Interferon Regulatory Factor Family Transcription Factor Expression in the Dorsal Root Ganglion of a Rat Model of Neuropathic Pain.

BACKGROUND

Peripheral nerve injury induces neuroinflammation in the dorsal root ganglion (DRG), which is a major cause of neuropathic pain. Interferon regulatory factors (IRFs) are a family of transcription factors that regulate the expression of inflammatory genes. Although several IRFs affect nociceptive transmission in the spinal cord, their roles in the DRG remain largely unknown.

METHODS

Spinal nerve ligation (SNL) was used to develop a rat neuropathic pain model. Pain-related behaviors were assessed by the von Frey test and Plantar test. Gene expression levels of IRF family members were examined using quantitative PCR or immunofluorescence. IRF8 expression was downregulated by intrathecal administration of small interfering RNA (siRNA).

RESULTS

IRF1, IRF5, and IRF8 were upregulated 4 days after nerve injury, but their expression gradually declined thereafter. In contrast, IRF4 and IRF7 expression gradually increased during an observation period of 14 days. No significant changes were observed in the expression of IRF2, IRF3, IRF6, or IRF9 after injury despite a slight increase. IRF8, which exhibited the greatest change in expression, was expressed in DRG neurons of naïve rats, and its distribution was not altered by nerve injury. IRF8 knockdown alleviated mechanical allodynia but not thermal hyperalgesia in neuropathic pain.

CONCLUSION

To our knowledge, these results are the first to show that multiple IRFs are upregulated in the DRG after peripheral nerve injury. The upregulated members of IRF family in the DRG after nerve injury may be involved in the pathophysiology of neuropathic pain.