Orofacial inflammation is associated with prostaglandin release and the sensitization of nociceptive receptors such as the transient receptor potential subtype V1 (TRPV1). We hypothesized that certain PGE2 receptor subtypes (EP1–EP4) are co-expressed with TRPV1 in trigeminal nociceptors and sensitize responses to a TRPV1 agonist, capsaicin. Accordingly, combined in situ hybridization was performed with immunohistochemistry on rat trigeminal ganglia. We next evaluated the effects of specific EP2 and EP3 agonists (butaprost and sulprostone) in cultured trigeminal ganglia neurons. The results showed that EP2 and EP3 are expressed in trigeminal neurons (58% and 53% of total neurons, respectively) and are co-expressed in TRPV1-positive neurons (64% and 67 % of TRPV1-positive neurons, respectively). Moreover, most of the cells expressing EP2 or EP3 mRNA were of small to medium diameter (< 30 μm). The application of butaprost and sulprostone triggered neuropeptide exocytosis, and butaprost sensitized capsaicin responses. Analysis of these data, collectively, supports the hypothesis that prostaglandins regulate trigeminal TRPV1 nociceptors via activation of the EP2 and EP3 receptors.
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