Nerves in Bone: Evolving Concepts in Pain and Anabolism

Jennifer M. Brazill, Alec T. Beeve, Clarissa S. Craft, Jason J. Ivanusic, Erica L. Scheller

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations

Abstract

The innervation of bone has been described for centuries, and our understanding of its function has rapidly evolved over the past several decades to encompass roles of subtype-specific neurons in skeletal homeostasis. Current research has been largely focused on the distribution and function of specific neuronal populations within bone, as well as their cellular and molecular relationships with target cells in the bone microenvironment. This review provides a historical perspective of the field of skeletal neurobiology that highlights the diverse yet interconnected nature of nerves and skeletal health, particularly in the context of bone anabolism and pain. We explore what is known regarding the neuronal subtypes found in the skeleton, their distribution within bone compartments, and their central projection pathways. This neuroskeletal map then serves as a foundation for a comprehensive discussion of the neural control of skeletal development, homeostasis, repair, and bone pain. Active synthesis of this research recently led to the first biotherapeutic success story in the field. Specifically, the ongoing clinical trials of anti-nerve growth factor therapeutics have been optimized to titrated doses that effectively alleviate pain while maintaining bone and joint health. Continued collaborations between neuroscientists and bone biologists are needed to build on this progress, leading to a more complete understanding of neural regulation of the skeleton and development of novel therapeutics.

Original languageEnglish
Pages (from-to)1393-1406
Number of pages14
JournalJournal of Bone and Mineral Research
Volume34
Issue number8
DOIs
StatePublished - Aug 2019

Keywords

  • ANALYSIS/QUANTITATION OF BONE, OTHER
  • BONE-BRAIN-NERVOUS SYSTEM INTERACTIONS
  • SYSTEMS BIOLOGY - BONE INTERACTORS, OTHER
  • THERAPEUTICS
  • THERAPEUTICS, ANABOLICS

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