miR-506-3p relieves neuropathic pain following brachial plexus avulsion via mitigating microglial activation through targeting the CCL2-CCR2 axis.

Neuroinflammation results in neuropathic pain following brachial plexus avulsion (BPA). This research was designed for investigating the function of miR-506-3p in BPA-induced neuropathic pain (NP). A total brachial plexus root avulsion (tBPRA) model was produced in adult rats as well as IL-1β-treated motoneuron-like NSC-34 cells and the LPS-treated microglia cell line BV2 for in vivo and in vitro experiments, respectively. RT-PCR and western blot were performed to detect the profiles of miR-506-3p, CCL2 and CCR2, NF-κB, FOXO3a, TNF-α, IL-1β, and IL-6 in cells or the spinal cord close to the tBPI lesion. Neuronal apoptosis was evaluated by immunohistochemistry (IHC) in vivo. CCK8, TUNEL staining, and the LDH kit were adopted for the evaluation of neuronal viability or damage in vitro. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assays analyzed the targeted association between miR-506-3p and CCL2. As shown by the data, miR-506-3p was vigorously less expressed, while CCL2-CCR2, NF-κB TNF-α, IL-1β, and IL-6 were up-regulated in the spinal cord with tBPI. Overexpression of miR-506-3p attenuated neuronal apoptosis and microglial inflammation. Mechanistically, CCL2 was a downstream target of miR-506-3p. Up-regulating miR-506-3p dampened CCL2-CCR2 and NF-κB activation in the spinal cord and microglia. miR-506-3p had neuroprotective and inflammation-fighting functions in the tBPI rat model via CCL2/CCR2/NF-κB axis.