Electroacupuncture Alleviates Neuropathic Pain through Regulating miR-206-3p Targeting BDNF after CCI

Abstract

Background. Electroacupuncture (EA) has benefits for neuropathic pain. However, the underlying mechanisms are still unknown. The current study explores the underlying mechanisms of EA in neuropathic pain of chronic constriction injury (CCI) rats. Material/Methods. Overall, 126 Sprague-Dawley (200-250 g) rats were divided into nine groups randomly: the sham-operated, CCI, CCI+EA, CCI+sham EA, CCI+NS, CCI+AAV-NC, CCI+AAV-miR-206-3p, CCI+EA+NS, and CCI+EA+AAV-miR-206-3p groups. The animals were sacrificed 14 days postsurgery. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests were used to determine differences in neurobehavioral manifestations. qPCR, western blotting, and immunofluorescence (IF) were carried out to detect the expression levels of miR-206-3p, BDNF, BAX/Bcl-2, TNF-α, and IL-6. Nissl staining was measured to observe morphological changes in neurons. Transmission electron microscopy (TEM) was employed to evaluate microscopic changes in dorsal horn synapses. Results. Hyperalgesia was reduced markedly by EA in the CCI model. The expression level of miR-206-3p was elevated, whereas the expression levels of BDNF, BAX/Bcl-2, TNF-α, and IL-6 were decreased in EA-treated CCI rats. However, a miR-206-3p inhibitor partially abrogated the analgesic effect of EA and resulted in poor behavioral performance and the BDNF, BAX/Bcl-2, TNF-α, and IL-6 expression was elevated as well. Conclusions. EA can relieve neuropathic pain by regulating the miR-206-3p/BDNF pathway, thus exerting anti-inflammatory and antiapoptotic effect.

Unveiling the LncRNA-miRNA-mRNA Regulatory Network in Arsenic-Induced Nerve Injury in Rats through High-Throughput Sequencing

“…Research findings have provided evidence for the regulatory role of miR-206-3p as an upstream regulator of Bdnf. The inhibition of miR-206-3p has been shown to lead to the increased expression of Bdnf [ 52 ]. Our study discovered a novel hetero-lncRNA molecule, lncRNA-ENSRNOT00022622, through sequencing analysis.…”

BDNF Modulation by microRNAs: An Update on the Experimental Evidence

“…A list of microRNAs found to degrade BDNF mRNA transcripts in oncology research is as follows: miR-10a, miR-22, miR-204, miR-107, miR-382, miR-496, miR-497, miR-584, miR-744, miR-26a-1, and miR-26a-2 subtypes [24,28,58,60,72,75,78,88,93,94,96,102,112,125,126,128,132,133,137,190]. The evidence that miR-206 is able to suppress BDNF synthesis in diverse tissues such as the cardiac muscles, the skeletal muscles, and the endothelial tissue elucidates a role for microRNAs in tissue-tissue communication, although their actions might be locally regulated [30,43,45,48,61,92,102,115,120,139,142,169,171,177,191]. Some microRNAs are released from cells by membrane-derived vesicles, lipoproteins, and other ribonucleoprotein complexes and travel through the blood stream reaching recipient cells in distant tissues [192], providing communication between disparate cell types and diverse biological mechanisms and homeostatic pathways.…”

“…miR-584, miR-744, miR-26a-1, and miR-26a-2 subtypes [24,28,58,60,72,75,78,88,93,94,96,102,112,125,126,128,132,133,137,190]. The evidence that miR-206 is able to suppress BDNF synthesis in diverse tissues such as the cardiac muscles, the skeletal muscles, and the endothelial tissue elucidates a role for microRNAs in tissuetissue communication, although their actions might be locally regulated [30,43,45,48,61,92,102,115,120,139,142,169,171,177,191]. MicroRNAs play crucial roles in immunoinflammatory reactions.…”

The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation

“…For example, findings from animal research indicate that miR-206-3p regulates BDNF expression through a conserved binding site in its 3 ′ -UTR [160]. Notably, a study demonstrated that electroacupuncture alleviated neuropathic pain induced by chronic constriction injury by increasing miR-206-3p expression and inhibiting BDNF overexpression [161]. However, administration of the miR-206-3p inhibitor partially impaired the analgesic effect of electroacupuncture and the level of BDNF was elevated as well.…”