Detrusor nerve radiofrequency ablation (DENERA): Experimental study of safety and efficacy in an ovine model

Purpose: The subtrigonal perivesical nerve plexus contains a large proportion of the bladder's innervation. A transurethral radiofrequency ablation approach has successfully denervated this region to alleviate overactive bladder symptoms, with some urothelial heat injury. We report a novel transvaginal RFA device (DENERA) and assess its feasibility and efficacy in denervating the perivesical nerve plexus of in vivo sheep. Methods: In 14 adult female in vivo sheep, pulsed radiofrequency energy was applied transvaginally for three cycles of 4 min, maintaining the tissue temperature at 45°C, with 30 s of rest between each cycle. The control group (n = 4) was sacrificed without ablation, and various groups were sacrificed 1 week (n = 3), 4 weeks (n = 4), and 12 weeks (n = 3) after ablation. The bladder subtrigones were harvested then analyzed with H&E, S100, and TH immunostaining to quantify their neural density and neural vacuolization. Results: The ablation procedure increased the neural vacuolization the most at 1 week and decreased the neural density the most at 4 weeks, with both variables displaying a significant change followed by a slight rebound towards baseline at 12 weeks. The H&E analysis showed that the needles penetrated deep into the subtrigonal detrusor muscle. The sheep recovered from the procedure with no complications or damage in the bladder wall or urothelium. Conclusions: This study shows that one DENERA treatment can cause subtrigonal denervation with some rebound afterwards and no complications. DENERA may become a promising OAB treatment option that can ablate the perivesical plexus without harming the urothelium.