脊髓电压门控阴离子通道 1 的上调导致大鼠骨癌痛敏。
Upregulation of Spinal Voltage-Dependent Anion Channel 1 Contributes to Bone Cancer Pain Hypersensitivity in Rats.
机构信息
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric Diseases and Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, 215123, China.
Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, 215600, China.
出版信息
Neurosci Bull. 2017 Dec;33(6):711-721. doi: 10.1007/s12264-017-0195-1. Epub 2017 Dec 1.
Abstract
Voltage-dependent anion channel 1 (VDAC1) is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the expression of VDAC1 was upregulated in the L2-5 segments of the spinal dorsal horn at 2 and 3 weeks after injection of tumor cells into the tibial cavity. Intrathecal injection of a VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the over-expression of Toll-like receptor 4 (TLR4). Intrathecal injection of minocycline, an inhibitor of microglia, also attenuated the pain hypersensitivity of rat models of bone cancer pain. These results suggest that VDAC1 plays a significant role in the development of complicated cancer pain, possibly by regulating the expression of TLR4.
摘要
电压门控阴离子通道 1（VDAC1）被认为有助于肿瘤发展。然而，VDAC1 是否有助于骨癌疼痛尚不清楚。在这项研究中，我们发现肿瘤细胞注入胫骨腔后 2 至 3 周，VDAC1 的表达在 L2-5 脊髓背角节段上调。鞘内注射 VDAC1 抑制剂可显著逆转痛觉过敏，并降低 Toll 样受体 4（TLR4）的过度表达。鞘内注射小胶质细胞抑制剂米诺环素也可减轻骨癌痛大鼠模型的痛觉过敏。这些结果表明，VDAC1 在复杂癌痛的发展中起重要作用，可能通过调节 TLR4 的表达。
相似文献
1
Upregulation of Spinal Voltage-Dependent Anion Channel 1 Contributes to Bone Cancer Pain Hypersensitivity in Rats.脊髓电压门控阴离子通道 1 的上调导致大鼠骨癌痛敏。
Neurosci Bull. 2017 Dec;33(6):711-721. doi: 10.1007/s12264-017-0195-1. Epub 2017 Dec 1.
2
Toll-like receptor-4/p38 MAPK signaling in the dorsal horn contributes to P2X4 receptor activation and BDNF over-secretion in cancer induced bone pain.背角中的Toll样受体4/p38丝裂原活化蛋白激酶信号传导促进癌症诱导的骨痛中P2X4受体激活和脑源性神经营养因子过度分泌。
Neurosci Res. 2017 Dec;125:37-45. doi: 10.1016/j.neures.2017.06.006. Epub 2017 Jun 28.
3
The up-regulation of spinal Toll-like receptor 4 in rats with inflammatory pain induced by complete Freund's adjuvant.完全弗氏佐剂诱导的炎性疼痛大鼠脊髓Toll样受体4的上调
Brain Res Bull. 2015 Feb;111:97-103. doi: 10.1016/j.brainresbull.2015.01.002. Epub 2015 Jan 12.
4
Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia.脊髓背角激活小胶质细胞与神经元之间的串扰导致应激性痛觉过敏。
Sci Rep. 2016 Dec 20;6:39442. doi: 10.1038/srep39442.
5
XPro1595 ameliorates bone cancer pain in rats via inhibiting p38-mediated glial cell activation and neuroinflammation in the spinal dorsal horn.XPro1595 通过抑制脊髓背角中 p38 介导的神经胶质细胞激活和神经炎症改善大鼠骨癌痛。
Brain Res Bull. 2019 Jul;149:137-147. doi: 10.1016/j.brainresbull.2019.04.009. Epub 2019 Apr 16.
6
The analgesic effects of pioglitazone in the bone cancer pain rats via regulating the PPARγ/PTEN/mTOR signaling pathway in the spinal dorsal horn.吡格列酮通过调节脊髓背角的 PPARγ/PTEN/mTOR 信号通路对骨癌痛大鼠的镇痛作用。
Biomed Pharmacother. 2020 Nov;131:110692. doi: 10.1016/j.biopha.2020.110692. Epub 2020 Sep 14.
7
Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll-like receptor 4 expression in neuropathic rats.抑制小胶质细胞活性可改变脊髓广动力范围神经元放电，并降低神经病理性大鼠小胶质细胞Toll样受体4的表达。
Clin Exp Pharmacol Physiol. 2015 Jul;42(7):772-9. doi: 10.1111/1440-1681.12414.
8
P2X4 receptor in the dorsal horn partially contributes to brain-derived neurotrophic factor oversecretion and toll-like receptor-4 receptor activation associated with bone cancer pain.背角中的P2X4受体部分导致了与骨癌疼痛相关的脑源性神经营养因子过度分泌和Toll样受体4激活。
J Neurosci Res. 2014 Dec;92(12):1690-702. doi: 10.1002/jnr.23443. Epub 2014 Jul 1.
9
Impacts of anti-nerve growth factor antibody on pain-related behaviors and expressions of opioid receptor in spinal dorsal horn and dorsal root ganglia of rats with cancer-induced bone pain.抗神经生长因子抗体对癌性骨痛大鼠疼痛相关行为及脊髓背角和背根神经节中阿片受体表达的影响
Mol Pain. 2016 Apr 26;12. doi: 10.1177/1744806916644928. Print 2016.
10
Mechanism of Toll-like Receptor 4 on Chronic Post-thoracotomy Pain Via Caspase-1 Activation.Toll 样受体 4 通过半胱天冬酶-1 激活在慢性开胸术后疼痛中的作用机制。
Curr Neurovasc Res. 2020;17(5):667-675. doi: 10.2174/1567202617666201106150620.
引用本文的文献
1
GluR2 overexpression in ACC glutamatergic neurons alleviates cancer-induced bone pain in rats.前扣带回谷氨酸能神经元中GluR2的过表达可减轻大鼠癌症诱发的骨痛。
Mol Med. 2025 Apr 7;31(1):130. doi: 10.1186/s10020-025-01183-9.
2
CXCR1 participates in bone cancer pain induced by Walker 256 breast cancer cells in female rats.CXCR1 参与了雌性大鼠 Walker 256 乳腺癌细胞诱导的骨癌痛。
Mol Pain. 2022 Apr;18:17448069221135743. doi: 10.1177/17448069221135743.
3
Toll-like receptor 2 and 4 antagonism for the treatment of experimental autoimmune encephalomyelitis (EAE)-related pain.Toll 样受体 2 和 4 拮抗剂治疗实验性自身免疫性脑脊髓炎（EAE）相关疼痛。
Brain Behav Immun. 2021 Mar;93:80-95. doi: 10.1016/j.bbi.2020.12.016. Epub 2021 Jan 7.
4
Modulation of Rat Cancer-Induced Bone Pain is Independent of Spinal Microglia Activity.大鼠癌症诱导性骨痛的调节与脊髓小胶质细胞活性无关。
Cancers (Basel). 2020 Sep 24;12(10):2740. doi: 10.3390/cancers12102740.
5
Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues Memory Impairment in Rats with Type 2 Diabetes.嘌呤能 P2X4 受体在海马中的过表达可挽救 2 型糖尿病大鼠的记忆障碍。
Neurosci Bull. 2020 Jul;36(7):719-732. doi: 10.1007/s12264-020-00478-7. Epub 2020 Mar 20.
6
Blockade of c-Src Within the Paraventricular Nucleus Attenuates Inflammatory Cytokines and Oxidative Stress in the Mechanism of the TLR4 Signal Pathway in Salt-Induced Hypertension.室旁核内 c-Src 阻断减轻 TLR4 信号通路中介盐诱导高血压的炎症细胞因子和氧化应激。
Neurosci Bull. 2020 Apr;36(4):385-395. doi: 10.1007/s12264-019-00435-z. Epub 2019 Oct 22.
7
Endoplasmic reticulum stress promoting caspase signaling pathway-dependent apoptosis contributes to bone cancer pain in the spinal dorsal horn.内质网应激促进半胱天冬酶信号通路依赖性细胞凋亡导致脊髓背角骨癌痛。
Mol Pain. 2019 Jan-Dec;15:1744806919876150. doi: 10.1177/1744806919876150.
8
Decreased miR-325-5p Contributes to Visceral Hypersensitivity Through Post-transcriptional Upregulation of CCL2 in Rat Dorsal Root Ganglia.miR-325-5p 下调通过在后根神经节中转录后上调 CCL2 导致内脏敏感性增加。
Neurosci Bull. 2019 Oct;35(5):791-801. doi: 10.1007/s12264-019-00372-x. Epub 2019 Apr 12.
9
Downregulation of glucose-6-phosphate dehydrogenase contributes to diabetic neuropathic pain through upregulation of toll-like receptor 4 in rats.葡萄糖-6-磷酸脱氢酶下调通过上调大鼠 Toll 样受体 4 导致糖尿病性神经病理性疼痛。
Mol Pain. 2019 Jan-Dec;15:1744806919838659. doi: 10.1177/1744806919838659.
10
Characterization of novel lnc RNAs in the spinal cord of rats with lumbar disc herniation.腰椎间盘突出症大鼠脊髓中新型长链非编码RNA的特征分析
J Pain Res. 2019 Jan 30;12:501-512. doi: 10.2147/JPR.S164604. eCollection 2019.
本文引用的文献
1
Voltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-Cancer Therapeutics.电压依赖性阴离子通道1作为新型抗癌治疗的新兴药物靶点。
Front Oncol. 2017 Jul 31;7:154. doi: 10.3389/fonc.2017.00154. eCollection 2017.
2
The Mitochondrial Voltage-Dependent Anion Channel 1, Ca Transport, Apoptosis, and Their Regulation.线粒体电压依赖性阴离子通道1、钙转运、细胞凋亡及其调控
Front Oncol. 2017 Apr 10;7:60. doi: 10.3389/fonc.2017.00060. eCollection 2017.
3
Overexpression of suppressor of cytokine signaling 3 in dorsal root ganglion attenuates cancer-induced pain in rats.背根神经节中细胞因子信号传导抑制因子3的过表达减轻大鼠癌症诱导的疼痛。
Mol Pain. 2017 Jan;13:1744806916688901. doi: 10.1177/1744806916688901.
4
Diclofenac pretreatment modulates exercise-induced inflammation in skeletal muscle of rats through the TLR4/NF-κB pathway.双氯芬酸预处理通过TLR4/NF-κB途径调节大鼠骨骼肌运动诱导的炎症。
Appl Physiol Nutr Metab. 2017 Jul;42(7):757-764. doi: 10.1139/apnm-2016-0593. Epub 2017 Feb 24.
5
Down-Regulation of CXCL12/CXCR4 Expression Alleviates Ischemia-Reperfusion-Induced Inflammatory Pain via Inhibiting Glial TLR4 Activation in the Spinal Cord.CXCL12/CXCR4表达下调通过抑制脊髓胶质细胞TLR4激活减轻缺血再灌注诱导的炎性疼痛。
PLoS One. 2016 Oct 19;11(10):e0163807. doi: 10.1371/journal.pone.0163807. eCollection 2016.
6
Modulation of Nav1.8 by Lysophosphatidic Acid in the Induction of Bone Cancer Pain.溶血磷脂酸对Nav1.8的调节在骨癌疼痛诱导中的作用
Neurosci Bull. 2016 Oct;32(5):445-54. doi: 10.1007/s12264-016-0060-7. Epub 2016 Sep 9.
7
The cystine/glutamate antiporter system xc- drives breast tumor cell glutamate release and cancer-induced bone pain.胱氨酸/谷氨酸逆向转运体系统xc-驱动乳腺肿瘤细胞释放谷氨酸并引发癌症诱导的骨痛。
Pain. 2016 Nov;157(11):2605-2616. doi: 10.1097/j.pain.0000000000000681.
8
Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity.肥胖对内脏痛产生影响：高脂饮食诱导Toll样受体4依赖性内脏超敏反应。
PLoS One. 2016 May 9;11(5):e0155367. doi: 10.1371/journal.pone.0155367. eCollection 2016.
9
Effects of Src-kinase inhibition in cancer-induced bone pain.Src激酶抑制对癌症诱导的骨痛的影响。
Mol Pain. 2016 Apr 18;12. doi: 10.1177/1744806916643725. Print 2016.
10
Differences in electrophysiological properties of functionally identified nociceptive sensory neurons in an animal model of cancer-induced bone pain.癌症诱导骨痛动物模型中功能鉴定的伤害性感觉神经元电生理特性的差异。
Mol Pain. 2016 Mar 1;12. doi: 10.1177/1744806916628778. Print 2016.
Zotero 插件