Crosstalk Between Sensory Nerves and Cancer in Bone

Toshiyuki Yoneda, Masahiro Hiasa, Tatsuo Okui

Research output: Contribution to journalReview articlepeer-review

26 Citations (Scopus)


Purpose of Review: Sensory nerves (SNs) richly innervate bone and are a component of bone microenvironment. Cancer metastasis in bone, which is under the control of the crosstalk with bone microenvironment, induces bone pain via excitation of SNs innervating bone. However, little is known whether excited SNs in turn affect bone metastasis. Recent Findings: Cancer cells colonizing bone promote neo-neurogenesis of SNs and excite SNs via activation of the acid-sensing nociceptors by creating pathological acidosis in bone, evoking bone pain. Denervation of SNs or inhibition of SN excitation decreases bone pain and cancer progression and increases survival in preclinical models. Importantly, patients with cancers with increased SN innervation complain of cancer pain and show poor outcome. Summary: SNs establish the crosstalk with cancer cells to contribute to bone pain and cancer progression in bone. Blockade of SN excitation may have not only analgesic effects on bone pain but also anti-cancer actions on bone metastases.

Original languageEnglish
Pages (from-to)648-656
Number of pages9
JournalCurrent Osteoporosis Reports
Issue number6
Publication statusPublished - Dec 1 2018


  • Bone microenvironment
  • Hypoxia
  • Neo-neurogenesis
  • Perineural invasion
  • TRPV1
  • Warburg effect

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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