Ma Shaojun, Zhang Ying, Li Xiaojiang, Zhang He, Jia Yingjie
Department of Oncology, Tianjin Nankai Hospital, Nan Kai District, Tianjin, China.
Department of Oncology, First Affiliated Hospital to Tianjin University of Traditional Chinese Medicine, Nan Kai District, Tianjin, China.
Integr Cancer Ther. 2015 May;14(3):282-90. doi: 10.1177/1534735414568722. Epub 2015 Jan 18.
Visceral pain is one of the most important pains caused by cancer or other diseases, and most of the medications may lead to tolerance, addiction, and toxic side effects. Hua-Jian-Ba-Du Ointment (HJBDO), which is a commonly used conjugate based on traditional Chinese medicine theory, has been effective against visceral pain. Here, we verify the efficacy and underlying mechanism of HJBDO in an acetic-acid induced visceral pain model.
Mice were subjected to acetic acid with or without HJBDO. Hua-Jian-Ba-Du Ointment at low (7.5 mL/kg•d), moderate (15 mL/kg•d), and high (30 mL/kg•d) dosages was applied on the abdomen, 3 times per day for 3 days. The acetic acid writhing test was used to evaluate antinociception. Interleukin-2 (IL-2) in serum, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in peritoneal fluid were detected by ELISA. 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), and β-endorphin (β-EP) were examined by high performance liquid chromatography and radioimmunoassay, respectively. N-methyl-D-aspartic acid receptor (NMDAR1) and c-fos expressions in both rostral ventromedial medulla (RVM) and spinal dorsal horn were determined by western blot.
Hua-Jian-Ba-Du Ointment at 3 dosage levels produced dose-dependent antinociception and shortened the latent time. Hua-Jian-Ba-Du Ointment at high or moderate dosage inhibited the release of TNF-α, IL-6, and PGE2, as well as increased the release of IL-2. Hua-Jian-Ba-Du Ointment could also increase NE and 5-HT contents and decrease the NE content. No effect of HJBDO at 3 dosages on the DA system was detected. Furthermore, HJBDO could suppress the expressions of NMDAR and c-fos in both RVM and spinal dorsal horn.
Our results exhibited the analgesic effect of HJBDO on visceral pain in mice, and this effect might be mediated by the regulation of inflammation and neurotransmitters.
内脏痛是癌症或其他疾病引发的最重要疼痛之一，并且大多数药物可能会导致耐受性、成瘾性和毒副作用。化坚拔毒膏（HJBDO）是一种基于中医理论的常用复方制剂，已被证明对内脏痛有效。在此，我们在醋酸诱导的内脏痛模型中验证了化坚拔毒膏的疗效及其潜在机制。
对小鼠给予醋酸，同时或不同时给予化坚拔毒膏。将低剂量（7.5 mL/kg•d）、中剂量（15 mL/kg•d）和高剂量（30 mL/kg•d）的化坚拔毒膏涂抹于腹部，每天3次，持续3天。采用醋酸扭体试验评估镇痛效果。通过酶联免疫吸附测定法检测血清中的白细胞介素-2（IL-2）、腹腔液中的肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和前列腺素E2（PGE2）。分别采用高效液相色谱法和放射免疫分析法检测5-羟色胺（5-HT）、去甲肾上腺素（NE）、多巴胺（DA）和β-内啡肽（β-EP）。通过蛋白质免疫印迹法测定延髓头端腹内侧网状结构（RVM）和脊髓背角中N-甲基-D-天冬氨酸受体（NMDAR1）和c-fos的表达。
3个剂量水平的化坚拔毒膏均产生剂量依赖性镇痛作用，并缩短了潜伏期。高剂量或中剂量的化坚拔毒膏抑制了TNF-α、IL-6和PGE2的释放，同时增加了IL-2的释放。化坚拔毒膏还可增加NE和5-HT含量，并降低NE含量。未检测到3个剂量的化坚拔毒膏对DA系统有影响。此外，化坚拔毒膏可抑制RVM和脊髓背角中NMDAR和c-fos的表达。
我们的研究结果显示了化坚拔毒膏对小鼠内脏痛的镇痛作用，且这种作用可能是通过调节炎症和神经递质来介导的。
