Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p‐PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn

Abstract

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

Electroacupuncture alleviates diabetes-induced mechanical allodynia and downregulates bradykinin B1 receptor expression in spinal cord dorsal horn

“…Although there was slight reduction on day 21, the expression of p65 remained at a high level in comparison to control. Moreover, substance P and CGRP expression level in SCDH gradually enhanced from day 7 to day 21 and were higher than controls, which was similar with previous researches [33,34,37]. The elevated expression of p65, CGRP, and substance P may be one of the potential mechanisms contributing to the allodynia in DNP rats.…”

“…Nevertheless, the possible upstream and downstream pathway inducing the increased expression of p65, substance P, and CGRP in SCDH of DNP rats still need further researches to explore. Previous study has showed electroacupuncture could inhibit the activation of p65 and substance P and CGRP expression in neuropathic pain-affected rats’ SCDH [37,38] and our research attempts to verify these results. The study demonstrated that the p65, substance P, and CGRP expression of DNP rats was all impaired after receiving the electroacupuncture treatment, even the expression level of p65 was lower than controls, indicating our result was same with previous studies [37,38].…”

“…Previous study has showed electroacupuncture could inhibit the activation of p65 and substance P and CGRP expression in neuropathic pain-affected rats’ SCDH [37,38] and our research attempts to verify these results. The study demonstrated that the p65, substance P, and CGRP expression of DNP rats was all impaired after receiving the electroacupuncture treatment, even the expression level of p65 was lower than controls, indicating our result was same with previous studies [37,38]. Therefore, the decreased expression of p65, CGRP, and substance P in SCDH after DNP rats received the electroacupuncture intervention may be one of the potential reasons leading to the relief of DNP.…”

“…When nociceptive sensory fibers receive nociceptive signals, substance P and CGRP are released by the fibers, regulating the neuropathic pain [35,36]. Relative research has revealed that the expression of substance P and CGRP in SCDH and dorsal root ganglia of DNP rats increased [37]. Our study systematically explored the expression of p65, substance P, and CGRP in SCDH at different time points during the development of DNP and the alterations of expression level after the electroacupuncture intervention.…”

Electroacupuncture Induces Bilateral S1 and ACC Epigenetic Regulation of Genes in a Mouse Model of Neuropathic Pain

“…Mice assigned to the EA group were treated with 2/100 Hz EA at the bilateral Yanglingquan (GB34) acupoints located between the heads of the tibia and fibula ( Figure 1 A) for 15 min daily from day 7 to day 14 after TNI or sham surgery. This treatment period has been shown to induce a stable antinociceptive effect on neuropathic pain [ 27 , 28 , 29 ]. Constant current square-wave electrical stimulation generated by a HANS acupoint nerve stimulator (HANS-200A, Nanjing Jisheng Medical Technology Co., Ltd., Nanjing, China) was administered via two acupuncture needles.…”