KLF15 regulates dopamine D2 receptor and participates in mouse models of neuropathic pain

Neuropathic pain is caused by damage to the nervous system, resulting in aberrant pain. The mechanism underlying neuropathic pain remains largely unknown. Krüppel-like factor 15 (KLF15) is a member of the Krüppel-like factor family of transcriptional factors. Here in this study, we aimed to investigate the potential role of the transcriptional factor KLF15 in neuropathic pain. The mRNA and protein levels of Klf15 were significantly increased in the neurons of mouse undergoing neuropathic pain induced by sciatic nerve chronic constrictive injury (CCI) or unilateral spared nerve injury (SNI). In neurons, the upregulation of Klf15 was triggered by the inflammatory factor tumor necrosis factor alpha (TNF-α). As a transcriptional factor, KLF15 promoted the expression of dopamine D2 receptor (Drd2), which is a receptor essentially involved in neuropathic pain. KLF15 bound to the promoter of Drd2 directly and promoted the promoter activity of Drd2. Finally, we showed that knockout of Klf15 repressed the sensitivity in neuropathic pain induced by CCI or SNI. In conclusion, KLF15 is induced in neuropathic pain via a TNF-α-dependent manner and contributes to neuropathic pain partially through promoting the expression of dopamine D2 receptor.