Molecular Pain最新文献

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EXPRESS: Gabapentin's effect on human dorsal root ganglia: Donor-specific electrophysiological and transcriptomic profiles. EXPRESS:加巴喷丁对人类背根神经节的影响:供体特异性电生理和转录组谱。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-07-14 DOI: 10.1177/17448069251361712
Jenna B Demeter, Nesia A Zurek, Maddy R Koch, Aleyah E Goins, Cristian O Holguin, Mark W Shilling, Michael S Davis, Reza Ehsanian, Sascha Ra Alles, June Bryan de la Peña
{"title":"EXPRESS: Gabapentin's effect on human dorsal root ganglia: Donor-specific electrophysiological and transcriptomic profiles.","authors":"Jenna B Demeter, Nesia A Zurek, Maddy R Koch, Aleyah E Goins, Cristian O Holguin, Mark W Shilling, Michael S Davis, Reza Ehsanian, Sascha Ra Alles, June Bryan de la Peña","doi":"10.1177/17448069251361712","DOIUrl":"https://doi.org/10.1177/17448069251361712","url":null,"abstract":"<p><p>Neuropathic pain affects approximately 10% of the adult population and is commonly treated with gabapentin (GBP), a repurposed anticonvulsant drug. Despite its widespread use, GBP's effectiveness varies significantly among patients, highlighting the need to better understand its functional and molecular impacts on human nociceptors. Here we characterized the electrophysiological and transcriptomic effects of GBP on primary neurons derived from the dorsal root ganglia (DRGs) of ethically consented human donors. Using patch-clamp electrophysiology, we demonstrated that GBP treatment reduced neuronal excitability, with more pronounced effects in multi-firing vs. single-firing neurons. Notably, significant donor-specific variability was observed in electrophysiological responsiveness to GBP treatment in vitro. RNA sequencing of DRG tissue from the donor that was more responsive to GBP revealed differences in transcriptome-wide expression of genes associated with ion transport, synaptic transmission, inflammation, and immune response. Cross-transcriptomic analyses further showed that GBP treatment counteracted these alterations, rescuing aberrant gene expression at the pathway level and for several key genes. This study provides a comprehensive electrophysiological and transcriptomic profile of the effects of GBP on human DRG neurons. These findings enhance our understanding of GBP's mechanistic actions on peripheral sensory neurons and could help optimize its use for managing neuropathic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251361712"},"PeriodicalIF":2.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
EXPRESS: Ascorbic acid relieves neuropathic pain and depressive behavior by reducing inflammation and activating antioxidant responses. EXPRESS:抗坏血酸通过减少炎症和激活抗氧化反应来缓解神经性疼痛和抑郁行为。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-07-05 DOI: 10.1177/17448069251359598
Xin Li Yao, Mengwei Zhang, Shuang Wang, Qing Yao, Shaohui Chen, Zhongli Qiin, Wei Meng, Haili Zhu, Ling Liu
{"title":"EXPRESS: Ascorbic acid relieves neuropathic pain and depressive behavior by reducing inflammation and activating antioxidant responses.","authors":"Xin Li Yao, Mengwei Zhang, Shuang Wang, Qing Yao, Shaohui Chen, Zhongli Qiin, Wei Meng, Haili Zhu, Ling Liu","doi":"10.1177/17448069251359598","DOIUrl":"https://doi.org/10.1177/17448069251359598","url":null,"abstract":"<p><p>Neuropathic pain (NP), a specific subtypes of chronic pain, can induce depression-like behavior, presenting significant challenges for clinical treatment. Ascorbic acid (AA) is a free radical scavenger; however, its regulatory effects on NP, particularly within the spinal cord, remain ambiguous. In this research, we examined the impact of AA on NP and associated depression-like behavior by establishing a spinal nerve injury (SNI) NP model. Behavioral tests showed that mice in the SNI group exhibited hyperalgesia and depression-like behavior. Contrasted with the control group, the SNI group showed attenuated antioxidant responses (impaired Nrf2 signaling), excessive NLRP3 inflammasome activation, and elevated AMPK activity in spinal cord tissues. However, treatment with AA alleviated NP and depression-like behavior in mice with SNI by suppressing NLRP3-mediated inflammation and enhancing Nrf2-driven antioxidant responses. In vivo electrophysiology demonstrated that AA reversed the increase in theta, alpha, and beta band energies in mice with SNI. The results suggest that AA mitigates NP and comorbid depression-like behavior by inhibiting the activity of NLRP3 inflammasome and activating the Nrf2 pathway. Its ability to normalize neurophysiological rhythms further supports its therapeutic potential for NP. These findings imply that AA is a novel therapeutic agent for NP.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251359598"},"PeriodicalIF":2.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
EXPRESS: Mitochondrial Dysfunction/Hyperfunction Inducing Excessive mtROS in Inflammatory and Neuropathic Pain. 表达:线粒体功能障碍/功能亢进在炎症和神经性疼痛中诱导过量mtROS。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-07-05 DOI: 10.1177/17448069251359601
Xiaoye Zhu, Saige Chen, Mengqi Li, Yunchuan Xiong, Zhigang Cheng, Xiaoyan Zhu, Qu-Lian Guo
{"title":"EXPRESS: Mitochondrial Dysfunction/Hyperfunction Inducing Excessive mtROS in Inflammatory and Neuropathic Pain.","authors":"Xiaoye Zhu, Saige Chen, Mengqi Li, Yunchuan Xiong, Zhigang Cheng, Xiaoyan Zhu, Qu-Lian Guo","doi":"10.1177/17448069251359601","DOIUrl":"https://doi.org/10.1177/17448069251359601","url":null,"abstract":"<p><p>Mitochondria, known as the powerhouses of cells, are considered a key source of reactive oxygen species (ROS) production in various cell types. In the context of neuropathic and inflammatory pain, both mitochondrial dysfunction and hyperfunction can lead to aberrant production of mitochondrial reactive oxygen species (mtROS) , which has been implicated in the development and persistence of pain hyperalgesia. This comprehensive review delves into the compelling correlation between mitochondrial functional activity and diverse pain conditions, with a special emphasis on inflammatory pain and chemotherapy-induced peripheral neuropathy (CIPN). Furthermore, it explores the therapeutic potential of targeting mitochondrial protection and mtROS scavenging to maintain mitochondrial redox homeostasis, offering a novel approach for pain management. The findings presented here provide valuable insights into the multifaceted role of mitochondria in pain modulation, laying a solid foundation for future research and the development of innovative analgesic strategies.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251359601"},"PeriodicalIF":2.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
EXPRESS: Seeking the Root Causes of Menstrual Pain: A Systematic Review of Biomarkers in Menstrual Effluent. EXPRESS:寻找月经疼痛的根本原因:月经流出物生物标志物的系统综述。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-07-05 DOI: 10.1177/17448069251360092
Chandrashekara N Kyathanahalli, Frank F Tu, Gabriela Ashenafi, Margaret S Schroer, Kevin M Hellman
{"title":"EXPRESS: Seeking the Root Causes of Menstrual Pain: A Systematic Review of Biomarkers in Menstrual Effluent.","authors":"Chandrashekara N Kyathanahalli, Frank F Tu, Gabriela Ashenafi, Margaret S Schroer, Kevin M Hellman","doi":"10.1177/17448069251360092","DOIUrl":"https://doi.org/10.1177/17448069251360092","url":null,"abstract":"<p><p>Dysmenorrhea (period pain) affects over 40% of women and is a leading cause of missed school and workdays. However, the molecular mechanisms underlying this pain are not fully understood. We conducted a systematic review (Prospero registration: CRD42024535081) to identify and evaluate the biomolecules in menstrual effluent that may contribute to dysmenorrhea and assess how non-hormonal medications (e.g., NSAIDs) impact these biomarkers. Fifteen studies involving 223 participants met the inclusion criteria. We used the Newcastle-Ottawa Scale (for observational studies) and the Cochrane RoB2 tool (for randomized controlled trials) to evaluate the risk of bias and the quality of studies. Eight studies consistently reported elevated prostaglandin levels in the menstrual effluent of women with dysmenorrhea, though sample sizes were generally small, and methodological issues were noted. Seven studies demonstrated that NSAIDs reduce prostaglandin concentrations; however, these trials utilized multiple-day dosing protocols instead of single-dose regimens, leaving questions about acute treatment effects. Two studies highlighted alternative molecular targets, such as 12-HETE and platelet-activating factor (PAF), that may also play key roles in menstrual pain. Overall, elevated prostaglandins are a recurring finding, but the limited scope and design of existing studies indicate a need for larger, methodologically rigorous investigations. Nevertheless, the few studies that identified molecules other than prostaglandins suggest there are viable druggable targets for clinical trials to reduce menstrual pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251360092"},"PeriodicalIF":2.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
EXPRESS: The Involvement of Spinal lncRNA RT1-CE10 in Chronic Functional Visceral Pain. 表达:脊髓lncRNA RT1-CE10参与慢性功能性内脏疼痛。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-07-03 DOI: 10.1177/17448069251358692
Ying Tang, Zihan Liu, Xianhe Wu, Zhengqing He, Fan Yang, Huiqin Chen, Yu Chen, Qibin Zheng, Yang Huang, Aiqin Chen, Chun Lin
{"title":"EXPRESS: The Involvement of Spinal lncRNA RT1-CE10 in Chronic Functional Visceral Pain.","authors":"Ying Tang, Zihan Liu, Xianhe Wu, Zhengqing He, Fan Yang, Huiqin Chen, Yu Chen, Qibin Zheng, Yang Huang, Aiqin Chen, Chun Lin","doi":"10.1177/17448069251358692","DOIUrl":"https://doi.org/10.1177/17448069251358692","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS) is characterised by chronic visceral pain, but its molecular mechanisms remain controversial, hindering effective treatment.This research is to investigate the role of lncRNA RT1-CE10 in chronic visceral pain associated with IBS and to elucidate the underlying molecular mechanisms. An IBS rat model was developed in rats, and RNA-Seq analysis was conducted to assess lncRNA RT1-CE10 expression. The subcellular localization of lncRNA RT1-CE10 and its co-localization with ATP1a3 in spinal cord neurons were examined. AAV was used to over-express lncRNA RT1-CE10 in the spinal cord to study its effects on ATP1a3 levels and pain response, with knockdown experiments to evaluate the impact of reduced lncRNA RT1-CE10.The RNA-Seq analysis revealed a significant down-regulation of lncRNA RT1-CE10 in IBS rats. The lncRNA was found to be expressed in both the cytoplasm and the nucleus and to co-localize with ATP1a3 in spinal cord neurons. Over-expression of lncRNA RT1-CE10 via AAV-lncRT1-CE10 increased ATP1a3 levels and alleviated visceral pain response, while knockdown of lncRNA RT1-CE10 decreased ATP1a3 levels and enhanced visceral pain response. Additionally, a marked decrease in ATP1a3 expression was observed in the spinal cords of IBS rats. Modulating ATP1a3 expression either through over-expression or knockdown could alleviate or aggravate chronic visceral pain, respectively. LncRNA RT1-CE10, which is lowly expressed in the spinal cord of IBS rats, interacts with ATP1a3 and influences chronic visceral pain. These findings could lead to the development of targeted therapeutic interventions for IBS.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251358692"},"PeriodicalIF":2.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
EXPRESS: Expression of Tacr1 and Gpr83 by spinal projection neurons. 表达:Tacr1和Gpr83在脊髓投射神经元中的表达。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-05-07 DOI: 10.1177/17448069251342409
Wenhui Ma, Allen Dickie, Erika Polgár, Mansi Yadav, Raphaelle Quillet, Maria Gutierrez-Mecinas, Andrew M Bell, Andrew Todd
{"title":"EXPRESS: Expression of Tacr1 and Gpr83 by spinal projection neurons.","authors":"Wenhui Ma, Allen Dickie, Erika Polgár, Mansi Yadav, Raphaelle Quillet, Maria Gutierrez-Mecinas, Andrew M Bell, Andrew Todd","doi":"10.1177/17448069251342409","DOIUrl":"https://doi.org/10.1177/17448069251342409","url":null,"abstract":"<p><p>Anterolateral system (ALS) projection neurons underlie perception of pain, itch and skin temperature. These cells are heterogeneous, and there have therefore been many attempts to define functional populations. A recent study identified two classes of ALS neuron in mouse superficial dorsal horn (SDH) based on expression of the G protein-coupled receptors Tacr1 or Gpr83. It was reported that cells expressing these receptors formed largely non-overlapping populations, and that ~60% of ALS cells in SDH expressed Tacr1. An additional finding was that while Tacr1- and Gpr83-expressing ALS cells projected to several brain nuclei, their axons did not reach the ventral posterolateral (VPL) thalamic nucleus, which is reciprocally connected to the primary somatosensory cortex. These results were surprising, because we had reported that ~90% of SDH ALS neurons in the mouse possess the neurokinin 1 receptor (NK1r), which is encoded by Tacr1, and in addition the VPL is thought to receive input from lamina I ALS cells. Here we use retrograde and anterograde labelling in Tacr1CreERT2 and Gpr83CreERT2 mice to reinvestigate the expression of the receptors by ALS neurons and to reassess their projection patterns. We find that ~90% of ALS neurons in SDH express Tacr1, with 40-50% expressing Gpr83. We also show that axons of both Tacr1- and Gpr83-expressing ALS neurons reach the VPL. These results suggest that ALS neurons in the SDH that express these GPCRs show considerable overlap, and that they are likely to contribute to the sensory-discriminative dimension of pain through their projections to VPL.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251342409"},"PeriodicalIF":2.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
PDCD4 inhibition alleviates neuropathic pain by regulating spinal autophagy and neuroinflammation. 表达:PDCD4抑制通过调节脊髓自噬和神经炎症减轻神经性疼痛。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-03-28 DOI: 10.1177/17448069251333928
Ting Zhang, Le Qi, Kai Sun, Xiang Huan, Hao Zhang, Liwei Wang
{"title":"PDCD4 inhibition alleviates neuropathic pain by regulating spinal autophagy and neuroinflammation.","authors":"Ting Zhang, Le Qi, Kai Sun, Xiang Huan, Hao Zhang, Liwei Wang","doi":"10.1177/17448069251333928","DOIUrl":"10.1177/17448069251333928","url":null,"abstract":"<p><p>Neuropathic pain is still a clinical challenge. Inflammatory responses and autophagy in the spinal cord are important mechanisms for the occurrence and maintain of neuropathic pain. PDCD4 is an important molecule that regulates inflammation and autophagy. However, the regulatory role of PDCD4 is unknown in pain modulation. In this study we found that the expression of PDCD4 in the spinal cord of CCI mice was increased. Inhibition of PDCD4 by intrathecal injection of adeno-associated virus alleviated neuropathic pain hypersensitivity and enhanced autophagy in CCI mice, and inhibited the activation of MAPKs, as well as the expression of inflammatory factors. Intrathecal injection of autophagy inhibitor 3-MA reversed PDCD4 inhibition induced pain relief and change of autophagy. Our results indicate that spinal cord inhibition of PDCD4 alleviates pain sensitization in neuropathic pain mice through MAPKs and autophagy, and PDCD4 may be developed into a therapeutic target of neuropathic pain treatment.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251333928"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advanced cancer perineural invasion induces profound peripheral neuronal plasticity, pain, and somatosensory mechanical deactivation, unmitigated by the lack of TNFR1. Part 2. Biophysics and gene expression. 表达:晚期癌症侵袭周围神经诱导周围神经元的可塑性,疼痛和躯体感觉机械失活,而TNFR1的缺乏则无法减轻。第2部分。生物物理学和基因表达。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-02-13 DOI: 10.1177/17448069251323666
Silvia Gutierrez, Renee A Parker, Morgan Zhang, Maria Daniela Santi, Yi Ye, Mario Danilo Boada
{"title":"Advanced cancer perineural invasion induces profound peripheral neuronal plasticity, pain, and somatosensory mechanical deactivation, unmitigated by the lack of TNFR1. Part 2. Biophysics and gene expression.","authors":"Silvia Gutierrez, Renee A Parker, Morgan Zhang, Maria Daniela Santi, Yi Ye, Mario Danilo Boada","doi":"10.1177/17448069251323666","DOIUrl":"10.1177/17448069251323666","url":null,"abstract":"<p><p>Preclinical studies addressing the peripheral effects of cancer perineural invasion report severe neuronal availability and excitability changes. Oral cell squamous cell carcinoma perineural invasion (MOC2-PNI) shows similar effects, modulating the afferent's sensibility (tactile desensitization with concurrent nociceptive sensitization) and demyelination without inducing spontaneous activity (see Part 1.). The current study addresses the electrical status (normal or abnormal) of both active (low threshold mechano receptors (LT) and high threshold mechano receptors (HT)) and inactive (F-type and S-type) afferents. Concurrently, we have also evaluated changes in the genetic landscape that may help to understand the physiological dynamics behind MOC2-PNI-induced functional disruption of the peripheral sensory system. We have observed that the altered cell distribution and mechanical sensibility of the animal's somatosensory system cannot be explained by cellular electrical dysfunction or MOC2-PNI-induced apoptosis. Although PNI does modify the expression of several genes related to cellular hypersensitivity, these changes are insufficient to explain the MOC2-PNI-induced aberrant neuronal excitability state. Our results indicate that genetic markers provide limited information about the functional hyperexcitable state of the peripheral system. Importantly, our results also highlight the emerging role of plasma membrane Ca<sup>2+</sup>-ATPase activity (PMCA) in explaining several aspects of the observed gender-specific neuronal plasticity and the reported cellular distribution switch generated by MOC2-PNI.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251323666"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gut microbiota-derived short-chain fatty acid suppresses the excitability of rat nociceptive secondary neurons via G-protein-coupled receptor 41 signaling. EXPRESS:肠道微生物源短链脂肪酸通过g蛋白偶联受体41信号抑制大鼠伤害性次级神经元的兴奋性
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 DOI: 10.1177/17448069251320233
Yukito Sashide, Mamoru Takeda
{"title":"Gut microbiota-derived short-chain fatty acid suppresses the excitability of rat nociceptive secondary neurons via G-protein-coupled receptor 41 signaling.","authors":"Yukito Sashide, Mamoru Takeda","doi":"10.1177/17448069251320233","DOIUrl":"10.1177/17448069251320233","url":null,"abstract":"<p><p>Short-chain free fatty acids (SCFAs) are generated by gut microbiota through anaerobic fermentation of dietary fibers. Although gut microbiota-derived SCFAs modulate voltage-gated Ca<sup>2+</sup> channels via G-protein-coupled receptor 41 (GPR41) in isolated sympathetic ganglion neurons, the influence of SCFAs, specifically propionic acid (PA), on the excitability of nociceptive neurons under in vivo conditions has yet to be ascertained. In the current study we assessed whether systemic PA administration diminishes the excitability of nociceptive trigeminal spinal nucleus caudalis (SpVc) wide-dynamic range neurons responding to mechanical stimulation. Extracellular single-unit recordings from SpVc wide-dynamic range neurons were performed in anesthetized rats after mechanical stimulation of the orofacial region. PA significantly and reversibly inhibited the mean firing frequency of SpVc neurons in response to both non-noxious and noxious mechanical stimuli in a dose-dependent manner. Simultaneous administration of a GPR41 inhibitor abolished the PA-induced inhibited firing rate of SpVc neurons, indicating that systemic PA decreased the excitability of nociceptive secondary trigeminal neurons by activating GPR41 signaling-mediated inhibition of voltage-gated Ca<sup>2+</sup> channels in the central terminals of the SpVc. Modulation of trigeminal nociception by systemic SCFA administration indicates that gut microbiota-derived SCFAs could be effective analgesic agents for relieving trigeminal pain, creating a new therapeutic strategy for the management of trigeminal pain, including clinical pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251320233"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of genetic variations in μ opioid receptor in cats. EXPRESS:猫μ阿片受体遗传变异的鉴定。
IF 2.8 3区 医学
Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-03-04 DOI: 10.1177/17448069251327805
Kazumasu Sasaki, Junko Hasegawa, Kazutaka Ikeda, Tatsuya Ishikawa, Shinya Kasai
{"title":"Identification of genetic variations in μ opioid receptor in cats.","authors":"Kazumasu Sasaki, Junko Hasegawa, Kazutaka Ikeda, Tatsuya Ishikawa, Shinya Kasai","doi":"10.1177/17448069251327805","DOIUrl":"10.1177/17448069251327805","url":null,"abstract":"<p><p>μ-opioid receptor (MOP) plays a critical role in mediating opioid analgesic effects. Genetic variations, particularly those in the MOP gene (<i>Oprm1</i>), significantly influence individual variations in opioid efficacy and side effects across species, highlighting the need for pharmacogenomic research in human and veterinary contexts. This study aimed to identify single-nucleotide variations (SNVs) within <i>Oprm1</i> in 100 cats of various breeds. <i>Oprm1</i> spans over 170 kb and consists of five exons that combine to yield three splice variants in the cat Ensembl database. Among these variants, <i>Oprm1-202</i> is an ortholog of the <i>MOR-1</i> transcript, which is the most abundant in humans and mice. <i>Oprm1-202</i> shares 92% and 87% coding sequences (CDS) and 96% and 94% amino acid sequence identity with human and mouse <i>MOR-1</i>, respectively. Phylogenetic trees were constructed from the CDS and amino acid sequences of nine species, including humans, cats, and mice. Both the CDS and amino acid sequences of MOP in cats showed phylogenetic development closer to that of primates than of rodents. Four SNVs were identified in the CDS of <i>Oprm1</i>. One SNV was located in exon 1 and the other three in exon 2 of <i>Oprm1</i>, all of which were synonymous substitutions. Although synonymous mutations generally have a limited functional impact, they may influence splicing and receptor expression. Further research is required to assess the effects of these SNVs on opioid efficacy, receptor expression, and analgesic responses across breeds, considering the potential breed-specific genetic factors in cat species.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251327805"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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