A critical role for miR‑135a‑5p‑mediated regulation of SLC24A2 in neuropathic pain

Zhou,Xiao‑Gang; He,Hui; Wang,Pei‑Ji

doi:10.3892/mmr.2020.11262

A critical role for miR‑135a‑5p‑mediated regulation of SLC24A2 in neuropathic pain

Authors:
- Xiao‑Gang Zhou
- Hui He
- Pei‑Ji Wang
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Affiliations: Department of Hand and Foot Surgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China, Department of Nursing, Health Higher Vocational and Technical School of Nantong, Nantong, Jiangsu 226010, P.R. China
Published online on: June 22, 2020 https://doi.org/10.3892/mmr.2020.11262
Pages: 2115-2122

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Abstract

Neuropathic pain (NP) is a refractory and long‑lasting disease caused mostly by peripheral nerve injury. Currently, the mechanism of NP is yet to be elucidated. Intracellular calcium homeostasis is critical for some physiological functions, including the occurrence of NP. NCKX2, encoded by the solute carrier family 4 member 2 (SLC24A2) gene, is an important K+‑dependent Na+‑Ca2+ exchanger that mediates Ca2+ extrusion. The role of NCKX2 in the development of NP is unknown. For this purpose, a sciatic nerve chronic constriction injury (CCI) model was established and it was revealed that the expression levels of SLC24A2 and its encoded protein NCKX2 were both downregulated in the posterior horn of the spinal cord. Overexpression of SLC24A2 reduced both mechanical and thermal hyperalgesia and decreased the expression of inflammatory cytokines [interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α] in CCI rats. Using bioinformatics analyses, luciferase reporter assays, and a series of behavioral tests, it was demonstrated that the decrease in SLC24A2 after CCI treatment was directly regulated by increased microRNA (miR)‑135a‑5p in the spinal cord. Moreover, the effects of miR‑135a‑5p on NP were SLC24A2‑dependent. In conclusion, the present results highlighted the suppressive role of NCKX2 in NP, which is mainly regulated by miR‑135a‑5p and mediates the release of inflammatory cytokines in the dorsal horn of the spinal cord. These findings deepen our understanding of the development of NP and provide novel candidates for NP treatment.

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