• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

代谢型谷氨酸受体 5（mGluR5）调节膀胱痛觉。

Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception.

机构信息

Neuroscience Program, Washington University School of Medicine, St, Louis, MO 63110, USA.

出版信息

Mol Pain. 2012 Mar 26;8:20. doi: 10.1186/1744-8069-8-20.

DOI:10.1186/1744-8069-8-20
PMID:22449017
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3369204/
Abstract

BACKGROUND

Interstitial cystitis/painful bladder syndrome (IC/PBS), is a severely debilitating chronic condition that is frequently unresponsive to conventional pain medications. The etiology is unknown, however evidence suggests that nervous system sensitization contributes to enhanced pain in IC/PBS. In particular, central nervous system plasticity of glutamatergic signaling involving NMDA and metabotropic glutamate receptors (mGluRs) has been implicated in a variety of chronic pain conditions. Here, we test the hypothesis that mGluR5 mediates both non-inflammatory and inflammatory bladder pain or nociception in a mouse model by monitoring the visceromotor response (VMR) during graded bladder distention.

RESULTS

Using a combination of genetic and pharmacologic approaches, we provide evidence indicating that mGluR5 is necessary for the full expression of VMR in response to bladder distention in the absence of inflammation. Furthermore, we observed that mice infected with a uropathogenic strain of Escherichia coli (UPEC) develop inflammatory hyperalgesia to bladder distention, and that the selective mGluR5 antagonist fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl) urea], reduces the VMR to bladder distention in UPEC-infected mice.

CONCLUSIONS

Taken together, these data suggest that mGluR5 modulates both inflammatory and non-inflammatory bladder nociception, and highlight the therapeutic potential for mGluR5 antagonists in the alleviation of bladder pain.

摘要

背景

间质性膀胱炎/膀胱疼痛综合征（IC/PBS）是一种严重的使人衰弱的慢性疾病，通常对常规止痛药物没有反应。其病因尚不清楚，但有证据表明，神经系统敏化导致 IC/PBS 中疼痛加剧。特别是，涉及 NMDA 和代谢型谷氨酸受体（mGluRs）的中枢神经系统谷氨酸能信号转导的可塑性与各种慢性疼痛状况有关。在这里，我们通过监测分级膀胱扩张时的内脏运动反应（VMR）来测试 mGluR5 介导非炎症和炎症性膀胱疼痛或伤害感受的假设。

结果

使用遗传和药理学方法的组合，我们提供的证据表明，mGluR5 是在没有炎症的情况下，对膀胱扩张的 VMR 完全表达所必需的。此外，我们观察到感染尿路致病性大肠杆菌（UPEC）的小鼠对膀胱扩张产生炎症性痛觉过敏，而选择性 mGluR5 拮抗剂芬巴姆[ N-（3-氯苯基）-N '-(4,5-二氢-1-甲基-4-氧代-1H-咪唑-2-基）脲]，降低了 UPEC 感染小鼠对膀胱扩张的 VMR。

结论

综上所述，这些数据表明 mGluR5 调节炎症和非炎症性膀胱伤害感受，突出了 mGluR5 拮抗剂在缓解膀胱疼痛方面的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/c35f37a875e9/1744-8069-8-20-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/81ec33f973b8/1744-8069-8-20-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/2e14c750ce4b/1744-8069-8-20-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/46e48e0dfbe8/1744-8069-8-20-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/a6105fbbbb44/1744-8069-8-20-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/1fc9a0da0426/1744-8069-8-20-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/c35f37a875e9/1744-8069-8-20-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/81ec33f973b8/1744-8069-8-20-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/2e14c750ce4b/1744-8069-8-20-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/46e48e0dfbe8/1744-8069-8-20-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/a6105fbbbb44/1744-8069-8-20-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/1fc9a0da0426/1744-8069-8-20-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/475c/3369204/c35f37a875e9/1744-8069-8-20-6.jpg

相似文献

1
Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception.代谢型谷氨酸受体 5（mGluR5）调节膀胱痛觉。
Mol Pain. 2012 Mar 26;8:20. doi: 10.1186/1744-8069-8-20.
2
Central amygdala metabotropic glutamate receptor 5 in the modulation of visceral pain.中杏仁核代谢型谷氨酸受体 5 在内脏痛调制中的作用。
J Neurosci. 2012 Oct 10;32(41):14217-26. doi: 10.1523/JNEUROSCI.1473-12.2012.
3
Involvement of metabotropic glutamate 5 receptor in visceral pain.代谢型谷氨酸5受体在内脏痛中的作用
Pain. 2008 Jul 15;137(2):295-305. doi: 10.1016/j.pain.2007.09.008. Epub 2007 Oct 15.
4
The role of metabotropic glutamate receptor mGlu5 in control of micturition and bladder nociception.代谢型谷氨酸受体mGlu5在排尿和膀胱伤害感受控制中的作用。
Neurosci Lett. 2009 Jan 23;450(1):12-7. doi: 10.1016/j.neulet.2008.11.026. Epub 2008 Nov 14.
5
mGluR5 antagonist-induced psychoactive properties: MTEP drug discrimination, a pharmacologically selective non-NMDA effect with apparent lack of reinforcing properties.代谢型谷氨酸受体 5 拮抗剂引起的精神活性特性：MTEP 药物辨别，一种具有明显缺乏强化特性的药理学选择性非 NMDA 效应。
J Pharmacol Exp Ther. 2014 Apr;349(1):155-64. doi: 10.1124/jpet.113.211185. Epub 2014 Jan 28.
6
The metabotropic glutamate receptor 5 negative allosteric modulator fenobam: pharmacokinetics, side effects, and analgesic effects in healthy human subjects.代谢型谷氨酸受体 5 负变构调节剂非诺苯：在健康人体受试者中的药代动力学、副作用和镇痛作用。
Pain. 2020 Jan;161(1):135-146. doi: 10.1097/j.pain.0000000000001695.
7
mGluR5 antagonists that block calcium mobilization in vitro also reverse (S)-3,5-DHPG-induced hyperalgesia and morphine antinociceptive tolerance in vivo.在体外阻断钙动员的代谢型谷氨酸受体5（mGluR5）拮抗剂，在体内也能逆转（S）-3,5-二羟基苯基甘氨酸（DHPG）诱导的痛觉过敏和吗啡镇痛耐受性。
Brain Res. 2008 Jan 2;1187:58-66. doi: 10.1016/j.brainres.2007.10.007. Epub 2007 Oct 12.
8
Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity.非诺班：一种经临床验证的非苯二氮䓬类抗焦虑药，是一种具有反向激动剂活性的强效、选择性和非竞争性代谢型谷氨酸受体5（mGlu5）拮抗剂。
J Pharmacol Exp Ther. 2005 Nov;315(2):711-21. doi: 10.1124/jpet.105.089839. Epub 2005 Jul 22.
9
Role of metabotropic glutamate receptor subtype mGluR1 in brief nociception and central sensitization of primate STT cells.代谢型谷氨酸受体亚型mGluR1在灵长类脊髓丘脑束神经元的短暂伤害感受和中枢敏化中的作用
J Neurophysiol. 1999 Jul;82(1):272-82. doi: 10.1152/jn.1999.82.1.272.
10
Peripheral group I metabotropic glutamate receptors modulate nociception in mice.外周I型代谢型谷氨酸受体调节小鼠的伤害感受。
Nat Neurosci. 2001 Apr;4(4):417-23. doi: 10.1038/86075.

引用本文的文献

1
Disruption of circadian rhythm as a potential pathogenesis of nocturia.昼夜节律紊乱作为夜尿症的一种潜在发病机制。
Nat Rev Urol. 2025 May;22(5):276-293. doi: 10.1038/s41585-024-00961-0. Epub 2024 Nov 14.
2
Recent Advances in the Modulation of Pain by the Metabotropic Glutamate Receptors.代谢型谷氨酸受体对疼痛的调制：最新进展
Cells. 2022 Aug 21;11(16):2608. doi: 10.3390/cells11162608.
3
The effect of amino acids on the bladder cycle: a concise review.氨基酸对膀胱周期的影响：简要综述。

本文引用的文献

1
Involvement of metabotropic glutamate receptor 5 in pudendal inhibition of nociceptive bladder activity in cats.代谢型谷氨酸受体 5 参与阴部抑制猫伤害性膀胱活动。
J Physiol. 2011 Dec 1;589(Pt 23):5833-43. doi: 10.1113/jphysiol.2011.215657. Epub 2011 Oct 17.
2
Functional characterization of a chronic cyclophosphamide-induced overactive bladder model in mice.在小鼠中对慢性环磷酰胺诱导的过度活动膀胱模型进行功能表征。
Neurourol Urodyn. 2011 Nov;30(8):1659-65. doi: 10.1002/nau.21180. Epub 2011 Jun 29.
3
Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder.
Amino Acids. 2022 Jan;54(1):13-31. doi: 10.1007/s00726-021-03113-5. Epub 2021 Dec 1.
4
Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.头孢曲松抑制应激诱导的膀胱痛觉过敏，并改变大鼠的大脑排尿和痛觉传入回路：泌尿科慢性盆腔疼痛综合征研究网络研究的多学科方法。
Neurourol Urodyn. 2020 Aug;39(6):1628-1643. doi: 10.1002/nau.24424. Epub 2020 Jun 23.
5
Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network.泌尿科慢性盆腔疼痛综合征：来自 MAPP 研究网络的见解。
Nat Rev Urol. 2019 Mar;16(3):187-200. doi: 10.1038/s41585-018-0135-5.
6
Development of an AmpliSeq Panel for Next-Generation Sequencing of a Set of Genetic Predictors of Persisting Pain.用于对一组持续性疼痛遗传预测因子进行下一代测序的扩增子测序panel的开发。
Front Pharmacol. 2018 Sep 19;9:1008. doi: 10.3389/fphar.2018.01008. eCollection 2018.
7
Differential Regulation of Bladder Pain and Voiding Function by Sensory Afferent Populations Revealed by Selective Optogenetic Activation.通过选择性光遗传学激活揭示感觉传入群体对膀胱疼痛和排尿功能的差异调节
Front Integr Neurosci. 2018 Feb 12;12:5. doi: 10.3389/fnint.2018.00005. eCollection 2018.
8
Optogenetic silencing of nociceptive primary afferents reduces evoked and ongoing bladder pain.光遗传学抑制伤害性初级传入纤维可减少诱发性和持续性膀胱疼痛。
Sci Rep. 2017 Nov 20;7(1):15865. doi: 10.1038/s41598-017-16129-3.
9
Acyloxyacyl hydrolase modulates pelvic pain severity.酰氧基酰基水解酶调节盆腔疼痛的严重程度。
Am J Physiol Regul Integr Comp Physiol. 2018 Mar 1;314(3):R353-R365. doi: 10.1152/ajpregu.00239.2017. Epub 2017 Nov 8.
10
Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain.亲代谢型谷氨酸受体7（mGlu7）的负变构调节可降低应激敏感型大鼠品系的内脏超敏反应。
Neurobiol Stress. 2015 Apr 4;2:28-33. doi: 10.1016/j.ynstr.2015.04.001. eCollection 2015.
脊髓细胞外信号调节激酶（ERK）1/2 的激活与膀胱内脏痛觉过敏的发展有关。
Pain. 2011 Sep;152(9):2117-2124. doi: 10.1016/j.pain.2011.05.017. Epub 2011 Jun 25.
4
Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States.美国成年女性膀胱疼痛综合征/间质性膀胱炎症状的流行情况。
J Urol. 2011 Aug;186(2):540-4. doi: 10.1016/j.juro.2011.03.132. Epub 2011 Jun 16.
5
Mitochondrial reactive oxygen species are activated by mGluR5 through IP3 and activate ERK and PKA to increase excitability of amygdala neurons and pain behavior.线粒体活性氧物种通过 mGluR5 被 IP3 激活，并激活 ERK 和 PKA，从而增加杏仁核神经元的兴奋性和疼痛行为。
J Neurosci. 2011 Jan 19;31(3):1114-27. doi: 10.1523/JNEUROSCI.5387-10.2011.
6
The epidemiology of urinary tract infection.尿路感染的流行病学。
Nat Rev Urol. 2010 Dec;7(12):653-60. doi: 10.1038/nrurol.2010.190.
7
Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior.杏仁体内代谢型谷氨酸受体 5 的激活可调节痛觉样行为。
J Neurosci. 2010 Jun 16;30(24):8203-13. doi: 10.1523/JNEUROSCI.1216-10.2010.
8
Host-pathogen interactions mediating pain of urinary tract infection.介导尿路感染疼痛的宿主-病原体相互作用。
J Infect Dis. 2010 Apr 15;201(8):1240-9. doi: 10.1086/651275.
9
Urothelial signaling.尿路上皮信号转导
Auton Neurosci. 2010 Feb 16;153(1-2):33-40. doi: 10.1016/j.autneu.2009.07.005. Epub 2009 Aug 8.
10
A murine model of urinary tract infection.一种尿路感染的小鼠模型。
Nat Protoc. 2009;4(8):1230-43. doi: 10.1038/nprot.2009.116. Epub 2009 Jul 30.