Can stem cells inside a tooth help make its pain-sensing nerves more sensitive?

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Dental pulp stem cells (DPSCs) contribute to tooth development, repair, regeneration, and immunomodulation. However, their role in the inflammatory mechanisms underlying pulpitis is not well understood.

This laboratory experimental study examined how stimulating DPSCs with calcitonin gene-related peptide (CGRP), a proinflammatory neuropeptide, affected the expression of mediators released by these cells and how those mediators affected sensory neuron activity.

Human DPSCs were treated with either control media or media containing CGRP at 10⁻⁸ M for 7 days. The researchers then collected the conditioned media (CM), which contained mediators released by the DPSCs. They evaluated cytokine and chemokine expression using reverse transcription quantitative polymerase chain reaction.

The effects of conditioned media from CGRP-primed DPSCs (primed DPSC-CM) on sensory afferents were tested using primary cultures of mouse trigeminal neurons and an organotypic model of cultured human pulp slices. Mouse trigeminal neurons and human pulp explants were pretreated for 24 hours with control or primed DPSC-CM and then stimulated with capsaicin. Sensory afferent activity was quantified through capsaicin responses: live cell calcium imaging in mouse neurons and measurement of CGRP released from human pulp explants.

Gene expression analysis showed that CGRP-primed DPSCs overexpressed some proinflammatory cytokines and chemokines, including CXCL1 and CXCL8. Both chemokines are agonists of CXCR2, a receptor expressed in sensory neurons.

Compared with control DPSC-CM, primed DPSC-CM increased sensory afferent activity in human pulp. It also increased the intensity of calcium responses in cultured mouse trigeminal neurons. The CXCR2 antagonist SB225002 prevented the sensitization to capsaicin induced by primed DPSC-CM in trigeminal neurons.

The researchers concluded that mediators released by DPSCs primed with the proinflammatory mediator CGRP induce neuronal sensitization through the CXCR2 receptor. These findings suggest that DPSCs might contribute to the pain symptoms that develop in pulpitis.