The NK1 receptor is essential for the full expression of noxious inhibitory controls in the mouse
The NK1 receptor is essential for the full expression of noxious inhibitory controls in the mouse
复制标题
DOI：
10.1523/jneurosci.21-03-01039.2001
复制
发表时间：
2001-02-01
影响因子：
5.3
通讯作者：
Hunt, SP
中科院分区：
文献类型：
--
作者：
Bester, H;De Felipe, C;Hunt, SP
NK1受体基因敲除（NK1(-/-)）小鼠的行为分析表明，P物质密切参与协调动物对主要环境压力源的生理和行为反应。特别是，内源性疼痛控制机制，例如应激诱导的镇痛，在突变小鼠中显着受损，表明脑干对脊髓的下行抑制控制减少。为了直接测试 NK1(-/-) 小鼠中下行对照的完整性，我们在已知需要招募下行抑制对照的实验范式中分析了腰椎和颈髓的 I-II 层以及头端腹内侧延髓中的 c-Fos 表达。用50℃的水刺激麻醉小鼠的前爪、后爪或同时刺激后爪和前爪。将原始小鼠或用 NK1 拮抗剂 (RP67580) 或其无活性异构体 (RP68651) 治疗的野生型小鼠与 NK1(-/-) 小鼠进行比较。与NK1(-/-)小鼠相比，野生型双刺激情况下，腰椎板I-II水平的C-Fos表达显着降低，而中缝大核和苍白核中的C-Fos表达显着升高。阻断 NK1 受体以对映体选择性方式在药理学上再现 NK1(-/-) 小鼠的数据，没有证据表明前爪刺激后腰脊髓水平会出现下降抑制。本研究表明 NK1 受体对于有害诱发的下行抑制的全面发展至关重要。
Behavioral analysis of the NK1 receptor gene knock-out (NK1(-/-)) mouse indicated that substance P was closely involved in orchestrating the physiological and behavioral response of the animal to major environmental stressors. In particular, endogenous pain control mechanisms, such as stress-induced analgesia were substantially impaired in mutant mice, suggesting a reduction in descending inhibitory controls to the spinal cord from the brainstem. To directly test the integrity of descending controls in NK1(-/-) mice, we have analyzed c-Fos expression in laminae I-II of the lumbar and cervical cord and in the rostral ventromedial medulla in an experimental paradigm known to require recruitment of descending inhibitory controls. Anesthetized mice were stimulated with water at 50 degreesC either on their forepaw, hindpaw, or on both the hindpaw plus forepaw concurrently. Wild-type mice, naive or treated with an NK1 antagonist (RP67580) or its inactive isomer (RP68651), were compared with NK1(-/-) mice. C-Fos expression at the lumbar laminae I-II level was significantly reduced, whereas it was significantly greater in the raphe magnus and pallidus nuclei in the double stimulation situation in wild-type compared with NK1(-/-) mice. Blocking the NK1 receptor pharmacologically reproduced, in an enantiomere-selective manner, the data from NK1(-/-) mice, with no evidence for recruitment of descending inhibition at the lumbar cord level after forepaw stimulation. The present study demonstrates that the NK1 receptor is essential for the full development of noxiously evoked descending inhibition.