Expression Profiling of L5-S2 Spinal Cord Dorsal Horn in a Rat Model of Chronic Pelvic Pain Syndrome Uncovers Potential Mechanism of Electroacupuncture Mediated Inflammation and Pain Responses

Abstract

Chang Xu,1 Kai Cheng,1 Xiao-Ling Wu,1 Heng Yap Tai,1 Ye-Mao Chai,1 Zhi-Wen Yang,1 Qian-Hui Sun,1 Xing-Hua Qiu,1 Xing-Yue Yang,1 Na Li,1 Yan Tan,2 Shao-Ming Liu,3 Wei Chen4 1College of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Na Li, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, People’s Republic of China, Tel [phone], Email [email protected]: We aim to explore expression profiles of genes in SCDH of CPPS model rat relevant to pain and inflammation by RNA-Seq and to investigate the mechanism of anti-inflammatory and analgesic of EA.Methods: Thirty-six SD male rats were randomly divided into three groups (n = 12): sham operation, model, and EA. The rat CPPS model was established by injecting CFA into the ventral lobes of the prostate. The rats in EA group were treated at Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) for a total of 20 times, with a frequency of 2/100Hz. Mechanical allodynia, H&E staining and ELISA were used to detect the changes of pain threshold and tissue inflammation; RNA-Seq technique was used for profiling gene changes in SCDH and qRT-PCR was used for further validation.Results: Persistent mechanical allodynia and severe tissue inflammatory reaction both occurred in CPPS rats. After EA therapy, the pain sensitivity and inflammatory response of CPPS rats decreased significantly. RNA-Seq identified that a total of 46 DEGs were significantly up-regulated and 65 DEGs down-regulated after EA. GO enrichment showed that EA was mainly reflected in the regulation of the immune system by participating in the regulation of leukocyte, neutrophil cellular processes and cytokine metabolism. KEGG enrichment demonstrated that signal transduction and immune system were the most significant pathways. We further identified that the expressions of Pik3r2, Akt1, and Casp9 were significantly up-regulated and Jak2 and Stat3 down-regulated in the PI3K-AKT/JAK-STAT signal pathway.Conclusion: Our study revealed that immune and inflammatory responses are the main biological events that induce chronic pelvic pain in rats, and EA can exert anti-inflammatory and analgesic effects by regulating the expression of related genes on PI3K-AKT/JAK-STAT signal pathway in SCDH. This study provided putative novel targets of EA, which may have anti-inflammatory and analgesic effects of CPPS.Keywords: electroacupuncture therapy, chronic pelvic pain, anti-inflammatory and analgesia, RNA-seq technique, cytokine, spinal cord dorsal horn

Keywords

• electroacupuncture therapy
• chronic pelvic pain
• anti-inflammatory and analgesia
• rna-seq technique
• cytokine
• spinal cord dorsal horn