MiR-122-5p suppresses neuropathic pain development by targeting PDK4.

ABSTRACT

The complex pathogenesis and limited efficacy of available treatment make neuropathic pain difficult for long periods of time. Several findings suggested the regulatory role of microRNA in the development of neuropathic pain. This study aims to investigate the functional role of miR-122-5p in the development of neuropathic pain. Down-regulation of miR-122-5p was observed in spinal cords of rats with neuropathic pain. We also found that overexpressing miR-122-5p by intrathecal injection of miR-122-5p lentivirus in a mouse model of chronic sciatic nerve injury (CCI) prevented neuropathic pain behavior. In HEK-293 T cells, luciferase activity was significantly decreased in the transfection group with mimic-miR-122-5p in wild-type PDK4 reporter, compared with mutant PDK4 reporter. Increased PDK4 expression was also observed during the progression of neuropathic pain. Intrathecal injection of both mimic-miR-122-5p and shPDK4 in CCI mice downregulated PDK4 expression to a lower level when compared with injected with shPDK4. In CCI mice, transfection of shPDK4 suppressed mechanical allodynia and thermal hyperalgesia, while co-transfection of shPDK4 and LV-miR-122-5p resulted in stronger levels of mechanical allodynia and thermal hyperalgesia inhibition. Taken together, the data suggest that miR-122-5p inhibits PDK4 expression, attenuating neuropathic pain. This result suggests the potential role of miR-122-5p acting as a target for the treatment of neuropathic pain.