Does prostaglandin upregulate the tetrodotoxin-resistant Na+ current in DRG neurons?

One possible mechanism underlying the inflammation-induced sensitization of primary afferent neurons 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 E2 (PGE2) in dorsal root ganglion (DRG) neurons. However, no information was available on the property of the novel type of TTX-R Na+ channel, NaV1.9, at the time when these reports were published. Hence, the contribution of NaV1.9 to the PGE2-induced upregulation of TTX-R Na+ current remains to be elucidated. To further examine the modulation of TTX-R Na+ current by PGE2, two components of TTX-R Na+ current have been recorded in isolation from small (<25 μm in diameter) DRG neurons using wild-type and NaV1.8 knock-out mice. Unexpectedly, neither the component mediated by NaV1.8 nor the persistent component mediated by NaV1.9 was affected by PGE2 (1 and 10 μM). These results raise a question regarding the well-known modulatory role of PGE2 on TTX-R Na+ current in inflammatory hyperalgesia. Here we will review these recent data in context with the current literature relating to this issue.