右美托咪定对神经病理性痛大鼠脊髓背角COX-2和c-fos表达的影响

Effect of Dexmedetomidine on spinal expression of COX-2 and c-fos in rat models of neuropathic pain

摘要:

目的探讨右美托咪定对神经病理性痛大鼠脊髓背角COX-2 和c-fos表达的影响。方法90 只健康成年雄性Wistar 大鼠随机分为假手术组（n =30）、神经病理性痛组（ n=30）和右美托咪定组（n =30），利用坐骨神经结扎的方法复制神经病理性痛模型，右美托咪定组大鼠于术后即刻开始至处死前1 天，每天腹腔注射50 μg/kg 右美托咪定，1 次/d，其他两组大鼠给予等容量生理盐水腹腔注射。分别于术前1 d（T0）、术后3 d（T1）、术后7 d（T2）和术后14 d（T3）对造模大鼠热痛阈（TWL）和机械痛阈（MWT）进行测定，分别于T1、T2和T3时测定完TWL和MWT后，处死并取脊髓组织，利用实时荧光定量PCR检测大鼠脊髓背角中COX-2 mRNA和c-fos mRNA 表达。结果与假手术组比较，神经病理性痛组和右美托咪定组大鼠T1～T3时TWL均缩短，MWT 均降低，差异有统计学意义（P <0.05），与神经病理性痛组比较，右美托咪定组大鼠T1～T3时TWL 均延长，而MWT 均升高，差异有统计学意义（P <0.05）；与假手术组比较，神经病理性痛组和右美托咪定组大鼠T1～T3时COX-2 mRNA 相对表达量和c-fos mRNA相对表达量均升高，差异均有统计学意义（P <0.05），与神经病理性痛组相比，右美托咪定组大鼠T1～T3时COX-2 mRNA 相对表达量和c-fos mRNA 相对表达量均降低，差异有统计学意义（P <0.05）。结论右美托咪定可有效抑制神经病理性痛大鼠中枢痛觉敏化，其机制可能与下调脊髓背角COX-2 和c-fos 表达有关。

Abstract:

Objective To investigate the effects of Dexmedetomidine on spinal expressions of cyclooxygenase-2 (COX-2) and c-fos in spinal dorsal horns of rat models of neuropathic pain. Methods A total of 90 healthy adult male Wistar rats were randomly divided into sham group (n = 30), neuropathic pain group (n = 30) and Dexmedetomidine group (n = 30). Rat models of neuropathic pain were established by sciatic nerve ligation. Sham operated rats received all procedure except for sciatic nerve ligation. Dexmedetomidine was intraperitoneally injected (50 μg/kg) daily in the Dexmedetomidine group. Vehicle saline were administered into the remaining animals. Thermal pain threshold (TWL) and mechanical pain threshold (MWT) were measured 1 day before operation (T0), and the 3th d (T1), 7th d (T2) and 14th d (T3) after surgery, then spine were harvested immediately. COX-2 and c-fos in spinal cord dorsal horns were determined by real-time quantitative PCR. Results Compared with the sham group, TWL and MWT in the neuropathic pain group and Dexmedetomidine group decreased significantly at T1~T3 (P < 0.05); TWL and MWT in the Dexmedetomidine group increased. at T1~T3 (P < 0.05) compared with the neuropathic pain group. Expression levels of COX-2 mRNA and c-fos mRNA in the neuropathic pain group and the Dexmedetomidine group were increased at T1~T3 dramatically (P < 0.05), but was alleviated by treatment of Dexmedetomidine compared between the neuropathic pain group and Dexmedetomidine group (P < 0.05). Conclusion Dexmedetomidine inhibits central neuropathic hyperalgesia in rat models of neuropathic pain, which may be related to down-regulation of COX-2 and c-fos.