Prostaglandin E2 has no effect on two components of tetrodotoxin-resistant Na+ current in mouse dorsal root ganglion

One possible mechanism underlying inflammation-induced sensitization of the primary afferent neuron is the upregulation of tetrodotoxin-resistant (TTX-R) Na(+) current by inflammatory mediators such as prostaglandins. This notion is based on reports that showed an augmentation of TTX-R Na(+) current following an application of prostaglandin E(2) (PGE(2)) in dorsal root ganglion (DRG) neurons. However, no information was available on the properties of the novel type of TTX-R Na(+) channel, Na(V)1.9, at times when these reports were published. Hence, the contribution of Na(V)1.9 to the PGE(2)-induced upregulation of TTX-R Na(+) current remains to be elucidated. To further examine the modulation of TTX-R Na(+) current by PGE(2), we recorded two components of TTX-R Na(+) current in isolation from small (<25 microm in diameter) DRG neurons using wild-type and Na(V)1.8 knock-out mice. Unexpectedly, neither the component mediated by Na(V)1.8 nor the persistent component mediated by Na(V)1.9 was affected by PGE(2) (1 and 10 microM). Our results raise a question regarding the well-known modulatory role of PGE(2) on TTX-R Na(+) current in inflammatory hyperalgesia.