0.501 for MIG. Sensitivity analyses confirmed the robustness of the findings. Reverse MR analysis showed no causal relationship between DFU and these cytokines. Clinical validation revealed lower protein and mRNA levels of CTACK and MIG in DFU patients. This study provides evidence for a protective role of CTACK and MIG in DFU development, suggesting that they could serve as biomarkers or therapeutic targets for diabetic wound care.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

TRPV1, endocannabinoid, and opioid systems in analgesia: molecular mechanisms and drug development strategies. TRPV1、内源性大麻素和阿片系统在镇痛中的作用：分子机制和药物开发策略。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0328

Kaoutar Benkhraba, Jesus D Castaño, Francis Beaudry

{"title":"TRPV1, endocannabinoid, and opioid systems in analgesia: molecular mechanisms and drug development strategies.","authors":"Kaoutar Benkhraba, Jesus D Castaño, Francis Beaudry","doi":"10.1139/cjpp-2025-0328","DOIUrl":"10.1139/cjpp-2025-0328","url":null,"abstract":"Pain modulation relies on complex molecular interactions among ion channels, G protein-coupled receptors, and intracellular signaling cascades. The Transient Receptor Potential Vanilloid 1 (TRPV1) channel serves as a polymodal detector and integrator of noxious stimuli, linking sensory transduction with broader neuromodulatory systems. This review delineates the mechanistic crosstalk between TRPV1, endocannabinoid, and opioid pathways in nociceptive regulation. TRPV1 activation by heat, protons, or endogenous lipids induces calcium influx and engages protein kinase C (PKC), protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) pathways that modulate channel phosphorylation and neuronal excitability. Endocannabinoids such as anandamide act as dual CB1 and TRPV1 agonists, establishing feedback loops that adjust nociceptive thresholds, while μ-opioid receptor activation inhibits adenylate cyclase and TRPV1 sensitization through Gi/o-mediated signaling. Given the recent progress in cryo-electron microscopy and molecular modeling, simulation studies have been possible, revealing key structural determinants underlying key receptor interactions. Integrating pharmacophore modeling, molecular docking, and artificial intelligence-based screening enables rational design of multi-target ligands that exploit TRPV1-endocannabinoid-opioid synergy. This mechanistic framework supports the development of next-generation analgesics that achieve potent, sustained, and safe modulation of nociceptive signaling.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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