The role of genital nerve afferents in the physiology of the sexual response and pelvic floor function

IntroductionOur understanding of genital and pelvic floor physiology is rapidly expanding. Penile erection is a neurovascular event controlled by spinal autonomic centers, the activity of which is dependent on input from supraspinal centers and the genitalia. Genital afferent stimulation excites spinal autonomic nuclei and supraspinal sexual centers of both genders.AimTo present a detailed understanding of the functional importance of genital afferent neuroanatomy and neurophysiology.MethodsEnglish-written articles of diverse disciplines from 1980 to 2010 that contained information on genital anatomy, pudendal/dorsal/perineal/cavernous nerves, vibratory stimulation, reflexogenic erection, peripheral/central nervous system-mediated erectile and micturition pathways, and sexual arousal in animals and humans were reviewed.Main Outcome MeasuresAnalysis of supporting evidence for the role of genital afferents in the physiology of erectile response and pelvic floor function.ResultsBasic science and clinical studies support the concept that pudendal nerve circuitry serves an essential purpose for sexual behavior, erectile function, penile rigidity, ejaculation, and micturition. Males and females share a comparable pattern of genital afferent neuroanatomy and neurophysiology, and sexual and micturition reflexes are similar in both genders. Pudendal nerve branches communicate with the cavernous nerves and are nitric oxide synthase positive. Genital afferents activate multiple spinal reflexes that modulate erection and micturition. Genital sensory information is transmitted to supraspinal centers important for sexual function.ConclusionsThere is expanding support for the critical role of genital afferent neurophysiology in the mechanisms of erectile function and micturition. Genital afferent stimulation is a safe and natural modality that can be harnessed to amplify autonomic and somatic activity within the penis, female genitalia, spinal cord, and higher centers via established neurological principles. Such physiological adaptive processes may be beneficial in improving sexual response, erectile function, and micturition in many disease states, including in men after radical pelvic surgery. Well-designed and -executed studies in each specific population are needed to authenticate such prospects. Tajkarimi K and Burnett AL. The role of genital nerve afferents in the physiology of the sexual response and pelvic floor function.     

Intraoperative Cavernous Nerve Stimulation and Laser-Doppler Flowmetry during Radical Prostatectomy

IntroductionErectile dysfunction is a common side effect following radical prostatectomy mainly due to damage of the pelvic autonomic nerve fibers (cavernous nerves). Intraoperative electrical stimulation of the cavernous nerves while measuring changes in penile girth has previously been shown to provide the surgeon with feedback of nerve integrity.AimTo test the feasibility of recording changes in glans penis blood flow by Laser Doppler flowmetry from cavernous nerve stimulation.MethodsFifteen patients with localized prostate cancer undergoing radical prostatectomy had electrical stimulation of the proximal and distal parts of the neurovascular bundles after prostate removal. The stimulation consisted of 30–40 seconds biphasic constant current (10–30 mA) with 0.5 millisecond pulse duration.Main Outcome MeasuresStimulus induced changes in penile blood flow was recorded from a Laser Doppler probe attached to the glans penis. Changes in penile girth were simultaneously recorded from a mercury-in rubber strain gauge. Erectile function was evaluated three months after surgery.ResultsTen patients had stimulus induced increase in Laser Doppler flow unilaterally (N = 7) or bilaterally (N = 3). Out of 10 patients, 6 reported some preserved erectile function postoperatively at 3 months follow-up (indicating 6 true and 4 false positives). Three patients had no Doppler response from stimulation and had no postoperative erectile function postoperatively (indicating three true negatives). Two patients were excluded from the study due to bad signal quality in the Laser Doppler signal. In the majority of patients, stimulation produced increase in penile girth sensed by the strain gauge.ConclusionThis preliminary report provides evidence that Laser Doppler Flowmetry is able to detect increased penile blood flow from intraoperative electrical stimulation of the neurovascular bundles. However, further improvement in the recording technique is required. Laser Doppler Flowmetry may also be feasible to confirm autonomic nerve sparing in women undergoing pelvic surgery. Axelson HW, Johansson E, and Bill-Axelson A. Intraoperative cavernous nerve stimulation and Laser-Doppler flowmetry during radical prostatectomy. J Sex Med 2013;10:2842–2848     

Neural supply to the clitoris: immunohistochemical study with three-dimensional reconstruction of cavernous nerve, spongious nerve, and dorsal clitoris nerve in human fetus

IntroductionLittle detailed information is available concerning autonomic and somatic nerve supply to the clitoris, potentially causing difficulties for nerve preservation during pelvic and perineal surgery.AimTo identify the location and type (nitrergic, adrenergic, cholinergic and sensory) of nerve fibers in the clitoris and to provide a three‐dimensional (3D) representation of their structural relationship in the human female fetus.MethodsSerial transverse sections were obtained from five human female fetuses (18–31 weeks of gestation) and subjected to histological and immunohistochemical investigations; digitized serial sections were used to construct a 3D representation of the pelvis.Main Outcome MeasuresPelvic‐perineal nerve location and type were evaluated qualitatively.ResultsThe female neurovascular bundle (NVB) is the anteroinferior terminal portion of the inferior hypogastric plexus that runs along the postero‐lateral then lateral face of the vagina and is rich in nNOS‐positive fibers. The cavernous nerve (CN) is a thin ventrocaudal collateral projection of the NVB, and this projection does not strictly follow the NVB course. The CN runs along the lateral surface of the vagina and urethra and penetrates the homolateral clitoral crus. The CN provides adrenergic, cholinergic, and nitrergic innervation to the clitoris, but not sensory innervation. The spongious nerve (SN) is the terminal and main projection of the NVB and provides nitrergic innervation to the vestibular bulbs. The dorsal clitoris nerve (DCN), somatic branche of the pudendal nerve, runs along the superior surface of the clitoral crus and body and has a segmental proerectile nitrergic activity related to communicating branches with the CN.Conclusions“Computer‐assisted anatomic dissection” allowed the identification of the precise location and distribution of the autonomic and somatic neural supply to female erectile bodies, providing an anatomical basis for nerve‐sparing surgical techniques, and participating to the understanding of neurogenic female sexual dysfunction. Moszkowicz D, Alsaid B, Bessede T, Zaitouna M, Penna C, Benoit G, and Peschaud F. Neural supply to the clitoris: Immunohistochemical study with 3D reconstruction of cavernous nerve, spongious nerve and dorsal clitoris nerve in human fetus.     

Standard Operating Procedures for Neurophysiologic Assessment of Male Sexual Dysfunction

IntroductionCan neurophysiological testing in male patients with sexual dysfunction benefit the decision‐making process? The answer remains unclear.AimTo provide standard operating procedures for the neurophysiologic assessment of male sexual dysfunction.MethodsMedical literature was reviewed and combined with expert opinion of the authors.ResultsBulbocavernosus reflex latency time, pudendal somatosensory evoked potentials, and sympathetic skin responses have been considered as potential candidates for the diagnosis and assessment of erectile dysfunction (ED). Currently, there is no consensus on a standardized methodology for these neurophysiological investigations in the overall assessment of ED. These procedures are unable to assess the integrity of the efferent parasympathetic proerectile penile innervation; accordingly, none of these assessment procedures is recommended for ED patients. Corpus cavernosum electromyography (CC‐EMG) can detect abnormalities in cavernous smooth muscle although these alterations can be attributed both to damage to autonomic penile innervation and to degenerative processes of the cavernous smooth muscle. CC‐EMG is still considered experimental. Evidence does not support that men with premature ejaculation (PE) are consistently characterized by penile hypersensitivity; accordingly, penile threshold determination is not recommended to in the diagnosis of PE. Neurophysiological investigation of other components of the penile sensory pathways in PE patients has not provided any definitive contribution to the diagnosis.ConclusionNo neurophysiological assessment procedures yield additional information that consistently aids in the assessment of PE and ED.     

Excessive Penile Norepinephrine Level Underlies Impaired Erectile Function in Adenosine A1 Receptor Deficient Mice

IntroductionPenile erection is a complex neurovascular physiological event controlled by multiple factors and signaling pathways. A considerable amount of evidence indicates that adenosine plays a significant role in cavernosal smooth muscle relaxation. However, the specific role of adenosine and its receptors in erectile physiology and pathology is not fully understood.AimTo determine the role of the adenosine A₁ receptor (ADORA1) in penile erection.MethodAdenosine A₁ receptor deficient (Adora1^‐/‐) mice and aged‐matched wild‐type (WT) mice were utilized. We evaluated the in vivo erectile function by measuring the intracavernosal pressure (ICP) in response to cavernous nerve stimulation (CNS). Enzyme‐linked immunosorbent assay was used to measure the norepinephrine (NE) plasma concentration in the corpus cavernosum and systemic circulation. We also evaluated the myosin light chain phosphorylation (p‐MLC) in penile tissue pre‐ and post‐CNS.Main Outcome MeasurementThe main outcome measurement of this research was the evaluation of in vivo erectile response to CNS by measuring the ICP in Adora1^‐/‐ mice and WT mice and to identify the localization and specific neuron types of ADORA1 expression by dual immunostaining and immunofluorescence co‐localization.ResultIn vivo, both the ratio of CNS‐induced Maximum ICP to mean arterial pressure and CNS‐induced slope in Adora1^‐/‐ mice were significantly lower than WT mice. At the cellular level in penile tissue, we determined that ADORA1 was highly abundant in neuronal cells. During penile erection, Adora1^‐/‐ mice exhibited a higher level of NE plasma concentration in the penis than WT mice. And WT mice had a significantly greater reduction in p‐MLC compared to Adora1^‐/‐ mice.ConclusionOur results show that ADORA1 is enriched on neuron cells where it functions to control NE release. Activation of this receptor during penile erection results in reduced NE release and reduced cavernosal smooth muscle contraction, therefore facilitating penile erection. Ning C, Qi L, Wen J, Zhang Y, Zhang W, Wang W, Blackburn M, Kellems R, and Xia Y. Excessive penile norepinephrine level underlies impaired erectile function in adenosine A1 receptor deficient mice.     

Plexiform neurofibroma of the penis associated with erectile dysfunction due to arterial steeling

IntroductionSolitary involvement of the genitourinary tract by Von Recklinghousen disease (VRD) is extremely rare.AimsThis report documents the management of a case of a plexiform neurofibroma on the penile shaft associated with erectile dysfunction. The literature surrounding VRD and its effects on the genital area was also investigated.MethodsAfter a complete preoperative investigation of the nature of the mass and of the erectile dysfunction, the neurofibroma was completely excised with preservation of the neurovascular bundle.ResultsAt 6-months postoperative follow-up, there was no sign of tumor recurrence and the glans sensation was maintained. The erectile dysfunction persisted postoperatively and failed to respond to medical treatment.ConclusionsA complete excision of penile neurofibromas is mandatory to prevent recurrence or malignant degeneration and can be safely performed preserving the neurovascular bundle. Garaffa G, Bettocchi C, Christopher N, and Ralph D. Plexiform neurofibroma of the penis associated with erectile dysfunction due to arterial steeling.     

Erectile Hydraulics: Maximizing Inflow While Minimizing Outflow

IntroductionPenile rigidity depends on maximizing inflow while minimizing outflow.AimThe aim of this review is to describe the principal factors and mechanisms involved.Main Outcome MeasureErectile quality is the main outcome measure.MethodsData from the pertinent literature were examined to inform our conclusions.ResultsNitric oxide (NO) is the principal factor increasing blood flow into the penis. Penile engorgement and the pelvic floor muscles maintain an adequate erection by impeding outflow of blood by exerting pressure on the penile veins from within and from outside of the penile tunica. Extrinsic pressure by the pelvic floor muscles further raises intracavernosal pressure above maximum inflow pressure to achieve full penile rigidity. Aging and poor lifestyle choices are associated with metabolic impediments to NO production. Aging is also associated with fewer smooth muscle cells and increased fibrosis within the corpora cavernosa, preventing adequate penile engorgement and pressure on the penile veins. Those same penile structural changes occur rapidly following the penile nerve injury that accompanies even “nerve‐sparing” radical prostatectomy and are largely prevented in animal models by early chronic use of a phosphodiesterase type 5 (PDE5) inhibitor. Pelvic floor muscles may also decrease in tone and bulk with age, and pelvic floor muscle exercises have been shown to improve erectile function to a similar degree compared with a PDE5 inhibitor in men with erectile dysfunction (ED).ConclusionsBecause NO is critical for vascular health and ED is strongly associated with cardiovascular disease, maximal attention should be focused on measures known to increase vascular NO production, including the use of PDE5 inhibitors. Attention should also be paid to early, regular use of PDE5 inhibition to reduce the incidence of ED following penile nerve injury and to assuring normal function of the pelvic floor muscles. These approaches to maximizing erectile function are complementary rather than competitive, as they operate on entirely different aspects of erectile hydraulics. Meldrum DR, Burnett AL, Dorey G, Esposito K, and Ignarro LJ. Erectile hydraulics: Maximizing inflow while minimizing outflow. J Sex Med 2014;11:1208–1220.     

Pericyte-Derived Extracellular Vesicle–Mimetic Nanovesicles Restore Erectile Function by Enhancing Neurovascular Regeneration in a Mouse Model of Cavernous Nerve Injury

BackgroundExtracellular vesicle (EV)–mimetic nanovesicles (NVs) from embryonic stem cells have been observed to stimulate neurovascular regeneration in the streptozotocin-induced diabetic mouse. Pericytes play important roles in maintaining penile erection, yet no previous studies have explored the effects of pericyte-derived NVs (PC-NVs) in neurovascular regeneration in the context of erectile dysfunction.AimTo investigate the potential effect of PC-NVs in neurovascular regeneration.MethodsPC-NVs were isolated from mouse cavernous pericytes, and neurovascular regeneration was evaluated in an in vitro study. Twelve-week-old C57BL/6J mice were used to prepare cavernous nerve injury model. Erectile function evaluation, histologic examination of the penis, and Western blots were assessed 2 weeks after model creation and PC-NVs treatment.OutcomesThe main outcomes of this study are PC-NVs characterization, intracavernous pressure, neurovascular regeneration in the penis, and in vitro functional evaluation.ResultsThe PC-NVs were extracted and characterized by cryotransmission electron microscopy and EV-positive (Alix, TSG101, CD81) and EV-negative (GM130) markers. In the in vivo studies, PC-NVs successfully improved erectile function in cavernous nerve injury mice (∼82% of control values). Immunofluorescence staining showed significant increases in pericytes, endothelial cell, and neuronal contents. In the in vitro studies, PC-NVs significantly increased mouse cavernous endothelial cells tube formation, Schwann cell migration, and dorsal root ganglion and major pelvic ganglion neurite sprouting. Finally, Western blot analysis revealed that PC-NVs upregulated cell survival signaling (Akt and eNOS) and induced the expression of neurotrophic factors (brain-derived neurotrophic factor, neurotrophin-3, and nerve growth factor).Clinical ImplicationsPC-NVs may be used as a strategy to treat erectile dysfunction after radical prostatectomy or in men with neurovascular diseases.Strengths & LimitationsWe evaluated the effect of PC-NVs in vitro and in a mouse nerve injury model, cavernous nerve injury. Additional studies are necessary to determine the detailed mechanisms of neurovascular improvement. Further study is needed to test whether PC-NVs are also effective when given weeks or months after nerve injury.ConclusionPC-NVs significantly improved erectile function by enhancing neurovascular regeneration. Local treatment with PC-NVs may represent a promising therapeutic strategy for the treatment of neurovascular diseases.Yin GN, Park S-H, Ock J, et al. Pericyte-Derived Extracellular Vesicle–Mimetic Nanovesicles Restore Erectile Function by Enhancing Neurovascular Regeneration in a Mouse Model of Cavernous Nerve Injury. J Sex Med 2020;17:2118–2128.     

Risk of Damage to the Somatic Innervation of the Penis during the AdVance™ Procedure: An Anatomical Study

IntroductionOne of the methods to treat post radical prostatectomy stress urinary incontinence is the AdVance™ (American Medical Systems®, Minnetonka, MN, USA) male sling procedure. During this procedure, the somatic innervation of the penis may be at risk for injury. Six AdVance™ procedures were performed in six donated bodies at the Anatomy and Embryology Department of the Leiden University Medical Centre. The pelves were dissected and the shortest distance between the sling and the dorsal nerve of the penis (DNP) was documented.AimThe aim of this study was to describe the anatomical relation between the AdVance™ male sling and penile nerves based on the dissection of six adult male pelves.MethodsThe AdVance™ male sling procedure was conducted in six donated male bodies. After placement, the pelves were dissected and the shortest distance between sling and the DNP was documented.Main Outcome MeasureThe main outcome measure was the distance between the AdVance™ male sling and the DNP.ResultsThe mean distance of the sling to the DNP was 4.1 mm and was found situated directly next to the nerve (distance 0 mm) in 4 out of 12 (33%) hemipelves. The distance of the sling to the obturator neurovascular bundle was 30 mm or more in all six bodies.ConclusionsDamage to the DNP caused by the AdVance™ male sling procedure appears to be an extremely rare complication, which has not been described in current literature. The proximity of the AdVance™ to the DNP could, however, pose a risk that should be taken into consideration by physicians and patients when opting for surgery. Hogewoning CRC, Elzevier HW, Pelger RCM, Bekker MD, and DeRuiter MC. The risk of damage to the somatic innervation of the penis during the AdVance™ procedure; An anatomical study. J Sex Med 2015;12:1705–1710.     

Neurophysiological Testing to Assess Penile Sensory Nerve Damage After Radical Prostatectomy

IntroductionRadical prostatectomy (RP) can lead to erectile dysfunction due to surgical injury of the cavernous nerves. However, there is no simple, objective test to evaluate cavernous nerve damage caused by RP in clinical practice.AimTo assess the value of the measurement of penile thermal and vibratory sensory thresholds to reflect cavernous nerve damage caused by RP.MethodsWe included 42 consecutive patients who underwent RP with cavernous nerve sparing (laparoscopic approach, N = 12) or without cavernous nerve sparing (laparoscopic, N = 13; retropubic, N = 11; or transperineal, N = 6). Penile thermal (warm and cold) and vibratory sensory thresholds were measured twice, together with the Erectile Dysfunction Symptom Score (EDSS), 1 month before and 2 months after RP.Main Outcome MeasuresPenile sensory thresholds for warm, cold, and vibration sensations.ResultsPenile sensory thresholds for warm (P < 0.0001) and cold (P < 0.0001) sensations significantly increased after non‐nerve‐sparing RP, but not after nerve‐sparing RP. Vibration threshold only increased after transperineal non‐nerve‐sparing RP (P = 0.031). EDSS values were significantly increased in all groups of patients 2 months after surgery.ConclusionsSensory nerve fibers carrying penile skin sensations travel with the cavernous nerves in the pelvis. Therefore, testing these sensations may help to evaluate the extent of cavernous nerve damage caused by RP. In this series, post‐operative changes in penile sensory thresholds differed with the surgical technique of RP, as the cavernous nerves were preserved or not. The present results support the value of quantitative penile sensory threshold measurement to indicate RP‐induced cavernous nerve injury. Yiou R, De Laet K, Hisano M, Salomon L, Abbou C‐C, and Lefaucheur J‐P. Neurophysiological testing to assess penile sensory nerve damage after radical prostatectomy. J Sex Med 2012;9:2457–2466.     

The Somatic and Autonomic Innervation of the Clitoris; Preliminary Evidence of Sexual Dysfunction after Minimally Invasive Slings

IntroductionVaginal sling procedures may have a negative effect on sexual function due to damage to vascular and/or neural genital structures. Even though autonomic innervation of the clitoris plays an important role in female sexual function, most studies on the neuroanatomy of the clitoris focus on the sensory function of the dorsal nerve of the clitoris (DNC). The autonomic and somatic pathways in relationship to sling surgery have up to the present not been described in detail.AimThe aim of this study is to reinvestigate and describe the neuroanatomy of the clitoris, both somatic and autonomic, in relation to vaginal sling procedures for stress urinary incontinence.MethodSerially sectioned and histochemically stained pelves from 11 female fetuses (10–27 weeks of gestation) were studied, and three-dimensional reconstructions of the neuroanatomy of the clitoris were prepared. Fourteen adult female hemipelves were dissected, after a tension-free vaginal tape (TVT) (7) or tension-free vaginal tape-obturator (TVT-O) (7) procedure had been performed.Main Outcome MeasuresThree-dimensional (3-D) reconstruction and measured distance between the clitoral nerve systems and TVT/TVT-O.ResultsThe DNC originates from the pudendal nerve in the Alcock's canal and ascends to the clitoral bodies. In the dissected adult pelves, the distance of the TVT-O to the DNC had a mean of 9 mm. The cavernous nerves originate from the vaginal nervous plexus and travel the 5 and 7 o'clock positions along the urethra. There, the autonomic nerves were found to be pierced by the TVT needle. At the hilum of the clitoral bodies, the branches of the cavernous nerves medially pass/cross the DNC and travel further alongside it. Just before hooking over the glans of the clitoris, they merge with DNC.ConclusionsThe DNC is located inferior of the pubic ramus and was not disturbed during the placement of the TVT-O. However, the autonomic innervation of the vaginal wall was disrupted by the TVT procedure, which could lead to altered lubrication-swelling response. Bekker MD, Hogewoning CRC, Wallner C, Elzevier HW, and DeRuiter MC. The somatic and autonomic innervation of the clitoris; preliminary evidence of sexual dysfunction after minimally invasive slings. J Sex Med 2012;9:1566–1578.     

A New,Innovative, Lengthening Surgical Procedure for Peyronie's Disease by Penile Prosthesis Implantation with Double Dorsal‐Ventral Patch Graft: The “Sliding Technique”

IntroductionPeyronie's disease is the result of the formation of fibrous plaques in the tunica albuginea of the penis; typical presentations of the disease are represented by pain during erection, erectile dysfunction, and penile deformities, such as curvature, narrowing, and penile shortening. The most complex treatment is related to penile shortening.AimTo find a safe procedure in penile shortening due to Peyronie's disease providing a satisfactory lengthening, allowing an early stabilization of the penis, and preventing axial tension on the neurovascular bundles during dilation.MethodsWe describe a new lengthening surgical procedure based on a ventro‐dorsal incision of the tunica albuginea, penile prosthesis implantation, and double dorsal‐ventral patch grafting with porcine small intestinal submucosa. Three patients, affected by Peyronie's disease with penile shortening and erectile dysfunction, underwent this procedure with approval of our local ethical committee.We evaluated the penis lengthening, intraoperative and postoperative complications, patient's preoperative and postoperative sexual life satisfaction (International Index of Erectile Function [IIEF] questionnaire).ResultsThe average operative time was 2 hours and 50 minutes. No major intraoperative nor postoperative complications occurred. No significant bleedings were recorded. Patients were discharged after 48–72 hours.The average increase in length obtained was 3.2 cm. All patients resumed sexual intercourses with satisfaction; no significant loss of sensitivity or any sign of vascular distress of the glans was recorded. The follow‐up is 13 months. The average IIEF score is 60.ConclusionsThe lengthening of the penis by a double dorsal‐ventral patch graft is an innovative procedure that is based on current techniques of plaque incision and grafting, and that can easily resolve severe shortening of the penis due to Peyronie's disease. In the cases presented, this procedure resulted easily, effectively, and safely. Nevertheless, the technique proposed in this article shall be validated through prospective studies with larger samples. Rolle L, Ceruti C, Timpano M, Sedigh O, Destefanis P, Galletto E, Falcone M, and Fontana D. A new, innovative, lengthening surgical procedure for Peyronie's disease by penile prosthesis implantation with double dorsal‐ventral patch graft: The “sliding technique.” J Sex Med 2012;9:2389–2395.     

Erectile Function Restoration After Repair of Excised Cavernous Nerves by Autologous Vein Graft in Rats

IntroductionCavernous nerves (CNs) injury is the main cause of erectile dysfunction (ED) following radical prostatectomy. Its restoration remains challenging.AimTo investigate the feasibility of erectile function recovery by autologous vein graft after bilateral CNs being excised in a rat model.MethodsA total of 36 adult male Sprague-Dawley rats were randomized into three groups. A 5 mm segment of CN was excised bilaterally in group B and C. In group B, a 7-mm segment of autologous saphenous vein was interposed at the defect site bilaterally, with two nerve stumps inserted into the vein lumen. Group C underwent no repair. Group A was accepted a sham operation. 4 months later, apomorphine tests were performed on each rat, followed by injection of 4% fluorogold into bilateral corpus cavernous. 5 days later, after monitoring intracorporal pressure (ICP) changes induced by electrostimulation of CN, rats were sacrificed and their bilateral major pelvic ganglions were obtained for detection of fluorogold, and penile tissues of middle shaft were obtained for detecting nitric oxide synthase-containing nerve fibers in penile dorsal nerves.Main Outcome MeasuresErectile function was assessed by apomorphine test and ICP monitoring. CN regeneration was judged by fluoroglod tracing and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining.ResultsApomorphine tests resulted in 58% rats with erectile responses in group B, whereas no erection was observed in group C. ICP monitoring also demonstrated a significant recovery in erectile function in group B compared with group C. Much more and brighter fluorogold coloring cells were examined in major pelvic ganglions of group B than those of group C. NADPH-diaphorase staining also showed much more positive fibers were detected in penile dorsal nerves in group B than in group C.ConclusionAutologous vein graft could provide a guide channel to induce CN regeneration and successfully restore autonomic erectile function after CNs being excised in rats. Hu W, Cheng B, Liu T, Li S, and Tian Y. Erectile function restoration after repair of excised cavernous nerves by autologous vein graft in rats.     

Valproic Acid Prevents Penile Fibrosis and Erectile Dysfunction in Cavernous Nerve‐Injured Rats

IntroductionBilateral cavernous nerve injury (BCNI) causes profound penile changes such as apoptosis and fibrosis leading to erectile dysfunction (ED). Histone deacetylase (HDAC) has been implicated in chronic fibrotic diseases.AimsThis study will characterize the molecular changes in penile HDAC after BCNI and determine if HDAC inhibition can prevent BCNI‐induced ED and penile fibrosis.MethodsFive groups of rats (8–10 weeks, n = 10/group) were utilized: (i) sham; (ii and iii) BCNI 14 and 30 days following injury; and (iv and v) BCNI treated with HDAC inhibitor valproic acid (VPA 250 mg/kg; 14 and 30 days). All groups underwent cavernous nerve stimulation (CNS) to determine intracavernosal pressure (ICP). Penile HDAC3, HDAC4, fibronectin, and transforming growth factor‐β1 (TGF‐β1) protein expression (Western blot) were assessed. Trichrome staining and the fractional area of fibrosis were determined in penes from each group. Cavernous smooth muscle content was assessed by immunofluorescence to alpha smooth muscle actin (α‐SMA) antibodies.Main Outcome MeasuresWe measured ICP; HDAC3, HDAC4, fibronectin, and TGF‐β1 protein expression; penile fibrosis; penile α‐SMA content.ResultsThere was a voltage‐dependent decline (P < 0.05) in ICP to CNS 14 and 30 days after BCNI. Penile HDAC3, HDAC4, and fibronectin were significantly increased (P < 0.05) 14 days after BCNI. There was a slight increase in TGF‐β1 protein expression after BCNI. Histological analysis showed increased (P < 0.05) corporal fibrosis after BCNI at both time points. VPA treatment decreased (P < 0.05) penile HDAC3, HDAC4, and fibronectin protein expression as well as corporal fibrosis. There was no change in penile α‐SMA between all groups. Furthermore, VPA‐treated BCNI rats had improved erectile responses to CNS (P < 0.05).ConclusionHDAC‐induced pathological signaling in response to BCNI contributes to penile vascular dysfunction. Pharmacological inhibition of HDAC prevents penile fibrosis, normalizes fibronectin expression, and preserves erectile function. The HDAC pathway may represent a suitable target in preventing the progression of ED occurring post‐radical prostatectomy. Hannan JL, Kutlu O, Stopak BL, Liu X, Castiglione F, Hedlund P, Burnett AL, and Bivalacqua TJ. Valproic acid prevents penile fibrosis and erectile dysfunction in cavernous nerve‐injured rats. J Sex Med 2014;11:1442–1451.     

Determination of Human Penile Electrical Resistance and Implication on Safety for Electrosurgery of Penis

IntroductionElectrosurgery has been a surgical application since the late 19th century. Although many urologists take this daily application for granted, the effects of electrical treatment on penile nerves and vessels have not been well documented.AimTo investigate the electrical characteristics of the penis and erectile tissues and to discover the potential hazards of electrosurgery on the penis.MethodsMeasurement of the electrical characteristics of three human penises in order to create models to analyze the effect of electricity on penile nerves and vessels.Main Outcome MeasuresElectrical resistivity of the penile shaft, electrical current density, and electric field strength on penile nerves and vessels, proportion of generated heat on the penis and electrical current density of the electrosurgery return electrode.ResultsElectrical resistivity (ρ) of the penile shaft is 127.14 Ω · cm at 500 kHz. Electrical current density (J) of the penis shaft is 71.06 mA/cm², nerve (60.23 mA/cm²), vessel (67.93 mA/cm²), and return electrode (2.11 mA/cm²). Electrical field strength (E) of the whole penis shaft is 9.03 volt/cm. The proportion of generated heat on the penis is four times as much as on other body parts of the circuit.ConclusionsPotential and subclinical injury to erectile tissue caused by electrosurgery on the penis cannot be underestimated. The injury mechanism can be attributed to a thermal (electrical current) effect and a nonthermal (mainly electrical field) effect. Ways to avoid the electrosurgical injury are: using less power (W)/electrical field and less time, biopolar electrosurgery confining the injured area, ligation to achieve hemostasis, and new laser technologies. Tsai VFS, Chang H-C, Liu S-P, Kuo Y-C, Chen J-H, Jaw F-S, and Hsieh J-T. Determination of human penile electrical resistance and implication on safety for electrosurgery of penis.     

Male Urogenital System Mapped Onto the Sensory Cortex: Functional Magnetic Resonance Imaging Evidence

IntroductionThe projection of the human male urogenital system onto the paracentral lobule has not previously been mapped comprehensively.AimTo map specific urogenital structures onto the primary somatosensory cortex toward a better understanding of sexual response in men.MethodsUsing functional magnetic resonance imaging, we mapped primary somatosensory cortical responses to self-stimulation of the penis shaft, glans, testicles, scrotum, rectum, urethra, prostate, perineum, and nipple. We further compared neural response with erotic and prosaic touch of the penile shaft.Main Outcome MeasureWe identified the primary mapping site of urogenital structures on the paracentral lobule and identified networks involved in perceiving touch as erotic.ResultsWe mapped sites on the primary somatosensory cortex to which components of the urogenital structures project in men. Evidence is provided that penile cutaneous projection is different from deep penile projection. Similar to a prior report in women, we show that the nipple projects to the same somatosensory cortical region as the genitals. Evidence of differential representation of erotic and nonerotic genital self-stimulation is also provided, the former activating sensory networks other than the primary sensory cortex, indicating a role of “top-down” activity in erotic response.Clinical ImplicationsWe map primary sites of projection of urogenital structures to the primary somatosensory cortex and differentiate cortical sites of erotic from nonerotic genital self-stimulation.Strength & LimitationsTo our knowledge, this is the first comprehensive mapping onto the primary somatosensory cortex of the projection of the components of the urogenital system in men and the difference in cortical activation in response to erotic vs nonerotic self-stimulation. The nipple was found to project to the same cortical region as the genitals. Evidence is provided that superficial and deep penile stimulation project differentially to the cortex, suggesting that sensory innervation of the penis is provided by more than the (pudendal) dorsal nerve.ConclusionThis study reconciles prior apparently conflicting findings and offers a comprehensive mapping of male genital components to the paracentral lobule. We provide evidence of differential projection of light touch vs pressure applied to the penile shaft, suggesting differential innervation of its superficial, vs deep structure. Similar to the response in women, we found nipple projection to genital areas of the paracentral lobule. We also provide evidence of differential representation of erotic and nonerotic genital self-stimulation, the former activating sensory networks other than the primary sensory cortex, indicating a role of top-down activity in erotic response.Allen K, Wise N, Frangos E, et al. Male Urogenital System Mapped Onto the Sensory Cortex: Functional Magnetic Resonance Imaging Evidence. J Sex Med 2020;17:603–613.     

Shaeer’s Punch Technique: Transcorporeal Peyronie’s Plaque Surgery and Penile Prosthesis Implantation

BackgroundPenile prosthesis implantation in cases of severe Peyronie’s disease may require plaque excision/incision and grafting, which may require mobilization of the neurovascular bundle or urethra, posing the risks of penile hyposensitivity or urethral injury, and is time-consuming, possibly increasing infection risk.AimEvaluating transcorporeal debulking of Peyronie’s plaques by “Shaeer’s punch technique.”MethodsPenile prosthesis implantation and punch technique (PPI-Punch) was performed for 26 patients. After corporotomy and dilatation, Peyronie’s plaques were punched out from within the corpora cavernosa using the punch forceps, and then a penile prosthesis was implanted. Comparison to a matching retrospective group of 18 patients operated upon by plaque excision-grafting and penile prosthesis implantation was performed.OutcomesThe study outcomes were straightness of the erect penis, complication, satisfaction with length on a 5-point scale, the International Index of Erectile Function-5, and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire.ResultsAverage preoperative curvature angle was 58.1 ± 11.7 in the Punch group and 58 ± 14.8 in the excision-grafting group, p=0.99. After surgery, all patients had a straight penis. No tunical perforations, urethral injuries, or extrusions were noted. Average additional operative time for Punch technique ranged from 5 to 10 minutes (7.3 ± 1.7), in contrast to the excision-grafting group where plaque surgery duration was 50.8 minutes ± 11.1, an 85% difference, p < 0.0001. Septal plaques in the latter group could not be removed. In the PPI-Punch group, penile sensitivity was preserved in all patients, compared with the excision/grafting group, with 7 of 18 patients reporting hyposthesia of the glans. Infection occurred in 1 of 26 patients in the PPI-Punch group, compared with 2 of 18 patients in the excision/grafting group. Satisfaction with length on a 5-point scale was 3.8 ± 0.9 in the punch group, versus 3.1 ± 1.1 in the excision-grafting group, p=0.009.Clinical ImplicationsThe proposed technique is minimally invasive and prompt, possibly decreasing the known complications of plaque surgery and PPI including sensory loss.Strengths & LimitationsOne limitation is the inability to accurately measure preoperative erect length in patients with erectile dysfunction with poor response to intracavernous injections.ConclusionShaeer’s punch technique is a minimally invasive procedure for transcorporeal excavation of Peyronie’s plaques before penile prosthesis implantation, omitting the need for mobilization of the neurovascular bundle or spongiosum, and hence, there is low or no risk for nerve or urethral injury and brief plaque surgery time.Shaeer O, Soliman Abdelrahman IF, Mansour M, et al. Shaeer’s Punch Technique: Transcorporeal Peyronie’s Plaque Surgery and Penile Prosthesis Implantation. J Sex Med 2020;17:1395–1399.     

Hyperinnervation in Intestinal Deep Infiltrating Endometriosis

Study ObjectiveTo investigate the extent and types of innervation of endometriotic lesions in various regions of the bowel.DesignRetrospective nonrandomized immunohistochemical study (Canadian Task Force classification II-3.SettingUniversity-based laboratory.PatientsThirty-six women undergoing laparoscopy or laparotomy because of deep infiltrating endometriosis in various regions of the bowel, including the sigmoid colon, appendix, and rectum.InterventionsImmunohistochemical staining of endometriotic specimens with antibodies against protein gene product 9.5, neurofilament, nerve growth factor, nerve growth factor receptors tyrosine kinase receptor A and p75, growth-associated protein 43, substance P, neuropeptide Y, and vasoactive intestinal peptide to demonstrate myelinated, unmyelinated, sensory, and autonomic nerve fibers.Measurements and Main ResultsThere were significantly more nerve fibers in intestinal deep infiltrating endometriosis (mean [SD] 172.6 [94.2]/mm²) than in other deep infiltrating endometriotic lesions (e.g., cul-de-sac and uterosacral ligament) (67.6 [65.1]/mm²; p < .01). Intestinal deep infiltrating endometriosis was innervated abundantly by sensory Aδ,sensory C, cholinergic, and adrenergic nerve fibers. Nerve growth factor, tyrosine kinase receptor A, and p75 were strongly expressed in endometriotic lesions, and growth-associated protein-43 was also strongly expressed in the endometriosis-associated nerve fibers.ConclusionThe hyperinnervation in intestinal deep infiltrating endometriosis may help to explain why patients with this type of lesion have more severe pain.