title: Overexpression of miR-206 ameliorates chronic constriction injury-induced neuropathic pain in rats via the MEK/ERK pathway by targeting brain-derived neurotrophic factor.
abstract: Neuropathic pain is chronic pain caused by lesions or diseases of the somatosensory system and existing tolerance to currently available analgesics. MicroRNAs (miRNAs) have been widely studied in the development of neuropathic pain and neuro-inflammation resulting from nerve injury. However, the precise mechanism of miRNAs involved in neuropathic pain remains largely unknown. In the present study, we investigated the vital roles of miR-206 and its putative target gene, brain-derived neurotrophic factor (BDNF), in neuropathic pain in the rat model of chronic constriction injury (CCI). The levels of miR-206 were down-regulated in the dorsal root ganglion (DRG) of rats following CCI, while the expressions of BDNF mRNA and protein were up-regulated in vivo. MiR-206 mimics attenuated mechanical allodynia and thermal hyperalgesia in a time-dependent manner in CCI rats. The changes were most significant at 7days. And, the levels of TNF-α, IL-1β, and IL-6 were decreased by miR-206 mimics. A direct interaction between miR-206 and the 3'-UTR of BDNF was verified by a dual-luciferase reporter assay. MiR-206 mimics inhibited the expression levels of BDNF mRNA and protein. Moreover, miR-206 mimics suppressed the activation of the MEK/ERK pathway in the DRG of CCI rats. Overexpression of BDNF abrogated the effects of miR-206 inhibition on neuropathic pain, neuro-inflammation and the MEK/ERK pathway. Treatment with U0126, an ERK inhibitor, exerted the same effect as treatment with miR-206 mimics. These results demonstrate that miR-206 alleviates neuropathic pain development via targeting of BDNF, and negatively mediates the MEK/ERK pathway, suggesting that miR-206 may act as a potential target for the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesia, Cangzhou Central Hospital, CangZhou, 061000, Hebei, China; Department of Anesthesia, Cangzhou Central Hospital, NO. 16 Xinhuaxi Road, Yunhe District, Cangzhou, 061000, Hebei, China. Electronic address: wenbosunss@163.com.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Anesthesia, Cangzhou Central Hospital, CangZhou, 061000, Hebei, China; Department of Anesthesia, Cangzhou Central Hospital, NO. 16 Xinhuaxi Road, Yunhe District, Cangzhou, 061000, Hebei, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, Cangzhou Central Hospital, CangZhou, 061000, Hebei, China; Department of Anesthesia, Cangzhou Central Hospital, NO. 16 Xinhuaxi Road, Yunhe District, Cangzhou, 061000, Hebei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D059350:Chronic Pain / Q000235:genetics* / Q000378:metabolism; D003250:Constriction; D006930:Hyperalgesia / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009437:Neuralgia / Q000235:genetics* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D015850:Interleukin-6; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; C522220:mirn206 microRNA, rat
keywords: BDNF; MEK/ERK; MiR-206; Neuro-inflammation; Neuropathic pain