触液核组蛋白去乙酰化酶6参与调控大鼠神经病理性疼痛

The HDAC6 in CSF-contacting nucleus is involved in regulating neuropathic pain in rats

目的:探讨触液核组蛋白去乙酰化酶6 (histone deacetylases 6, HDAC6)在大鼠神经病理性疼痛中的作用。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, CCI)建立神经病理性疼痛模型,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疼痛大鼠触液核中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疼痛的影响。结果:神经病理性疼痛大鼠触液核HDAC6表达明显减少,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疼痛大鼠,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疼痛的调控。

Objective: To investigate the role of histone deacetylases 6(HDAC6) in the cerebrospinal fluid(CSF)-contacting nucleus on neuropathic pain in rats. Methods: Adult male SD rats, weighing 240-290 g, were used in this study. Chronic constriction injury(CCI) was used to establish a neuropathic pain model. von Frey hair 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. 1 hour after injection of Tubasatin A, pain threshold was significantly reduced in rats(P < 0.05) and recovered to normal 24 hours later. Consistent with the above results, the pain thresholds of rats with neuropathic pain after HDAC6 overexpression virus injection into the lateral ventricle were increased significantly, compared with the control virus injection group(P < 0.05). Conclusion: The HDAC6 in the CSF-contacting nucleus is involved in the regulation of neuropathic pain in rats.