Reactive oxygen species in rats with chronic post-ischemia pain

Reactive oxygen species in rats with chronic post-ischemia pain
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DOI:
10.1111/j.1399-6576.2009.01937.x
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发表时间:
2009-05-01
影响因子:
2.1
通讯作者:
Lim, D. G.
Lim, D. G.
中科院分区:
医学4区
文献类型:
--
作者:
Kwak, K. H.;Han, C. G.;Lim, D. G.

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持续性疼痛的病理生理学研究中的一个新兴主题是活性氧(ROS)的作用。在本研究中,我们研究的假设,即外源性供应的抗氧化剂药物在围再灌注会减弱疼痛引起的缺血/再灌注(IR)损伤。我们研究了三种抗氧化剂的镇痛作用,在围再灌注期使用的动物模型,复杂的区域疼痛综合征I型组成的慢性缺血后疼痛(CPIP)的后paw.Application的一个紧密配合的止血带的一段时间为3小时产生的CPIP在雄性Sprague-Dawley大鼠。在止血带应用后即刻和再灌注后第1和第2天腹腔注射低剂量别嘌呤醇(4 mg/kg)、高剂量别嘌呤醇(40 mg/kg)、超氧化物歧化酶(SOD,4000 U/kg)、N-硝基-L-精氨酸甲酯(l-NAME,10 mg/kg)或SOD(4000 U/kg)+l-NAME(10 mg/kg),共3天。抗氧化剂在大鼠中的作用进行了研究,使用机械和冷刺激。每组包括7只大鼠。别嘌呤醇引起显著缓解机械和冷异常性疼痛的CPIP大鼠为期4周。用SOD和l-NAME研究超氧化物歧化酶(O2-center dot(-))和一氧化氮(NO)在疼痛中的作用,结果表明O2-center dot(-)和NO介导了IR损伤引起的慢性疼痛,再灌注期给予ROS清除剂具有长期的镇痛作用。
An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw.Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague-Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N-nitro-l-arginine methyl ester (l-NAME, 10 mg/kg), or SOD (4000 U/kg)+l-NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats.Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and l-NAME, which were used to investigate the roles of superoxide (O-2 center dot(-)) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks.Our findings suggest that O-2 center dot(-) and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects.