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Efferent Targets of Osseous CGRP‐Immunoreactive Nerve Fiber Before and After Bone Destruction in Adjuvant Arthritic Rat: An Ultramorphological Study on Their Terminal‐Target Relations

We report the ultramorphological characterization of the terminal‐target relation of sensory peptidergic nerve fibers in healthy and diseased osseous tissues. Bone tissue sections were immunoelectronmicroscopically investigated for calcitonin gene‐related peptide (CGRP), a neuropeptide widely distributed in sensory peptidergic fibers. Ultramorphological relation of the osseous CGRP‐immunoreactive (ir) nerve terminals and their target cells was comparatively analyzed using healthy, arthritic, and postarthritic bone specimens from control and adjuvant‐induced arthritic rats. Terminal‐like profiles of the osseous CGRP‐ir axons were evidenced in direct contact with the metaphyseal osteoblasts and osteoclasts of the control animals. Terminal‐like profiles were also noted in the vicinity of the periosteal lining cells. Nonterminal‐like profiles did not make intimate spatial relation to the cells/structures surrounding the nerve. Osseous CGRP‐ir terminals and axons, which are either uncovered or thinly ensheathed by the supportive tissues, were extensively degenerated in adjuvant‐induced infiltration, whereas larger fibers were relatively resistant. Numerous CGRP‐ir axons with distinctive features reinnervated the postarthritic, ossifying periosteum. CGRP‐ir axons appeared to reinnervate the eroded surface of metaphyseal bone and cartilage as early as the recruited osteoblasts resume osteogenesis in the postarthritic metaphysis. The observed terminal‐target relations in the healthy and diseased bone tissues give an ultramorphological basis for the putative trophic, modulatory actions of CGRP innervation of the bone cells.