Carbon monoxide as potent modulator of pain- and anxiety-related behavior in experimental chronic pelvic pain syndrome

Chronic pelvic pain syndrome (CP/CPPS) is frequently accompanied by brain-related comorbidities including anxiety, but the mechanisms of this relationship are far from being elucidated. Having in mind that gaseous neurotransmitter CO signaling could be included in anxiogenesis, we hypothesized that some of the anxiety states in CPPS could be attributed to CO signaling. Therefore, this study aimed to investigate the effects of CORM-A1 (slow realizing CO donor) on anxiety-related behavior and pain sensitivity in rats with experimentally induced CP/CPPS. CP/CPPS was induced in male rats by 3% λ-carrageenan intraprostatic injection. CORM-A1 (2 mg/kg/day, i.p.) was administered for one week upon CP/CPPS induction. Corresponding controls received appropriate vehicles in congruent design (n=8 in each, total n=32). Mechanical pain thresholds in scrotal skin were measured by von Frey aesthesiometer (evF) before and during one week upon CP/CPPS induction. The battery of three ethological tests (open field (OF), elevated plus maze (EPM), and light/dark (L/D) test was used to assess anxiety-like behavior at the same time points as evF.Rats with developed CP/CPPS exhibited mechanical allodynia with increased anxiety-like behavior revealed in these rats by OF, EMP, and L/D tests. Postoperative CORM-A1 treatment of CP/CPPS led to a reversion of anxiety-like behavior in comparison to the control rats. Also, CORM-A1 in rats with prostatitis demonstrated an analgetic effect by increased scrotal pain threshold in comparison to the controls.Carbon monoxide postoperative treatment led to amelioration of anxiety-related and pain-related behavior in rats with experimental CP/CPPS.Funded by FA4Lin (MNTR and TUBITAK).