室旁核IL-1β介导CRH神经元敏化参与大鼠慢性内脏痛的调节

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

摘要:

目的: 探讨室旁核IL-1β介导CRH神经元敏化对大鼠慢性内脏痛影响。方法: 清洁级健康雄性SD大鼠32只,8日龄,采用随机数字表法分为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)。Sham组大鼠不进行结直肠扩张；CRD组大鼠于出生后第8、10和12天,通过每天给予2次结直肠扩张制备大鼠慢性内脏痛模型；出生后第8周,通过立体定位法室旁核微量注射0.5 μl的IL-1β抑制剂Gevokizumab 5μg或PBS,2h后测定内脏痛阈值；免疫荧光检测PVN内c-fos表达变化及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,且室旁核内c-fos表达及CRH与c-fos共标比列明显增加(P < 0.05)；CRD+Gevokizumab组较CRD+PBS组大鼠痛阈值增加,且室旁核内c-fos表达及CRH与c-fos共标比列明显降低(P < 0.05)。结论: 室旁核IL-1β介导CRH神经元敏化参与了大鼠慢性内脏痛的调节。

Abstract:

Objective: To investigate the effects of IL-1β whereby CRH neuronal sensitization within paraventricular nucleus (PVN) 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 plus phosphate buffer solution group (Sham＋PBS group), sham operation plus Interleukin-1 beta inhibitor group (Sham＋Gevokizumab group) , colorectal distension plus phosphate buffer solution group (CRD＋PBS group), colorectal distension plus Interleukin-1 beta inhibitor group (CRD＋Gevokizumab group). Colorectal distension was not performed in Sham group. In CRD group, chronic visceral pain was induced by performing colorectal distension twice daily on postnatal days 8, 10, and12. 0.5μl of Gevokizumab 5μg or PBS was injected into PVN by stereotaxic method at 8_^th week after birth, and then 2h later for measurement of visceral pain threshold. 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 the c-fos expression and the proportion of activated CRH neurons in PVN (P＜0.05); Compared with CRD+PBS group, CRD+Gevokizumab group rats exhibited an increase in pain threshold and a significantly decrease in the c-fos expression and the proportion of activated CRH neurons in PVN(P＜0.05). Conclusion: IL-1β whereby CRH neuronal sensitization within PVN is involved in the regulation of chronic visceral pain in rats.