MicroRNA-182 Alleviates Neuropathic Pain by Regulating Nav1.7 Following Spared Nerve Injury in Rats

Abstract

The sodium channel 1.7 (Nav1.7), which is encoded by SCN9A gene, is involved in neuropathic pain. As crucial regulators of gene expression, many miRNAs have already gained importance in neuropathic pain, including miR-182, which is predicted to regulate the SCN9A gene. Nav1.7 expression in L4-L6 dorsal root ganglions (DRGs) can be up regulated by spared nerve injury (SNI), while miR-182 expression was down regulated following SNI model. Exploring the connection between Nav1.7 and miR-182 may facilitate the development of a better-targeted therapy. In the current study, direct pairing of miR-182 with the SCN9A gene was verified using a luciferase assay in vitro. Over-expression of miR-182 via microinjection of miR-182 agomir reversed the abnormal increase of Nav1.7 at both mRNA and protein level in L4-6 DRGs of SNI rats, and significantly attenuated the hypersensitivity to mechanical stimulus in the rats. In contrast, administration of miR-182 antagomir enhanced the Nav1.7 expression at both mRNA and protein level in L4-6 DRGs, companied with the generation of mechanical hypersensitivity in naïve rats. Collectively, we concluded that miR-182 can alleviate SNI- induced neuropathic pain through regulating Nav1.7 in rats.

Long-lasting Analgesia via Targetedin vivoEpigenetic Repression of Nav1.7

“…In these studies, we found that mice injected with either epigenetic platform had significantly reduced DRG expression of Na V 1.7. Other studies have shown that partial repression of Na V 1.7 [78][79][80][81][82][83] is sufficient to ameliorate pain. This knock down serves to produce a significant reversal of the hyperalgesia induced by hind paw inflammation.…”

“…Using antisense oligonucleotides, mechanical pain could be ameliorated with 30 to 80% Na V 1.7 repression levels 81 . Using microRNA 30b, around 50% repression of Na V 1.7 relieved neuropathic pain 82 , while more recently microRNA182 ameliorated pain preventing Na V 1.7 overexpression in spared nerve injury rats 79 . Similarly, shRNA mediated knockdown of Na V 1.7 prevented its overexpression in burn injury relieving pain 78 .…”

Activating Sirt1 by resveratrol suppresses Nav1.7 expression in DRG through miR-182 and alleviates neuropathic pain in rats

“…Sirt1 inhibitor EX527 (#E7034) and Sirt1 activator SRT1720 (#567,860) were also purchased from Sigma-Aldrich, and dissolved in DMSO. miR-182 antagomir and antagomir negative control were synthesized by BGI-Shenzhen (Shenzhen, China) using the sequences listed previously [14]. Most drugs were administered via the pre-placed intrathecal catheter once per day 7 days after CCI for 4 successive days except EX527, which was injected s.c. with the same time pattern.…”

“…The downstream effector and pathway after resveratrol-initiated Sirt1 activation hasn't been well elucidated. Considering miR-182 is the downstream effector of Sirt1 and miR-182 is reported to decrease Nav1.7 expression, one promising effector protein of neuropathic pain [13], to relive symptoms related with neuropathic pain [14], we hypothesized that Sirt1 might downregulated Nav1.7 expression via miR-182.…”

Protein kinase C‐α upregulates sodium channel Nav1.9 in nociceptive dorsal root ganglion neurons in an inflammatory arthritis pain model of rat

“…23,35 As for the membrane protein and cytosolic protein extraction, we used Mem-PER Plus Membrane Protein Extraction Kit (#89842; Thermo Fisher Scientific). After centrifugation (15 minutes at 1000g, 4°C), the supernatant was collected to isolate the protein for Nav1.9 detection as we did before.…”