Trigeminal Sensory Neurons and Pulp Regeneration.

The pulp-dentin complex is innervated by a high density of trigeminal neurons free nerve endings. These neuronal fibers are highly specialized to sense noxious stimuli such as thermal, mechanical, chemical, and biological cues. This robust alert system provides immediate feedback of potential or actual injury triggering reflex responses that protect the teeth from further injury. In the case of patients, pain is the most important experience that leads them to seek oral health care. The adequate removal of the etiology, such as caries, provides ample opportunity for the robust reparative and regenerative potential of the pulp-dentin complex to restore homeostasis. In addition to this elaborated surveillance system, evidence has accumulated that sensory neuronal fibers can potentially modulate various steps of the reparative and regenerative process through cellular communication processes. These include modulation of immunologic, angiogenic, and mineralization responses. Despite these orchestrated cellular events, the defense of the pulp-dentin complex may be overwhelmed, resulting in pulp necrosis and apical periodontitis. Regenerative endodontic procedures have evolved to restore the once lost function of the pulp-dentin complex. After these procedures, a large subset of successful cases demonstrates a positive response to sensitivity testing, suggesting reinnervation of the canal space. This process is likely mediated through cellular and noncellular release of neurotrophic factors such as brain-derived nerve growth factor. In addition, these newly recruited nerve fibers appear equipped to sense thermal stimuli through nonhydrodynamic mechanisms. Collectively, the significance of innervation in the normal physiology of the pulp-dentin complex and its role in regeneration need to be better appreciated to promote further research in this area that could potentially bring new therapeutic opportunities.