Prostaglandin E-2 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 mu m 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 mu M). Our results raise a question regarding the well-known modulatory role of PGE(2) on TTX-R Na+ current in inflammatory hyperalgesia.