Carbon Monoxide in an Experimental Model of Chronic Pelvic Pain Syndrome: The Effects of CORM-A1 on Pain and Anxiety-Related Behaviors.

Nikola Šutulović, Neriman Ezgin, Nela Puškaš, Emilija Đurić, Željko Grubač, Daniel Škrijelj, Milena Vesković, Dušan Mladenović, Isidora Savić, Djuro Macut, Yavuz Dodurga, Aleksandra Rašić-Marković, Olivera Stanojlović, Dragan Hrnčić
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Abstract

Current standard treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a urological disorder with anxiety as a major comorbidity, are limited in success rates. Recent findings revealed the anti-inflammatory and neuroprotective effects of CO-releasing molecules (CO-RMs), but there is a gap in the knowledge on its effects in CP/CPPS. Therefore, the objective of our study was to investigate the potential therapeutic effects of CORM-A1 on the scrotal pain threshold and anxiety-related behaviors in experimental model of CP/CPPS. Adult Wistar albino male rats were randomized to Sham (intraprostatic saline) or CP/CPPS (intraprostatic λ-carrageenan) groups (n = 12). Half received CORM-A1 (2 mg/kg/day, i.p., days 1-7), others PBS, forming four subgroups (n = 6). The pain threshold (by an electronic von Frey esthesiometer) and anxiety-like behavior (by an open field, elevated plus maze and light/dark test) were assessed; prostates were histologically examined. Carrageenan-induced CP/CPPS caused significant mechanical pain hypersensitivity (p < 0.001), anxiety-like behaviors (p < 0.001-0.05), and histological prostate damage when compared to corresponding Sham groups. CORM-A1 treatment increased pain thresholds (p < 0.001) and improved behavioral outcomes (p < 0.001-0.01) in all ethological tests. These findings indicate that CORM-A1 exerts analgesic and anxiolytic effects in an experimental model of CP/CPPS in rats.

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慢性骨盆疼痛综合征实验模型中的一氧化碳:CORM-A1对疼痛和焦虑相关行为的影响
慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)是一种以焦虑为主要共病的泌尿系统疾病,目前的标准治疗成功率有限。最近的研究发现CO-RMs具有抗炎和神经保护作用,但其在CP/CPPS中的作用尚不清楚。因此,我们的研究目的是探讨CORM-A1对CP/CPPS实验模型阴囊痛阈和焦虑相关行为的潜在治疗作用。成年Wistar白化雄性大鼠随机分为Sham(前列腺内生理盐水)组和CP/CPPS(前列腺内λ-卡拉胶)组(n = 12)。一半给予CORM-A1 (2 mg/kg/天,1-7天,1次),另一半给予PBS,共4个亚组(n = 6)。评估疼痛阈值(通过电子von Frey感测器)和焦虑样行为(通过开阔场地、高架加迷宫和光/暗测试);对前列腺进行组织学检查。与Sham组相比,卡拉胶诱导的CP/CPPS引起明显的机械性疼痛超敏反应(p < 0.001)、焦虑样行为(p < 0.001-0.05)和组织学前列腺损伤。在所有行为学测试中,CORM-A1治疗增加了疼痛阈值(p < 0.001)并改善了行为结果(p < 0.001-0.01)。这些结果表明,CORM-A1在CP/CPPS大鼠实验模型中具有镇痛和抗焦虑作用。
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