Fig. 10.
Putative model for elucidating the relationship between peripheral nerve injury–induced nociception and the alteration of PRDM1 as well as the mechanism by which PRDM1 modulates Kv4.3 channels. With nociception development, PRDM1 expression in dorsal root ganglion neurons is increased, which can initiate transcriptional repression of the Kcnd3 gene. Our results indicate that PRDM1-mediated Kcnd3 gene silencing can be accomplished by PRDM1 binding directly to the DNA promoter region to initiate transcriptional repression. This transcriptional repression leads to decreased Kcnd3 mRNA expression, fewer Kv4.3 ion channels, and ultimately decreased outward potassium current, increased dorsal root ganglion neuronal excitability, and sensitized neurons in the spinal dorsal horn. PRDM1, positive regulatory domain I–binding factor 1.