OR25 - Inflamed Human Dental Pulp Generates Endogenous TRPV1 Agonists (“Endo-capsaicins”)

Linoleic acid (LA) is an omega-6 polyunsaturated fatty acid that constitutes a major component of cellular plasma membranes. We previously demonstrated that oxidized linoleic acid metabolites (OLAMs) activate TRPV1 (capsaicin receptor), an important ion channel found in nociceptive neurons. Here, we tested the hypothesis that human dental pulp from teeth with a diagnosis of symptomatic irreversible pulpitis (SIP) have significantly greater capacity to form OLAMs compared to control human dental pulp. Control normal dental pulp (n=10) or SIP dental pulp samples (n=40) were collected and immediately frozen and pain was measured on a visual analog scale. To determine formation of OLAMs, teeth were split, pulp removed, cubed and incubated with [13C]-LA for 1h at 37°C. Lipid samples were extracted using the Bligh and Dyer method. Endogenous LA, exogenous LA (i.e., [C13]-LA) and respective metabolites were measuring using a Waters LC/MS/MS in negative ionization mode. Data were analyzed by t-test comparing SIP to control dental pulp. Compared to control samples, patients with a diagnosis of SIP had significantly greater levels of pain (p < 0.005) and significantly lower levels of endogenous LA (p < 0.005). Incubation of the dental pulp samples with [C13]-LA resulted in the formation of [C13]-oxoOde, an OLAM previously shown to activate TRPV1. To our knowledge this is the first study to demonstrate generation of TRPV1 agonists from inflamed human dental pulp. This suggests that interventions that block either the generation or action of OLAMs may constitute a novel approach for developing effective analgesics for treating odontogenic pain patients.