Innervation of the tibial epiphysis through the intercondylar foramen

Koichi Matsuo, Shuting Ji, Ayako Miya, Masaki Yoda, Yuzuru Hamada, Tomoya Tanaka, Ryoko Takao-Kawabata, Katsuhiro Kawaai, Yukiko Kuroda, Shinsuke Shibata

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


The periosteum and mineralized bone are innervated by nerves that sense pain. These include both myelinated and unmyelinated neurons with either free nerve endings or bearing nociceptors. Parasympathetic and sympathetic autonomic nerves also innervate bone. However, little is known about the route sensory nerves take leaving the epiphyses of long bones at the adult knee joint. Here, we used transgenic mice that express fluorescent Venus protein in Schwann cells (Sox10-Venus mice) to visualize myelinated and unmyelinated nerves in the tibial epiphysis. Immunofluorescence to detect a pan-neuronal marker and the sensory neuron markers calcitonin gene-related peptide (CGRP) and tropomyosin receptor kinase A (TrkA) also revealed Schwann cell-associated sensory neurons. Foramina in the intercondylar area of the tibia were conserved between rodents and primates. Venus-labeled fibers were detected within bone marrow of the proximal epiphysis, exited through foramina along with blood vessels in the intercondylar area of the tibia, and joined Venus-labeled fibers of the synovial membrane and meniscus. These data suggest that innervation of the subchondral plate and trabecular bone within the tibial epiphysis carries pain signals from the knee joint to the brain through intercondylar foramina.

Original languageEnglish
Pages (from-to)297-304
Number of pages8
Publication statusPublished - 2019 Mar


  • Epiphysis
  • Foramen
  • Knee joint
  • Schwann cells
  • Sensory neuron
  • Tibia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology


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