Innervation of bones. Sensory innervation. Part I: a literature review

BACKGROUND: Bone remodeling is a complex multifactorial process regulated by endocrine, paracrine, and mechanical factors. Nearly two decades ago, research showed that the nervous system is also involved in regulating bone remodeling. However, there is a very limited number of Russian publications on bone innervation mechanisms. AIM: The aim of this paper was to review publications that address the role of sensory innervation in regulation of bone metabolism and some pathophysiology of bone pain. MATERIALS AND METHODS: Data were searched in English and Russian in PubMed, Google Scholar, Cochrane Library, Crossref, eLibrary databases. Information was analyzed and synthesized for the purposes of this paper. Most studies in this review were published within the last 20 years. RESULTS: All structural parts of the bone are innervated by sensory nerve fibers that are receptive to nociceptive information. The type of bone pain depends on both the location and the nature of the disease process. Pain signals from the bones to the central nervous system are transmitted by A-delta and C-fibers, each with its own conduction velocity, neurotransmitters, receptor characteristics, and functions. In addition, sensory nerves regulate bone homeostasis by expressing calcitonin gene-related peptide and substance P as their major neurotransmitters. Sensory nerves play a key role in development of primary and secondary ossification centers during endochondral and intramembranous ossification. Some studies show that nerve fibers are present in articular cartilage at some point in time. CONCLUSIONS: Sensory fibers are an important link in the nervous regulation of bone and cartilage metabolism. Impaired sensory innervation leads to impaired bone remodeling and slows endochondral ossification and, consequently, bone growth and development. This should be considered, especially in patients with early onset bone innervation disorders. To prescribe the correct treatment, it is important to understand pathophysiology of bone pain.