Influence of Experimental Autoimmune Prostatitis on Sexual Function and the Anti-inflammatory Efficacy of Celecoxib in a Rat Model

Abstract

Experimental autoimmune prostatitis (EAP) is a well-established model induced by an autoimmune response to prostate antigen. The symptomatic, pathological, and immunological characteristics of EAP animals are highly consistent with human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which makes EAP an ideal model for this disease. Here, we investigate the influence of EAP on male rat sexual function and the efficacy of anti-inflammatory therapy with celecoxib. EAP rat models were established using male Wistar rats. Rats were randomly assigned to a normal control group, an EAP model group, or an EAP model with celecoxib treatment group (celecoxib group). Behavioral changes, sexual behavioral changes, and erectile function were estimated using an open-field test, a sucrose consumption test, mating experiments, and by intracavernous pressure/mean arterial pressure ratio (ICP/MAP). Histological changes in the prostate were observed by HE staining, and the serum inflammatory factors IL-1β and TNF-α levels were measured by enzyme-linked immunosorbent assay. In addition, serotonin (5-hydroxytryptamine, 5-HT), 5-HT 1A receptor, 5-HT 2C receptor, and serotonin transporter (SERT) expression levels in the hippocampus and spinal cord (T13-L1, L5-S2) were examined by immunohistochemistry and western blot analysis. Results showed that EAP rats exhibited characteristics of depression, decreased sexual drive, premature ejaculation, and increased threshold of penile erection. Moreover, all these changes were effectively alleviated by celecoxib. Significant increases in prostatic interstitial infiltration by inflammatory cells and in serum IL-1β and TNF-α levels were observed in EAP rats, and these were partially reduced by celecoxib. Additionally, the expression pattern of serotonin system regulators in the hippocampus and spinal cord were altered in EAP model rats, including a decrease in 5-HT levels and an increase in 5-HT 1A receptor levels. In conclusion, autoimmune prostatitis impaired rat sexual function, and this was effectively prevented by anti-inflammatory therapy with celecoxib. Moreover, a serotonin system disorder in the central nervous system was likely mediated via inflammation in EAP rats.

Targeting Ferroptosis Attenuates Inflammation, Fibrosis, and Mast Cell Activation in Chronic Prostatitis

“…Since autoimmunity is the potential etiology of CP/CPPS, the EAP model is considered a preferable animal model to explore the pathological mechanisms and molecular biological characteristics of CP/CPPS and is widely applied to discover novel therapeutical strategies [8,14]. The EAP model was generally established by immunization of various autoantigens, including PEs, male accessory gland (MAG) extracts, prostatic steroid-binding protein (PSBP), and T2 peptide [15,16].…”

Autonomic Nervous System Dysfunction Is Related to Chronic Prostatitis/Chronic Pelvic Pain Syndrome

“…These originate in the inferior hypogastric nerve (pelvic nerve) and connect to the spinal cord [ 16 17 ]. The spinal cord segments controlling prostate sensation are T13-L1 and L5-S2 [ 18 ]. Prostatic sensation conveys information accompanied by sympathetic and parasympathetic nerves from sensory nerves and DRG to T13-L1, L5-S2, and spinal cords, whereby the distribution and density of sensory nerves on the surface of the prostate are different ( Fig.…”

“…On the other hand, the disorders of 5-hydroxytryptamine (5-HT) levels in the CNS also contribute to dysfunctional ejaculation. Chronic prostatitis interrupts the balance of 5-HT levels in brains, decreasing 5-HT levels and increasing 5-HT1A receptors expression in the hippocampus to mediate dysfunctional ejaculation [ 18 ]. However, there is no clear explanation of their pathogenesis.…”

“…Various alterations in the spinal cords of chronic prostatitis mediate prostatitis generation and development. These include expressions of CCL2 [ 51 53 ], TRPV1 channels [ 44 ], 5-HT 1A receptors [ 18 ], and acid-sensing ion channel 1a (ASIC1a) channels [ 65 ]. Up-regulation in the spinal cords of chronic prostatitis contributes to central activation and sensitization.…”

The ALFF Alterations of Spontaneous Pelvic Pain in the Patients of Chronic Prostatitis/Chronic Pelvic Pain Syndrome Evaluated by fMRI

“…CP/CPPS is a kind of chronic pain disease, so the patients of CP/CPPS also manifest various psychiatric and/or psychosocial symptoms [ 3 ]. Due to the chronic pain and prevalent symptoms caused by CP/CPPS, the life quality of these male patients could be significantly influenced [ 4 ].…”