室旁核IL-1β介导CRH神经元敏化参与大鼠慢性内脏痛

IL-1β IS INVOLVED IN CHRONIC VISCERAL PAIN IN RATS BY REGULATION OF CRH NEURONAL SENSITIZATION WITHIN PARAVENTRICULAR NUCLEUS

目的:探讨室旁核(paraventricular nucleus,PVN)IL-1β介导促肾上腺皮质激素释放激素(corticotrophin-releasing hormone,CRH)神经元敏化对大鼠慢性内脏痛的影响.方法:雄性SD大鼠32只,8日龄,按随机数字表法分为4组(n=8):假手术+PBS组(Sham+PBS组)、假手术+IL-1β抑制剂组(Sham+Gevokizumab组)、模型+PBS组(CRD+PBS组)、模型+IL-1β抑制剂组(CRD+Gevokizumab组).CRD组大鼠出生后第8、10、12 d,每天给予2次结直肠扩张制备慢性内脏痛模型;出生后第8周,室旁核注射0.5μl的IL-1β抑制剂Gevokizumab 5μg或PBS,测定内脏痛阈值;免疫荧光检测室旁核c-Fos表达及CRH神经元的活化情况.结果:与Sham+PBS组、Sham+Gevokizumab组相比,CRD+PBS组大鼠痛阈值降低,且c-Fos表达及CRH与c-Fos共标比例增加(P<0.05);CRD+Gevokizumab组较CRD+PBS组大鼠痛阈值增加,且c-Fos表达及CRH与c-Fos共标比例明显降低(P<0.05).结论:室旁核IL-1β可能通过敏化CRH神经元参与了大鼠慢性内脏痛的调节.

Objective:To investigate the effects of Interleukin-1 beta (IL-1β) on corticotrophin-releasing hormone (CRH) neuronal sensitization within paraventricular nucleus (PVN) and on the regulation of chronic visceral pain in rats. Methods:Thirty-two pathogen-free healthy male Sprague-Dawley rats, aged 8 days, were divided into 4 groups (n = 8 each) using a random number table:sham operation and phosphate buffer solution group (Sham + PBS group), sham operation and IL-1β inhibitor group (Sham + Gevokizumab group), colorectal distension and PBS group (CRD + PBS group), colorectal distensionand IL-1β inhibitor group (CRD + Gevokizumab group). Colorectal distension was not performed in Sham group. In CRD group, chronic visceral pain was induced by colorectal distension twice daily on postnatal days 8, 10, and 12. The Gevokizumab (5 μg in 0.5 μl) or PBS was injected into PVN by stereotaxic method at 8th week after birth, and 2 h later visceral pain threshold was measured. The expression of c-fos and activation rate of CRH neurons in PVN were detected by immunofluorescent staining. Results:Compared with Sham + PBS group and Sham + Gevokizumab group, CRD + PBS group rats presented a decrease in pain threshold and a significantly increase in c-fos expression and the proportion of activated CRH neurons in PVN (P < 0.05);Compared with CRD + PBS group, CRD + Gevokizumabgroup rats exhibited an increase in pain threshold and a significantly decrease in c-fos expression and the proportion of activated CRH neurons in PVN (P < 0.05). Conclusion:IL-1β may be involved in chronic visceral pain via regulating CRH neuronal sensitization within PVN in rats.