脊髓背角核因子κB表达与佐剂关节炎大鼠的痛觉过敏

Correlation between hyperalgesia and nuclear factor-kappa B expression in spinal dorsal cord of rats with complete Freurd’s adjuvant arthritis

背景:核因子κB作为炎症反应的启动因子,可刺激损伤部位或炎症局部基因的转录,促进炎性因子的产生,导致疼痛的发生,但其在参与慢性炎性疼痛脊髓机制中的作用目前研究甚少。目的:制备稳定的油包水剂型完全弗式佐剂单关节炎大鼠模型,并对大鼠疼痛行为学痛觉过敏及脊髓背角核因子κB表达进行观察和探讨。方法:24只大鼠被随机分为假手术对照组、完全弗氏佐剂组,每组12只。大鼠右踝关节腔内注射含灭活结核杆菌的黏稠油包水型完全弗式佐剂,假手术组注射50μL生理盐水至大鼠右踝关节腔内,观察大鼠完全弗式佐剂注射前2d,注射后4,7,14,21,28d的机械压痛、辐射热痛、关节肿胀周径(内外踝下缘周长)及脊髓背角核因子κB表达的变化。结果与结论:①注射3h,大鼠右踝关节出现明显肿胀,但局部红、热不明显,注射24h,右踝关节红肿显著且波及足跖面,并持续4周。②注射4d～4周,大鼠右踝关节周径在较对侧及注射前显著增加(P<0.01)。③与注射前及假手术组相比,完全弗氏佐剂组机械压痛阈值在注射后4d明显下降,注射后21d降至最低值(P均<0.01);注射4d,与注射前相比,完全弗氏佐剂组大鼠患侧辐射热痛阈值明显下降,7d降至最低点后逐渐稳定,并持续4周(P均<0.01)。④完全弗氏佐剂组大鼠患侧腰段脊髓背角Ⅰ～Ⅵ层核因子κB表达明显高于假手术组(P<0.01)。证实关节腔内注射油包水型完全弗式佐剂可获得稳定的单关节炎疼痛模型,大鼠关节致炎后出现明显的辐射热及压痛痛觉过敏,且持续时间长,痛敏阈值稳定,脊髓背角Ⅰ～Ⅵ层核因子κB表达明显升高。

BACKGROUND： Nuclear factor-kappa B （NF-κB）, as a promoter of inflammatory reaction, stimulates injured parts or transcription of local inflammatory gene, promotes generation of inflammatory factors, and induces pain onset; however, the mechanism on chronic inflammatory pained spinal cord has been less reported. OBJECTIVE： To explore the NF-κB expression in spinal dorsal horn and behavioral hyperalgesia by preparing rat models of complete Freurd’s adjuvant arthritis. METHODS： A total of 24 SD rats were randomly divides into sham-surgery group and complete Freund’s adjuvant group, with 12 rats in each group. Adjuvant arthritis model was produced by injection of 50 μL complete Freund’s adjuvant （CFA） to the right ankle joint after anesthesia. The same volume saline was injected to the rat right ankle joint in sham-surgery group. The mechanical pain threshold, paw withdrawal thermal latency （PWTL）, the diameter of ankle, and NF-κB expression in spinal dorsal horn were investigated 2 days before and 4, 7, 14, 21, and 28 days after CFA injection. RESULTS AND CONCLUSION： ① Three hours after CFA injection, the ankle joint appeared edema, but local inflamed and thermal symptoms were not obvious. The inflamed symptoms significantly appeared on right ankle joint and developed to food surface at 24 hours after CFA injection, while the symptoms lasted for 4 weeks. ② Diameter of right ankle was significantly increased at 4 days-4 weeks after CFA injection compared to intralateral ankle and before CFA injection （P 0.01）. ③ Compared to before injection and sham-surgery group, the mechanical pain threshold was significantly decreased at 4 days after CFA injection, and reached the lowest value at 21 days （P 0.01）. The PWTL was significantly decreased at 4 days after CFA injection and reached at the lowest level at 7 days, while the lowest level lasted for 4 weeks （P 0.01）. ④ The expression of NF-κB was significantly increased in I-VI in spinal dorsal horn in the complete Freund’s adjuvant group, which was higher than sham-surgery group （P 0.01）. The results indicated that we could gain stable monoarthritis model by injecting CFA with oil-contained water into rat ankle joint space, and the model shown prolong and significant hyperalgesia to radial thermal and mechanical pressure; meanwhile, the NF-κB expression increased significantly in lamber I-VI in spinal dorsal horn after the ankle joint arthritis.