Work

Downregulation of lncRNA HOTTIP alleviates neuropathic pain and inflammation in chronic constriction injury rats by targeting miR-216a-5p

Year: 2025

Type: article

Abstract: Background: Neuropathic pain (NP) is a complex and intractable chronic pain condition. This study aims to clarify the functional role of lncRNA HOTTIP in NP. Methods: A chronic constriction injury (CCI) surgery was used to establish a NP rat model. Lipopolysaccharide (LPS) stimulation was employed to activate BV2 cells. Intrathecal administration of HOTTIP-targeting lentiviral vectors and antagomiR-216a-5p was performed to lower HOTTIP and miR-216a-5p expression. RT-qPCR analyzed HOTTIP, miR-216a-5p, and inflammatory markers (cyclooxygenase-2 [COX-2], inducible nitric oxide synthase [INOS], toll-like receptor 4 [TLR4]) in rat dorsal root ganglion and BV2 cells to evaluate their roles in NP, while also tracking pain behavior changes in CCI rats to correlate molecular targets with pain perception. ELISA measured anti-inflammatory (interleukin [IL]-4) and pro-inflammatory (IL-6, tumor necrosis factor [TNF]-α) factor levels to quantify inflammation and evaluate inflammatory response severity. A specific binding relationship between HOTTIP and miR-216a-5p was evaluated using bioinformatics prediction, dual-luciferase reporter assays, and RNA pull-down techniques. Results: In a rat model of CCI, inhibition of HOTTIP attenuated NP, decreased pro-inflammatory mediators (TNF-α, IL-6, COX-2, INOS, TLR4), and increased IL-4. In LPS-induced BV2 cells, inhibition of HOTTIP also exhibited antiinflammatory effects. HOTTIP targeted binding to miR-216a-5p. Inhibition of miR-216a-5p significantly counteracted the inhibitory effects of silencing HOTTIP on NP and neuroinflammatory responses. In addition, Janus kinase 2 (JAK2) was found to be a direct target of miR-216a-5p. Conclusions: HOTTIP contributes to the worsening of NP and neuroinflammation by modulating the miR-216a-5p/JAK2 pathway, exerting analgesic protective effects, indicating its potential as a therapeutic target for NP.

Source: The Korean journal of pain

DOI: 10.3344/kjp.25241

Authors: Gen Zan, Riluge Wu, Yasula Ba, Gerile Sude, Runa A, Lengge Si

Institution: Inner Mongolia Medical University

Language: English

Topic: Pain Mechanisms and Treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Inner Mongolia Medical University, Natural Science Foundation of Inner Mongolia