Abstract
Objective: Long non-coding RNAs (lncRNAs) exert a critical function in mediating neuropathic pain (NP). MEG3, a novel lncRNA, contributes to astrocyte activation and inflammation. However, its role in NP remains unclear.Methods: The chronic constriction injury (CCI) method was employed to construct an NP rat model. Astrocyte activation was induced by lipopolysaccharide (LPS). The profiles of MEG3, microRNA (miR)-130a-5p, CXC motif chemokine receptor 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4), and the Rac1/NF-κB pathway in CCI rats’ spinal cord tissues and astrocytes were monitored by reverse transcription-quantitative PCR (RT-qPCR) and western blot (WB). Pain scores of CCI rats were assessed. Enzyme-linked immunosorbent assay (ELISA) was adopted to monitor neuroinflammation alteration. The glial fibrillary acidic protein (GFAP)-labeled astrocytes were tested by immunohistochemistry (IHC). Bioinformatics, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were utilized to verify the molecular mechanism between MEG3 and miR-130a-3p.Results: MEG3, CXCL12 and CXCR4 were overexpressed and miR-130a-5p was knocked down in CCI rats and LPS-induced astrocytes. Up-regulating MEG3 aggravated NP, enhanced inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and interleukin-6 (IL-6) expression and release in CCI rats and LPS-induced astrocytes. Up-regulating miR-130-5p repressed LPS-induced inflammation in astrocytes. AS verified by the dual-luciferase reporter assay and RIP assay, MEG3 sponged miR-130a-5p as a competitive endogenous RNA (ceRNA). What’s more, miR-130a-5p up-regulation weakened the MEG3-induced proinflammatory effects on LPS-induced astrocytes.Conclusions: MEG3 aggravates NP and astrocyte activation via the miR-130a-5p/CXCL12/CXCR4 axis, which is a potential therapeutic target for NP.
Highlights
Neuropathic pain (NP) is a chronic secondary pain resulting from illness or injury to the nervous system, affecting up to 8% of the population [1]
To probe the function of MEG3 and miR-130a-5p in NP, we gauged the expression of MEG3, miR-130a-5p and CXCL12/CXC motif chemokine receptor 4 (CXCR4) and its downstream Rac1 and NF-κB in L4-L6 dorsal spinal cord tissues of constriction injury (CCI) rats and astrocytes following CCI (0, 1, 3, 5, 7, and 14 days) and LPS induction (6 hours, 12 hours, 1 day, 3 days, 7 days, 14 days), using reverse transcription-quantitative PCR (RT-qPCR) and western blot (WB)
By contrast with the sham group, the MEG3 expression in CCI rats and astrocytes significantly increased (Figure 1A, 1B; P
Summary
Neuropathic pain (NP) is a chronic secondary pain resulting from illness or injury to the nervous system, affecting up to 8% of the population [1]. NP is commonly caused by diabetes, reactivation of herpes zoster, nerve compression or radiculopathy, alcohol consumption, chemotherapy or certain drug abuse, and trigeminal neuralgia [2]. It is characterized by an abnormal hypersensitivity to stimuli (hyperalgesia) and a nociceptive response to non-harmful stimuli (abnormal pain) [3]. Neuroinflammation is closely related to NP, and inflammation-induced microglial activation and astrocytes contribute to NP evolvement [4]. In some www.aging-us.com cases, medication alone cannot control chronic pain. It is of great significance to find new treatments for NP
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