Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception
Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception
复制标题
DOI：
10.1186/1744-8069-8-20
复制
发表时间：
2012-03-26
期刊：
影响因子：
3.3
通讯作者：
Gereau, Robert W.
中科院分区：
文献类型：
--
作者：
Crock, Lara W.;Stemler, Kristina M.;Gereau, Robert W.
背景：间质性膀胱炎/膀胱疼痛综合征（IC/PBS）是一种严重衰弱的慢性疾病，通常对常规止痛药无反应。病因尚不清楚，但有证据表明，神经系统致敏有助于IC/PBS患者疼痛增强。特别是，涉及NMDA和代谢性谷氨酸受体（mGluRs）的谷氨酸能信号的中枢神经系统可塑性与多种慢性疼痛有关。在这里，我们通过监测分级膀胱膨胀期间的内脏运动反应（VMR），在小鼠模型中验证了mGluR5介导非炎症性和炎症性膀胱疼痛或伤害感受的假设。结果：通过遗传学和药理学方法的结合，我们提供的证据表明，在没有炎症的情况下，VMR的充分表达是mGluR5所必需的。此外，我们观察到感染尿路致病性大肠杆菌（UPEC）的小鼠对膀胱膨胀产生炎症性痛感过敏，并且选择性mGluR5拮抗剂非诺巴姆[N-（3-氯苯基）-N'-（4,5-二氢-1-甲基-4-氧- 1h -咪唑-2-基）尿素]降低了UPEC感染小鼠对膀胱膨胀的VMR。结论：综上所述，这些数据表明mGluR5可以调节炎症性和非炎症性膀胱痛觉，并强调了mGluR5拮抗剂在减轻膀胱疼痛方面的治疗潜力。
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 noninflammatory 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 noninflammatory bladder nociception, and highlight the therapeutic potential for mGluR5 antagonists in the alleviation of bladder pain.