Muthuraman Arunachalam, Sood Shailja
Rayat institute of pharmacy, Ropar campus, Nawanshahr district, Railmajra, Near Ropar-144533, Punjab, India.
J Brachial Plex Peripher Nerve Inj. 2010 Jun 7;5:13. doi: 10.1186/1749-7221-5-13.
Ischemia reperfusion (I/R) is common in various pathological conditions like diabetic complication, rheumatic arthritis, necrotizing vascular occlusive disease and trauma.
We have evaluated the effect of tacrolimus (1, 2 and 3 mg/kg, p.o. for 10 consecutive days) on femoral arterial ischemic reperfusion (I/R) induced neuropathic pain in rats. Behavioral parameters (i.e. hot plate, radiant heat, acetone drop, tail heat hyperalgesia, tail flick and tail cold allodynia tests) were assessed at different time intervals (i.e. 0, 1, 4, 7, 10, 13 and 16th day) and biochemical analysis in serum and tissue samples were also performed along with histopathological studies.
Behavioral pain assessment revealed increase in the paw and tail withdrawal threshold in tacrolimus treated groups against hyperalgesic and allodynic stimuli as compared to the sham control group. We observed a decrease in the serum nitrate and thiobarbituric acid reactive substance (TBARS) levels along with reduction in tissue myeloperoxidase (MPO) and total calcium levels, whereas, rise in tissue reduced glutathione levels in tacrolimus treated groups. However, significant results were obtained in medium and high dose treated group as compared to sham control group. Histopathological study had revealed the increase in the neuronal edema and axonal degeneration in the I/R group whereas, tacrolimus ameliorate these effects.
Our results indicate the anti-oxidative, anti-inflammatory and calcium modulatory actions of tacrolimus. Therefore, it can be used as a therapeutic agent for the treatment of vascular inflammatory related neuropathic pain.
缺血再灌注（I/R）在多种病理状况中常见，如糖尿病并发症、风湿性关节炎、坏死性血管闭塞性疾病和创伤。
我们评估了他克莫司（1、2和3毫克/千克，口服，连续10天）对大鼠股动脉缺血再灌注（I/R）诱导的神经性疼痛的影响。在不同时间间隔（即第0、1、4、7、10、13和16天）评估行为学参数（即热板法、辐射热、丙酮滴注、尾部热痛觉过敏、甩尾和尾部冷觉异常试验），并同时进行血清和组织样本的生化分析以及组织病理学研究。
行为学疼痛评估显示，与假手术对照组相比，他克莫司治疗组对痛觉过敏和异常性疼痛刺激的爪部和尾部退缩阈值增加。我们观察到他克莫司治疗组血清硝酸盐和硫代巴比妥酸反应性物质（TBARS）水平降低，同时组织髓过氧化物酶（MPO）和总钙水平降低，而组织还原型谷胱甘肽水平升高。然而，与假手术对照组相比，中、高剂量治疗组获得了显著结果。组织病理学研究显示，I/R组神经元水肿和轴突变性增加，而他克莫司可改善这些影响。
我们的结果表明他克莫司具有抗氧化、抗炎和钙调节作用。因此，它可作为治疗血管炎性相关神经性疼痛的治疗药物。
