miR-32-5p-mediated Dusp5 downregulation contributes to neuropathic pain

Abstract

Previous studies have demonstrated that microRNAs (miRNAs) play important roles in the pathogenesis of neuropathic pain. In the present study, we found that miR-32-5p was significantly upregulated in rats after spinal nerve ligation (SNL), specifically in the spinal microglia of rats with SNL. Functional assays showed that knockdown of miR-32-5p greatly suppressed mechanical allodynia and heat hyperalgesia, and decreased inflammatory cytokine (IL-1β, TNF-α and IL-6) protein expression in rats after SNL. Similarly, miR-32-5p knockdown alleviated cytokine production in lipopolysaccharide (LPS)-treated spinal microglial cells, whereas its overexpression had the opposite effect. Mechanistic investigations revealed Dual-specificity phosphatase 5 (Dusp5) as a direct target of miR-32-5p, which is involved in the miR-32-5p-mediated effects on neuropathic pain and neuroinflammation. We demonstrated for the first time that miR-32-5p promotes neuroinflammation and neuropathic pain development through regulation of Dusp5. Our findings highlight a novel contribution of miR-32-5p to the process of neuropathic pain, and suggest possibilities for the development of novel therapeutic options for neuropathic pain.