Membrane-Delimited Coupling of TRPV1 and mGluR5 on Presynaptic Terminals of Nociceptive Neurons
Membrane-Delimited Coupling of TRPV1 and mGluR5 on Presynaptic Terminals of Nociceptive Neurons
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DOI：
10.1523/jneurosci.5030-08.2009
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发表时间：
2009-08-12
影响因子：
5.3
通讯作者：
Oh, Seog Bae
中科院分区：
文献类型：
--
作者：
Kim, Yong Ho;Park, Chul-Kyu;Oh, Seog Bae
位于外周感觉末梢的瞬时受体电位香草酸亚型1（TRPV 1）和代谢型谷氨酸受体5（mGluR 5）在痛觉的传导和调节中起着重要作用。然而，迄今为止，关于mGluR 5和TRPV 1在脊髓背角感觉神经元中央末端功能表达的意义知之甚少。在这里，我们表明，中央突触前末梢上的TRPV 1耦合到mGluR 5在膜界定的方式，从而有助于脊髓胶状质神经元的伤害性突触传递的调制。此外，我们的研究结果表明，TRPV 1参与脊髓mGluR 5激活诱导的疼痛行为，和二酰基甘油的mGluR 5的激活产生介导的mGluR 5和TRPV 1的突触前末梢的功能耦合。因此，mGluR 5-TRPV 1耦合的伤害性神经元的中枢突触前末梢可能是一个重要的机制，在病理性疼痛条件下的中枢敏化。
Transient receptor potential vanilloid subtype 1 (TRPV1) and metabotropic glutamate receptor 5 (mGluR5) located on peripheral sensory terminals have been shown to play critical roles in the transduction and modulation of pain sensation. To date, however, very little is known regarding the significance of functional expression of mGluR5 and TRPV1 on the central terminals of sensory neurons in the dorsal horn of the spinal cord. Here we show that TRPV1 on central presynaptic terminals is coupled to mGluR5 in a membrane-delimited manner, thereby contributing to the modulation of nociceptive synaptic transmission in the substantia gelatinosa neurons of the spinal cord. Further, our results demonstrate that TRPV1 is involved in the pain behaviors induced by spinal mGluR5 activation, and diacylglycerol produced by the activation of mGluR5 mediates functional coupling of mGluR5 and TRPV1 on the presynaptic terminals. Thus, mGluR5-TRPV1 coupling on the central presynaptic terminals of nociceptive neurons may be an important mechanism underlying central sensitization under pathological pain conditions.