Pulpectomy and pulpal necrosis result in severance of the nerves that supply the pulp as well as loss of their target organ. Inflammatory changes commonly extend into the periapical region to involve those nerves. The neural response to pulpal loss combined with periapical inflammation is a derangement of the periodontal plexus normally located in the center of the periodontal space around the apical third of the root; the result is the formation of a disorganized group of sprouting and branching axons that have some features in common with neuromas. The inflammatory and neural responses continue for at least a year even when pulpectomy is followed by canal debridement and obturation. Then the responses are reduced but not eliminated by steroids. Root canal therapy with techniques that do not leave residual inflammation still results in increased periapical innervation; the increase seems to be an organized addition to the normal periradicular plexus.