Effect of intrathecal injection of miRNA-138 on neuropathic pain in rats undergoing partial sciatic nerve ligation and its underlying mechanism.

Abstract

microRNA-138 (miRNA-138) might have a promising therapeutic effect in the Neuropathic pain (NP). We aim to investigate the effects of miRNA-138 on NP and explore its underlying mechanism. we performed a partial sciatic nerve ligation (pSNL) surgery in rats to induce pain and inflammation. Rats were administrated by intrathecal injection of lentiviral (LV)-mediated miRNA-138. Mechanical withdrawal threshold (MWT) and paw withdrawal thermal latency (PWTL) were measured to evaluate the pain degree. The expression levels of miRNA-138, toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-α), interleukin-β (IL-β), and IL-6 in the spinal cord were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting was performed to measure the expressions of macrophage inflammatory protein-1 alpha (MIP-1α) and C-C chemokine receptor type 1 (CCR1). Next, the mechanism of miRNA-138 on NP was investigated by intrathecal injection of CCR1 inhibitor or MIP-1α neutralizing antibody. Inflammatory factors, MWT, and PWTL were also measured on day 7. Intrathecal injection of miRNA138 significantly reduced MWT and PWTL. qRT-PCR showed that miRNA138 mimic group significantly reduced the level of TLR4, TNF-α, Il-β, and IL-6 on day 7. Western blotting showed that the protein expressions of MIP-1α and CCR1 in pSNL + miRNA138 mimic group were significantly decreased on day 7. In addition, the miRNA138 inhibitor inversely increased MWT, PWTL and inflammatory cytokines. Further, the effect of miRNA138 inhibitor all were significantly reversed by CCR1 inhibitor or MIP-1α neutralizing antibody. Intrathecal injection of miRNA-138 can remarkably alleviate NP in rats with a pSNL, which may be achieved by suppressing the TLR4 and MIP-1α/CCR1 signaling pathways.