MiR-183-5p Alleviates Chronic Constriction Injury-Induced Neuropathic Pain Through Inhibition of TREK-1

Abstract

MicroRNAs have been implicated in nerve injury and neuropathic pain. In the previous study we had shown that miR-96 can attenuate neuropathic pain through inhibition of Nav1.3. In this study, we investigated the role of miR-183, a same cluster member of microRNA with miR-96, in neuropathic pain and its potential mechanisms. We found that the expression level of miR-183-5p in dorsal root ganglion was decreased with the development of neuropathic pain induced by chronic constriction sciatic nerve injury (CCI). By contrast, the TREK-1, a K channel, was increased. Further investigation identified that intrathecal injection of miR-183-5p mimic efficiently ameliorated neuropathic pain and inhibited the expression of TREK-1, a predicted target gene of miR-183-5p. Luciferase assays confirmed the binding of miR-183-5p and TREK-1. In addition, over-expression of TREK-1 blocked the roles of miR-183-5p in neuropathic pain. Our findings suggested that miR-183-5P participated in the regulation of CCI-induced neuropathic pain through inhibiting the expression of TREK-1.

Granulocyte Colony Stimulating Factor (GCSF) Can Attenuate Neuropathic Pain by Suppressing Monocyte Chemoattractant Protein-1 (MCP-1) Expression, through Upregulating the Early MicroRNA-122 Expression in the Dorsal Root Ganglia

“…Our study showed that the levels of microRNA-122 were downregulated in the DRGs of CCI rats on the 1st day after nerve injury but were upregulated by early GCSF treatment. Many studies have investigated the temporal profiles of microRNA expression in the DRGs of CCI rats, but those studies usually focused on microRNA expression in the late stage after nerve injury and did not achieve consistent results [18][19][20][21]24,25]. Li et al [19] screened the expression of different microRNAs in the DRGs of CCI rats by microarray analysis with quantitative reverse transcriptase PCR and found that the levels of microRNA-341 are upregulated on the 14th day after nerve injury.…”

“…However, alterations in the microRNA expression were not evaluated at an early time point in their study. Other studies focused on different microRNAs and showed that the levels of microRNA-21 [20] and microRNA-146a-5p [18] are upregulated but that the levels of microRNA-96 [21], microRNA-183-5p [24], and microRNA-34a [25] are downregulated in the DRGs of CCI rats in the late stage after nerve injury (>3 days). Zhang et al [22] and Sun et al [23] showed that the levels of microRNA-141 and microRNA-206 in the DRGs of CCI rats decrease from the 1st day after nerve injury and are more significantly decreased on the 7th day after nerve injury.…”

“…MicroRNAs have important roles in different research fields [8] and in chronic pain development [9][10][11][12][13][14][15]. Many studies have demonstrated temporal changes in the expression of different microRNAs in the DRGs of various animal models of inflammatory and neuropathic pain [16][17][18][19][20][21][22][23][24][25][26]. MicroRNAs can also attenuate inflammatory or neuropathic pain directly through modulating the expression of different cytokines/chemokines and ion channels in the DRGs of various animal models of pain [16,18,[20][21][22][23][24][26][27][28].…”

“…Many studies have demonstrated temporal changes in the expression of different microRNAs in the DRGs of various animal models of inflammatory and neuropathic pain [16][17][18][19][20][21][22][23][24][25][26]. MicroRNAs can also attenuate inflammatory or neuropathic pain directly through modulating the expression of different cytokines/chemokines and ion channels in the DRGs of various animal models of pain [16,18,[20][21][22][23][24][26][27][28]. In this study, we used the NanoString nCounter Analysis System [29] which can detect different gene expressions through a hybridizing special barcode system to evaluate the expression of 420 different rodent microRNAs in the DRGs of sham controls and CCI rats treated with or without GCSF at the early stage (1st day) after nerve injury.…”

Non-coding RNAs in neuropathic pain

“…Furthermore, transducer channels, such as TRPA1, can occur as a consequence of miR-449a down-regulation [113]. The only potential change counteracting these proalgesic alterations refers to the down-regulated miR-183-5p that targets potassium channel Trek1, a two pore domain potassium channel subfamily member 2 (Kcnk2), which as a leak current keeps the membrane potential hyperpolarized [106]. The up-regulation of this channel may counteract the brake set on potassium channel expression by the miR-17-92 cluster.…”