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

Abstract

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 E 2 (PGE 2 ) in dorsal root ganglion (DRG) neurons. However, no information was available on the property of the novel type of TTX-R Na + channel, Na V 1.9, at the time 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 , two components of TTX-R Na + current have been recorded in isolation from small (<25 μm 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 μM). These results raise a question regarding the well-known modulatory role of PGE 2 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.