触液核HDAC6参与调控大鼠神经病理性痛

THE HDAC6 IN CSF-CONTACTING NUCLEUS IS INVOLVED IN REGULATING NEUROPATHIC PAIN IN RATS

摘要:

目的: 探讨触液核HDAC6在大鼠神经病理性痛中的作用。方法: 成年雄性SD大鼠，体重240-290 g。利用慢性坐骨神经结扎（chronic constriction injury of sciatic nerve ligation, CCI）建立神经病理性痛模型，分别采用Von Frey丝和热辐射仪测量大鼠机械痛与热痛。采用免疫荧光共标技术，观察正常及神经病理性痛大鼠触液核中HDAC6的表达情况。通过侧脑室注射Tubastatin A观察拮抗HDAC6对大鼠痛阈的的影响。最后通过侧脑室注射HDAC6过表达病毒及对照病毒，观察触液核HDAC6过表达对大鼠神经病理性痛的影响。结果: 神经病理性痛大鼠触液核HDAC6表达明显减少（P < 0.05）。Tubastatin A拮抗HDAC6后1 h大鼠痛阈明显降低（P < 0.05），24 h后恢复至正常水平。与以上结果一致的是，侧脑室注射了HDAC6过表达病毒的神经病理性痛大鼠，其疼痛状况得到明显改善（P < 0.05）。结论: 触液核HDAC6参与了大鼠神经病理性痛的调控。

Abstract:

Objective: To investigate the role of HDAC6 in the cerebrospinal fluid (CSF)-contacting nucleus on neuropathic pain in rats. Methods: Adult male Sprague-Dawley (SD) rats, weighing 240-290 g. Chronic constriction injury of sciatic nerve ligation was used to establish a neuropathic pain model. Von Frey wire and thermal radiation meter were used to measure mechanical and thermal pain threshold in rats. The immunofluorescence technique was used to observe the expression of HDAC6 in the CSF-contacting nucleus of normal and neuropathic rats. The effect of antagonizing HDAC6 on the pain threshold of rats was observed by injection of Tubastatin A. Finally, HDAC6 overexpression and control virus were injected into the lateral ventricle to observe the effect of HDAC6 overexpression on the neuropathic pain in rats. Results: The expression of HDAC6 in the CSF-contacting nucleus of neuropathic pain rats was significantly decreased (P < 0.05). Regarding antagonism to HDAC6, it was found that the pain threshold was significantly reduced in rats at 1 h after injection of Tubasatin A (P < 0.05), but returned to normal levels after 24 hours. Consistent with the results, the pain threshold of the neuropathic pain rats with HDAC6 overexpression virus injected into the lateral ventricle had significantly increased (P < 0.05). Conclusion: The HDAC6 in the CSF-contacting nucleus is involved in the regulation of neuropathic pain in rats.