miR-129-5p Alleviates Neuropathic Pain Through Regulating HMGB1 Expression in CCI Rat Models
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miR-129-5p Alleviates Neuropathic Pain Through Regulating HMGB1 Expression in CCI Rat Models Jun Tian 1 & Tieying Song 2
&
Wenli Wang 3 & Hong Wang 2 & Zaiwang Zhang 4
Received: 18 June 2019 / Accepted: 27 August 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Recently, microRNAs are reported to be participated in the development of pain and persistence of neuropathic and inflammatory pain in animal models. Here, we characterized the functional role of miR-129-5p in pain processing in chronic constriction injury (CCI) rat models. Bilateral CCI operation was used to generate neuropathic pain rat model. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to assess pain-related behaviors. Gene expression was evaluated using qRT-PCR, luciferase assay, western blotting, and enzyme-linked immunosorbent assay. Compared with the control rats, expression level of miR-129-5p was downregulated significantly over time in CCI rats post operation. Interestingly, downregulation of miR-129-5p in CCI rats was correlated with increased proinflammatory cytokine expression and pain-related behaviors. Furthermore, we found that miR-129-5p alleviated neuropathic pain through downregulating high mobility group protein B1 (HMGB1) expression in CCI rats as overexpression of miR-129-5p suppressed expression of both HMGB1 and proinflammatory cytokine and alleviated pain sensation in CCI rats. In summary, our results show that alteration in miR-129-5p expression contributes to pain processing in our CCI pain rat model, suggesting miR-129-5p could be a causal factor in neuropathic pain and serve as a promising potential biomarker and therapeutic target for neuropathic pain. Keywords miR-129-5p . Neuropathic pain . HMGB1 . Cytokines . CCI rat models
Introduction Chronic neuropathic pain is a devastating condition with few effective therapeutic treatments (Attal 2000). Its prevalence in the general population was reported to be as high as 30% (Bouhassira et al. 2008). Generally, patients with chronic neuropathic pain suffer from poor life quality and have higher prevalence of depression and anxiety disorder than the general population (McCarberg and Billington 2006). Many medical causes can lead to chronic neuropathic pain including surgery, trauma, toxicity, aging-related medical conditions, and
* Tieying Song [email protected] 1
Department of Neurosurgery, the First Hospital of Shijiazhuang, Shijiazhuang, China
2
Department of Anesthesiology, the First Hospital of Shijiazhuang, No.36 Fanxi Road, Chang’an District, Shijiazhuang 050000, China
3
Department of Gynaecology, Maternal and Child Health Care Hospital of Shijiazhuang, Shijiazhuang, China
4
Department of Anesthesiology, the Bethune International Peace Hospital of P.L.A, Shijiazhuang, China
congenital disorders, all of which can evolve chronic inflammation in the central and peripheral nervous system (Blom et al. 2014; Colloca et al. 2017; Colvin and Dougherty 2015; Doyen et al. 2017). A characteristic feature of chro
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