The ion channels open based on pain stimuli propagating action potentials in sensory neurons.In order for excitability and conduction to occur, voltage-gated sodium channels must be activated. Changes in sodium channel (NaCH)  expression occur after inflammatory lesions, which may generate different pain states seen when neuronal fibers are activated. Studies have been done on major NaCh isoforms to examine expression patterns. Nav1.6 nodal accumulations do not vary in size or immunofluorescence staining activity in typical or atypical nodal sites; however, the proportion of typical nodal sites decreases and increase in atypical nodes in painful tooth samples compared to normal tooth samples. Nav1.7 has an increased expression in typical and atypical nodal sites in painful samples. As a result, an increased co-expression of multiple isoforms at demyelinating nodal sites in painful dental pulp. This isoforms of sodium channels may be a main factor in pain sensations due to their production of axonal excitability properties.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.
The inflammation may be acute or chronic because just like other tissues in the body, the pulp will react to irritants with innate and/or adaptive immune responses.Innate immunity in the pulp is not specific but uses receptors to recognize molecular patterns common to microbes to initiate bacterial killing (phagocytosis). The components of the innate response of the dentin/pulp complex to caries include at least the following six: (1) outward flow of dentinal fluid; (2) odontoblasts; (3) neuropeptides and neurogenic inflammation; (4) innate immune cells, including immature dendritic cells (DCs), natural killer (NK) cells, and T cells, as well as (5) their cytokines and (6) chemokines. Although the first two items are not classic components of innate immunity, they are uniquely involved in the initial inflammatory response to caries.Odontoblasts, (the cells that form dentin) have cellular processes that extend into dentinal tubules and are the first to encounter the caries bacterial antigens. They express low levels of interleukin 8 (IL-8) and genes related to chemokines and chemokine receptors. The odontoblasts have been shown to attract immature dendritic cells.Dendritic cells (DCs) are a heterogeneous leukocyte (white blood cell) population. DCs in healthy peripheral tissues (steady state) are in an immature state. The cells are capable of sensing microbes as well as antigen capture and processing capabilities. A rapid accumulation of pulpal DCs has been observed beneath cavity preparations, and an increased number of DCs accumulated under caries.