Hu Chuanyin, Zhao Yun-Tao, Zhang Guoping, Xu Ming-Feng
Department of Biology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
Modern Biochemistry Center, Guangdong Ocean University, Zhanjiang, Guangdong 524088, P.R. China.
Mol Med Rep. 2017 Feb;15(2):975-980. doi: 10.3892/mmr.2016.6071. Epub 2016 Dec 23.
Chemotherapeutic drugs commonly induce peripheral neuropathic pain, which limit their clinic use. In the present study, the effect of fucoidan on the development of vincristine‑induced neuropathic pain was evaluated and the underlying mechanism was examined. A neuropathy model was established in Sprague‑Dawley rats by intraperitoneal injection of vincristine sulfate 50 µg/kg once a day for 10 consecutive days. Fucoidan (50, 100 or 200 mg/kg.) and pregabalin (10 mg/kg) were injected for 14 consecutive days. Behavioral assessments were then performed and the expression of GABAB receptor was determined. The results showed that a single treatment with fucoidan did not prevent the induction of vincristine‑induced mechanical or cold allodynia. However, repeated fucoidan administration attenuated vincristine‑induced mechanical and cold allodynia in a dose‑dependent manner. Additionally, the analgesic effects of fucoidan contributed to an upregulation in the expression of GABAB receptor in the spinal cord. Furthermore, all the effects of fucoidan against vincristine‑induced neuropathy were reversed by saclofen, a selective GABAB receptor antagonist. These results suggested that the antinociceptive effects of fucoidan may be through activation of GABAB receptor, and fucoidan may be a promising drug for the treatment of chemotherapeutic drug-induced neuropathic pain.
化疗药物通常会诱发周围神经性疼痛,这限制了它们在临床上的应用。在本研究中,评估了岩藻依聚糖对长春新碱诱导的神经性疼痛发展的影响,并研究了其潜在机制。通过连续10天每天腹腔注射50μg/kg硫酸长春新碱,在Sprague-Dawley大鼠中建立神经病变模型。连续14天注射岩藻依聚糖(50、100或200mg/kg)和普瑞巴林(10mg/kg)。然后进行行为评估并测定GABAB受体的表达。结果表明,单次给予岩藻依聚糖并不能预防长春新碱诱导的机械性或冷觉异常性疼痛的诱发。然而,重复给予岩藻依聚糖以剂量依赖的方式减轻了长春新碱诱导的机械性和冷觉异常性疼痛。此外,岩藻依聚糖的镇痛作用导致脊髓中GABAB受体表达上调。此外,岩藻依聚糖对长春新碱诱导的神经病变的所有作用均被选择性GABAB受体拮抗剂沙氯芬逆转。这些结果表明,岩藻依聚糖的抗伤害感受作用可能是通过激活GABAB受体实现的,岩藻依聚糖可能是一种治疗化疗药物诱导的神经性疼痛的有前景的药物。