TRPV1, Targeted by miR-338-3p, Induces Neuropathic Pain by Interacting with NECAB2

Abstract

A variety of studies have proposed that transient receptor potential vanilloid 1 (TRPV1) is involved in the progression of multiple diseases, including neuropathic pain. Although increased expression of TRPV1 in chronic constriction injury was described earlier, the underlying regulatory mechanisms of TRPV1 in neuropathic pain remain largely unknown. In our study, we constructed a chronic constriction injury (CCI) rat model to deeply analyze the mechanisms underlying TRPV1. RT-qPCR-indicated TRPV1 mRNA and protein expression were extremely upregulated in CCI rat dorsal spinal cord tissues. Then, TRPV1 was corroborated to interact with N-terminal EF-hand Ca2+-binding protein 2 (NECAB2). The mRNA and protein levels of NECAB2 were increased in CCI tissues. Moreover, TRPV1 and NECAB2 together regulated nociceptive procession-associated protein metabotropic glutamate receptor 5 (mGluR5), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and Ca2+ in isolated microglia of CCI rats. Moreover, TRPV1 upregulation apparently increased mechanical allodynia and thermal hyperalgesia as well as the expression of inflammation-associated genes (COX-2, TNF-α, and IL-6). In addition, downregulation of NECAB2 significantly decreased mechanical allodynia and thermal hyperalgesia as well as the expression of COX-2, TNF-α, and IL-6. Furthermore, TRPV1 was confirmed to be a downstream target of miR-338-3p. TRPV1 overexpression abolished the inhibitory effect by miR-338-3p elevation on neuropathic pain development. In summary, this study proved TRPV1, targeted by miR-338-3p, induced neuropathic pain by interacting with NECAB2, which provides a potential therapeutic target for neuropathic pain treatment.

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Acknowledgments

We appreciate the support of Taizhou Hospital, Wenzhou Medical University, Zhejiang Province.

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Correspondence to Mingcang Wang.

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The Institutional Animal Care and Use Committee of Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University (Zhejiang, China), approved the protocols for our study.

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The authors declare that they have no competing interests.

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Ma, Y., Deng, Q., Li, S. et al. TRPV1, Targeted by miR-338-3p, Induces Neuropathic Pain by Interacting with NECAB2. J Mol Neurosci (2020). https://doi.org/10.1007/s12031-020-01626-4

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Keywords

  • TRPV1
  • NECAB2
  • miR-338-3p
  • Neuropathic pain