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

Meng Xue,Cheng Huang,Guo-Gang Xing,Yang-Yang Xia,Ya-Lan Sun,Zhi-Hua Huang

doi:10.3390/ijms21186524

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/TrκB 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/TrκB 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 TrκB 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 TrκB 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/TrκB signaling pathway-mediated central sensitization in SNI rats. Therefore, targeting BDNF/TrκB cascade in the spinal cord may be a potential mechanism of EA against neuropathic pain.

Highlights

Neuropathic pain is a type of chronic pain syndrome induced by peripheral or central nervous system injuries, lesions, and dysfunction [1]
Compared with the spared nerve injury (SNI) group, after 2 Hz EA stimulation was given to SNI rats, The paw withdrawal threshold (PWT) of rats in the SNI+EA group was significantly increased (p < 0.01, p < 0.001), while the PWT of rats in the SNI + Mock EA group has no significant difference compared with the SNI group
In order to further examine the effect of exogenous brain-derived neurotrophic factor (BDNF) in the inhibitory effect of 2 Hz EA on SNI-evoked mechanical hypersensitivity, intrathecally injected 100 ng BDNF or PBS on SNI rats starting from day 12 of 2 Hz EA treatment

Summary

Introduction

Neuropathic pain is a type of chronic pain syndrome induced by peripheral or central nervous system injuries, lesions, and dysfunction [1]. Central sensitization is identified to be an important factor in the pathogenesis of neuropathic pain [14,15], which promotes the excitability of nociceptive signaling cascade in pain-related neurons [15] It is clear the effects of spinal BDNF on the C-fiber responses of dorsal horn wide dynamic range (WDR) neurons, which are closely associated with nociceptive transmission and central sensitization [16,17]. Administration of BDNF produced hyperexcitability of spinal dorsal horn WDR neurons as determined by detecting C-fiber-evoked discharges, the increased BDNF in the spinal cord leads to the development of hyperexcitability of dorsal horn WDR neurons as well as pain hypersensitivity after spinal nerve injury [9] Overall, these data suggested that BDNF/TrκB signaling cascade-mediated central sensitization plays a critical role in neuropathic pain development

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