Zhou Hong-Yi, Chen Shao-Rui, Chen Hong, Pan Hui-Lin
Department of Anesthesiology and Pain Medicine, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
J Neurochem. 2009 Jan;108(1):305-18. doi: 10.1111/j.1471-4159.2008.05772.x. Epub 2008 Nov 19.
The transient receptor potential vanilloid receptor 1 (TRPV1) is expressed on primary afferent terminals and spinal dorsal horn neurons. However, the neurochemical phenotypes and functions of TRPV1-expressing post-synaptic neurons in the spinal cord are not clear. In this study, we tested the hypothesis that TRPV1-expressing dorsal horn neurons are glutamatergic. Immunocytochemical labeling revealed that TRPV1 and vesicular glutamate transporter-2 were colocalized in dorsal horn neurons and their terminals in the rat spinal cord. Resiniferatoxin (RTX) treatment or dorsal rhizotomy ablated TRPV1-expressing primary afferents but did not affect TRPV1- and vesicular glutamate transporter-2-expressing dorsal horn neurons. Capsaicin significantly increased the frequency of glutamatergic spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in almost all the lamina II neurons tested in control rats. In RTX-treated or dorsal rhizotomized rats, capsaicin still increased the frequency of spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in the majority of neurons examined, and this effect was abolished by a TRPV1 blocker or by non-NMDA receptor antagonist. In RTX-treated or in dorsal rhizotomized rats, capsaicin also produced an inward current in a subpopulation of lamina II neurons. However, capsaicin had no effect on GABAergic and glycinergic spontaneous inhibitory post-synaptic currents of lamina II neurons in RTX-treated or dorsal rhizotomized rats. Collectively, our study provides new histological and functional evidence that TRPV1-expressing dorsal horn neurons in the spinal cord are glutamatergic and that they mediate excitatory synaptic transmission. This finding is important to our understanding of the circuitry and phenotypes of intrinsic dorsal horn neurons in the spinal cord.
瞬时受体电位香草酸受体1（TRPV1）表达于初级传入神经末梢和脊髓背角神经元上。然而，脊髓中表达TRPV1的突触后神经元的神经化学表型和功能尚不清楚。在本研究中，我们验证了表达TRPV1的背角神经元是谷氨酸能神经元这一假说。免疫细胞化学标记显示，TRPV1与囊泡谷氨酸转运体2在大鼠脊髓背角神经元及其终末中共定位。树脂毒素（RTX）处理或背根切断术可消除表达TRPV1的初级传入神经，但不影响表达TRPV1和囊泡谷氨酸转运体2的背角神经元。辣椒素显著增加了对照大鼠几乎所有Ⅱ层神经元中谷氨酸能自发性兴奋性突触后电流和微小兴奋性突触后电流的频率。在RTX处理或背根切断的大鼠中，辣椒素仍能增加大多数被检测神经元中自发性兴奋性突触后电流和微小兴奋性突触后电流的频率，并且这种效应可被TRPV1阻滞剂或非NMDA受体拮抗剂消除。在RTX处理或背根切断的大鼠中，辣椒素还能在Ⅱ层神经元的一个亚群中产生内向电流。然而，辣椒素对RTX处理或背根切断的大鼠中Ⅱ层神经元的GABA能和甘氨酸能自发性抑制性突触后电流没有影响。总体而言，我们的研究提供了新的组织学和功能证据，表明脊髓中表达TRPV1的背角神经元是谷氨酸能的，并且它们介导兴奋性突触传递。这一发现对于我们理解脊髓内源性背角神经元的神经回路和表型具有重要意义。
