<p>Electroacupuncture treatment upregulates α7nAChR and inhibits JAK2/STAT3 in dorsal root ganglion of rat with spared nerve injury</p>

Abstract

Background Neuropathic pain with complicated mechanism severely disrupts patient quality of life. The novel approaches and more effective management should be further investigated. It was reported that alpha-7 nicotinic acetylcholine receptor (α7nAChR) and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling in dorsal root ganglion (DRG) contributed to the pathogenesis of neuropathic pain. Our previous study has shown that electroacupuncture (EA) alleviated neuropathic pain via activating α7nAChR in the spinal cord. However, whether the effect of 2 Hz EA on spared nerve injury (SNI)-induced neuropathic pain is mediated through modulation of α7nAChR and JAK2/STAT3 pathway in the DRG remains unclear. Materials and methods The SNI-induced neuropathic pain rat model was used in this study. After application of 2 Hz EA treatment to SNI rats on day 3, 7, 14 and 21 post-surgery, the expression levels of α7nAChR, JAK2/STAT3 and some cytokines in DRG were determined by qRT-PCR and Western blot analysis. Results We found that SNI induced significant down-regulation of α7nAChR mRNA and protein expression. SNI also obviously elicited the decrease in anti-inflammatory cytokine IL-10 protein expression. The enhancement of p-JAK2, p-STAT3, pro-inflammatory cytokines IL-1β and IL-6 protein levels induced by SNI were also observed. However, 2 Hz EA treatment to SNI rats distinctly improved α7nAChR and IL-10 levels and reduced p-JAK2, p-STAT3, IL-1β and IL-6 expression in the DRG. Conclusion Our present study suggested that 2 Hz EA treatment indeed activated α7nAChR, suppressed JAK2/STAT3 signaling and re-balanced the relationship between pro-inflammatory and anti-inflammatory cytokines in DRG of SNI rat, which provided insight into our understanding of the mechanism for 2 Hz EA to attenuate neuropathic pain.

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

“…Therefore, we presently selected 2 Hz EA treatment of SNI-induced neuropathic pain rats with once every other day to avoid the tolerance to EA stimulation. This is consistent with the previous studies [ 28 , 29 ], in this research, following 2 Hz EA stimulation of the acupoints of Zusanli and Sanyinjiao in SNI rats, the PWT is significantly increased, indicating that 2 Hz EA indeed alleviated SNI-induced mechanical hypersensitivity. Additionally, with the extension of 2 Hz EA treatment, the analgesic effect was gradually improved, suggesting that 2 Hz EA stimulation has a cumulative relieving effect on SNI rats.…”

“…In other studies, it was also found that 2 Hz EA caused LTD formation in the spinal cord of SNL rats [ 27 ]. Subsequently, the neurotrophic factors, inflammatory factors, neuroplasticity, and related signal pathways in rat DRG treated with EA are significantly regulated in neuropathic pain [ 28 , 38 , 39 ]. The analgesic effect induced by EA treatment is mainly dependent on EA stimulation-frequencies and -intervals.…”

“…After rats were adapted to the surrounding for 5 days, the rat model of spared nerve injury (SNI) was established according to the method described in previous study [ 28 ]. Briefly, rats were anesthetized with isoflurane (C002170901, YiPin Pharmaceutical, Shijiazhuang, Hebei, China) at a concentration of 2–3%.…”

“…After rats were anesthetized with 2–3% isoflurane, the implantation of intrathecal cannula to rats were performed as described previously study [ 28 ]. Briefly, a PE-10 polyethylene catheter (BB31695-PE/1, American Health & Medical Supply International Corp, New York, NY, USA) was implanted between the L5 and L6 vertebrae to the lumber enlargement level (3.5–4 cm rostral than the cannula) of the spinal cord.…”

“…Stimulation with 2 Hz EA alleviates SNL-induced neuropathic pain by promoting the occurrence of long-term depression (LTD) in the spinal dorsal horn [ 27 ]. Our previous studies have demonstrated that 2 Hz EA successfully ameliorated mechanical hypersensitivity through blockade of microglial activation and pro-inflammatory cytokine IL-1β production in the spinal cord of SNI rats [ 23 , 28 , 29 ], but the underlying mechanisms remain largely unknown. Based on the fact that neuroinflammatory response is regarded as a crucial role in the pathogenesis of neuropathic pain, including the alterations of pain-related signaling molecules [ 30 , 31 ], BDNF is known to be an endogenous neuromodulator in the nociceptive pathway and exerts a critical action via its interactions with TrκB receptor [ 8 ], and the BDNF/TrκB signaling pathway plays an important role in central sensitization and neuropathic pain development.…”