JMJD6 exerts function in neuropathic pain by regulating NF‑κB following peripheral nerve injury in rats

Wen,Cen; Xu,Mengyuan; Mo,Cheng; Cheng,Zhigang; Guo,Qulian; Zhu,Xiaoyan

doi:10.3892/ijmm.2018.3613

JMJD6 exerts function in neuropathic pain by regulating NF‑κB following peripheral nerve injury in rats

Authors:
- Cen Wen
- Mengyuan Xu
- Cheng Mo
- Zhigang Cheng
- Qulian Guo
- Xiaoyan Zhu
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Affiliations: Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
Published online on: April 3, 2018 https://doi.org/10.3892/ijmm.2018.3613
Pages: 633-642

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Abstract

Treatment of neuropathic pain (NPP) continues to be a major challenge, and the underlying mechanisms remain to be elucidated. Previous studies have demonstrated that histone methylation is important in synaptic plasticity of the nervous system and may affect nuclear factor‑κB (NF‑κB) signaling through epigenetic mechanisms. The present study aimed to investigate the role of Jumonji C domain 6 (JMJD6), a histone demethylase, in a chronic constriction injury (CCI) model of NPP. On the third day post‑CCI surgery, a JMJD6 overexpressing lentiviral vector (LV‑JMJD6) was intrathecally injected in the rats. Mechanical withdrawal threshold and thermal withdrawal latency were assessed prior surgery and on days 3, 7, 10 and 14 post‑CCI. The results showed that intrathecal injection with the LV‑JMJD6 attenuated CCI‑induced pain facilitation. The expression of JMJD6 was lower following CCI surgery, and its expression was significantly increased following intrathecal injection with LV‑JMJD6, compared with levels in normal saline (NS)‑ and negative control lentiviral vector (NC)‑treated rats. The expression of spinal NF‑κB phosphorylated (p‑)p65 subunit and its downstream pain‑associated effectors, including interleukin 1β (IL‑1β), tumor necrosis factor‑α (TNF‑α) and vascular endothelial growth factor (VEGF), were increased following CCI surgery. Intrathecal injection with LV‑JMJD6 suppressed activation of the p‑p65 subunit in CCI rats. In addition, expression levels of its downstream effectors IL‑1β, TNF‑α and VEGF were attenuated by intrathecal treatment with LV‑JMJD6, compared with those in the NS‑ and NC‑treated CCI rats. Furthermore, the JMJD6‑ and p65‑immunoreactive cells overlapped in the spinal dorsal horn, however, co‑immunoprecipitation showed that JMJD6 and the NF‑κB p65 subunit did not directly interact, indicating other functional connections may exist between these factors following CCI surgery. Collectively, these findings indicated an important mechanism underlying the pathogenesis of NPP. JMJD6 may exert its therapeutic function in NPP by regulating NF‑κB following CCI.

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