NK-1 receptors modulate the excitability of ON cells in the rostral ventromedial medulla
NK-1 receptors modulate the excitability of ON cells in the rostral ventromedial medulla
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DOI：
10.1152/jn.00450.2006
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发表时间：
2007-02-01
影响因子：
2.5
通讯作者：
Simone, Donald A.
中科院分区：
文献类型：
--
作者：
Budai, Denes;Khasabov, Sergey G.;Simone, Donald A.
用细胞外单细胞记录结合微电泳技术研究了延髓头端腹内侧区（RVM）神经激肽1（NK-1）受体的作用。在大鼠中，ON-和OFF-型神经元被确定使用有害热或机械刺激施加到尾部。诱发的N-甲基-D-天冬氨酸（NMDA）的离子电渗应用程序的前，后足底注射辣椒素或P物质的离子电渗应用程序。在OFF细胞，辣椒素产生了延长暂停正在进行的活动，但没有改变随后的自发放电率或NMDA诱发的反应。相反，辣椒素后ON细胞的自发放电率增加，它们对NMDA的反应比对照值增加> 100%。辣椒素后增加的NMDA反应被选择性NK-1受体拮抗剂L-733，060的离子导入应用减弱。与辣椒素类似，离子电渗应用选择性NK-1受体激动剂[Sar（9），Met（O-2）（11）]-P物质（SM-SP）可使ON细胞的自发放电率和NMDA诱发反应增加>对照值的100%。这些作用被L-733，060拮抗。免疫组织化学研究表明，在RVM标记NK-1受体的神经元的子集，几乎所有这些神经元的NMDA受体的NMDAR 1亚基的免疫反应。这些结果表明，RVM中的NK-1受体的活化增强了由NMDA诱发的ON细胞的反应。这表明，NK-1受体在RVM的激活和随后的ON细胞的敏化可能有助于组织损伤和炎症后的中枢敏化和痛觉过敏的发展。
The role of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) was studied using extracellular single-unit recording combined with microiontophoresis. In rats, ON- and OFF-type neurons were identified using noxious heat or mechanical stimuli applied to the tail. Responses evoked by iontophoretic application of N-methyl-D-aspartate ( NMDA) were determined before and after intraplantar injection of capsaicin or iontophoretic application of substance P. In OFF cells, capsaicin produced an extended pause in ongoing activity but did not alter the subsequent spontaneous discharge rate or NMDA-evoked responses. In contrast, spontaneous discharge rates of ON cells increased after capsaicin, and their responses to NMDA increased > 100% above control values. The increased responses to NMDA after capsaicin were attenuated by iontophoretic application of the selective NK-1 receptor antagonist L-733,060. Similarly to capsaicin, iontophoretic application of the selective NK-1 receptor agonist, [Sar(9), Met(O-2)(11)]-substance P (SM-SP), increased the spontaneous discharge rate and NMDA-evoked responses of ON cells by > 100% of control values. These effects were antagonized by L-733,060. Immunohistochemical studies showed that a subset of neurons in the RVM labeled NK-1 receptors and that nearly all of these neurons were immunoreactive for the NMDAR1 subunit of the NMDA receptor. These results demonstrate that activation of NK-1 receptors in the RVM enhances responses of ON cells evoked by NMDA. It is suggested that activation of NK-1 receptors in the RVM and the ensuing sensitization of ON cells may contribute to the development of central sensitization and hyperalgesia after tissue injury and inflammation.