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Abstract 24

Sensory Denervation and Histamine (H1) Receptor Blocking Prevent Prostatitis in Rats

I Keith, B Teunissen, T Moon

University of Wisconsin-Madison

We earlier reported that sensory nerve fiber density correlated with mast cell innervation and degranulation, and degree of inflammation, during development of spontaneous, chronic prostatitis (CP) in Wistar rats. We here examine whether chronic sensory-peptide depletion with capsaicin (CAP), or H1 receptor blocking, would prevent Estradiol (EST)-enhanced spontaneous CP. Virus free, 6-week-old, male Wistar rats were divided into groups of 8: (1)17 EST (.25 mg/kg/ day, im) in sesame oil (SO); (II) CAP (40 mg/kg ip at 6 w)+EST; (111) CAP+SO; (IV) Hyd roxyzi ne ( HYD , 1 . 2 5 mg/kg i m )+ EST ; (V) SO+HYD; (Vl) SO; and (Vu) Saline (SAL). Rats were treated during weeks 8-12 and killed at 16 weeks with pentobarbital. Prostates were aseptically excised for bacterial culture and histological indexing of mucosal inflammation, and sensory nerve density (fibers displaying calcitonin gene-related peptide-like immunoreactivity). EST increased prostatic inflammatory index (Iymphocytes, mast cells, plasma cells, macrophages) by 16 weeks (66% above SO, 122% above SAL), i.e., 4 weeks after last injection. Bacterial cultures revealed no significant infection, thus indicating nonbacterial CP. CAP and HYD prevented the inflammatory-cell increase, but the SO vehicle tended to increase inflammation above SAL control. Mucosal sensory nerve fibers were increased by EST (48% above SO and 79% above SAL) but remained at SAL control levels in CAP-treated rats with EST and SO. However, sensory- nerve density was unaffected by HYD. Moreover, HYD did not significantly alter spontaneous CP and associated sensory nerve density in Group V. Prostatic weights were reduced to half by EST, by 17% in SO rats, and were unaffected by CAP. We conclude that EST increases sensory nerve fiber density and nonbacterial inflammation in the rat prostate, which can be prevented by chronic depletion of sensory peptides.