脊髓CXCR2在CCI大鼠神经病理性疼痛中的作用研究

Role of spinal CXCR2 in neuropathic pain of rats suffered from chronic constriction injury

摘要:

探讨脊髓趋化因子受体2（CXCR2）在坐骨神经慢性压迫（CCI）模型大鼠神经病理性疼痛（NPP）中的作用。方法18 只成年Sprague-Dawley 雄性大鼠，随机分为3 组，每组6 只。对照组：大鼠不做任何处理；模型组：复制CCI大鼠模型；实验组：复制CCI 大鼠模型后第3 天腹腔注射漆树酸5 mg/kg。于复制大鼠CCI模型前1 天，以及第1、3、5 和7 天分别测定大鼠后足热痛阈及机械痛阈，并应用Western blot测定腰段脊髓CXCR2 的蛋白表达。结果CCI 大鼠术后第3天开始术侧下肢热痛阈值降低，模型组、实验组术侧下肢热 痛阈值与对照组比较，差异有统计学意义（p <0.05）；实验组大鼠第5 和7 天术侧热痛阈值与模型组比较，差异有统计学意义（p <0.05）。机械痛阈变化趋势与热痛阈一致。模型组、实验组大鼠脊髓CXCR2 表达与对照组比较，差异有统计学意义（p <0.05）；实验组CXCR2 表达与模型组比较，差异有统计学意义（p <0.05）。结论脊髓CXCR2表达的异常上调，可导致NPP产生和维持。腹腔注射漆树酸能够部分抑制CCI大鼠脊髓腰段CXCR2的表达上调，并缓解CCI大鼠的疼痛行为。

关键词:神经病理性疼痛;趋化因子受体2;组蛋白乙酰化;表观遗传学

Abstract:

To explore the role of chemokine receptor 2 (CXCR2) of spinal cord in neuropathic pain of rats following sciatic nerve chronic constriction injury (CCI). Methods Eighteen adult male Sprague-Dawley rats were randomly divided into 3 groups (6 in each), i.e. N group (without any treatment), C group(CCI model) and T group (rats received intraperitoneal injection of 5 mg/kg Anacardic acid 3 d after CCI model establishment). Paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PTWL) were measured in the 3 groups 1 d before model establishment and on the 1st, 3rd, 5th and 7th d after CCI surgery. All lumbar spinal cords were dissected to examine the CXCR2 expression by Western blot. Results The PTWL of the CCI rats reduced from the 3rd d after surgery. Compared with te N group, the PTWL in the C and T groups were obviously reduced ( p< 0.05). Compared with the C group, the PTWL of the T group increased on the 5th and 7th d (p < 0.05). The variation tendency of PMWT was similar to that of PTWL. Compared with the N group, the CXCR2 expression in the C and T groups increased (p < 0.05).Compared with the C group, the CXCR2 expressions in the T group decreased ( p< 0.05). Conclusions Upregulation of CXCR2 in the spinal cord may play an important role in the pathogenesis of neuropathic pain.Intraperitoneal injection of Anacardic acid could partly reduce the expression of CXCR2 in the lumbar spinal cord in CCI rats and relieve pain.

Key words:neuropathic pain; chemokine receptor 2; histone acetylation; epigenetics