Department of Anesthesiology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Physiological Function, Medical College of Jiaxing University, Jiaxing, China.
Pharmacology. 2018;102(5-6):300-306. doi: 10.1159/000493144. Epub 2018 Sep 25.
Remifentanil-induced hyperalgesia (RIH) is known to be associated with oxidative stress and inflammation. Betulinic acid (BA) was reported to reduce visceral pain owing to its anti-oxidative and anti-inflammatory potential. Here, we -explored whether BA can attenuate RIH through inhibiting oxidative stress and inflammation in spinal dorsal horn. Sprague-Dawley rats were randomly divided into 4 groups: Control, Incision, RIH, and RIH pre-treated with BA. After pretreated with BA (25 mg/kg, i.g.) for 7 days, rats were subcutaneously infused with remifentanil (40 μg/kg) for 30 min during right plantar incision surgery to induce RIH. The paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), spinal oxidative stress and inflammatory mediators were determined. Intraoperative remifentanil infusion induced postoperative hyperalgesia, as evidenced by the significant decrease in PWMT and PWTL (p < 0.01), and the significant increase in oxidative stress and inflammation evidenced by up-regulations of malondialdehyde, 3-nitrotyrosine, interleukin-1β and tumour necrosis factor-α (p < 0.01) in spinal dorsal horn and matrix metalloproteinase-9 (MMP-9) activity (p < 0.01) in dorsal root ganglion, as well as a decrease in manganese superoxide -dismutase activity (p < 0.01) compared with control and -incision groups. All these results mentioned above were markedly reversed by pre-treatment with BA (p < 0.01) compared with RIH group. These findings demonstrated that BA can effectively attenuate RIH, which associates with potentially inhibiting oxidative stress and subsequently down-regulating MMP-9-related pro-inflammatory cyokines in spinal dorsal horn.
瑞芬太尼诱导的痛觉过敏（RIH）已知与氧化应激和炎症有关。白桦酸（BA）因其抗氧化和抗炎潜力被报道可减轻内脏疼痛。在这里，我们探讨了 BA 是否可以通过抑制脊髓背角的氧化应激和炎症来减轻 RIH。Sprague-Dawley 大鼠随机分为 4 组：对照组、切口组、RIH 组和 RIH 预处理组。BA（25mg/kg，ig）预处理 7 天后，大鼠右足底切口手术时皮下输注瑞芬太尼（40μg/kg）30min 诱导 RIH。测定爪退缩机械阈值（PWMT）、爪退缩热潜伏期（PWTL）、脊髓氧化应激和炎症介质。术中瑞芬太尼输注引起术后痛觉过敏，表现为 PWMT 和 PWTL 显著降低（p<0.01），脊髓背角氧化应激和炎症标志物上调，丙二醛、3-硝基酪氨酸、白细胞介素-1β和肿瘤坏死因子-α（p<0.01），以及背根神经节基质金属蛋白酶-9（MMP-9）活性（p<0.01），锰超氧化物歧化酶活性降低（p<0.01）与对照组和切口组相比。与 RIH 组相比，BA 预处理明显逆转了所有上述结果（p<0.01）。这些发现表明，BA 可有效减轻 RIH，其与潜在抑制氧化应激以及随后下调脊髓背角中 MMP-9 相关促炎细胞因子有关。
