miR-138-5p Alleviates Abnormal Pain and Neuroinflammation in Postherpetic Neuralgia by Inhibiting ROCK2.

Abstract

Postherpetic neuralgia (PHN) is a form of neuropathic pain that has significant detrimental effects. This study seeks to explore the potential association between miR-138-5p and PHN. A PHN model was established by infecting rats with the varicella-zoster virus. Following this, the expression level of miR-138-5p in spinal cord was quantified using RT-qPCR. To further investigate its role, miR-138-5p levels were modulated through the intrathecal administration of a lentivirus. The abnormal pain sensitivity in the rats was assessed utilizing the paw withdrawal threshold (PWT). Additionally, the levels of glial fibrillary acidic protein (GFAP) and pro-inflammatory cytokines (IL-1β and TNF-α) in spinal cord were measured by RT-qPCR or enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was used to verify the binding relationship between miR-138-5p and ROCK2. miR-138-5p is downregulated in the spinal cord tissue of PHN rats. Notably, the overexpression of miR-138-5p significantly enhances the PWT in PHN rats. Furthermore, the elevation of miR-138-5p markedly mitigates the abnormal increase of GFAP and pro-inflammatory factors. Mechanistically, ROCK2 has been identified as a downstream target of miR-138-5p. During the onset of PHN, ROCK2 is persistently upregulated, whereas the overexpression of miR-138-5p effectively inhibits this increase. Interestingly, the concurrent overexpression of miR-138-5p and ROCK2 can counteract the enhancement in PWT engendered solely by the upregulation of miR-138-5p, alongside the reduction in levels of GFAP, IL-1β, and IL-6. miR-138-5p plays a crucial role in modulating the development of PHN. In the context of PHN, miR-138-5p inhibits spinal cord inflammation and hyperalgesia by suppressing ROCK2.