Electroacupuncture Modulates Spinal BDNF/TrκB 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/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.

Electroacupuncture-Induced Muscular Inflammatory Pain Relief Was Associated With Activation of Low-Threshold Mechanoreceptor Neurons and Inhibition of Wide Dynamic Range Neurons in Spinal Dorsal Horn

“…It was demonstrated that noxious and non-noxious stimuli elicited a progressive increase of WDR neurons response along with the increasing of stimulation intensity. The present study demonstrated that the analgesic effect of EA-Ta may be involved in the inhibition of WDR neurons in the spinal dorsal horn, which is consistent with previous reports ( Yu et al, 2019 ; Wang et al, 2020 ; Xue et al, 2020 ).…”

Electroacupuncture Alleviates Neuropathic Pain through Regulating miR-206-3p Targeting BDNF after CCI

“…During the process of acupuncture-induced analgesia, signals are transferred from acupoints to the CNS, resulting in the spinal cord and brain to release neurotransmitters and neuromodulators (such as opioids, serotonin, and norepinephrine) to suppress pain [ 4 , 35 ]. Some studies revealed that EA can ameliorate neuropathic pain by inhibiting the activation of microglia and upregulating of BDNF expression in the CCI model [ 9 , 36 ], which is similar to the results of this study. Moreover, BDNF participates in the formation of spinal cord central sensitization by mediating LTP [ 33 ] and is related to synaptic remodelling [ 13 , 15 ].…”

Putting Cells in Motion: Advantages of Endogenous Boosting of BDNF Production

“…Consistently, a decrease in BDNF levels has been reported in neurodegenerative disorders, such as AD [ 69 , 71 ], Huntington’s disease (HD) [ 72 ], and epilepsy [ 73 ], and recent strategies aimed at sustaining or even amplifying the production of BDNF have been proved to be beneficial in patients with HD [ 74 ], AD [ 75 , 76 ], Parkinson’s disease (PD) [ 77 , 78 ], amyotrophic lateral sclerosis (ALS) [ 79 , 80 , 81 ], stroke [ 82 , 83 , 84 ], and spinal cord injury [ 85 , 86 , 87 , 88 ]. However, it is worth mentioning that despite the extensive literature dating back to the early 1990s, in which reduced BDNF levels in the brain have been associated with neurodegenerative diseases, only in patients with HD has a genetic defect in BDNF gene been mechanistically related to the pathology [ 89 ].…”