Neuropeptides are increasingly being researched for having a role in molecular mechanisms involved with pain, including ion channels and inflammation. Substance P (SP) is a neuropeptide produced by capsaicin neuron cell bodies (localized in trigeminal ganglia and dorsal root) and plays a major role in dental pain and inflammation. Other peptides include cGRP, galanin, somatostatin, and neurokinin A-B. The biological effects of SP are expressed by the binding of specific G protein-coupled NK receptors. Interaction with SP receptors induces vasodilation and allows for plasma extravasation and mastocyte degranulation. SP is highly expressed in dental pulp and dentin. When pain, thermal, and/or chemical stimulation is present, SP production and release increases. Current studies focus on whether controlling Substance P expression may control tooth pain.