Kaur Gurmanpreet, Bedi Onkar, Sharma Nidhika, Singh Shamsher, Deshmukh Rahul, Kumar Puneet
J Basic Clin Physiol Pharmacol. 2016 Jan;27(1):9-17. doi: 10.1515/jbcpp-2015-0026.
Neuropathic pain is associated with severe chronic sensory disturbances characterized by spontaneous pain, increased responsiveness to painful stimuli (hyperalgesia) and pain perceived in response to non-noxious stimuli (allodynia). Morphine is effective treatment for neuropathic pain but produces tolerance on chronic use. The present study was designed to explore the anti-nociceptive and anti-hyperalgesic effect of grape seed extract using sciatic nerve ligation-induced neuropathic pain in rats.
Chronic constructive injury (CCI) was performed under anesthesia, on one side leg exposed by making a skin incision, and chromic gut ligatures were tied loosely around the sciatic nerve at 1 mm intervals. The treatment with grape seed proanthocyanidin extract (GSPE) (100 and 200 mg/kg, p.o.) was initiated on 7th day post-surgery and continued for next 14 days. Morphine (10 mg/kg, s.c.) alone and morphine in combination with GSPE (100 mg/kg, p.o.) were administered in CCI rats for 5 days starting from 7th day. On 3rd, 7th, 14th and 21st day, behavioral parameters (mechanical allodynia and thermal hyperalgesia) were assessed. Then the animals were killed on 22nd day and biochemical parameters [reduced glutathione (GSH), lipid peroxidation (LPO), catalase, nitrite, superoxide dismutase (SOD)] were assessed.
Ligation of the sciatic nerve significantly induced mechanical allodynia and thermal hyperalgesia and induces oxidative stress (increase in LPO and nitrite) and decline of anti-oxidant enzyme levels (catalase, SOD, GSH) in sciatic nerve homogenate. GSPE (100 and 200 mg/kg, p.o.) attenuated all the behavioural and biochemical parameters. Morphine also significantly reversed the symptoms of neuropathic pain but produced tolerance after 5 days. Further, co-treatment of GSPE (100 mg/kg) with morphine (10 mg/kg, s.c.) in CCI rats significantly reversed the morphine tolerance and enhanced its anti-hyperalgesic effect as compared to the morphine-alone-treated group.
In the present set of experiments, GSPE showed a significant anti-hyperalgesic and anti-nociceptive effect in rats.
神经性疼痛与严重的慢性感觉障碍相关，其特征为自发痛、对疼痛刺激的反应性增加（痛觉过敏）以及对非伤害性刺激产生的疼痛（感觉异常）。吗啡是治疗神经性疼痛的有效药物，但长期使用会产生耐受性。本研究旨在利用坐骨神经结扎诱导的大鼠神经性疼痛模型，探讨葡萄籽提取物的抗伤害感受和抗痛觉过敏作用。
在麻醉下进行慢性坐骨神经结扎术，在一侧腿部做皮肤切口暴露坐骨神经，用铬制肠线以1毫米的间隔松散地结扎坐骨神经。术后第7天开始用葡萄籽原花青素提取物（GSPE）（100和200毫克/千克，口服）进行治疗，并持续14天。从第7天开始，单独给予吗啡（10毫克/千克，皮下注射）以及吗啡与GSPE（100毫克/千克，口服）联合给药，对CCI大鼠进行5天的治疗。在第3、7、14和21天评估行为学参数（机械性感觉异常和热痛觉过敏）。然后在第22天处死动物，评估生化参数[还原型谷胱甘肽（GSH）、脂质过氧化（LPO）、过氧化氢酶、亚硝酸盐、超氧化物歧化酶（SOD）]。
坐骨神经结扎显著诱导了机械性感觉异常和热痛觉过敏，并诱导了氧化应激（LPO和亚硝酸盐增加）以及坐骨神经匀浆中抗氧化酶水平的下降（过氧化氢酶、SOD、GSH）。GSPE（100和200毫克/千克，口服）减轻了所有行为学和生化参数。吗啡也显著逆转了神经性疼痛的症状，但5天后产生了耐受性。此外，与单独使用吗啡治疗的组相比，在CCI大鼠中GSPE（100毫克/千克）与吗啡（10毫克/千克，皮下注射）联合治疗显著逆转了吗啡耐受性并增强了其抗痛觉过敏作用。
在本系列实验中，GSPE在大鼠中显示出显著的抗痛觉过敏和抗伤害感受作用。
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