Rezaee Ramin, Monemi Alireza, SadeghiBonjar Mohammad Amin, Hashemzaei Mahmoud
Clinical Research Unit, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
J Pharmacopuncture. 2019 Jun;22(2):90-94. doi: 10.3831/KPI.2019.22.011. Epub 2019 Jun 30.
Paclitaxel (PTX) as an anticancer drug used against solid cancers, possesses adverse reactions such as neuropathic pain which has confined its use. PTX-induced neuropathic pain is mediated via activation of oxidative stress. Berberine (BER), an isoquinoline phytochemical found in several plants, exerts strong antioxidant and painkilling properties. In the current study, we aimed to evaluate pain-relieving effect of BER in a mouse model of PTX-induced neuropathic pain.
This study was done using 42 male albino mice that were randomly divided into 6 groups (n = 7) as follow: Sham-operated (not treated with PTX), negative control group (PTX-treated mice receiving normal saline), BER 5, 10, and 20 mg/kg (PTX-treated mice receiving BER) and positive control group (PTX-treated mice receiving imipramine 10 mg/kg). Neuropathic pain was induced by intraperitoneal administration of four doses of PTX (2 mg/kg/day) on days 1, 3, 5 and 7. Then, on day 7, hot plate test was done to assess latency to heat to measure possible anti-neuropathic pain effect of BER.
Four doses of PTX 2 mg/kg/day induced neuropathy that was reduced by BER at all time-points (i.e. 0, 30, 60, 90 and 120 min) after injection (P < 0.001 in comparison to control). The statistical analysis of data showed significant differences between groups (P < 0.001 in comparison to negative control), at 30, 60, 90 and 120 min after injection of BER 5, 10 and 20 mg/kg; in other words, 30, 60, 90 and 120 min after BER administration, neuropathic pain was significantly reduced as compared to normal saline-treated mice.
Altogether, our results showed that PTX could induce neuropathic pain as reflected by hyperalgesia and BER could alleviate PTX-induced thermal hyperalgesia.
紫杉醇(PTX)作为一种用于治疗实体癌的抗癌药物,具有诸如神经性疼痛等不良反应,这限制了其应用。PTX诱导的神经性疼痛是通过氧化应激的激活介导的。黄连素(BER)是一种在多种植物中发现的异喹啉类植物化学物质,具有强大的抗氧化和止痛特性。在本研究中,我们旨在评估BER在PTX诱导的神经性疼痛小鼠模型中的止痛效果。
本研究使用42只雄性白化小鼠,随机分为6组(n = 7),如下:假手术组(未用PTX治疗)、阴性对照组(接受PTX治疗并给予生理盐水的小鼠)、BER 5、10和20 mg/kg组(接受PTX治疗并给予BER的小鼠)以及阳性对照组(接受PTX治疗并给予10 mg/kg丙咪嗪的小鼠)。在第1、3、5和7天通过腹腔注射四剂PTX(2 mg/kg/天)诱导神经性疼痛。然后,在第7天进行热板试验以评估对热的潜伏期,以测量BER可能的抗神经性疼痛效果。
每天2 mg/kg的四剂PTX诱导了神经病变,在注射后的所有时间点(即0、30、60、90和120分钟)BER均使其减轻(与对照组相比,P < 0.001)。数据的统计分析显示,在注射BER 5、10和20 mg/kg后的30、60、90和120分钟,各组之间存在显著差异(与阴性对照组相比,P < 0.001);换句话说,在给予BER后30、60、90和120分钟,与给予生理盐水的小鼠相比,神经性疼痛显著减轻。
总体而言,我们的结果表明,PTX可诱导如痛觉过敏所反映的神经性疼痛,而BER可减轻PTX诱导的热痛觉过敏。