目的观察鞘内注射钙调蛋白依赖性激酶Ⅱ特异性抑制剂m—AIP对坐骨神经结扎大鼠疼痛感觉分辨和情绪体验的影响。方法sD雄性大鼠18只按随机数字表法分为3组(每组n=6):假手术对照Sham组(S组)、坐骨神经结扎模型对照Control组(C组)、m-AIP组。C组和m—AIP组制备坐骨神经慢性挤压伤(CCI)模型,S组仅显露坐骨神经不结扎。术后7dS组和C组鞘内注射0.9%NaCl20μl,m-AlP组鞘内注射溶于0.9%NaCl的m—AIP0.5nmo/20μl。各组于给药后1.5h行反映痛情绪的大鼠位置逃避实验(Placeescape/avoidanceparadigm,PEAP),给药前及给药后2h、4h、8h检测大鼠的热缩足反射潜伏期(Pawwithdrawalthermallatency,PWTL)和机械性缩足反射阈值(Pawwithdrawalmechanicalthreshold,PWMT)。结果鞘内给予m—AIP0.5nmol能够改善大鼠痛行为反应,减少位置逃避行为。给药后2h、4hm—AlP组PwTL[(11.45±2.04)S,(10.26±1.48)S],PWMT[(21.15±4.32)g,(20.45±4.09)g]比c组PwTL[(9.63±1.65)S,(9.30±0.73)S],PWMT[(13.87±2.36)g,(14.804-3.12)g]升高,差异有统计学意义(P〈0.05)。给药前及给药后8hm—AIP组PWTL,PWMT与C组PWTL,PWMT相比,差异无统计学意义(P〉0.05)。结论CaMKII在坐骨神经痛的感觉分辨和情绪体验中起重要作用,鞘内注射m—AIP能够改善CCI大鼠痛行为和痛相关负性情绪。
Objective To investigate the sensory-discriminative and affective-motivational pain response of intrathecal injection of m-AIP, a special inhibitor of CaMKII, in a rat model of chronic constriction injury of sciatic nerve(CCI). Methods Eighteen SD rats were divided randomly into 3 groups(n=6) : Group S(sham) , Group C (control) and Group m-AIP. Group C and m-AIP were operated with the model of neuropathic pain induced by chronic constriction injury of sciatic nerve ; Group S were treated as sham operated rats. Seven days after operation, Group S and C received intrathecal injection of 0.9% NaCI 20 μ1, while Group m-AIP received intrathe- cal injection of m-AIP 0.5 nmo]/20 μl. Escape/avoidance behavior refrecting the affective-motivational dimension of pain was measured on 1.5 h after administration. Rats received pain behavior tests including paw withdrawal mechanical threshold(PWMT) and paw withdrawal thermal latency(PWTL) before and 2 h,4 h,8 h after adminis- tration. Results Treatment with m-AIP attenuated escape/avoidance behavior and reversed pain behaviors after CCI. At 2h and 4h after administration, Group m-AIP PWTL( ( 11.45 ± 2.04) s, ( 10.26 ±1.48 ) s) and PWMT ( (21.15 ±4.32 )g, (20.45 ±4.09 ) g) were increased when compared with Group C PWTL ( (9.63 ± 1.65 ) s, (9.30 ±.73) s) ,PWMT( ( 13.87 ±2.36)g, ( 14.80 ±3.12)g) (P〈0.05). Before and 8 h after administration, Group m-AIP PWTL, PWMT had no significant difference when compared with Group C (P 〉 0.05 ). Conclu- sion CaMKII may play an important role in sensory and affective pain processing in neuropathic rats. Intrathecal injection of m-AIP can effectively improve pain behaviors and attenuate negative affect.