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

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.

The Therapeutic Potential of Acupuncture in Chronic Prostatitis/Chronic Pelvic Pain Syndrome

“…In addition, the above-mentioned role of the spinal cord pathway in analgesia was further confirmed. Xu et al 67 found that EA could exert anti-inflammatory and analgesic effects by regulating the expression of related genes in the PI3K-AKT/JAK-STAT signaling pathway in the spinal cord dorsal horn, and they believe that this study provides a putative new target of EA, which may have the anti-inflammatory and analgesic effects of CPPS. Capsaicin transmits information about noxious stimuli to the sensory neurons of the central nervous system through selective activation, triggering a burning sensation.…”

Research Trends of Acupuncture Therapy on Chronic Pelvic Pain Syndrome from 2000 to 2022: A Bibliometric Analysis

“…The mechanism of electro-needle treatment of CPPS has attracted much attention. Through rats experiments, 65 Xu C believes that immune and inflammation reactions are the main biological events that induce chronic pelvic pain in rats. The expression of related genes on PI3K-AKT/JAK-STAT signal pathway to play an anti-inflammatory and analgesic effect.…”

Effect of electroacupuncture on cyclic adenosine monophosphate-protein kinase A-vanillic acid receptor subtype 1 of the transient receptor potential/PLK-protein kinase C-vanillic acid receptor subtype 1 of the transient receptor potential pathway based on RNA-seq analysis in prostate tissue in rats with chronic prostatitis/chronic pelvic pain syndrome

“…Combined with medication, it can significantly improve the clinical efficacy of the medication, including improving various symptoms and indicators in CP/CPPS patients ( Liang et al, 2021 ). Our previous studies ( Wu et al, 2022 ; Xu et al, 2022 ) also assessed the effects of EA on the behavioral pain profile of CP/CPPS rats. The result showed that EA was effective in reducing mechanical and thermal pain in CP/CPPS rats; it also revealed a decrease in serum substance P (SP) and prostaglandin E2 (PGE2) and a decrease in cyclooxygenase-2 (COX-2) and PGE2 in prostate tissue, suggesting that the analgesic mechanism of EA in CP/CPPS rats may be related to the modulation of the body’s inflammatory response.…”