Calcitonin gene-related peptide, substance P, and tyrosine hydroxylase-immunoreactive innervation of rat bone marrows: An immunohistochemical and ultrastructural investigation on possible efferent and afferent mechanisms

The presence of nerve fibers in bone marrow has been noted by various investigators, and recent developments in immunohistochemistry have enabled differential localization of the intramedullary nerve fibers. Much interest has been devoted to the efferent activities of the afferent fibers, which probably act on the target tissues by secreting a variety of neurotransmitters. The present study aimed to further characterize intramedullary substance P, calcitonin gene-related peptide, and tyrosine hydroxylase-immunonactive nerve fibers of the rat lower limb by comparing those of the knee, ankle, and tarsal joints. The ultrastructural details of intramedullary calcitonin gene-related peptide-immunoreactive axons were also investigated to provide a morphological basis for their possible efferent actions. Intramedullary calcitonin gene-related peptide and substance P-immunoreactive fibers in the proximal tibia and the knee joint were found to be as reported earlier, but the marrow of the distal metaphysis was also noted to be richly innervated, and the tarsal joints displayed dense innervation at the subchondral regions that underlie the joint cartilage. The articular and intramedullary innervations that function for joint protection might participate in characteristic clinical features of joint damage secondary to the neuropathies. Ultrastructurally, the intramedullary calcitonin gene-related peptide-immunoreactive axons were minimally engulfed by the Schwann cell, and naked intramedullary calcitonin gene-related peptide-immunoreactive axons were noted along an extraordinarily long extension, suggesting much efferent activity.