Development of a novel analgesic for neuropathic pain targeting brain-derived neurotrophic factor

Kae Ikeda, Keita Hazama, Yoshitaro Itano, Mamoru Ouchida, Hideki Nakatsuka

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)390-395
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume531
Issue number3
DOIs
Publication statusPublished - Oct 20 2020

Keywords

  • Brain-derived neurotrophic factor
  • Liposome
  • Neuropathic pain
  • Tyrosine kinase receptor B

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Development of a novel analgesic for neuropathic pain targeting brain-derived neurotrophic factor'. Together they form a unique fingerprint.

Cite this