Innervation of bone from healthy and arthritic rats by substance P and calcitonin gene related peptide containing sensory fibers.

Mechanical stress causes remodelling of bone, a transformation of bone structure by physical forces through an unknown mechanism. Inflammation also affects bone structure, through altered use and the production of various inflammatory mediators. The peripheral nervous system may play both a sensory and an efferent role in the mechanical and inflammatory influences on bone structure. We studied the occurrence of substance P and calcitonin gene related peptide (CGRP) containing nerves in periosteal tissue, bone marrow, diaphysis and epiphysis of the ankle and knee joints of healthy and adjuvant arthritic rats. In arthritic animals, only ankle joints were affected by the inflammation. The periosteum was richly innervated both in healthy and arthritic animals. In arthritic rats few nerve fibers penetrated the woven, callous bone underlying the periosteum. Also bone marrow contained substance P and CGRP immunoreactive nerves in normal bone, whereas the hypercellular bone marrow of arthritic rats showed a decrease in the density of substance P and CGRP containing fibers. Epiphysis had a dense innervation compared to diaphysis. In contrast to large erosions, small peripheral erosions contained some CGRP immunoreactive fibers, perhaps as a sign of attempts of reactive repair. Our results suggest a local delivery system of potent peptide regulatory factors in bone, a system also affected by the pathophysiology of arthritis.