Fig. 3

Schematic diagram illustrating sensory nerve innervation in bone. Dorsal root ganglion (DRG) contains the cell bodies of primary sensory neurons which are pseudo‐unipolar. The peripheral axons of small-diameter (red) and medium-diameter (yellow) neurons innervate periosteum and bone marrow, and can be activated by various injury insults. The majority of bone-innervating sensory fibers are unmyelinated, CGRP⁺/TrkA⁺ peptidergic C-fibers (red) from small-diameter neurons. Some thinly myelinated Aδ-fibers (yellow) from medium-diameter neurons also innervate bone. It remains uncertain whether IB4⁺/non-peptidergic C-fibers (green) also innervate bone. The centrally projecting axons of small- and medium-diameter neurons mostly terminate into superficial dorsal horn of the spinal cord. Aβ-fibers from large-diameter (blue) neurons are prevalent in the skin, but rarely found in bone. In addition to sensory fibers, bone is also innervated by sympathetic fibers (not shown) either adrenergic or cholinergic. TrkA tyrosine kinase receptor type 1; CGRP = calcitonin gene‐related peptide; IB4 = isolectin‐B4; NF200 = neurofilament 200.