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特立帕肽迅速改善去卵巢小鼠的疼痛样行为,同时下调炎症细胞因子的表达。

Teriparatide rapidly improves pain-like behavior in ovariectomized mice in association with the downregulation of inflammatory cytokine expression.

机构信息

Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

J Bone Miner Metab. 2018 Sep;36(5):499-507. doi: 10.1007/s00774-017-0865-0. Epub 2017 Oct 5.

Abstract

Recent studies have indicated that teriparatide, an anti-osteoporosis agent, significantly improves back pain regardless of the presence of vertebral fracture in osteoporosis patients. The aims of this study were to examine whether teriparatide improves pain-like behavior in an ovariectomized (OVX) mouse model, and to evaluate changes in osteoclast marker levels and inflammatory cytokine expression levels induced by teriparatide treatment in bone tissue in association with improvements in pain-like behavior. OVX and sham operations were performed in 8-week-old mice, followed by teriparatide treatment for 2 weeks. Pain-like behavior tests (von Frey, paw flick and spontaneous pain test), and the measurement of serum tartrate-resistant acid phosphatase 5b (TRAP5b) level and inflammatory cytokine (interleukin [IL]-1β, IL-6 and tumor necrosis factor [TNF]-α) expression levels in the bone tissue were conducted after teriparatide treatment in OVX mice. Pain-like behavior in the von Frey test was significantly improved by teriparatide treatment in OVX mice. With regard to the early phase (within the first 7 days of treatment), teriparatide significantly improved pain-like behavior in the von Frey test, the paw flick test and the spontaneous pain test. Teriparatide significantly inhibited the expression of IL-1β, IL-6 and TNF-α in OVX mice in the early phase of the treatment, while the TRAP5b level in OVX mice was not significantly affected. We demonstrated that the teriparatide-induced rapid improvement effect on pain-like behavior in OVX mice was associated with the downregulation of inflammatory cytokine expression, including IL-1β, IL-6 and TNF-α.

摘要

最近的研究表明,骨质疏松症患者无论是否存在椎体骨折,抗骨质疏松药物特立帕肽均可显著改善背痛。本研究旨在探讨特立帕肽是否能改善去卵巢(OVX)小鼠模型的疼痛样行为,并评估特立帕肽治疗后骨组织中破骨细胞标志物水平和炎症细胞因子表达水平的变化与疼痛样行为改善的关系。8 周龄小鼠行 OVX 和假手术,随后给予特立帕肽治疗 2 周。在 OVX 小鼠给予特立帕肽治疗后进行疼痛样行为测试(von Frey、足爪拍打和自发性疼痛测试),并测量血清抗酒石酸酸性磷酸酶 5b(TRAP5b)水平和骨组织中炎症细胞因子(白细胞介素[IL]-1β、IL-6 和肿瘤坏死因子[TNF]-α)的表达水平。特立帕肽治疗可显著改善 OVX 小鼠 von Frey 测试中的疼痛样行为。在早期(治疗的前 7 天内),特立帕肽可显著改善 OVX 小鼠的 von Frey 测试、足爪拍打测试和自发性疼痛测试中的疼痛样行为。特立帕肽在治疗的早期阶段显著抑制 OVX 小鼠中 IL-1β、IL-6 和 TNF-α的表达,而 OVX 小鼠的 TRAP5b 水平无明显变化。我们的研究表明,特立帕肽诱导 OVX 小鼠疼痛样行为迅速改善与炎症细胞因子表达(包括 IL-1β、IL-6 和 TNF-α)的下调有关。

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