A mechanism for sympathectomy-induced bone resorption in the middle ear

Abstract

The results of the in vitro study revealed that substance P at 10(-8) mol/L (11.05 +/- 3.37 micrograms/ml) induced significant calcium release from cultured neonatal mouse calvaria when compared with control bone incubated in base media alone (0.92 +/- 2.85 micrograms/ml, p < 0.01). The process was completely inhibited by 5.0 x 10(-7) indomethacin. The results of the in vivo study showed 6-hydroxydopamine treatment significantly increased both the osteoclast number (NOc/TL = 3.14 +/- 1.33/mm) and the osteoclast surface (OcS/BS = 16.04% +/- 6.95%) of bone when compared with bone from saline-treated controls (NOc/TL = 1.77 +/- 0.79/mm, p < 0.01; OcS/BS = 8.88% +/- 4.15%, p < 0.01). These 6-hydroxydopamine-induced increases were eliminated, however, in animals pretreated with capsaicin before sympathectomy (NOc/TL = 1.86 +/- 0.68/mm, p > 0.05; OcS/BS = 9.92 +/- 3.73, p > 0.05), whereas treatment with capsaicin alone had no effect when compared with bone from saline-treated controls (NOc/TL = 2.02 +/- 0.50/mm, p > 0.05; OcS/BS = 10.28% +/- 2.62%, p > 0.05). Substance P has thus been shown to induce calcium release from membranous bone in vitro, whereas capsaicin, a substance P-specific sensory neurolytic chemical, eliminates the in vivo osteoclast-inductive effects of 6-hydroxydopamine when given 12 hours before treatment. The results indicate that substance P is capable of inducing resorption and that substance P-containing sensory ne