Y1受体基因敲除增强痛觉感受并阻止神经肽Y的抗痛觉过敏作用。
Y1 receptor knockout increases nociception and prevents the anti-allodynic actions of NPY.
作者信息
Kuphal K E, Solway B, Pedrazzini T, Taylor B K
机构信息
Division of Pharmacology, University of Missouri-Kansas City, Kansas City, Missouri, USA.
出版信息
Nutrition. 2008 Sep;24(9):885-91. doi: 10.1016/j.nut.2008.06.022.
Abstract
OBJECTIVE
Recent pharmacologic studies in our laboratory have suggested that the spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY. To rule out off-target effects, the present study used Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1 receptors to pain modulation.
METHODS AND RESULTS
Y1(-/-) mice exhibited reduced latency in the hotplate test of acute pain and a longer-lasting heat allodynia in the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did not change CFA-induced inflammation. Upon targeting the spinal NPY systems with intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA model and the partial sciatic nerve ligation model of neuropathic pain. Importantly, we show for the first time that NPY does not exert these anti-allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice, concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti-allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the Rotorod test, arguing against an indirect effect of motor function.
CONCLUSION
The Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY.
摘要
目的
我们实验室最近的药理学研究表明，脊髓神经肽Y（NPY）的Y1受体有助于疼痛抑制及NPY的镇痛作用。为排除脱靶效应，本研究使用Y1受体缺陷型（-/-）小鼠进一步探究Y1受体在疼痛调节中的作用。
方法与结果
Y1（-/-）小鼠在急性疼痛热板试验中的潜伏期缩短，在完全弗氏佐剂（CFA）诱导的炎性疼痛模型中热痛觉过敏持续时间延长。Y1基因缺失并未改变CFA诱导的炎症反应。通过鞘内给药靶向脊髓NPY系统后，NPY可减轻CFA模型和坐骨神经部分结扎所致神经性疼痛模型中的触觉和热痛觉过敏。重要的是，我们首次发现NPY在Y1（-/-）小鼠中不发挥这些抗痛觉过敏作用。此外，在神经损伤的CD1小鼠中，同时注射强效Y1拮抗剂BIBO3304可阻止NPY的抗痛觉过敏作用。NPY和BIBO3304均未改变转棒试验的表现，排除了对运动功能的间接影响。
结论
Y1受体有助于疼痛抑制及NPY的镇痛作用。
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