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Electroacupuncture Modulates Spinal BDNF/Tr?B Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats.

ABSTRACT: Neuropathic pain is more complex and severely affects the quality of patients' life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/Tr?B signaling cascade in the spinal cord is involved in the inhibitory effect of 2 Hz EA on neuropathic pain in SNI rats. The paw withdrawal threshold (PWT) of rats was used to detect SNI-induced mechanical hypersensitivity. The expression of BDNF/Tr?B cascade in the spinal cord was evaluated by qRT-PCR and Western blot assay. The C-fiber-evoked discharges of wide dynamic range (WDR) neurons in spinal dorsal horn were applied to indicate the noxious response of WDR neurons. The results showed that 2 Hz EA significantly down-regulated the levels of BDNF and Tr?B mRNA and protein expression in the spinal cord of SNI rats, along with ameliorating mechanical hypersensitivity. In addition, intrathecal injection of 100 ng BDNF, not only inhibited the analgesic effect of 2 Hz EA on pain hypersensitivity, but also reversed the decrease of BDNF and Tr?B expression induced by 2 Hz EA. Moreover, 2 Hz EA obviously reduced the increase of C-fiber-evoked discharges of dorsal horn WDR neurons by SNI, but exogenous BDNF (100 ng) effectively reversed the inhibitory effect of 2 Hz EA on SNI rats, resulting in a remarkable improvement of excitability of dorsal horn WDR neurons in SNI rats. Taken together, these data suggested that 2 Hz EA alleviates mechanical hypersensitivity by blocking the spinal BDNF/Tr?B signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/Tr?B cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.

SUBMITTER: Xue M

PROVIDER: S-EPMC7555233 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Electroacupuncture Modulates Spinal BDNF/TrκB Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats.

Xue Meng M Sun Ya-Lan YL Xia Yang-Yang YY Huang Zhi-Hua ZH Huang Cheng C Xing Guo-Gang GG

International journal of molecular sciences 20200907 18

Neuropathic pain is more complex and severely affects the quality of patients' life. However, the therapeutic strategy for neuropathic pain in the clinic is still limited. Previously we have reported that electroacupuncture (EA) has an attenuating effect on neuropathic pain induced by spared nerve injury (SNI), but its potential mechanisms remain to be further elucidated. In this study, we designed to determine whether BDNF/TrκB signaling cascade in the spinal cord is involved in the inhibitory ...[more]

PMID: 32906633

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Project description:The electroacupuncture-induced analgesic effect has been used widely to alleviate diverse pains. However, significant individual variations in analgesic effect of EA for both experiments and clinics were reported. According to the sensitivity of the analgesic response to EA stimulation, the subjects could be categorized into high responders (HR) and low responders (LR). However, the molecular mechanism of individual variability in the analgesic response to acupuncture stimulation is still uncertain. This study aims to investigate the potential gene expression in spinal dorsal horn induced by 2Hz/100Hz electroacupuncture in HR and LR rats. Rats were given 2Hz or 100Hz electroacupuncture for 30 min and using cDNA microarrays to compare different gene expression in dorsal horn. Transcriptome profiling analysis found that some co-regulated genes related with electroacupuncture or 2Hz or 100Hz freqencies. These co-regulated genes were plasticity-related by GO analysis. We also found some special regulated genes in HR vs. LR in 2Hz/100Hz electroacupuncture stimulation. These results suggested that neurotransmitter system and cytokine different between HR with LR in 2Hz electroacupuncture. But in 100Hz electroacupunture, there were many different regulated genes related with ribosome between HR with LR, which needs more studies to research the function and may play an important role in HR vs. LR by 100Hz electroacupuncture. Keywords: Transcriptome analysis Rats were exposed to different frequencies (2Hz or 100Hz) electroacupuncture stimlation for 30 min and nociceptive testing and returned to home cages for 1 hours before sacrificed. According to the sensitivity of the analgesic response to 2Hz or 100Hz EA stimulation, the rats divided into four groups: 2Hz-HR group, 2Hz-LR group, 100Hz-HR group and 100Hz-LR group. Subsequently analyzed their dorsal horn transcript profile using cDNA microarrays, the rats were without receiving electroacupuncture as control. The tissue of dorsal horn (DH) of the fifth and sixth lumbar (L5 and L6) of four or five rats were selected for transcript analysis in each group. The five control rats were mixed and labeled with cy5, each rat of experiment groups was labeled with cy3.

Dataset Information

Electroacupuncture Modulates Spinal BDNF/Tr?B Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats.

Publications

Electroacupuncture Modulates Spinal BDNF/TrκB Signaling Pathway and Ameliorates the Sensitization of Dorsal Horn WDR Neurons in Spared Nerve Injury Rats.

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