Basic Research And Clinical Assessment Of Modified Penile Dorsal Nerve Neurectomy In The Treatment Of Primary Premature Ejaculation

Background and objectives:It is generally accepted that premature ejaculation (PE) is a more common problem than erectile dysfunction. Several surveys demonstrated that approximately 50% adults have suffered from PE. Other researches also revealed very high prevalence of PE with the highest being 70%. It is similarly poorly understood and inadequately treated. The cause for PE is largely unknown. In only a small percentage of patients with PE can an organic cause be found (such as multiple sclerosis). Penile hypersensitivity and reflex hyper-excitability have been investigated in different studies by the penile Bio-Thesiometer or genital somato- sensory. They demonstrated that penile hypersensitivity and reflex hyper-excitability cause the PE happened. Although there are several definitions, there has not been one that has been universally accepted. Conventionally, PE is assessed in terms of latency of ejaculation in male and frequency of orgasm in female. If a man is unable to delay ejaculation until his partner sexually satisfied in at least 50% of their sexual encounters is considered PE too. It is usually defined as intravaginal latency of less than 2 minutes. The American Urology Association (AUA) recommended that PE should be identified as ejaculation before expectation, before or after intercourse, as well as the resulting partner or couple distress. Previous studies of PE mainly depended on subjective self-assessment, which may lead to underestimate of prevalence. The differences of PE's prevalence maybe due to different diagnosticcriteria used in different investigations.Intravaginal ejaculatory latency time (IELT) is defined as the time between vaginal intromission and ejaculation. In 2008, International Society for Sexual Medicine (ISSM) for the Definition of Premature Ejaculation determined that 1 min was an appropriate cutoff point to diagnose premature ejaculation, as 90% of men complaining of primary premature ejaculation ejaculated within 1 min after penetration as compared with a median of 5.4 min in men not suffering from premature ejaculation. Stopwatch measure or estimated IELT correlate reasonably well, providing support for the use of self-estimation of IELT for the diagnosis of premature ejaculation in clinical practice.The dorsal nerve of the penis, a sensory branch of the pudendal nerve, carries impulses from sensory receptors and free nerve endings located in the glans, the penile skin and the scrotum to the upper sacral and lower lumbar segment of the spinal cord. This nerve has been reported to be the major contributor to the sensory input necessary for ejaculation, as its bilateral transsection prevents ejaculation. Ejaculation is mostly under sympathetic control, mainly throughα1-receptor activation. The pudendal nerve innervates all the striated muscles that play a role in the expulsive phase of ejaculation.The patients with PE are increasing in recent years, and about 1/3 of married men have different degrees of premature ejaculation now. Although there is no doubt that daily drug therapies (Such SSRIs, clomipramine) are highly effective in the treatment of PE, the accompanying nuisance side effects (such as sleepiness, yawning, dry mouth, nausea, headaches and dizziness). These annoying problems may lead to treatment discontinuations. So drug therapies is limited by its side effects. Behavioural techniques is likely to be more effective in the long-term treatment. But it very difficult to perseverance.Premature ejaculation is divided into primary premature ejaculation and secondary premature ejaculation. Primary premature ejaculation:intravaginal ejaculation latency time is short since the the first time. Surgical treatment of primary premature ejaculation(modified dorsal penile neurectomy) have been carried out in our country for many years, but many Urology and Andrology doctors worry about postoperative complications, especially erectile dysfunction, so the surgery was not carried out widely.Objective:1. Identify the quantity of dorsal nerve of penis of health adult and primary premature ejaculation, and compare them. If the quantity of dorsal nerve of penis of primary premature ejaculation is more than health adult obviously, the quantity of dorsal nerve of penis is maybe important etiological factor to premature ejaculation.2. Identify the relationship between dorsal penile nerve and penis erection.3. Identify dorsal penile nerve loss will not affect the cell of cavernous body of penis and will not lead to erectile dysfunction.4. Eliminate the worry of Urology and Andrology doctors of the dorsal penile nerve cut too much maybe led to erectile dysfunction, and profit dorsal penile neurectomy carry out extensively.The research was divided into four parts. Part one:topographic anatomy study of dorsal nerve of penis. Part two:establishment of animal model with absence of rabbit penile dorsal nerve and observation of penis erectile function after surgery. Part three:apoptosis in rabbits corpus cavernous penis after neruotomy of bilateral dorsal nerve of penis and/or cavernous nerve. Part four:surgical method and complications of primary premature ejaculation.Part one topographic anatomy study of dorsal nerve of penis1. ObjectiveTo investigate the number, course and distribution of normal dorsal penile nerves. The research have important clinical value for selective neurectomy of the dorsal penile nerve to the treatment of primary premature ejaculation (PPE). It is guide to dorsal penile neurectomy for primary premature ejaculation (PPE) patients. 2. Material and methods1) The study comprised 47 adult male autopsy specimens. In order to displayed clearly, we educe and cut superficial fascia, deep fascia of back, expose dorsal nerve of penis and blood vessel between deep fascia and albuginea. Educe dorsal nerve of penis, deep dorsal vein of penis and dorsal artery of penis carefully. We observe and count them, with specific attention on the course, distribution and quantity of the dorsal nerve of penis.2) Following the cavernous nerve of the neurovascular bundle, we give penile cavernous nerve detailed anatomical observation and measurement.The penile cavernous nerve were performed on 3 adult formalin preserved cadavers with operative microscope SXP1B. The genital tissue and penile cavernous nerves were explored with HE staining and nitric oxide synthase immunohistochemistry staining. The sections were then observed under microscope. The purpose is to know the relationship between them cavernous nerve and dorsal nerve of penis.2. Results1) Summary of dorsal nerve of penis quantity are as follows:7 branches 1 corpse; 6 branches 2 corpse; 5 branches 7 corpse; 4 branches 9 corpse; 3 branches 18 corpse; 2 branches 10 corpse. Most of them are parallel each other. Only a small quantity of autopsy specimens have communicating branches to connect adjacent branches. The lateral portions of the penile shaft were innervated by branches arcading from the dorsal midline radiating toward the ventral surface. In a few specimens, some branches continue their pathway over the ventral portions of penis. During its pathway, fine nerve fibers course into the corpus spongiosum and corpus cavernosum. We also observed that fine nerve fibers course into coronary sulcus to glans. Most specimens have one dorsal nerve of penis go along with deep dorsal vein of penis.2) 2 The penile cavernous nerve of the neurovascular bundle pierced the inferior genitourinary diaphragm at the postero lateral border of the urethral external sphincter. The cavernous nerve traveled under the penile dorsal nerve and blood vessels after piercing the genitourinary diaphragm. One branch of the cavernous nerve joined the dorsal nerve, and the other 2～3 branches of the cavernous nerve entered into the crural body of the penile corporal body. The positive staining for nitricoxide synthase nerve fibers had been noted in the distal part of the dorsal nerve. The positive staining for nitric oxide synthase nerve fibers was noted in the distal part of the dorsal nerve and penile cavernous nerve.3. Conclusions1) Average quantity of dorsal nerve of penis is 3.49±1.23 in 47 autopsy specimens.2) There is one branch of the cavernous nerve joined the dorsal nerve.Part two:establishment of animal model with absence of rabbit penile dorsal nerve and observation of penis erectile function after surgery1. ObjectiveTo clear whether the total penile dorsal nerves removal will lead to erectile dysfunction or not.2. Material and methods1) removal of all 20 male rabbits penile dorsal nerves.2) observed if these rabbits still be able to penile erection and mate after 1 month.3) Confirming the tissue of excised is nerves by staining immunohistochemistry.3. Results2 rabbits died 1 week after operation, and the remainings all have penile erection, and can carry out mating.4. ConclusionsIt will not lead to erectile dysfunction if dorsal penile nerves cut too much.Part three:apoptosis in rabbits corpus cavernous penis after neruotomy of bilateral dorsal nerve of penis and/or cavernous nerve1. Objective To observe the apoptosis in penile corpus cavernous after neurotomy.For sure even all the dorsal penile nerves transection will not induces apoptosis in smooth muscle cells of the rabbits penis. It indicated even even all the dorsal penile nerves transection will not lead to erectile dysfunction indirectly. The purpose of this reseach is to discuss the feasibility of modified dorsal penile neurectomy to primary premature ejaculation (PPE) by animal experiment.2. Material and methods25 male rabbits were randomly assigned to experimental and normal control groups, and every group have 5 rabbits. The quantity of cavernous apoptosis cells was measured by TUNEL2 days after neurotomy.3. ResultsAfter transaction, the apoptosis in experimental in A showed a statistically significant difference(P<0.001) to B group and A+B group; however there was no statistically significant difference after bilateral dorsal nerve transaction (A) to control C (P=0.054)and D (P=0.233). A+B showed a statistically significant difference to C group and D group(P<0.001); B showed a statistically significant difference to C group and D group(P<0.001).4. ConclusionsCavernous nerve transection induces apoptosis in smooth muscle cells of the rabbits penis, but nor does dorsal nerve transaction alone. There is no statistically significant difference in apoptosis between cavernous nerve injury alone and combination injuries of cavernous nerve and dorsal nerve.Part four:Surgical method and complications of primary premature ejaculation1. ObjectiveTo intrduce the Operation indication,extensional surgical methods and surgical attention of primary premature ejaculation (PPE) detailedly. And share the operation experience with others.2. Material and methods1) Total of 338 PPE patients who come from Guangzhou, Yueqing, Harbin three tertiary hospitals in September 2007 to February 2011, were analyzed retrospectively. The efficacy and postoperative complications were given objective assessment.123 patiens is above 2 years follow up time. IELT, patiens sexual life satisfaction score and spouse sexual life satisfaction score of these patiens is given statistics analysis.2) curative effect standardImprovement:2min< IELTpostop≤5min; obvious effect:IELTpostop> 5min; inefficacy:IELTpostop≤2min. Patiens sexual life satisfaction score (IIEF no. 6,7,80～15score) and spouse sexual life satisfaction score (IIEF no.10,13,14 0-15score) were recorded and compared. At the same time the complications incidence rate (such as anejaculation and erectile dysfunction) were observed.3. Results1) Dorsal nerve of penis quantity of 123 above 2 years follow up patiens:4 branches 5 cases; 5 branches 9 cases; 6 branches 16 cases; 7 branches 26 cases; 8 branches 26 cases; 9branches 25 cases; 10 branches 9 cases; 11 branches 4 cases; 12 branches 3 cases. Average 7.69±1.77.2) The follow up time of 123 cases is over 2 years of all 338 cases. Most of these 123 cases IELT have different degree extension.Among them:obvious effect 57cases; improvement 48cases; inefficacy 18 cases, obvious effective rate is 46.30%; total effective rate is 85.4%. Ejaculation latency did not change after surgery 18cases, penile numbness 2 cases, erectile dysfunction 1 case, penile hematoma 1 case, wound infection 2 cases.3) Statistics analysis The IELT of preoperative and postoperative showed statistically significant difference (t=19.630, P<0.001); Sexual life satisfaction score of preoperative and postoperative showed statistically significant difference (t=39.527, P<0.001); spouse sexual life satisfaction score of preoperative and postoperative showed statistically significant difference (t=38.738, P<0.001).4. ConclusionsModified dorsal penile neurectomy is safe and effective to PPE patients. Conclusions of full text1) Dorsal nerve of penis lies between penis deep fascia of back and albuginea. the number of dorsal penile nerves in patients with primary premature ejaculation (PPE) is not consistent with the average number (2 branches), but 3.49±1.23. All the three specimens which we anatomized have a fine nerve fibers connect with dorsal nerve of penis. Topographic anatomy study of dorsal nerve of penis is the theory foundation of modified dorsal penile neurectomy.2) It will not lead to erectile dysfunction or ejaculatory dysfunction if dorsal penile nerve cut too much to rabbits, and the rabbits can copulation and ejaculation normally. It indirect indicateing that It will not lead to man erectile dysfunction if all dorsal penile nerve resected. Eliminate the worry of urinary surgery and andriatry doctors that dorsal penile nerve cut too much may lead to erectile dysfunction.3) Cavernous nerve transection induces apoptosis in smooth muscle cells of the rabbits penis, but nor does dorsal nerve transaction alone. It means dorsal nerve have no relationship with cavernous cells. It indirect indicateing that It will not lead to man erectile dysfunction if dorsal penile nerve resected.4) Animal experiment indicate dorsal nerve ectomy is safe and will not lead to erectile dysfunction, and the at same time it will not lead to anejaculation.By this theory,338 PPE patients were given modified dorsal penile neurectomy. We summarize operation indication, complication,surgical methods and surgical attention of primary premature ejaculation detailedly. Modified dorsal penile neurectomy is effective and safe to primary premature ejaculation.