摘要目的 探讨导水管周围灰质(PAG)注射zeta假底物抑制肽(ZIP)对疼痛感觉和疼痛厌恶情绪的影响.方法 大鼠足底注射甲醛50μl作为条件刺激与条件位置回避训练结合,建立甲醛诱导的条件位置回避(F-CPA)模型,观察PAG注射ZIP对F-CPA的影响,以明确ZIP对疼痛厌恶情绪的作用.大鼠足底注射5％甲醛50μl建立炎性疼痛模型,观察PAG注射ZIP对甲醛引起的伤害性疼痛行为学的影响,以确定ZIP对疼痛感觉的作用.结果 甲醛诱导的条件位置回避实验中,大鼠条件性位置回避建立1、7d,PAG注射生理盐水后2、24 h大鼠在条件室内停留的时间较训练前明显减少.NS-1 d-2 h组训练前后条件室内停留的时间分别为(465.1±40.6)和(133.8 ±29.4) s(P＜0.001);NS-7 d-2 h组分别为(432.3±43.7)和(150.5±26.6)s(P ＜0.001);NS-1 d-24 h分别为(500.5±20.6)和(107.0±15.7)s(P＜0.001);NS-7 d-24 h组分别为(450.8±27.4)和(129.4±21.1)s(P＜0.001).与之相反,ZIP组大鼠在条件室内停留的时间与训练前相比无显著变化.ZIP各组的回避分数均显著低于同时间点生理盐水组(均P ＜0.05).ZIP组大鼠与生理盐水组大鼠相比,甲醛引起的累积疼痛评分差异均无统计学意义(均P＞0.05).结论 PAG参与了疼痛厌恶情绪的整合过程,其机制可能是ZIP作用靶点的激活.

abstractsObjective To explore the effects of intra-PAG injection of ZIP on sensory and affective components of pain.Methods For determining the role of ZIP on pain-induced aversion,the effects of intra-PAG injection of ZIP on formalin-induced conditioned place avoidance (F-CPA) was investigated.To determine the role of ZIP on pain perception,formalin-induced inflammatory pain model was established and the effects of intra-PAG injection of ZIP on formalin-induced nociceptive behaviors was investigated.Results In the NS-treated rats,the time in the pain-paired compartment during the test session was significantly shorter than that during the preconditioning session 2 and 24 hours after administration of the drug at both 1 and 7 day post-training(Group NS-1 d-2 h:(465.1 ±40.6) vs (133.8 ±29.4)s(P ＜0.001) ; Group NS-7 d-2 h:(432.3 ±43.7) vs (150.5 ±26.6)s(P ＜0.01) ; Group NS-1 d-24 h:(500.5 ±20.6) vs (107.0 ± 15.7)s(P＜0.001); Group NS-7 d-24 h:(450.8±27.4) vs(129.4±21.1)s(P＜0.001)).On the contrary,in the ZIP-treated rats,no significant differences were observed in the time in the pain-paired compartment between the post-conditioning and pre-conditioning sessions at the same time-points.CPA scores also showed the attenuation of F-CPA by intra-PAG injection of ZIP in comparison to the salineinjected rats (P ＜ 0.05).Compared with the intra-PAG saline-injected group,intra-PAG microinjection of ZIP did not affect the formalin-induced nociceptive behaviors (P ＞ 0.05).Conclusion The study suggests that PAG contributes to pain-related aversion in rats,and the mechanism of pain emotion encoding in PAG may attribute to the activation of targets of ZIP.