RAPID PROLIFERATION OF CALCITONIN GENE-RELATED PEPTIDE-IMMUNOREACTIVENERVES DURING HEALING OF RAT TIBIAL FRACTURE SUGGESTS NEURAL INVOLVEMENT IN BONE-GROWTH AND REMODELING

The nervous system may be actively involved in bone repair and in remo delling of callous tissue in bone fractures, as well as in the regulat ion of nociceptive impulses from the site of the trauma. The aim of th is study was to assess the distribution and nature of the periosteal i nnervation of normal control bone and during bone healing subsequent t o fracture of rat tibiae at seven, 14 and 21 days after experimental f racture using immunocytochemistry and image analysis quantification of the neuronal marker protein gene product 9.5 and sensory neuropeptide calcitonin gene-related peptide. At seven days, periosteal protein ge ne product 9.5- and calcitonin gene-related peptide-immunoreactive fib res showed dense ramifications and terminal sprouting. In addition to periosteum, the nerve fibres were found in the middle of the callus in terspersed with inflammatory cells and penetrating into secondary mino r fractures. At days 14 and 21 many tortuous nerves were found in the periosteum but not in mid callus. Image analysis quantification reveal ed a uniform increased proliferation of nerves after seven days. At 21 days, the intercept countings showed in excess of a three-fold increa se of calcitonin gene-related peptide-immunoreactive nerve fibres comp ared with the normal control group (P less-than-or-equal-to 0.0001) an d were almost as numerous as protein gene product 9.5-immunoreactive f ibres (P < 0.005). It is postulated that calcitonin gene-related pepti de-containing sensory innervation may have a potential importance in t he fracture vascular control, angiogenesis and osteogenesis in additio n to a protective role against excessive fracture movement. The result s are consistent with the neural involvement in bone growth and remode lling.