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

Area of Science:

• Neuroscience
• Molecular Biology
• Pain Research

Background:

• Postherpetic neuralgia (PHN) is a debilitating neuropathic pain condition.
• The molecular mechanisms underlying PHN, particularly the role of microRNAs, require further elucidation.

Purpose of the Study:

• To investigate the association between microRNA-138-5p (miR-138-5p) and the development of PHN.
• To explore the therapeutic potential of modulating miR-138-5p in a rat model of PHN.

Main Methods:

• Established a PHN rat model using varicella-zoster virus infection.
• Quantified miR-138-5p expression via RT-qPCR and modulated its levels using lentiviral vectors.
• Assessed pain sensitivity (paw withdrawal threshold), glial activation (GFAP), and inflammatory cytokines (IL-1β, TNF-α) using PWT, RT-qPCR, and ELISA. Verified miR-138-5p targeting of ROCK2 using dual-luciferase reporter assay.

Main Results:

• miR-138-5p expression was significantly downregulated in the spinal cords of PHN rats.
• Overexpression of miR-138-5p ameliorated hyperalgesia, reduced GFAP and pro-inflammatory cytokine levels, and suppressed ROCK2 expression.
• ROCK2 was identified as a direct downstream target of miR-138-5p, and its upregulation was observed in PHN.

Conclusions:

• miR-138-5p plays a critical protective role in mitigating spinal cord inflammation and hyperalgesia during PHN.
• Suppression of ROCK2 by miR-138-5p represents a key mechanism underlying its anti-nociceptive and anti-inflammatory effects in PHN.