Sildenafil relieves pain and inflammation by promoting M2-type polarization of macrophages in rats with chronic pelvic pain
Objective:To investigate mechanism of phosphodiesterase 5(PDE5)inhibitor Sildenafil in treatment of pain and inflammation in chronic pelvic pain mediated by macrophage polarization.Methods:A total of 32 adult Wistar rats were divided into 4 groups:Sham group,Experimental autoimmune prostatitis(EAP)group,Sildenafil+EAP group,MET+Sildenafil+EAP group,with 8 rats in each group.EAP model was induced by subcutaneous injection of prostate antigen(PAg)and complete Fredrin adjuvant,Sham group was injected with equivalent normal saline.EAP rats were treated with Sildenafil.Metformin was injected on basis of Silde-nafil+EAP.HE staining was used to analyze pathological changes of prostate.Response rate of pelvic pain in rats was measured by von Frey fiber method.Serum cytokines IL-10 and TNF-α levels were determined by ELISA.Numbers of iNOS+and CD16/32+macrophages and CD206+and CD10+macrophages in serum were detected by flow cytometry.Results:Compared with Sham group,EAP group showed obvious focal or multifocal inflammation in ventral prostate gland tissues,pelvic pain response rate,serum inflammatory factor TNF-α level,and number of M1-type polarization characteristic iNOS+and CD16/32+cells in EAP group were significantly increased(all P<0.05),while M2-type polarization characteristics of macrophages,IL-10 level and number of CD206+and CD10+macrophages were significantly decreased(all P<0.05).Compared with EAP group,pelvic pain response rate,TNF-α level,iNOS+and CD16/32+cell number in Sildenafil+EAP group were significantly decreased(all P<0.05),while IL-10 level and CD206+and CD10+macrophage number were significantly increased(all P<0.05).Compared with Sildenafil+EAP group,pelvic pain response rate,TNF-α level,iNOS+and CD16/32+cells in MET+Sildenafil+EAP group were significantly increased(all P<0.05),while IL-10 level and number of CD206+and CD10+macrophages were significantly decreased(all P<0.05).Conclusion:Sildenafil,a PDE5 inhibitor,blocks chronic pelvic pain and inflammation by promoting polarization of M2 macrophages.
Phosphodiesterase 5 inhibitorSildenafilM2-type polarization of macrophagesChronic pelvic painInflammation
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