Regeneration of Nitric Oxide Synthase-Containing Nerves After Cavernous Nerve Neurotomy in the Rat

Abstract

In patients who recover erectile function after radical prostatectomy (with preservation of at least 1 neurovascular bundle), a recovery time of 6 to 18 months is not uncommon. As this is also the usual time required for regeneration of spinal nerves, we believe that regeneration of cavernous nerves, partially damaged inadvertently, may be responsible. In a rat model, we examined the long-term effect of unilateral and bilateral cavernous nerve transection on the nonadrenergic/noncholinergic (NANC) nervous system and erectile function. In 31 rats, nitric oxide synthase (NOS), the enzyme that catalyzes nitric oxide production, was identified in penile nerve fibers from a mid-shaft segment with nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and antibody to neuronal NOS. Animals were divided into three groups: 5 rats underwent pelvic exploration without transection of cavernous nerves (sham group); 13 rats underwent unilateral neurotomy of a 5-mm. segment of the cavernous nerve; and 13 rats underwent bilateral neurotomy. After bilateral ablation, the NOS-positive nerve fibers were significantly decreased at 3 weeks and remained so at 6 months; no erectile response could be elicited by pelvic nerve stimulation. After unilateral ablation, the NOS-positive nerve fibers were similarly decreased on the side of the neurotomy at 3 weeks, but by 6 months the number had increased significantly and approximated the level on the contralateral side. Furthermore, electrostimulation of the intact side induced a greater intracavernous pressure response at 6 months than at 3 weeks (N.B. the rat has an incomplete septum). Fibers positive for NOS were also identified in the dorsal nerve. The staining pattern diminished as rapidly and significantly on the side of neurotomy as in tissue from the corpus cavernosum. However, regeneration was not seen. To our knowledge, this is the first demonstration of regeneration of NOS-containing nerves after cavernous nerve neurotomy. Our findings support the reports by others that unilateral nerve-sparing is sufficient to preserve erectile function.

Preservation of penile length after radical prostatectomy: early intervention with a vacuum erection device

“…Initiating intervention early in the postoperative period may be critical, as neural injury has been shown to result in immediate cellular changes, [8][9][10] which may contribute to future failure of penile recovery even with neural pathway healing. We therefore began penile rehabilitation immediately after catheter removal, using an intervention that could easily be performed even if patients had urinary incontinence issues, did not require an extended period of time each day and had no systemic sequelae.…”

Efficacy of sildenafil in erectile dysfunction after radical prostatectomy

“…It may be that in all cases of RRP trauma to the autonomic cavernous nerves may result in transient but decreased nitric oxide signaling to cavernous smooth muscle which might be effectively augmented by a PDE V inhibitor. 8 …”

Impact of Total Mesorectal Excision on Bladder and Sexual Function in Rectal Cancer

“…In general there is a good response in 87% of patients, but the effect of such a drug is dependent on, at least partially, intact cavernous nerves to produce nitric oxide. Erectile function was satisfactorily improved by use of sildenafil (Viagra) only in 79% of male patients with ED after rectal excision for either rectal cancer or inflammatory bowel disease [35,36].…”