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

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Abstract

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.

About the authors

Alina M. Khodorovskaya

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Author for correspondence.
Email: alinamyh@gmail.com
ORCID iD: 0000-0002-2772-6747
SPIN-code: 3348-8038
Russian Federation, Saint Petersburg

Olga E. Agranovich

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: olga_agranovich@yahoo.com
ORCID iD: 0000-0002-6655-4108
SPIN-code: 4393-3694

MD, PhD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Margarita V. Savina

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: drevma@yandex.ru
ORCID iD: 0000-0001-8225-3885
SPIN-code: 5710-4790

MD, PhD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Yuri E. Garkavenko

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery; North-Western State Medical University named after I.I. Mechnikov

Email: yurijgarkavenko@mail.ru
ORCID iD: 0000-0001-9661-8718
SPIN-code: 7546-3080

MD, PhD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg; Saint Petersburg

Evgeny V. Melchenko

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: emelchenko@gmail.com
ORCID iD: 0000-0003-1139-5573
SPIN-code: 1552-8550

MD, PhD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Yana A. Filin

Almazov National Medical Research Center

Email: filin_yana@mail.ru
ORCID iD: 0009-0009-0778-6396
Russian Federation, Saint Petersburg

Konstantin E. Gorelik

Sertolovo City Hospital

Email: tmsk@bk.ru
ORCID iD: 0009-0009-2151-1815
SPIN-code: 3454-5743

MD, PhD, Cand. Sci. (Medicine)

Russian Federation, Sertolovo

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