-Original-

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

Yuji Watanabe¹, Motoyo Maruyama^1,2, Miki Yokoyama^1,3, Ryosuke Arakawa¹ and Atsushi Sakai¹

¹Department of Pharmacology, Nippon Medical School, Tokyo, Japan
²Division of Laboratory Animal Science, Nippon Medical School, Tokyo, Japan
³Department of Dental Anesthesiology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan

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.

J Nippon Med Sch 2026; 93: 244-251

Keywords
dorsal root ganglion, interferon regulatory factor, IRF8, neuropathic pain

Correspondence to
Atsushi Sakai
sa19@nms.ac.jp

Received, December 2, 2025
Accepted, January 5, 2026