Proteomics Analysis of the Spinal Dorsal Horn in Diabetic Painful Neuropathy Rats With Electroacupuncture Treatment

Abstract

BackgroundClinical evidence demonstrates that electro-acupuncture (EA) of the Zu sanli (ST36) and Shen shu (BL23) acupoints is effective in relieving diabetic painful neuropathy (DPN); however, the underlying molecular mechanism requires further investigation, including the protein molecules associated with EA’s effects on DPN.MethodsSprague-Dawley adult male rats (n =36) were randomly assigned into control, DPN, and EA groups (n=12 each). After four weeks of EA treatment, response to mechanical pain and fasting blood glucose were analyzed. A tandem mass tag (TMT) labeling approach coupled with liquid chromatography with tandem mass spectrometry was used to identify potential biomarkers in the spinal dorsal horn. Further, proteomics analysis was used to quantify differentially expressed proteins (DEPs), and gene ontology, KEGG pathways, cluster, and string protein network interaction analyses conducted to explore the main protein targets of EA.ResultsCompared with the DPN model group, the mechanical pain threshold was significantly increased, while the fasting blood glucose levels were clearly decreased in EA group rats. Proteomics analysis was used to quantify 5393 proteins, and DEPs were chosen for further analyses, based on a threshold of 1.2-fold difference in expression level (P < 0.05) compared with control groups. Relative to the control group, 169 down-regulated and 474 up-regulated proteins were identified in the DPN group, while 107 and 328 proteins were up- and down-regulated in the EA treatment group compared with the DPN group. Bioinformatics analysis suggested that levels of proteins involved in oxidative stress injury regulation were dramatically altered during the EA effects on DPN.ConclusionsOur results provide the valuable protein biomarkers, which facilitates unique mechanistic insights into the DPN pathogenesis and EA analgesic, antioxidant stress and hypoglycemic effect.

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

“…Te analgesic efect of 2 Hz EA has also been demonstrated in other pain models [54,55]. Numerous studies have shown that EA intervention on ST36 and BL60 in rats can alleviate diferent types of neuropathic pain [56][57][58]. Te preliminary study of our research group showed that the intervention of EA of ST36 and BL60 can efectively alleviate diabetic neuropathic pain [59,60].…”

Acupuntura como tratamento adjuvante da neuropatia diabética: revisão de literatura sistemática

“…Atualmente 20% dos pacientes desenvolvem a DNP apresentando hiperalgesia, dor espontânea e alodinia. Com isso os especialistas perceberam que vários pacientes tinham danos na medula espinhal e passaram a utilizar animais para fazer experiências com a eletroacupuntura no corno dorsal desses animais para analisar os efeitos no tratamento da dor e na melhora da qualidade de vida desses indivíduos (Yu, et al, 2021).…”

“…Os ratos foram divididos em 3 grupos para serem avaliados: controle, DNP e EA, e para realizar os experimentos esses animais do grupo DNP e EA foram induzidos por uma injeção intraperitoneal de STZ (estreptozotocina), antibiótico que destroem as células do pâncreas causando a diabetes. No grupo da EA, os animais são presos num suporte de madeira por 14 dias após a aplicação da STZ e submetidos a eletroacupuntura em dois pontos com a estimulação de 10Hz mantida 30 minutos uma vez por dia por 4 semanas (Yu, et al, 2021).…”

“…Essa terapia chinesa inibe a fosforilação oxidativa e a produção de ROS, ou seja, quando o receptor de ATP neuronal P2X7 é ativado, eleva a produção de ROS, e que reduz a produção de ATP, reduzindo a sensibilidade no corno dorsal espinhal e justamente a terapia da eletroacupuntura inibindo a fosforilação oxidativa. No geral esse foi mais um estudo que justifica os potenciais se biomarcadores aspirantes ao tratamento da neuropatia periférica diabética (Yu, et al, 2021).…”

Differential Proteomic Analysis of the Hippocampus in Rats with Neuropathic Pain to Investigate the Use of Electroacupuncture in Relieving Mechanical Allodynia and Cognitive Decline

“…All methods of proteomic detection and analysis were according to our team's previous research as follows [ 21 ].…”