In vivo patch-clamp analysis of hyperalgesia induced in ovarlectomized rats

去卵巢大鼠痛觉过敏的体内膜片钳分析

• 批准号: 13480276
• 负责人: YOSHIMURA Megumu
• 金额: $ 8.9万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13480276/
• 关键词: hyperalgesia; serotonin; descending inhibitory system; ovariectomy; spinal dorsal horn; in vivo patch-clamp; Calcitonin; substantia gelatinosa; 骨粗鬆症; in vivoパッチクランプ法; C線維; in vivoパッチ; 卵巣摘出ラット; 可塑性; 脊髄スライス; パッチクランプ記録

In vivo patch-clamp recordings were made from substantia gelatinosa (SG) neurons in the spinal dorsal horn to analyze a mechanism of hyperalgesia ovserved in ovariectomized rats. Noxious or non-noxious stimuli applied to the hind limb in normal rats elicited a barrage of EPSCs in all SG neurons tested and no significant difference was observed in amplitudes in both stimuli. While in OVX rats, the amplitude of noxious response was significantly larger than that of non-noxious one. Serotonin (40 μM) applied to the surface of the spinal cord depressed both responses in amplitude in normal rats, while in OVX rats, serotonin depressed only the touch-evoked responses but not pinch evoked one. Pre-treatment of OVX rats with Calcitonin prevented the augmentation of EPSCs in amplitude by noxious stimuli and the ineffectiveness of serotonin on the pinch-evoked response. Together with results obtained from slice examinations, these observations suggest that Aδ and C afferent terminals express distinct 5-HT receptor subtypes that are tonically controlled by the descending sertonergic system. In OVX rats, the receptor expressed at C afferent terminal is eliminated and results in increasing of glutamatergic transmission. After the treatment of rats with Calcitonin, the eliminated 5-HT receptor is restored. This plastic change in 5-HT receptor expression will be an underlying mechanism of hyperalgesia observed in OVX rats and its relief by Calcitonin.

体内贴片钳记录是由脊柱背角中的蛋白质明胶（SG）神经元制成的，以分析在卵巢切除大鼠中发出的高敏性机制。在正常大鼠中应用于后肢的有害或无毒性刺激在所有测试的SG神经元中引起了EPSC的弹性，并且在两个刺激中都没有观察到放大器中的显着差异。在OVX大鼠中，有害反应的放大器明显大于非氧化反应。 5-羟色胺（40μM）应用于正常大鼠的脊髓表面抑制两个反应的表面，而在OVX大鼠中，5-羟色胺仅抑制了接触式诱发的反应，但不捏夹引起了诱发的反应。用降钙素对OVX大鼠进行预处理，可以通过有害刺激在放大器中增加EPSC，而5-羟色胺在捏诱发的反应中的无效性。这些观察结果与从切片检查获得的结果一起表明，Aδ和C传统末端表达了通常由降级Serantergic System控制的不同的5-HT受体亚型。在OVX大鼠中，消除了在C传播末端表达的受体，并导致谷氨酸能传播的增加。用降钙素治疗大鼠后，恢复了消除的5-HT受体。 5-HT受体表达中的这种塑性变化将是在OVX大鼠中观察到的痛觉过敏的潜在机制及其降压蛋白的缓解。

项目成果

Kawasaki Y., Kumamoto E., Furue H., Yoshimura M.: "α2 adrenoceptor-mediated presynaptic inhibition of primary-afferent glutamatergic transmission in rat substantia gelatinosa neurons"Anesthesiology. 98. 682-689 (2003)

Kawasaki Y.、Kumamoto E.、Furue H.、Yoshimura M.：“α2 肾上腺素受体介导的大鼠胶质神经元初级传入谷氨酸传递的突触前抑制”麻醉学 98. 682-689 (2003)。

Matsumoto N., Kumamoto E., Furue H., Yoshimura M.: "GABA-mediated inhibition of glutamate release during ischemia in substantia gelatinosa of the adult rat."Journal of Neurophysiology. 89(1). 257-264 (2003)

Matsumoto N.、Kumamoto E.、Furue H.、Yoshimura M.：“成年大鼠凝胶质缺血期间 GABA 介导的谷氨酸释放抑制。”神经生理学杂志。

Yang K., Furue H., Kumamoto E., Dong Y-X., Yoshimura M..: "Pre- and postsynaptic inhibition mediated by GABAB receptors in rat ventrolateral periaqueductal gray neurons"Biochemical and Biophysical Research Communications. 302(2). 233-237 (2003)

Yang K.、Furue H.、Kumamoto E.、Dong Y-X.、Yoshimura M..：“大鼠腹外侧导水管周围灰色神经元中 GABAB 受体介导的突触前和突触后抑制”生物化学和生物物理研究通讯。

吉村 恵 et al.: "骨粗鬆症の痛みの発生とカルシトニンによる静痛作用"Clinical Calcium. 11・9. 1153-1157 (2002)

Megumi Yoshimura 等：“骨质疏松性疼痛的发生和降钙素的镇痛作用”临床钙 11・9（2002）。

Matsumoto N et al.: "GABA-mediated inhibition of glutamate release during ischemia in substantia gelatinosa of the adult rat"Journal of Neurophysiology. 89/1. 257-264 (2003)

Matsumoto N 等人：“成年大鼠凝胶质缺血期间 GABA 介导的谷氨酸释放抑制”神经生理学杂志。