Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, 25000, Pakistan.
Department of Pharmacy, CECOS University of IT and Emerging Sciences, Peshawar, Pakistan.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Apr;394(4):603-617. doi: 10.1007/s00210-020-01995-y. Epub 2020 Oct 20.
The current pharmacotherapy of neuropathic pain is inadequate as neuropathic pain involves varied clinical manifestations with multifactorial etiology, modulated by a cascade of physical and molecular events leading to different clinical presentations of pain. There is an accumulating evidence of the involvement of oxidative stress in neuropathy, and antioxidants have shown promise in mitigating neuropathic pain syndromes. To explore the evidence supporting this beneficial proclivity of antioxidants, this study investigated the antinociceptive effectiveness of N-(2-mercaptopropionyl)glycine or tiopronin, a well-recognized aminothiol antioxidant, in a refined chronic constriction injury (CCI) rat model of neuropathic pain. Tiopronin (10, 30, and 90 mg/kg, i.p.) and pregabalin (30 mg/kg, i.p.) were administered daily after CCI surgery. The neuropathic paradigms of mechanical/cold allodynia and mechanical/heat hyperalgesia were assessed on days 3, 7, 14, and 21 post-nerve ligation. At the end of study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were estimated in the sciatic nerve, dorsal root ganglion, and spinal cord for assessing the extent of oxidative stress. The expression of neuropathic nociception was attenuated by tiopronin which was observed as a significant attenuation of CCI-induced allodynia and hyperalgesia. Tiopronin reversed the neuronal oxidative stress by significantly reducing MDA, and increasing SOD, CAT, and GSH levels. Pregabalin also showed similar beneficial propensity on CCI-induced neuropathic aberrations. These findings suggest prospective neuropathic pain attenuating efficacy of tiopronin and further corroborated the notion that antioxidants are effective in mitigating the development and expression of neuropathic pain and underlying neuronal oxidative stress.
目前针对神经性疼痛的药物治疗效果并不理想，因为神经性疼痛涉及多种临床表现，具有多因素病因，受一系列物理和分子事件的调节，导致不同的疼痛表现。越来越多的证据表明氧化应激与神经病变有关，抗氧化剂在减轻神经性疼痛综合征方面显示出了良好的效果。为了探讨支持抗氧化剂这种有益倾向的证据，本研究在改良的慢性缩窄性损伤（CCI）大鼠神经性疼痛模型中，研究了 N-(2-巯基丙酰基)甘氨酸（即硫普罗宁）或一种公认的氨基硫醇抗氧化剂的抗伤害作用。CCI 手术后，每天给予硫普罗宁（10、30 和 90mg/kg，腹腔注射）和普瑞巴林（30mg/kg，腹腔注射）。在神经结扎后第 3、7、14 和 21 天评估机械/冷触痛和机械/热痛觉过敏的神经性模型。在研究结束时，在坐骨神经、背根神经节和脊髓中评估丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽（GSH）水平，以评估氧化应激的程度。硫普罗宁减弱了神经性疼痛的表达，这表现为对 CCI 诱导的触痛和痛觉过敏的显著减轻。硫普罗宁通过显著降低 MDA 并增加 SOD、CAT 和 GSH 水平来逆转神经元的氧化应激。普瑞巴林对 CCI 诱导的神经性异常也表现出类似的有益作用。这些发现表明硫普罗宁具有潜在的神经性疼痛缓解作用，并进一步证实了抗氧化剂在减轻神经性疼痛的发展和表达以及潜在的神经元氧化应激方面是有效的。
