Single subject and group whole-brain fMRI mapping of male genital sensation at 7 Tesla.

Processing of genital sensations in the central nervous system of humans is still poorly understood. Current knowledge is mainly based on neuroimaging studies using electroencephalography (EEG), magneto-encephalography (MEG), and 1.5- or 3- Tesla (T) functional magnetic resonance imaging (fMRI), all of which suffer from limited spatial resolution and sensitivity, thereby relying on group analyses to reveal significant data. Here, we studied the impact of passive, yet non-arousing, tactile stimulation of the penile shaft using ultra-high field 7T fMRI. With this approach, penile stimulation evoked significant activations in distinct areas of the primary and secondary somatosensory cortices (S1 & S2), premotor cortex, insula, midcingulate gyrus, prefrontal cortex, thalamus and cerebellum, both at single subject and group level. Passive tactile stimulation of the feet, studied for control, also evoked significant activation in S1, S2, insula, thalamus and cerebellum, but predominantly, yet not exclusively, in areas that could be segregated from those associated with penile stimulation. Evaluation of the whole-brain activation patterns and connectivity analyses indicate that genital sensations following passive stimulation are, unlike those following feet stimulation, processed in both sensorimotor and affective regions.

Quality of Life After Radical Cystectomy.

Approximately 1 in 5 new cases of clinically localized bladder cancer is muscle invasive and requires the patient to choose from 1 of 2 prevailing options for treatment: radical cystectomy or radiation to the bladder. However, these treatments are associated with detrimental effects on patient well-being and quality of life, particularly with respect to functional independence, urinary and sexual function, social and emotional health, body image, and psychosocial stress. Compared with the literature on other malignancies like breast or prostate cancer, high-quality studies evaluating the effects of bladder cancer treatment on quality of life are lacking.

Neurons and a sensory organ in the pedipalps of male spiders reveal that it is not a numb structure.

The primary function of male copulatory organs is depositing spermatozoa directly into the female reproductive tract. Typical male copulatory organs are sensorily active. This is in contrast to the copulatory organs of male spiders (i.e. palpal bulbi), which have been assumed to lack nerves and muscles until recently. Neurons have been found within the bulbus of the spider Hickmania troglodytes, a taxon basal to all Neocribellata. We provide the first evidence for neurons and an internalized multi-sensillar sensory organ in the bulbus of an entelegyne spider (Philodromus cespitum). The sensory organ likely provides mechanical or chemical feedback from the intromitting structure, the embolus. We found further neurons associated with two glands within the bulbus, one of which is likely responsible for sperm extrusion during mating. These findings provide a new framework for studies on reproductive behaviour and sexual selection in spiders.

The role of the pubococcygeus muscle in the urethrogenital reflex of male rats.

AIM: To determine the response of the pubococcygeus muscle (Pcm) during the urethrogenital reflex (UGR). METHODS: Urethane-anesthetized male rats (n = 20) were used to describe the gross anatomy of the Pcm (n = 3), the effect of the electrical stimulation of the Pcm on the urethral pressure (n = 3), and the reflex activity of the Pcm due to the mechanical stimulation of the urethra (n = 3) and during penile and urethrogenital reflexes (n = 11). The urethral pressure (UP) was recorded as a response to penile stimulation (brushing, extension, and occlusion) and during the UGR; the electromyographic activity of the Pcm was simultaneously evaluated. The role of the Pcm was assessed by measuring urethral pressure variables before and after denervation of this muscle. RESULTS: The Pcm is innervated by the caudal branch of the somatomotor branch of the pelvic nerve. The electrically induced contraction of the Pcm increased the UP. The mechanical stimulation of the urethra during the induced micturition caused the reflex activity of the Pcm. The different penile stimuli caused bursts of activity of the Pcm. During the UGR, the Pcm exhibited a tonic activity. The transection of the caudal branch of the Smb reduced the maximal UP during the penile stimulation. The same was true regarding the duration of the UGR, the pressure that triggers the UGR, and the highest pressure observed during the UGR. CONCLUSION: Our results suggest that the activation of the Pcm is relevant for the UGR in male rats. Neurourol. Urodynam. 36:80-85, 2017. © 2015 Wiley Periodicals, Inc.

Modulation of Dopaminergic Pathways to Treat Erectile Dysfunction.

The currently recommended first-line treatments of erectile dysfunction (ED), phosphodiesterase type 5 inhibitors (PDE5i), for example sildenafil, are efficacious in many patients with ED of vascular origin, but this therapy is insufficient in approximately 30-40% of men with ED where there is also a neuronal affection. There is a demand of novel approaches to treat the condition. We review the possibility of modulating the dopaminergic pathways to improve erectile function. Dopamine D1 (D1 , D5 )- and D2 (D2 -D4 )-like receptors in the paraventricular area, the medial pre-optic area, the spinal cord, and in the erectile tissue are involved in erection, and several agonists developed for the treatment of Parkinson's disease are associated with increased libido. A therapeutic window for the treatment of ED was found by sublingual administration of the general dopamine receptor agonist apomorphine, but it failed mainly due to less efficacy on erectile function compared with PDE5i. To avoid the dose-limiting side effects mediated by D2 receptors, nausea and emesis, dopamine D4 receptor agonists were developed, and they induce erection in rodents, but these drugs were never introduced clinically. The ß-lactamase inhibitor clavulanic acid increases dopamine and serotonin and was found to increase sexual arousal and erections, but the dose-response curve is bell-shaped. Bupropion has selectivity for inhibition of the dopamine reuptake transporter and can be used to alleviate sexual symptoms caused by other antidepressant medication, hence providing an interesting approach to treat ED. In summary, modulation of the dopaminergic pathways provides a possibility to improve the treatment of ED.

Nerve Sparing, Robot-Assisted Radical Cystectomy with Intracorporeal Bladder Substitution in the Male.

PURPOSE: We provide a step-by-step description of our technique of nerve and seminal vesicle sparing robot-assisted radical cystectomy with an orthotopic neobladder. We also present preliminary oncologic and functional outcomes. MATERIALS AND METHODS: Nerve and seminal vesicle sparing robot-assisted radical cystectomy with a modified Y-shaped orthotopic neobladder was performed by the same surgeon in 40 men with clinically localized bladder cancer from January 2011 to September 2014. Operative, perioperative and pathological data as well as continence and erectile function outcomes are presented. RESULTS: Median followup was 26.5 months (range 8 to 52). A soft tissue positive surgical margin was found in a patient with pT3a disease. A global rate of 30% early and 32.5% late complications was observed. However, the grade III or higher complication rate was low in both settings at 2.5% and 5%, respectively. There was 1 cancer related death 23 months after surgery. Of the 40 patients 30 (75%) gained daytime continence (0 pad) within 1 month postoperatively. The 12-month nocturnal continence rate was 72.5% (29 of 40 patients). Mean preoperative IIEF-6 (International Index of Erectile Function-6) score was 24.4. Erectile function returned to normal, defined as an IIEF-6 score greater than 17, in 31 of 40 patients (77.5%) within 3 months while 29 of 40 patients (72.5%) returned to the preoperative IIEF-6 score within 12 months. CONCLUSIONS: In the hands of an experienced surgeon nerve and seminal vesicle sparing robot-assisted radical cystectomy with intracorporeal reconstruction of the neobladder seems feasible and safe. It provides short-term oncologic efficacy and promising functional outcomes. Yet comparative, long-term followup studies with standard open cystectomy are required.

Physiology and Pharmacology of Ejaculation.

Ejaculation is the final stage of coitus in mammalian male and is mandatory for natural procreation. Two synchronized phases, emission and expulsion, form the ejaculatory response and involve specific organs and anatomical structures. The peripheral events leading to ejaculation are commanded by autonomic (sympathetic and parasympathetic) and somatic divisions of the nervous system. The autonomic and somatic motor efferents originate in spinal nuclei located in thoracolumbar and lumbosacral segments. Co-ordinated activation of autonomic and somatic spinal nuclei is orchestrated by a group of lumbar spinal interneurons defined as the spinal generator of ejaculation. The generator of ejaculation together with the autonomic and somatic spinal nuclei constitutes a spinal network that is under the strong influence of stimulating or inhibiting genital sensory and supraspinal inputs. A brain circuitry dedicated to ejaculation has been delineated that is part of a more global network controlling other aspects of the sexual response. This circuitry includes discrete neuronal populations distributed in all divisions of the brain. The corollary to the expanded CNS network is the variety of neurotransmitter systems participating in the ejaculatory process. Among them, serotonin neurotransmission plays a key role and its targeting led to the development of the first registered pharmacological treatment of premature ejaculation in human beings. Critical gaps remain in the understanding of neurophysiopharmacology of ejaculation and management of ejaculatory disorders in human beings needs improvement. Because the ejaculatory response in laboratory animals and in human beings shares many similarities, the use of animal models will certainly provide further advances in the field.

Novel presentation of a cricket ball-related intra-abdominal injury: genitofemoral nerve referred pain.

Serious intra-abdominal injuries are very uncommon in cricket; traumatic cricket injuries are traditionally musculoskeletal, soft tissue or maxillofacial in origin. The cause of such cricket injuries can be broadly divided into collision type injuries (a result of direct contact with the ball or bat, another player, the ground or boundary) or overuse injuries (due to running, throwing, batting, bowling, repetitive movements and overexertion). This case report describes a rare cause of small bowel perforation and suspected genitofemoral nerve injury secondary to the direct impact of a cricket ball, and includes a brief review of blunt abdominal injuries resulting in isolated small bowel perforations.

First evidence of neurons in the male copulatory organ of a spider (Arachnida, Araneae).

Spider males have evolved a remarkable way of transferring sperm by using a modified part of their pedipalps, the so-called palpal organ. The palpal organ is ontogenetically derived from tarsal claws; however, no nerves, sensory organs or muscles have been detected in the palpal bulb so far, suggesting that the spider male copulatory organ is numb and sensorily blind. Here, we document the presence of neurons and a nerve inside the male palpal organ of a spider for the first time. Several neurons that are located in the embolus are attached to the surrounding cuticle where stresses and strains lead to a deformation (stretching) of the palpal cuticle on a local scale, suggesting a putative proprioreceptive function. Consequently, the male copulatory organ of this species is not just a numb structure but likely able to directly perceive sensory input during sperm transfer. In addition, we identified two glands in the palpal organ, one of which is located in the embolus (embolus gland). The embolus gland appears to be directly innervated, which could allow for rapid modulation of secretory activity. Thus, we hypothesize that the transferred seminal fluid can be modulated to influence female processes.

Terminal innervation of the male genitalia, cutaneous sensory receptors of the male foreskin.

PURPOSE: Understanding the types of sensory nerve termini within the glabrous skin of the human male foreskin could throw light on surgical outcomes and therapeutic possibilities for the future. Various receptor types sense changes in temperature, position, pressure, pain, light touch, itch, burning and pleasurable sexual sensations. Similarities and differences in innervation characteristics and density might become apparent when the glans penis is compared with homologous structures in the female genitalia. The aim of this study is to document the presence and characteristics of cutaneous sensory receptors in the human penile foreskin using a histopathological study of the nerve termini to achieve a more complete understanding of sensory experiences. METHODS: Foreskin samples were obtained from ten boys (aged 1-9 years) who had undergone circumcision. Informed consent was obtained from the parent/legal guardian. The samples were examined after modified Bielschowsky silver impregnation of neural tissue, and immunocytochemistry against gene protein product (PGP) 9.5 and neuron-specific enolase (NSE). RESULTS: PGP 9.5 appeared to be the most sensitive neural marker. Free nerve endings were identified in the papillary dermis visualized as thin fibers, mostly varicose, with either branched or single processes, either straight or bent. Two types of sensory corpuscle were identified: capsulated and non-capsulated. Meissner-like corpuscles were located in the papillary dermis. Capsulated corpuscles resembled typical Pacinian corpuscles, comprising a single central axon surrounded by non-neural periaxonic cells and lamellae. The capsulated corpuscles were strongly positive for PGP 9.5 and NSE. CONCLUSIONS: Free nerve endings, Meissner's corpuscles and Pacinian corpuscles are present in the human male foreskin and exhibit characteristic staining patterns.

Computed tomographic-guided genitofemoral nerve block: a simple anterior approach.

Chronic groin pain, often as a consequence from surgery, is a challenge from both a diagnostic and treatment standpoint. Interventional therapy is often attempted.Genitofemoral nerve block can be used for the diagnosis and treatment of groin pain. Classically, this nerve is blocked blindly at the level of the pubic tubercle, or more recently, with ultrasound. We present a novel technique to blocking the genitofemoral nerve in males using an anterior approach with computed tomographic guidance.

Sexual arousal in men: a review and conceptual analysis.

Sexual arousal is an emotional/motivational state that can be triggered by internal and external stimuli and that can be inferred from central (including verbal), peripheral (including genital), and behavioral (including action tendencies and motor preparation) responses. This article, while focusing on sexual arousal in men, provides a conceptual analysis of this construct, reviews models of sexual arousal, and discusses the usefulness of perspectives derived from motivation and emotion research in improving our understanding of its determinants and behavioral correlates. In this, it considers the role of genital feedback in men's subjective sexual arousal and the connections between sexual arousal and sexual desire. Future research and definitions may increasingly focus on its central integrative functions (as opposed to its input and output characteristics). Yet, the study of sexual arousal can be expected to continue to benefit from the measurement of its genital, verbal, and behavioral components. Instances of discordance between response components suggest that they are, at least in part, under the control of different mechanisms, and it is proposed that a better understanding of sexual arousal will prove contingent on a better understanding of such mechanisms and the conditions under which they converge and diverge.

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

INTRODUCTION: Our 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. AIM: To present a detailed understanding of the functional importance of genital afferent neuroanatomy and neurophysiology. METHODS: English-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 MEASURES: Analysis of supporting evidence for the role of genital afferents in the physiology of erectile response and pelvic floor function. RESULTS: Basic 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. CONCLUSIONS: There 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.

The developmental anatomy of the human superior hypogastric plexus: A morphometrical investigation with clinical and surgical correlations.

The superior hypogastric plexus (SHP) is the part of the autonomic nervous system, which is responsible for the sympathetic innervation of pelvic organs and extrapelvic genitals in humans of both sexes. The SHP also functions as the anatomic pathway for the major part of visceral sensitive fibers originating from pelvic viscera. In this study, the morphology of the SHP was analyzed through anatomical dissections performed both in human adult and fetal cadavers. A computerized morphometrical investigation of the SHP was also performed and the resulting quantitative data statistically assessed. The comparison between fetal and adult SHP revealed that in the male group there was a developmental increase of six times (in height) and of about five times (in width); while in the female group, there was a developmental increase of 3.5 times both in height and width values. In addition, the distance from the superior border of the SHP to the bifurcation of the common iliac arteries presented a developmental increase of about six times in the male group, and about four times in the female group. We propose an original morphological classification with six types, based upon the anatomical arrangement of the nervous fibers in this autonomic plexus.

Drug-induced sexual dysfunction in rats.

This unit describes the testing of sexual behaviors of male Wistar rats. The described test enables the detection of stimulatory and inhibitory profiles of compounds. The test includes four training sessions to reach a stable sexual performance, followed by acute and/or chronic administration of drugs. The main quantifiable sexual behaviors are number of mounts (no vaginal penetration), intromissions (vaginal penetration), and ejaculations. By comparing the test compound to reference compound(s), sexual (side) effects can be determined.

Postmating change in physiology of male Drosophila mediated by serotonin (5-HT).

Sex peptides transferred during mating from male to female fly profoundly influence the female's behavior and physiology, including an increase in the movement of eggs along the oviduct. In the male ejaculatory duct, the authors have identified peristaltic waves that travel distally with an average frequency of 0.6 Hz. The frequency of peristalsis is increased by 0.1 microM serotonin (5-HT) and completely blocked by 5-HT antagonists (IC(50)< 1 microM). The authors also report that mating affects the male reproductive tract; peristaltic waves along the ejaculatory duct are significantly reduced postcopulation by 30%. Serotonergic neurons innervate the ejaculatory duct, but their genetic ablation does not prevent peristalsis. The authors propose that peristalsis may be modulated by serotonin circulating in the hemolymph. As serotonin is linked with attentiveness in both flies and mammals, this bioassay suggests reduced behavioral sensitivity of the male fly after mating.

Differences in the spinal command of ejaculation in rapid ejaculating rats.

INTRODUCTION: It has been hypothesized that lifelong premature ejaculation is part of a biological variation in the intravaginal ejaculation latency, but what causes this variation remains poorly understood. AIM: The aim of this study is to elucidate whether variations in ejaculation latencies in an experimental rat model for premature ejaculation are linked to differences in the spinal command of ejaculation. MAIN OUTCOME MEASURES: Electrical microstimulation of the spinal generator for ejaculation revealed an accelerated expulsion phase in rapid ejaculating rats. METHODS: Adult male Wistar rats were categorized as "sluggish,""normal," or "rapid" ejaculators on the basis of their ejaculation frequency in sexual mating tests. One to three weeks after selection, males were urethane anesthetized and electrically microstimulated in the spinal generator for ejaculation, evoking ejaculation. Bulbospongiosus muscle electromyographic and intraluminal vas deferens pressure were measured simultaneously, representing, respectively, the expulsion and emission phase in ejaculation. RESULTS: Electrical microstimulation of the spinal generator for ejaculation evoked ejaculation in "sluggish" (N = 9), "normal" (N = 13), and "rapid" (N = 11) ejaculating rats. Vas deferens contraction (emission phase) was evoked at different stimulation strengths, but response properties were not statistically different between "sluggish,""normal," and "rapid" ejaculator rats. Bulbospongiosus muscle contractions (expulsion phase) following microstimulation was significantly accelerated in "rapid" rats as compared with "sluggish" and "normal" rats. The total duration of bulbospongiosus muscle contractions remained unchanged between the three ejaculator groups. CONCLUSIONS: Our results provide the first scientific evidence supporting a neurophysiological difference between "rapid,""normal," and "sluggish" ejaculators, expressed as an accelerated expulsion phase in "rapid" ejaculator rats. This bridges the gap between a sexual behavior trait and the spinal command of ejaculation.