BDNF Participates in Chronic Constriction Injury-Induced Neuropathic Pain via Transcriptionally Activating P2X 7 in Primary Sensory Neurons

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 P2X 7 promoter activity was enhanced by CCI-induced increase of DRG BDNF protein and was involved in the CCI-induced upregulation of DRG P2X 7 protein. The overexpression of BDNF also increased P2X 7 expression in DRG neurons, which was validated in in vivo and in vitro experiments. BDNF may exert crucial effect via transcriptionally activating the P2X 7 gene in primary sensory neurons, since P2X 7 acts as a role of endogenous agitator in neuropathic pain and BDNF largely co-expresses with P2X 7 in DRG neurons. Therefore, our data provide evidence that BDNF may be a promising therapeutic target for neuropathic pain.