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

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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.

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Acknowledgements

The authors thank Asahi Kasei Pharma Co., Ltd. (Tokyo, Japan) for providing the teriparatide and Chugai Pharmaceutical Co., Ltd. (Tokyo, Japan) for providing MR16-1 (IL-6 receptor antagonist). We also thank Dr. Tadamitsu Kishimoto (Osaka University, Osaka, Japan) for his advice and invaluable contributions to this study. This study was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

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

    Takayuki Dohke, Kousuke Iba, Megumi Hanaka, Kumiko Kanaya, Shunichiro Okazaki & Toshihiko Yamashita

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  1. Takayuki Dohke
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  2. Kousuke Iba
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  3. Megumi Hanaka
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  4. Kumiko Kanaya
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  5. Shunichiro Okazaki
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  6. Toshihiko Yamashita
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Correspondence to Kousuke Iba.

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Dohke, T., Iba, K., Hanaka, M. et al. Teriparatide rapidly improves pain-like behavior in ovariectomized mice in association with the downregulation of inflammatory cytokine expression . J Bone Miner Metab 36, 499–507 (2018). https://doi.org/10.1007/s00774-017-0865-0

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  • DOI: https://doi.org/10.1007/s00774-017-0865-0

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