Effect of miRNA-146a-mediated TLR4 Signal Pathway on the Pain of Lumbar Disc Herniation

Abstract

The current experiment was carried out to explore the effect of the miR-146a-mediated TLR4 signaling pathway on the lumbar disc herniation pains. For this aim, a total of 32 rats were divided randomly into 4 groups – the blank group (Group C), Model group (M), miR-146a overexpression group (agomiR-146a group) and negative control group (NC group), with 8 rats in each group. Rats in Group M were prepared for the construction of lumbar disc herniation models, while those in the agomiR-146a group or NC group, in addition to the model construction, would receive the intrathecal injection of agomiR-146a or agomiRNA-146a NC. Thereafter, a series of tests were performed for rats, including the mechanical pain test and heat pain test to measure the pain threshold, RT-PCR to detect the expression of miR-146a, and the transcription of TLR4, IRAK1, TRAF6, IL-6 and TNF-α, Western blot to determine the expression of IRAK1 and TRAF6 and ELISA to determine the expression of IL-6 and TNF-α. Results showed that as compared to the blank group, rats in Group M were more sensitive to the pains, presenting with declines in the thresholds in the pain, and upregulation in the TRL4 signaling pathway (TLR4, IRAK1 and TRAF6) and pro-inflammatory factors, including IL-6 and TNF-α. In comparison with Group M, intrathecal injection of agomiR-146a relieved the pains, with significant upregulation of miR-146a and downregulation of TLR4, IRAK1, TRAF6, IL-6 and TNF-α. Then upregulation of miR-146a could reduce the activity of the TLR4 signaling pathway and the release of pro-inflammatory factors, which may be a potential strategy for the treatment of lumbar disc herniation.

Intradiscal inflammatory stimulation induces spinal pain behavior and intervertebral disc degeneration in vivo

“…28 Animal models of disc degeneration have also shown an association between increased TLR4 expression and pain, while inhibition of TLR4 decreased pain and pro-inflammatory cytokine production. [34][35][36] However, the extent to which inflammatory signaling resulting from TLR activation causes pain behavior requires further investigation.…”

“…Further, injection of LPS directly into the nucleus pulposus (NP) space of rat caudal IVDs has caused moderate degenerative changes in the IVD, with increases in tissue levels of IL‐1β, TNFα, HMGB1, and macrophage migration inhibitory factor (MIF) 28 . Animal models of disc degeneration have also shown an association between increased TLR4 expression and pain, while inhibition of TLR4 decreased pain and pro‐inflammatory cytokine production 34–36 . However, the extent to which inflammatory signaling resulting from TLR activation causes pain behavior requires further investigation.…”

Regulation of Circulating miR-342-3p Alleviates the Radiation-Induced Immune System Injury

“…To investigate the influences of circulating miR-342 on radiation-induced injury, the radiation-induced decrease in the level of miR-342 was reversed by tail vein injection with one kind of miR-342 mimetics (AgomiR-342). AgomiRNA is widely used to study the function of miRNAs in vivo ( 34 , 35 ). We found that injection with 5 nmol AgomiR-342 could upregulate the level of miR-342 in blood more than 8 times (Fig.…”

Tuina for peripherally-induced neuropathic pain: A review of analgesic mechanism

“…(Gada et al, 2021). Jing et al (2022) found that upregulating the expression of miR-146a in rats with LDH could reduce the activity of the TLR4 signaling pathway, thus relieving pain. Through highthroughput sequencing technology, Yao et al (2022b) found that there were 19 expressed miRNAs that were related to inflammation in chronic compression of dorsal root ganglia (CCD) rats treated with pressing and kneading "Weizhong" (BL40) compared to CCD model rats.…”