In this study, we sought to clarify the mechanism of ossification induced by direct current stimulation by analyzing changes in local blood flow and vascular permeability and by examining the involvement of chemical mediators. Changes in blood flow were studied with laser Doppler flowmetry, and vascular permeability was determined by microquantification. To examine the involvement of chemical mediators, we determined the effect on vascular permeability of histamine HI and H,-receptor blockers and indomethacin. In addition, direct current stimulation was performed during administration of indomethacin to determine whether indomethacin inhibits electrically induced callus formation. Local blood flow remained unchanged in the control group and in the group receiving 5 pA of stimulation, but it increased in the groups receiving 10 and 50 pA. Vascular permeability increased in the 5 and 10 pA stimulation groups. This increase was not suppressed by histamine-receptor blockers. but it was suppressed by indomethacin. Two weeks of electrical stimulation without concomitant indomethacin treatment resulted in active callus formation around the needle electrode and in the vicinity of the endosteum; however, direct current stimulation during administration of indomethacin inhibited callus formation. The results suggest that these changes serve as microenvironmental factors that play a n important role in the promotion of ossification and that a prostaglandin-mediated mechanism is involved in the promotion of ossification by direct current stimulation.
Studies of the relationship between bones and electrical phenomena have a long history. In 1953, Yasuda noted that bone deformation led to the appearance of a potential difference on the surface of the bone and called it piezoelectricity (35). Friedenberg and Brighton reported that living bone has an endogenous bioelectric potential and that areas of fracture repair or actively growing regions are electronegative in comparison with less active regions (9).
It also has been demonstrated that exogenous electrical stimulation with direct current promotes ossification (1). On the basis of these findings, vari-