Local injection of substance P increases bony formation during mandibular distraction osteogenesis in rats

Substance P is a neuropeptide that is distributed in those sensory nerve fibres that innervate the medullary tissues of bone. It is a potent accelerator of proliferation and differentiation of osteoblasts in vitro. However, its capacity for promoting repair of mandibular defects is not known. We have investigated the osteogenic effects of local injections of substance P during mandibular distraction osteogenesis in rats. Twenty Sprague-Dawley rats were randomly assigned to 2 groups (n = 10 in each): substance P 10−7 mmol/l in normal saline 0.2 ml was injected into the experimental group, and saline alone into the controls. The mandibular distraction rate was 0.2 mm every 12 hours for 10 days. Daily injections of substance P or saline were given during the distraction period. Regeneration of bone was assessed quantitatively on days 15 and 29 using microcomputed tomography (microCT), and histological analysis. The rate of bony union in the group treated with substance P was significantly higher than that in the saline alone group on day 29 (p=0.001) The microCT images and quantitation showed more callus and more mature cortical bone when substance P was given than with control. Histological examination showed that cartilaginous tissues had formed in the middle of the distraction gaps in both groups. Bony bridges were seen only in the substance P group at the final time point (day 29). Injection of substance P into the gap of a rat mandible during mandibular distraction improved formation of good-quality bone and accelerated bony union.