Upregulation of miR‐183 represses neuropathic pain through inhibiton of MAP3K4 in CCI rat models

Abstract

Many studies have verified that microRNAs contribute a lot to neuropathic pain progression. Furthermore, nerve‐related inflammatory cytokines play vital roles in neuropathic pain progression. miR‐183 has been identified to have a common relationship with multiple pathological diseases. However, the potential effects of miR‐183 in the process of neuropathic pain remain undetermined. Therefore, we performed the current study with the purpose of finding the functions of miR‐183 in neuropathic pain progression using a chronic sciatic nerve injury (CCI) rat model. We demonstrated that miR‐183 expression levels were evidently reduced in CCI rats in contrast with the control group. Overexpression of miR‐183 produced significant relief of mechanical hyperalgesia, as well as thermal hyperalgesia in CCI rats. Furthermore, neuropathic pain‐correlated inflammatory cytokine expression levels containing interleukin‐6 (IL‐6) and interleukin‐1β (IL‐1β), cyclooxygenase‐2 (COX‐2) were obviously inhibited by upregulation of miR‐183. Meanwhile, dual‐luciferase reporter assays showed MAP3K4 was a direct downstream gene of miR‐183. The expression levels of MAP3K4 were modulated by the increased miR‐183 negatively, which lead to the downregulation of IL‐6, IL‐1β, and COX‐2, and then reduced neuropathic pain progression, respectively. Overall, our study pointed out that miR‐183 was a part of the negative regulator which could relieve neuropathic pain by targeting MAP3K4. Thus it may provide a new clinical treatment for neuropathic pain patients clinical therapy.

LncRNA‐MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway andcis‐modulation of MAP3K4

“…23 MAP3K4 also regulates the stem cell epithelial-to-mesenchymal transition (EMT), [24][25][26] cell migration, 27,28 and several inflammatory mediators including IL-6, IL-1β, and COX2. 29 Long non-coding RNAs (lncRNAs) have emerged as a class of regulatory molecules with highly diverse structures and functions in both physiological and pathological contexts. [30][31][32][33] Genome-wide transcriptome analyses have identified thousands of lncRNAs throughout the human genome.…”

“…Chi et al reported that MAP3K4 is selective for the p38 pathway in MAP3K4 knockout mice 23 . MAP3K4 also regulates the stem cell epithelial‐to‐mesenchymal transition (EMT), 24‐26 cell migration, 27,28 and several inflammatory mediators including IL‐6, IL‐1β, and COX2 29 …”

Downregulation of long noncoding RNA DLEU1 attenuates hypersensitivity in chronic constriction injury-induced neuropathic pain in rats by targeting miR-133a-3p/SRPK1 axis

“…Recently, miRNAs have been reported to be abnormally expressed in the nervous system and exert essential effects to modulate neuropathic pain. For example, miR-183 overexpression inhibits neuropathic pain by targeting MAP3K4 in CCI rat models (Huang and Wang 2019 ). MiR-101 alleviates neuropathic pain in CCI rat models by downregulating mTOR expression (Xie et al 2019 ).…”

Advances With Non-coding RNAs in Neuropathic Pain

“…MiR-183 modulates the expression of MAP3K4, which in turn leads to the downregulation of inflammatory factors, and cyclooxygenase-2 (COX-2) which slows NP progression. In summary, the study stated that miR-183 was a part of the negative regulatory effector group, which could alleviate NP by targeting MAP3K4 ( Huang and Wang, 2020 ). MiR-21 can interact with toll-like receptor 8 (TLR8) in lysosome as an endogenous ligand, inducing extracellularly regulated protein kinase (ERK) activation and production of inflammatory mediators.…”