Hu J Y, Jin G Z
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Zhongguo Yao Li Xue Bao. 1999 Mar;20(3):193-200.
To study the effect of tetrahydropalmatine (THP) analogs on Fos protein expression induced by formalin-pain and elucidate analgesic mechanism of THP analogs.
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.
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.
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.
研究四氢巴马汀（THP）类似物对福尔马林致痛诱导的Fos蛋白表达的影响，并阐明THP类似物的镇痛机制。
将福尔马林皮下注射到Sprague Dawley大鼠右后足底诱导疼痛反应。采用免疫组织化学法研究脑和脊髓中Fos蛋白的表达。用Leica Q570图像分析仪计数Fos样免疫反应（FLI）神经元的数量。
在THP类似物和D2拮抗剂舒必利组中，腹腔注射THP类似物和舒必利诱导的FLI神经元主要位于纹状体和伏隔核，少数FLI神经元也位于感觉运动皮层。在D1拮抗剂、D1激动剂、D2激动剂、生理盐水和溶剂组中，纹状体和伏隔核中很少见到FLI神经元。此外，D2激动剂喹吡罗预处理可阻止左旋THP和舒必利诱导的Fos蛋白表达，而D1激动剂SKF38393则不能。在福尔马林致痛组中，FLI神经元主要分布在痛觉传入系统（APAS）和下行痛觉调制系统（DPMS）。然而，腹腔注射THP类似物后，APAS中福尔马林致痛诱导的FLI神经元数量，如背角（主要是I、II、IV - VI层）明显减少，而DPMS中FLI神经元数量，如导水管周围灰质（PAG）和网状巨细胞旁外侧核（RPLN）则显著增加。
THP类似物通过阻断纹状体和伏隔核中的D2受体增强脑干DPMS的活性，并依次在脊髓水平抑制外周痛觉传入信息的输入。
