Molecular Pain最新文献_第7页

Transcriptomic analysis of differentially alternative splicing patterns in mice with inflammatory and neuropathic pain 炎症性和神经性疼痛小鼠不同替代剪接模式的转录组分析

IF 3.3 3区医学

Molecular Pain Pub Date : 2024-04-10 DOI: 10.1177/17448069241249455

Mingzhu Zhai, Jiabin Huang, Shaomin Yang, Na Li, Jun Zeng, Yi Zheng, Wuping Sun, Benqing Wu

{"title":"Transcriptomic analysis of differentially alternative splicing patterns in mice with inflammatory and neuropathic pain","authors":"Mingzhu Zhai, Jiabin Huang, Shaomin Yang, Na Li, Jun Zeng, Yi Zheng, Wuping Sun, Benqing Wu","doi":"10.1177/17448069241249455","DOIUrl":"https://doi.org/10.1177/17448069241249455","url":null,"abstract":"Although the molecular mechanisms of chronic pain have been extensively studied, a global picture of alternatively spliced genes and events in the peripheral and central nervous systems of chronic pain is poorly understood. The current study analyzed the changing pattern of alternative splicing (AS) in mouse brain, dorsal root ganglion, and spinal cord tissue under inflammatory and neuropathic pain. In total, we identified 6495 differentially alternatively spliced (DAS) genes. The molecular functions of shared DAS genes between these two models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease. Additionally, we identified 509 DAS in differentially expressed genes (DEGs) shared by these two models, accounting for a small proportion of total DEGs. Our findings supported the hypothesis that the AS has an independent regulation pattern different from transcriptional regulation. Taken together, these findings indicate that AS is one of the important molecular mechanisms of chronic pain in mammals. This study presents a global description of AS profile changes in the full path of neuropathic and inflammatory pain models, providing new insights into the underlying mechanisms of chronic pain and guiding genomic clinical diagnosis methods and rational medication.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"49 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140583810","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

Long-term plasticity of NMDA GluN2B (NR2B) receptor in anterior cingulate cortical synapses. 前扣带回皮质突触中 NMDA GluN2B (NR2B) 受体的长期可塑性。

IF 3.3 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069241230258

Min Zhuo

引用次数: 0

The analgesic effects of botulinum neurotoxin by modulating pain-related receptors; A literature review. 肉毒杆菌神经毒素通过调节疼痛相关受体产生的镇痛效果；文献综述。

IF 2.8 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069241275099

Saereh Hosseindoost, Maziyar Askari Rad, Seyed Hassan Inanloo, Mojgan Rahimi, Samaneh Dehghan, Amirhossein Orandi, Ahmad Reza Dehpour, Hossein Majedi

{"title":"The analgesic effects of botulinum neurotoxin by modulating pain-related receptors; A literature review.","authors":"Saereh Hosseindoost, Maziyar Askari Rad, Seyed Hassan Inanloo, Mojgan Rahimi, Samaneh Dehghan, Amirhossein Orandi, Ahmad Reza Dehpour, Hossein Majedi","doi":"10.1177/17448069241275099","DOIUrl":"10.1177/17448069241275099","url":null,"abstract":"Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, have been used for the treatment of various central and peripheral neurological conditions. Recent studies have suggested that BoNTs may also have a beneficial effect on pain conditions. It has been hypothesized that one of the mechanisms underlying BoNTs' analgesic effects is the inhibition of pain-related receptors' transmission to the neuronal cell membrane. BoNT application disrupts the integration of synaptic vesicles with the cellular membrane, which is responsible for transporting various receptors, including pain receptors such as TRP channels, calcium channels, sodium channels, purinergic receptors, neurokinin-1 receptors, and glutamate receptors. BoNT also modulates the opioidergic system and the GABAergic system, both of which are involved in the pain process. Understanding the cellular and molecular mechanisms underlying these effects can provide valuable insights for the development of novel therapeutic approaches for pain management. This review aims to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions by inhibiting the transmission of pain-related receptors.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241275099"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879071","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

AMPAkines have site-specific analgesic effects in the cortex. AMPAkines在皮层具有特定部位的镇痛作用。

IF 3.3 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069231214677

Elaine Zhu, Dave Mathew, Hyun Jung Jee, Mengqi Sun, Weizhuo Liu, Qiaosheng Zhang, Jing Wang

引用次数: 0

Rapid cleavage of IL-1β in DRG neurons produces tissue injury-induced pain hypersensitivity. DRG 神经元中 IL-1β 的快速裂解会产生组织损伤诱导的痛觉过敏。

IF 2.8 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069241285357

Daisuke Fujita, Yutaka Matsuoka, Shunsuke Yamakita, Yasuhiko Horii, Daiki Ishikawa, Kohsuke Kushimoto, Hiroaki Amino, Fumimasa Amaya

{"title":"Rapid cleavage of IL-1β in DRG neurons produces tissue injury-induced pain hypersensitivity.","authors":"Daisuke Fujita, Yutaka Matsuoka, Shunsuke Yamakita, Yasuhiko Horii, Daiki Ishikawa, Kohsuke Kushimoto, Hiroaki Amino, Fumimasa Amaya","doi":"10.1177/17448069241285357","DOIUrl":"10.1177/17448069241285357","url":null,"abstract":"Background: IL-1β plays a critical role in the pathophysiology of neuroinflammation. The presence of cleaved IL-1β (cIL-1β) in the neurons of the dorsal root ganglion (DRG) implicates its function in biological signaling arising from the sensory neuron. This study was conducted to analyze the role of IL-1β in nociceptive transduction after tissue injury. Methods: A plantar incision was made in C57BL/6 mice, following which immunohistochemistry and RNA scope in situ hybridization were performed at various time points to analyze cIL-1β, caspase-1, and IL-1 receptor 1 (IL-1R1) expression in the DRG. The effect of intrathecal administration of a caspase-1 inhibitor or regional anesthesia using local anesthetics on cIL-1β expression and pain hypersensitivity was analyzed by immunohistochemistry and behavioral analysis. ERK phosphorylation was also analyzed to investigate the effect of IL-1β on the activity of spinal dorsal horn neurons. Results: cIL-1β expression was significantly increased in caspase-1-positive DRG neurons 5 min after the plantar incision. Intrathecal caspase-1 inhibitor treatment inhibited IL-1β cleavage and pain hypersensitivity after the plantar incision. IL-1R1 was also detected in the DRG neurons, although the majority of IL-1R1-expressing neurons lacked cIL-1β expression. Regional anesthesia using local anesthetics prevented cIL-1β processing. Plantar incision-induced phosphorylation of ERK was inhibited by the caspase-1 inhibitor. Conclusion: IL-1β in the DRG neuron undergoes rapid cleavage in response to tissue injury in an activity-dependent manner. Cleaved IL-1β causes injury-induced functional activation of sensory neurons and pain hypersensitivity. IL-1β in the primary afferent neurons is involved in physiological nociceptive signal transduction.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241285357"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11394351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140598","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

Whole-brain mapping of afferents to the anterior cingulate cortex in adult mice. 成年小鼠前扣带皮层传入事件的全脑映射。

IF 2.8 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069241300990

Man Xue, Qi-Yu Chen, Wantong Shi, Zhaoxiang Zhou, Xuhui Li, Fang Xu, Guoqiang Bi, Xixiao Yang, Jing-Shan Lu, Min Zhuo

{"title":"Whole-brain mapping of afferents to the anterior cingulate cortex in adult mice.","authors":"Man Xue, Qi-Yu Chen, Wantong Shi, Zhaoxiang Zhou, Xuhui Li, Fang Xu, Guoqiang Bi, Xixiao Yang, Jing-Shan Lu, Min Zhuo","doi":"10.1177/17448069241300990","DOIUrl":"10.1177/17448069241300990","url":null,"abstract":"The anterior cingulate cortex (ACC) is critical for pain perception, emotion and cognition. Previous studies showed that the ACC has a complex network architecture, which can receive some projection fibers from many brain regions, including the thalamus, the cerebral cortex and other brain regions. However, there was still a lack of whole-brain mapping of the ACC in adult mice. In the present study, we utilized a rabies virus-based retrograde trans-monosynaptic tracing system to map whole-brain afferents to the unilateral ACC in adult mice. We also combined with a new high-throughput, high-speed and high-resolution VISoR imaging technique to generate a three-dimensional whole-brain reconstruction. Our results showed that several principal groups of brain structures send direct monosynaptic inputs to the ACC, including the cerebral cortex, amygdala, striatum, the thalamus, and the brainstem. We also found that cortical neurons in the ACC mainly receive ipsilateral monosynaptic projections. Some cortical areas and forebrain regions also bilaterally projected to the ACC. These findings provide a complete analysis of the afferents to the ACC in adult mice, and whole-brain mapping of ACC afferents would provide important anatomic evidence for the study of pain, memory, and cognition.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"20 ","pages":"17448069241300990"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755541","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

Effects of systemic oxytocin administration on ultraviolet B-induced nociceptive hypersensitivity and tactile hyposensitivity in mice. 全身注射催产素对紫外线诱导的小鼠痛觉超敏和触觉减敏的影响

IF 3.3 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069241226553

M Danilo Boada, Silvia Gutierrez, James C Eisenach

{"title":"Effects of systemic oxytocin administration on ultraviolet B-induced nociceptive hypersensitivity and tactile hyposensitivity in mice.","authors":"M Danilo Boada, Silvia Gutierrez, James C Eisenach","doi":"10.1177/17448069241226553","DOIUrl":"10.1177/17448069241226553","url":null,"abstract":"Ultraviolet B (UVB) radiation induces cutaneous inflammation, leading to thermal and mechanical hypersensitivity. Here, we examine the mechanical properties and profile of tactile and nociceptive peripheral afferents functionally disrupted by this injury and the role of oxytocin (OXT) as a modulator of this disruption. We recorded intracellularly from L4 afferents innervating the irradiated area (5.1 J/cm2) in 4-6 old week male mice (C57BL/6J) after administering OXT intraperitoneally, 6 mg/Kg. The distribution of recorded neurons was shifted by UVB radiation to a pattern observed after acute and chronic injuries and reduced mechanical thresholds of A and C- high threshold mechanoreceptors while reducing tactile sensitivity. UVB radiation did not change somatic membrane electrical properties or fiber conduction velocity. OXT systemic administration rapidly reversed these peripheral changes toward normal in both low and high-threshold mechanoreceptors and shifted recorded neuron distribution toward normal. OXT and V1aR receptors were present on the terminals of myelinated and unmyelinated afferents innervating the skin. We conclude that UVB radiation, similar to local tissue surgical injury, cancer metastasis, and peripheral nerve injury, alters the distribution of low and high threshold mechanoreceptors afferents and sensitizes nociceptors while desensitizing tactile units. Acute systemic OXT administration partially returns all of those effects to normal.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241226553"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10846038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087632","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

Isolectin B4 (IB4)-conjugated streptavidin for the selective knockdown of proteins in IB4-positive (+) nociceptors. 等选蛋白 B4 (IB4) 连接链霉亲和素用于选择性敲除 IB4 阳性（+）神经感受器中的蛋白质。

IF 3.3 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069241230419

Oliver Bogen, Dionéia Araldi, Anatol Sucher, Kord Kober, Peter T Ohara, Jon D Levine

{"title":"Isolectin B4 (IB4)-conjugated streptavidin for the selective knockdown of proteins in IB4-positive (+) nociceptors.","authors":"Oliver Bogen, Dionéia Araldi, Anatol Sucher, Kord Kober, Peter T Ohara, Jon D Levine","doi":"10.1177/17448069241230419","DOIUrl":"10.1177/17448069241230419","url":null,"abstract":"In vivo analysis of protein function in nociceptor subpopulations using antisense oligonucleotides and short interfering RNAs is limited by their non-selective cellular uptake. To address the need for selective transfection methods, we covalently linked isolectin B4 (IB4) to streptavidin and analyzed whether it could be used to study protein function in IB4(+)-nociceptors. Rats treated intrathecally with IB4-conjugated streptavidin complexed with biotinylated antisense oligonucleotides for protein kinase C epsilon (PKCε) mRNA were found to have: (a) less PKCε in dorsal root ganglia (DRG), (b) reduced PKCε expression in IB4(+) but not IB4(-) DRG neurons, and (c) fewer transcripts of the PKCε gene in the DRG. This knockdown in PKCε expression in IB4(+) DRG neurons is sufficient to reverse hyperalgesic priming, a rodent model of chronic pain that is dependent on PKCε in IB4(+)-nociceptors. These results establish that IB4-streptavidin can be used to study protein function in a defined subpopulation of nociceptive C-fiber afferents.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241230419"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513385","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

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain. 电针可减轻癌痛小鼠模型的痛觉行为

IF 3.3 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069241240692

Yu-Xue Zhao, Ming-Jiang Yao, Jian-Wu Shen, Wen-Xi Zhang, Yuan-Xi Zhou

{"title":"Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.","authors":"Yu-Xue Zhao, Ming-Jiang Yao, Jian-Wu Shen, Wen-Xi Zhang, Yuan-Xi Zhou","doi":"10.1177/17448069241240692","DOIUrl":"10.1177/17448069241240692","url":null,"abstract":"Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241240692"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11010748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039827","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

Fat mass and obesity-related protein contributes to the development and maintenance of bone cancer pain in rats by abrogating m6A methylation of RNA. 脂肪量和肥胖相关蛋白通过减弱 RNA 的 m6A 甲基化，促进大鼠骨癌疼痛的发展和维持。

IF 2.8 3区医学

Molecular Pain Pub Date : 2024-01-01 DOI: 10.1177/17448069241295987

Beibei Liu, Danyang Meng, Man Luo, Longsheng Xu, Ming Yao

{"title":"Fat mass and obesity-related protein contributes to the development and maintenance of bone cancer pain in rats by abrogating m6A methylation of RNA.","authors":"Beibei Liu, Danyang Meng, Man Luo, Longsheng Xu, Ming Yao","doi":"10.1177/17448069241295987","DOIUrl":"10.1177/17448069241295987","url":null,"abstract":"Effective prevention and treatment options for bone cancer-related pain (BCP) are lacking. In recent years, numerous studies have investigated the association between m6A epigenetic modifications and pain, revealing their significant role in pain initiation and maintenance. This study aimed to provide theoretical support for the treatment of BCP and to identify target drugs for future development. Specifically, we investigated the involvement of fat mass and obesity-related protein (FTO) in rat models of BCP by administering varying doses (1/5/10 mg/kg) of the FTO inhibitor meclofenamic acid (MA) and assessing changes in mechanical sensitivity through domain analysis, gait analysis, and open-field experiments. After successfully establishing the BCP model, we verified it by performing mechanical sensitivity assessments. We observed significantly increased expression levels of the demethylase FTO within the spinal dorsal horn accompanied by decreased m6A methylation levels in the model. Compared with untreated BCP rats, remarkably improved behavioral responses indicative of reduced pain were observed in the model rats after administration of 10 mg/kg MA, concomitant with decreased expression levels of FTO and increased m6A methylation levels. Compared with untreated BCP rats, the expression levels of p-ERK and pro-inflammatory cytokines were also significantly decreased after MA administration. Taken together, FTO can downregulate m6A methylation level and activate ERK/inflammatory cytokines signaling pathway to maintain BCP in rats.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"20 ","pages":"17448069241295987"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470491","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