Bacterial products can directly activate trigeminal sensory neurons.

Objectives: Pulpal infection often results in acute and chronic dental pain. Evidence suggests that sensory neuronal activation can be initiated by the action of inflammatory mediators as well by the bacteria causing the infection, however, the mechanisms involved in the latter are unclear. The aims of this study were to determine whether trigeminal neurons are directly activated by bacterial cellular products and whether these lead to increased expression of calcium gene related peptide (CGRP).
Methods: LPS and arginine-gingipain from Porphyromonas gingivalis were used to stimulate mouse trigeminal ganglia cells that had been cultured in vitro for 2-3 days. Neuronal response was assessed by calcium-imaging using Cal-520 AM and intracellular levels of CGRP were assessed by immunocytochemistry. Neurons were differentiated from non-neuronal cells, such as satellite glial cells and Schwann cells, by response to 60 mM KCl. Responses were compared with that achieved with Escherichia coli LPS and with agonists for the PAR2, TRPA1, and TRPV1 receptors.
Results: P. gingivalis LPS stimulation resulted in an activation response in more than 20% (24/90) of trigeminal neurons and 40% (18/57) of non-neuronal cells using calcium imaging and there was increased neuronal expression of CGRP. Similar results were obtained with E. coli LPS. Arg-ginigpain mediated a response from 46% (11/24) of neurons and almost all of the non-neuronal cells present. However, the bacterial-responsive neurons were not always the same as those that responded to the TRPV1 agonist, capsaicin, or the TRPA1 agonist, cinnamaldehyde, suggesting differences between neuronal subpopulations.
Conclusions: These data suggest that direct activation of neurons by P. gingivalis LPS and arg-gingipain may contribute to pain processing. This is likely to involve alteration of CGRP expression as well as TLRs, TRPs, and PAR2. It is possible that non-neuronal cells are also involved in mediating neuronal responses to these bacterial agonists.