2020年10月20日
Development of a novel analgesic for neuropathic pain targeting brain-derived neurotrophic factor.
Biochemical and biophysical research communications
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- 巻
- 531
- 号
- 3
- 開始ページ
- 390
- 終了ページ
- 395
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bbrc.2020.07.109
Effective treatment of neuropathic pain is challenging as its underlying mechanism remains largely unknown. Recently, the participation of brain-derived neurotrophic factor (BDNF) in neuropathic pain has been attracting increased attention. BDNF binds to a member of the tyrosine kinase receptor family, the TrkB receptor, that is specific for BDNF and is the transmembrane receptor on the posterior horn of spinal cord. In the present study, we purified two proteins that included the BDNF-binding domain of TrkB (eTrkB) and eTrkB coupled with a liposomal outer surface (liposomal eTrkB) in order to inhibit the BDNF-TrkB pathway in neuropathic pain. Results of the pull-down assay showed that eTrkB was bound to BDNF. We investigated the neuropathic pain suppression effect of this purified protein by its intrathecal administration in a rat neuropathic pain model. Mechanical and thermal hyperalgesia induced by L5 lumbar nerve ligation was markedly suppressed by treatment with eTrkB protein. Furthermore, we showed a prolonged algetic inhibition by liposomal eTrkB protein treatment. In conclusion, this study suggests that eTrkB, which sequesters endogenous BDNF and inhibits the BDNF-TrkB pathway, may prove to be a novel analgesic to treat neuropathic pain.
- リンク情報
- ID情報
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- DOI : 10.1016/j.bbrc.2020.07.109
- PubMed ID : 32800540