四氢巴马汀同类物对福尔马林致痛诱导Fos蛋白表达的影响

目的 研究四氢巴马汀（ＴＨＰ）同类物对福尔马林致痛诱导的Ｆｏｓ蛋白表达的影响，以阐明ＴＨＰ同类物的镇痛机制。方法 在右后肢脚掌皮下注射５％福尔马林５０μＬ，诱发性疼痛，用免疫组织化学方法观察Ｆｏｓ的蛋白表达，结果：腹腔注射ＴＨＰ同类物和Ｄ２受体拮抗剂螺哌隆诱导的Ｆｏｓ蛋白表达主要位于纹状体和伏膈核，Ｄ２受体激动剂喹吡罗可阻滞ｌ－ＴＨＰ和螺哌隆诱导的Ｆｏｓ蛋白表达，ＴＨＰ同类物明显增加脑干下行痛觉调

Effect of tetrahydropalmatine analogs on Fos expression induced by formalin-pain.

AIM: To study the effect of tetrahydropalmatine (THP) analogs on Fos protein expression induced by formalin-pain and elucidate analgesic mechanism of THP analogs. METHODS: The pain response to Sprague Dawley rats was induced with formalin injected s.c. into the plantar surface of the right hindpaw. Fos protein expression in brain and spinal cord was investigated with immunohistochemistry. The numbers of Fos-like immunoreactive (FLI) neurons were counted with Leica Q570 image analyzer. RESULTS: In the groups of THP analogs and D2 antagonist spiperone, FLI neurons induced by intraperitoneal (i.p.) injection of THP analogs and spiperone were mainly located in the striatum and accumbens nucleus, and a few FLI neurons were also in sensorimotor cortex. In the D1 antagonist, D1 agonist, D2 agonist, saline and vehicle groups, FLI neurons were seldom seen in the striatum and accumbens nucleus. Moreover, the Fos protein expression induced by l-THP and spiperone could be prevented by the pre-treatment of the D2 agonist quinpirole but not D1 agonist SKF38393. In the formalin-pain group, FLI neurons were mainly distributed in ascending pain afferent system (APAS) and descending pain modulation system (DPMS). Following i.p. THP analogs, however, the numbers of FLI neurons induced by formalin-pain in the APAS, such as dorsal horn (mainly laminae I, II, IV-VI) were markedly decreased, while the numbers of FLI neurons in the DPMS, such as periaqueductal gray (PAG) and reticular paragigantocellular lateral nucleus (RPLN) were significantly increased. CONCLUSION: THP analogs enhanced the activity of brainstem DPMS by the blockade of D2 receptors in the striatum and accumbens nucleus, and sequentially inhibited the inputs of peripheral pain afferent message in spinal cord level.