The effects of neuropeptides (calcitonin gene-related peptide and substance P) on cultured human pulp cells.

The sensory neuropeptides substance P and calcitonin gene-related peptide have been implicated in the mediation of pulpal inflammation. A possible role in healing following injury has also been suggested (Byers et al., 1990). This possibility has been investigated by an examination of a direct effect of substance P and calcitonin gene-related peptide in vitro on fibroblast-like cells derived from human dental pulp. Cells were cultured for 48 hr in Dulbecco's modified Eagle medium plus 20% fetal calf serum and antibiotics. Substance P and calcitonin gene-related peptide were added in the range from 10(-12) to 10(-4) mol/L. Fibroblast growth factor was used as a positive control. Effects on cell proliferation were assessed by cell counts (daily for 6 days) and [3H]-thymidine uptake (24 hr after the addition of peptides). An effect on cellular functional activity was measured by [35S]-sulfate incorporation into glycosaminoglycans, in confluent cell cultures. Both substance P and calcitonin gene-related peptide showed concentration-dependent stimulation of cell proliferation. The maximum stimulation of approximately 40% was achieved at substance P and calcitonin gene-related peptide concentrations of 10(-6) mol/L, comparable with stimulation by fibroblast growth factor. By contrast, little increase in glycosaminoglycan synthesis by confluent cells could be detected. The direct effect on pulp cells is consistent with a role of the neuropeptides in pulp healing. This is exerted at the level of cell proliferation, rather than functional activity.