Esmaeili-Mahani Saeed, Ebrahimi Bahareh, Abbasnejad Mehdi, Rasoulian Bahram, Sheibani Vahid
Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center (KNRC), Kerman University of Medical Sciences, Kerman, Iran,
J Nat Med. 2015 Apr;69(2):165-70. doi: 10.1007/s11418-013-0796-6. Epub 2013 Aug 14.
Glial cell activation and oxidative stress are important factors in the induction of opioid side effects such as tolerance and dependence. It has been demonstrated that Satureja khuzistanica extract (SKE) has antioxidative, antinociceptive and anti-inflammatory properties; however, its influences on opioid analgesic tolerance have not yet been clarified. Adult male Wistar rats were rendered analgesic-tolerant by injection of 10 mg/kg morphine twice daily for 8 days. To determine the effect of SKE on the development of morphine tolerance, different doses of SKE (25, 50 and 100 mg/kg i.p.) were injected simultaneously with morphine. The tail-flick test was used to assess the nociceptive threshold. The lumbar spinal cord was assayed to determine glial fibrillary acidic protein (GFAP) and tumor necrosis factor alpha (TNFα) levels by the Western blotting method. Our results showed that chronic morphine produced tolerance to the antinociceptive effect of morphine. However, SKE could prevent, in a dose-dependent manner, morphine tolerance development. In tolerant animals, a significant increase in GFAP and TNFα levels was observed in the lumbar spinal cord, and was reversed to control levels by 100 mg/kg SKE. Our data revealed that Satureja khuzistanica had beneficial effects in preventing opioid tolerance and the underlying mechanisms of those effects may be due, at least in part, to reduce spinal glial cell activation.
神经胶质细胞激活和氧化应激是导致阿片类药物副作用（如耐受性和依赖性）的重要因素。已证明，胡齐斯坦鼠尾草提取物（SKE）具有抗氧化、抗伤害感受和抗炎特性；然而，其对阿片类镇痛耐受性的影响尚未阐明。成年雄性Wistar大鼠通过每天两次注射10 mg/kg吗啡，连续注射8天，使其产生镇痛耐受性。为了确定SKE对吗啡耐受性发展的影响，将不同剂量的SKE（25、50和100 mg/kg腹腔注射）与吗啡同时注射。采用甩尾试验评估伤害感受阈值。通过蛋白质免疫印迹法检测腰段脊髓，以确定胶质纤维酸性蛋白（GFAP）和肿瘤坏死因子α（TNFα）水平。我们的结果表明，慢性吗啡产生了对吗啡镇痛作用的耐受性。然而，SKE可以剂量依赖性方式预防吗啡耐受性的发展。在耐受性动物中，观察到腰段脊髓中GFAP和TNFα水平显著升高，而100 mg/kg SKE可将其逆转至对照水平。我们的数据显示，胡齐斯坦鼠尾草在预防阿片类药物耐受性方面具有有益作用，其作用的潜在机制可能至少部分归因于减少脊髓神经胶质细胞的激活。
