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BDNF Participates in Chronic Constriction Injury-Induced Neuropathic Pain via Transcriptionally Activating P2X7 in Primary Sensory Neurons

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Abstract

Neuropathic pain, resulting from the pathological changes of the somatosensory nervous system, remains a severe public health problem worldwide. The effect of treatment targeting neuropathic pain is very limited, as the underlying mechanism of neuropathic pain is largely unknown. In this study, we demonstrated that the expression level of brain-derived neurotrophic factor (BDNF) was remarkably and time-dependently increased in dorsal root ganglion (DRG) neurons. DRG microinjection of BDNF siRNA in DRG ameliorated chronic constriction injury (CCI) induced mechanical, thermal, and cold nociceptive hypersensitivities. Overexpressing BDNF through microinjection of the AAV5-BDNF in DRG caused enhanced responses to basal mechanical, thermal, and cold stimuli in mice exposed to CCI. Mechanically, the P2X7 promoter activity was enhanced by CCI-induced increase of DRG BDNF protein and was involved in the CCI-induced upregulation of DRG P2X7 protein. The overexpression of BDNF also increased P2X7 expression in DRG neurons, which was validated in in vivo and in vitro experiments. BDNF may exert crucial effect via transcriptionally activating the P2X7 gene in primary sensory neurons, since P2X7 acts as a role of endogenous agitator in neuropathic pain and BDNF largely co-expresses with P2X7 in DRG neurons. Therefore, our data provide evidence that BDNF may be a promising therapeutic target for neuropathic pain.

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Data will be made available on reasonable request.

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Funding

This work was supported by the Natural Science Foundation of Guangdong Province, China (No.2016A030313251, No.2018A0303130272); and the Science and Technology Planning Project of Guangzhou, China (No. 201707010207).

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Author notes

  1. Yi Wu, Zhiwen Shen, and Hui Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Yi Wu, Zhiwen Shen, Hui Xu, Kun Zhang, Mingyan Guo, Fei Wang & Junhua Li

  2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Yi Wu, Zhiwen Shen, Hui Xu, Kun Zhang, Mingyan Guo, Fei Wang & Junhua Li

  3. Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China

    Junhua Li

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  1. Yi Wu
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Contributions

Yi Wu, Zhiwen Shen, and Hui Xu: investigation, methodology, writing-original draft preparation. Kun Zhang: visualization, software. Mingyan Guo: conceptualization, data curation. Fei Wang and Junhua Li: writing-reviewing and editing.

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Correspondence to Fei Wang or Junhua Li.

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Wu, Y., Shen, Z., Xu, H. et al. BDNF Participates in Chronic Constriction Injury-Induced Neuropathic Pain via Transcriptionally Activating P2X7 in Primary Sensory Neurons. Mol Neurobiol 58, 4226–4236 (2021). https://doi.org/10.1007/s12035-021-02410-0

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  • DOI: https://doi.org/10.1007/s12035-021-02410-0

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