Prolonged PGE₂ treatment increased TTX-sensitive but not TTX-resistant sodium current in trigeminal ganglionic...

Prostaglandin E₂ (PGE₂) is an important inflammatory mediator for the initiation and maintenance of inflammatory and neuropathic pain. The acute effect of PGE₂ on sodium currents has been widely characterized in sensory neurons; however, the prolonged effect of PGE₂ remains to be determined. Here, we performed patch clamp recordings to evaluate the acute and prolonged effects of PGE₂ on sodium currents in trigeminal ganglionic (TG) neurons from male Sprague-Dawley rats. We found that 24-h treatment with PGE₂ (10 μM) increased the peak sodium current density by approximately 31% in a voltage-dependent manner and shifted the activation curve in a hyperpolarized direction but did not affect steady-state inactivation. Furthermore, treatment with PGE₂ for 24 h increased the current density of tetrodotoxin-sensitive (TTX-S) but not TTX-resistant (TTX-R) channels significantly. Interestingly, TTX-S current was increased mostly in medium-sized, but not in small-sized, neurons after 24 h of treatment with PGE₂. Moreover, the mRNA level of TTX-S Nav1.1 but not TTX-R Nav1.8 or Nav1.9 was significantly increased after 24 h of treatment with PGE_2. In contrast, 5-min treatment with PGE₂ (10 μM) increased the peak sodium current density by approximately 29% and increased TTX-R sodium currents, but not TTX-S currents, in both small- and medium-sized TG neurons. Our results presented a differential regulation of subtypes of sodium channels by acute and prolonged treatments of PGE₂, which may help to better understand the mechanism of PGE₂-mediated orofacial pain development.