Autonomic dysfunctions are a major challenge to individuals following spinal cord injury. Despite this, these consequences receive far less attention compared with motor recovery. This review will highlight the major autonomic dysfunctions following SCI predominantly based on our present understanding of the anatomy and physiology of autonomic control and available clinical data.

This study aimed at determining whether stimulation of sacral spinal roots can induce penile erection in cats.

In anesthetized cats, a 20-gauge catheter was inserted into the corpus cavernosum to measure the penile pressure. Stimulus pulses (5-80 Hz, 0.2 ms) were applied through bipolar hook electrodes to sacral ventral roots alone or to combined ventral and dorsal roots of a single S1-S3 segment to induce penile pressure increases and penile erection.

Stimulation of the S1 or S2 ventral root at 30 to 40 Hz induced observable penile erection with rigidity and the largest increase (169 ± 11 cmH2O) in penile pressure. Continuous stimulation (10 minutes) of afferent and efferent axons by simultaneous stimulation of the S1 or S2 dorsal and ventral roots at 30 Hz also produced a large increase (190 ± 8 cmH2O) in penile pressure that was sustainable during the entire stimulation period. After a complete spinal cord transection at the T9-T10 level, simultaneous stimulation of the S1 or S2 dorsal and ventral roots induced large (186 ± 9 cmH2O) and sustainable increases in penile pressure.

This study indicates the possibility to develop a novel neuromodulation device to restore penile erection after spinal cord injury using a minimally invasive surgical approach to insert a lead electrode through the sacral foramen to stimulate a sacral spinal root.

Priapism is defined as a persistent penile erection in the absence of sexual arousal. This symptom has been documented in patients with spinal stenosis although it is considered a rare finding. The European Association of Urology guidelines on priapism [Salonia et al., 2014] list cauda equina syndrome and spinal stenosis as causative factors for ischemic priapism although the literature describing this phenomenon appears sparse. Priapism can be a rare symptom of lumbar spine stenosis/transient cauda equina compression. This presentation is complex and believed to be a parasympathetic mediated autonomic disorder. This article discusses the relationship between spinal stenosis, cauda equina syndrome and priapism using available literature. Greater awareness of this clinical finding may help clinicians in their clinical decision making. In patients with suspected cauda equina syndrome, subjective enquiry regarding the symptom priapism may add to the patients overall clinical picture.

Objective: To present the current understanding of normal anatomy, physiology, sexual physiology, pathophysiology and the consequential sexual changes and dysfunctions following a spinal cord injury (SCI). Methods: Narrative review of the latest literature. Results: Peripheral innervations of the pelvis involve 3 sets of efferent neurons coordinated though the pelvic plexus (somatic, thoracolumbar sympathetic, and sacral parasympathetic), and these are under cerebral descending excitatory and inhibitory control. SCI, depending on the level of lesion and completeness, can alter this cerebral control, affecting the psychological and reflexogenic potential for genital arousal and also ejaculation and orgasm. During arousal, nitric oxide is the main neurotransmitter for smooth muscle relaxation in both male and female erectile tissue. In men, erection, ejaculation, and orgasm are under separate neurological control and can be individually affected by SCI. Conclusions: Since sexual function is rated amongst the highest priorities by individuals living with SCI, methods employed to affect the neurological changes to maximize sexual neurophysiology prior to initiating medical therapies including paying attention to sexual sensate areas and visceral signals with mindfulness techniques, practicing body mapping, and sexual stimulation of sensate areas to encourage neuroplasticity. Attention should be paid to the biopsychosocial sexual contexts within which persons with SCI live to maximize their sexual and fertility rehabilitation.

Male sexual response is controlled by a series of neurally mediated phenomena regulating libido, motivation, arousal and genital responses such as penile erection and ejaculation. These neural events that occur in a hormonally defined milieu involve different neurophysiological, neurochemical, and neuropsychological parameters controlled by central mechanisms, spinal reflexes and peripheral nervous system. Epidemiologic studies have suggested the high prevalence of male sexual dysfunction worldwide with significant impact on the quality of life of patients suffering from this problem. The incidence of sexual dysfunction is particularly high among men with neurologic disorders. Sexual dysfunction in men, such as loss of sexual desire, erectile dysfunction (ED), changes in arousal, and disturbances in orgasm and ejaculation may involve organic causes, psychological problems, or both. Organic male sexual disorders include a wide variety of neurologic, vasculogenic, neurovascular or hormonal factors that interfere with libido, erection, ejaculation and orgasm. Neurogenic sexual dysfunction may result from a specific neurologic problem or it could be the presenting symptom of a developing neurologic disease. Neurologic ED could result from complications of chronic neurologic disorders, trauma, surgical injury or iatrogenic causes. These etiologic factors and the underlying pathophysiologic conditions could overlap, which should be considered when making a diagnosis and selecting a treatment. A detailed history of physical examination, neurologic disorders, as well as any past history of psychological and psychiatric disturbances, and a thorough neurological examination will provide better understanding of the underlying causes of neurogenic sexual dysfunction. In patients with spinal cord injury, the location of the lesion and the time of onset of injury should be determined. Therapeutic strategies against erectile dysfunction are initiated with the least invasive options using the phosphodiesterase inhibitors. When oral medication options are exhausted, intraurethral and intracavernosal therapies and ultimately vacuum constriction devices and penile implants are considered. Recent basic research has suggested the potential role of stem cell-based therapeutic strategies to protect penile neural integrity and reverse cavernosal neurodegeneration in experimental models. Further insight into the central, spinal and peripheral neural mechanisms of male sexual response may help precise diagnosis and better management of neurogenic sexual dysfunction in men.

Sexuality is the embodiment of sexual and reproductive activities involving complex interactions among biological, psychological, and social systems. An individual's perception of their sexuality, as well as society's perception, can have an inestimable impact on self-esteem, and hence willingness to openly address these issues Earle S (2001). Disability, facilitated sex and the role of the nurse. J Adv Nurs 3: 433-440. Such barriers to communication represent a real challenge to practicing clinicians. However, advances in treatment options obligate the clinician providing care to those with neurogenic sexual/reproductive dysfunction to learn to communicate effectively about these issues, provide effective therapies, and refer patients to appropriate specialists. This chapter will address counseling, an overview of male and female sexual and reproductive physiological responses in the case of an intact nervous system, and a description of the impact of disorders of the nervous system on sexual function and reproductive health. Treatment options are also reviewed.

The purpose of this study was to determine whether spinal cord functional magnetic resonance imaging could be used to map neural activity throughout the lower thoracic, lumbar, and sacral spinal cord regions during sexual arousal in healthy men. The authors found that viewing erotic films and genital self-stimulation elicited predominantly increased signal, indicative of amplified neuronal input to the dorsal and ventral horns and in the autonomic preganglionic nuclei of the lower thoracic, lumbar, and sacral spinal cord. In addition, linear regression analyses revealed a number of robust correlations (|R| ≥ 0.7) between signal intensity changes in these spinal cord regions and self-reported ratings of mental and physical sexual arousal. Taken together, these results demonstrate that spinal cord functional magnetic resonance imaging is an effective and sensitive technique for mapping the neural correlates of sexual arousal in the spinal cords of able-bodied men. Most important, the results from this study indicate that spinal cord functional magnetic resonance imaging may have important applications as a clinical tool for assessing and mapping the changes that occur in the spinal cords of men suffering from sexual dysfunction as a result of spinal cord trauma.

Thanks to the Internet, we can now have access to more information about spinal cord repair. Spinal cord injured (SCI) patients request more information and hospitals offer specific spinal cord repair medical consultations.

Provide practical and relevant elements to physicians and other healthcare professionals involved in the care of SCI patients in order to provide adequate answers to their questions.

Our literature review was based on English and French publications indexed in PubMed and the main Internet websites dedicated to spinal cord repair.

A wide array of research possibilities including notions of anatomy, physiology, biology, anatomopathology and spinal cord imaging is available for the global care of the SCI patient. Prevention and repair strategies (regeneration, transplant, stem cells, gene therapy, biomaterials, using sublesional uninjured spinal tissue, electrical stimulation, brain/computer interface, etc.) for the injured spinal cord are under development. It is necessary to detail the studies conducted and define the limits of these new strategies and benchmark them to the realistic medical and rehabilitation care available to these patients.

Research is quickly progressing and clinical trials will be developed in the near future. They will have to answer to strict methodological and ethical guidelines. They will first be designed for a small number of patients. The results will probably be fragmented and progress will be made through different successive steps.

To review and to summarize the literature on anatomy and physiology of erection in the past three decades, especially the work done in our institution.

A search of the PubMed database was performed using keywords erection, anatomy and erectile dysfunction (ED). Relevant articles were reviewed, analyzed and summarized.

Penile vascularisation and innervation vary substantially. Internal pudendal artery is the major source of penile blood supply, but a supralevator accessory pudendal artery that may originate from inferior vesical or obturator or external iliac arteries is not uncommon. Section of this artery during radical prostatectomy (RP) may adversely affect postoperative potency. Anastomoses between the supra and the infralevator arterial pathways are frequent. The cavernous nerves (CNs) contain parasympathetic and sympathetic nerve fibers and these nerves lie within leaves of the lateral endopelvic fascia. Anastomoses between the CNs and the dorsal nerve of the penis are common. Nitric oxide released from noradrenergic, noncholinergic neurotransmission of the CN and from the endothelium is the principal neurotransmitter-mediating penile erection. Interactions between pro-erectile and anti-erectile neurotransmitters are not completely defined. Finally, medial preoptic area and paraventricular nucleus are the key structures in the central control of sexual function and penile erection.

The surgical and functional anatomy of erection is complex. Precise knowledge of penile vascularisation and innervation facilitates treatment of ED especially after RP.

Significant scientific advances during the past 3 decades have deepened our understanding of the physiology and pathophysiology of penile erection. A critical evaluation of the current state of knowledge is essential to provide perspective for future research and development of new therapies.

To develop an evidence-based, state-of-the-art consensus report on the anatomy, physiology, and pathophysiology of erectile dysfunction (ED).

Consensus process over a period of 16 months, representing the opinions of 12 experts from seven countries.

Expert opinion was based on the grading of scientific and evidence-based medical literature, internal committee discussion, public presentation, and debate.

ED occurs from multifaceted, complex mechanisms that can involve disruptions in neural, vascular, and hormonal signaling. Research on central neural regulation of penile erection is progressing rapidly with the identification of key neurotransmitters and the association of neural structures with both spinal and supraspinal pathways that regulate sexual function. In parallel to advances in cardiovascular physiology, the most extensive efforts in the physiology of penile erection have focused on elucidating mechanisms that regulate the functions of the endothelium and vascular smooth muscle of the corpus cavernosum. Major health concerns such as atherosclerosis, hyperlipidemia, hypertension, diabetes, and metabolic syndrome (MetS) have become well integrated into the investigation of ED.

Despite the efficacy of current therapies, they remain insufficient to address growing patient populations, such as those with diabetes and MetS. In addition, increasing awareness of the adverse side effects of commonly prescribed medications on sexual function provides a rationale for developing new treatment strategies that minimize the likelihood of causing sexual dysfunction. Many basic questions with regard to erectile function remain unanswered and further laboratory and clinical studies are necessary.

The effects of melanotan-II, a non-specific agonist of melanocortin receptors, on erection and its possible sites of action were investigated in anesthetized rats. Delivered i.v. (0.1, 0.3 and 1 mg/kg) or within the paraventricular nucleus of the hypothalamus (0.1 and 1 microg), melanotan-II exerted a dose-dependent inducer activity on erection by eliciting erectile events and shortening latency of the first erectile event to occur. Erectile events were of higher amplitude in rats treated with melanotan-II i.t. (0.2 microg) delivered at the L6-S1 level than in animals treated with the vehicle i.t. delivered. Erectile responses elicited by cavernous nerve stimulation were increased after i.v. melanotan-II (1 mg/kg), thereby exerting facilitator effect on erection. In contrast, melanotan-II injected within the corpus cavernosum (1 microg) did not display any facilitator activity. To investigate the neural pathways involved in the facilitator effect of melanotan-II, we performed acute spinalization (T8 level) and differential selective nerve transections. Neither spinalization nor bilateral transection of pelvic nerves or dorsal penile nerves impaired facilitator activity of i.v. melanotan-II (1 mg/kg). Conversely, the facilitator effect of melanotan-II was abolished after acute removal of the lumbar paravertebral sympathetic chain. These results lead to the conclusion that central and peripheral melanocortin pathways are recruited by melanotan-II, depending on its route of delivery, to exert both inducer and facilitator activities on erection.

The paraventricular nucleus of the hypothalamus is an integration centre between the central and peripheral autonomic nervous systems. It is involved in numerous functions from feeding, metabolic balance, blood pressure and heart rate, to erectile function and sexual behaviour. In particular, a group of oxytocinergic neurons originating in this nucleus and projecting to extra-hypothalamic brain areas (e.g., hippocampus, medulla oblongata and spinal cord) control penile erection in male rats. Activation of these neurons by dopamine and its agonists, excitatory amino acids (N-methyl-D-aspartic acid) or oxytocin itself, or by electrical stimulation leads to penile erection, while their inhibition by gamma-amino-butyric acid (GABA) and its agonists or by opioid peptides and opiate-like drugs inhibits this sexual response. The activation of these neurons is secondary to the activation of nitric oxide synthase, which produces nitric oxide. Nitric oxide in turn causes, by a mechanism that is as yet unidentified, the release of oxytocin in extra-hypothalamic brain areas. Other compounds recently identified that facilitate penile erection by activating central oxytocinergic neurons are peptide analogues of hexarelin, a growth hormone releasing peptide, pro-VGF-derived peptides, endogenous peptides that may be released by neuronal nerve endings impinging on oxytocinergic cell bodies, SR 141716A, a cannabinoid CB1 receptor antagonist, and, less convincingly, adrenocorticotropin-melanocyte-stimulating hormone (ACTH-MSH)-related peptides. Paraventricular oxytocinergic neurons and similar mechanisms are also involved in penile erection occurring in physiological contexts, namely noncontact erections that occur in male rats in the presence of an inaccessible receptive female, and during copulation. These findings show that the paraventricular nucleus of the hypothalamus plays an important role in the control of erectile function and sexual activity. As the male rat is a model of sexual behaviour and penile physiology, which has largely increased in the last years our knowledge of peripheral and central mechanisms controlling erectile function (drugs that induce penile erection in male rats usually do so also in man), the above results may have great significance in terms of a human perspective for the treatment of erectile dysfunction.

Nitric oxide (NO) is formed from the conversion of L-arginine by nitric oxide synthase (NOS), which exists in three isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). nNOS is expressed in penile neurons innervating the corpus cavernosum, and eNOS protein expression has been identified primarily in both cavernosal smooth muscle and endothelium. NO is released from nerve endings and endothelial cells and stimulates the activity of soluble guanylate cyclase (sGC), leading to an increase in cyclic guanosine-3',5'-monophosphate (cGMP) and, finally, to calcium depletion from the cytosolic space and cavernous smooth muscle relaxation. The effects of cGMP are mediated by cGMP dependent protein kinases, cGMP-gated ion channels, and cGMP-regulated phosphodiesterases (PDE). Thus, cGMP effect depends on the expression of a cell-specific cGMP-receptor protein in a given cell type. Numerous systemic vasculature diseases that cause erectile dysfunction (ED) are highly associated with endothelial dysfunction, which has been shown to contribute to decreased erectile function in men and a number of animal models of penile erection. Based on the increasing knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation, selective PDE inhibitors have recently been introduced in the treatment of ED. Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates NO-cGMP-mediated smooth muscle relaxation. Inhibition of PDE5 is expected to enhance penile erection by preventing cGMP degradation. Development of pharmacologic agents with this effect has closely paralleled the emerging science.

Penile erection is a vascular event controlled by the autonomic nervous system. The spinal cord contains the autonomic preganglionic neurons that innervate the penile erectile tissue and the pudendal motoneurons that innervate the perineal striated muscles. Sympathetic pathways are anti-erectile, sacral parasympathetic pathways are pro-erectile, and contraction of the perineal striated muscles upon activity of the pudendal nerves improves penile rigidity. Spinal neurons controlling erection are activated by information from peripheral and supraspinal origin. Both peripheral and supraspinal information is capable of either eliciting erection or modulating or inhibiting an erection already present. Sensory information from the genitals is a potent activator of pro-erectile spinal neurons and elicits reflexive erections. Some pre-motor neurons of the medulla, pons and diencephalon project directly onto spinal sympathetic, parasympathetic and pudendal motoneurons. They receive in turn sensory information from the genitals. These spinal projecting pathways release a variety of neurotransmitters, including biogenic amines (serotonin, dopamine, noradrenaline, and adrenaline) and peptides that, through interactions with many receptor subtypes, exert complex effects on the spinal network that controls penile erection. Some supraspinal structures (e.g. the paraventricular nucleus and the medial preoptic area of the hypothalamus, the medial amygdala), whose roles in erection have been demonstrated in animal models, may not project directly onto spinal pro-erectile neurons. They are nevertheless prone to regulate penile erection in more integrated and coordinated responses of the body, as those occurring during sexual behavior. The application of basic and clinical research data to treatment options for erectile dysfunction has recently proved successful. Pro-erectile effects of phosphodiesterase type 5 inhibitors, acting in the penis, and of melanocortin agonists, acting in the brain, illustrate these recent developments.

For more then 15 years, there has been speculation on the significance of serotonergic pathways in the control of male sexual function, especially in the maintenance of penile flaccidity and the initiation of detumescence. However, only a few in vivo studies on peripheral serotonergic transmission have been carried out. The aim of the present study was to evaluate further the effects of serotonin (5-HT) on isolated human erectile tissue and to detect serum levels of 5-HT in the systemic and cavernous blood taken during different penile conditions from healthy males. The effects of 5-HT on isolated human corpus cavernosum (HCC) were investigated using the organ bath technique. A total of 41 healthy, adult male subjects were exposed to erotic stimuli in order to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during different penile conditions. Serum levels of 5-HT (ng/ml) were determined by means of an enzyme-linked immunosorbent assay. The cumulative addition of 5-HT (0.001-10 microM) induced contraction in the isolated HCC strips. The contractile response was abolished in the presence of 5-HT(1alpha)-receptor antagonist NAN-190. No attenuating effect of 5-HT was observed on electrically induced relaxation of the tissue. Moreover, amplitudes of relaxation remained unaltered in the presence of NAN-190. In the healthy volunteers, a significant increase in 5-HT levels was detected in the cavernous serum from flaccidity (113+/-62) to tumescence and rigidity (140+/-69 and 141+/-54, respectively), followed by a decrease in the detumescence phase (123+/-79). Changes in 5-HT levels in the systemic serum were less pronounced. Under all penile conditions, systemic 5-HT levels were higher than those registered in the cavernous serum. Although 5-HT does not appear to be involved in postsynaptic transmission in the HCC, our results may provide evidence for a physiological significance of 5-HT in the control of penile flaccidity and detumescence. Thus, our findings may give a rationale for the use of 5-HT antagonists in the pharmacotherapy of erectile dysfunction.

Control of penile erection requires the coordination of the hypothalamus and the L6-S1 region of the spinal cord. Erection requires the activation of neuronal nitric oxide synthase (nNOS), which is tightly regulated. Because variants of nNOS (penile nNOS: PnNOS) and the N-methyl-D-aspartate receptor (truncated NMDAR subunit 1: NMDAR1-T) as well as protein inhibitor of NOS (PIN) have all been located in the pelvic ganglia and penile nerves, this work aims to determine whether these proteins are also present in the hypothalamus. It was found that PnNOS, the brain-type nNOS, and PIN, were expressed in the hypothalamus. In contrast, NMDAR1-T was expressed only in the penis, whereas the brain-type NMDAR1 was present in the brain and sacral spinal cord and not in the penis. PnNOS was found in the media preoptic area, posterior magnocellular, and the parvocellular regions of the paraventricular nucleus, supraoptic nucleus, septohypothalamic nucleus, medial septum, cortex, and in some of the nNOS staining neurons throughout the brain. It was absent in the organum vasculosum of the lamina terminalis. PIN staining was present in neurons of the medial preoptic area, paraventricular nucleus, medial septum, and cortex, but not in the supraoptic nucleus, septohypothalamic nucleus, or organum vasculosum of the lamina terminalis. Colocalization between PnNOS and PIN was found in the medial preoptic area, medial septum, and cortex, and less in the paraventricular nucleus. PnNOS and oxytocin were colocalized in the paraventricular nucleus and supraoptic nucleus. In hypothalamic extracts, recombinant PIN-GST protein bound to PnNOS in the extracts and partially inhibited NOS activity. These results indicate that both nNOS variants, and their respective regulatory proteins are present and colocalize in the hypothalamic and spinal cord regions involved in penile erection.

To investigate the effects of cauda equina lesions on sexual function in men.

Sexual function was investigated in 46 men with long standing cauda equina/conus medullaris lesions. All had clinical and radiological findings supporting the diagnosis. The validated Slovene translation of the international index of erectile function (IIEF) was used. The responses were scored and sexual dysfunction categorised as absent, mild, moderate, or severe. The number of patients receiving help for sexual dysfunction was noted. Neurological examination of the trunk and lower limbs, electromyographic (EMG) evaluation of the sacral reflex, and quantitative EMG of the external anal sphincter muscles were done.

Severe sexual dysfunction was reported by 35% of patients, moderate dysfunction by 24%, and slight dysfunction by 26%; normal sexual function was reported by 15%. Orgasmic function was slightly more impaired than erectile function, and sexual desire slightly less. The patients' age, but no findings on clinical neurological or EMG examination, correlated with sexual function. Only five men had received medical attention for sexual dysfunction.

There is significant sexual impairment in men with lesions of the cauda equina or conus medullaris. This is poorly correlated with neurological and EMG findings and has received insufficient medical attention.

By using a combination of genetic, pharmacological, and anatomical approaches, we show that the melanocortin 4 receptor (MC4R), implicated in the control of food intake and energy expenditure, also modulates erectile function and sexual behavior. Evidence supporting this notion is based on several findings: (i) a highly selective non-peptide MC4R agonist augments erectile activity initiated by electrical stimulation of the cavernous nerve in wild-type but not Mc4r-null mice; (ii) copulatory behavior is enhanced by administration of a selective MC4R agonist and is diminished in mice lacking Mc4r; (iii) reverse transcription (RT)-PCR and non-PCR based methods demonstrate MC4R expression in rat and human penis, and rat spinal cord, hypothalamus, brainstem, pelvic ganglion (major autonomic relay center to the penis), but not in rat primary corpus smooth muscle cavernosum cells; and (iv) in situ hybridization of glans tissue from the human and rat penis reveal MC4R expression in nerve fibers and mechanoreceptors in the glans of the penis. Collectively, these data implicate the MC4R in the modulation of penile erectile function and provide evidence that MC4R-mediated proerectile responses may be activated through neuronal circuitry in spinal cord erectile centers and somatosensory afferent nerve terminals of the penis. Our results provide a basis for the existence of MC4R-controlled neuronal pathways that control sexual function.

The lumbosacral spinal cord contains neurones that control the lower urogenital and digestive tracts. Spinal neurones respond to activation from the periphery and supraspinal nuclei. Glutamate, acting through a variety of receptors, is an established transmitter of excitatory pathways to the spinal cord. Using immunohistochemical methods, we reveal the presence of the N-methyl-D-aspartic acid R1 (NMDAR1) glutamatergic receptor subunit in the lumbosacral spinal network that controls urogenital and digestive functions: the dorsal horn; the area around the central canal including the dorsal grey commissure; the sacral parasympathetic nucleus; and pudendal motoneurones. A complete thoracic spinal section did not alter labelling. Using retrograde labelling techniques, we identify sacral preganglionic neurones and pudendal neurones that are NMDAR1 immunoreactive. Glutamate, acting at NMDA receptors, can therefore co-ordinate the activity of the autonomic and somatic outflows to the pelvic organs.

Erectile dysfunction (ED) has been the most neglected complication of diabetes. It is a common abnormality that affects more than 20 million American men. The prevalence of ED in the general population between the ages of 40 to 70 years is 52%. In men with diabetes, it ranges from 35% to 75%, and occurs at an earlier age. There have been several advances in the understanding of the physiologic and biochemical mechanisms controlling penile erections. Improved techniques in diagnoses and treatment of impotence have given the male with diabetes some hope in the management of this prevalent and emotionally disturbing complication.

Review of literature.

To review the physical aspects related to penile erection, ejaculatory dysfunction, semen characteristics, and techniques for enhancement of fertility in spinal cord lesioned (SCL) men.

Worldwide: individuals with traumatic as well as non-traumatic SCL.

Recommendations for management of erectile dysfunction in SCL men: If it is possible to obtain a satisfactory erection but of insufficient duration, then try to use a venous constrictor band to find out if this is sufficient to maintain the erection. Otherwise we recommend Sildenafil. If Sildenafil is not satisfactory then use intracavernous injection with prostaglandin E(1) (some SCL men may prefer cutaneous or intraurethral application). We discourage the implantation of penile prosthesis for the sole purpose of erection. Recommendations for management of ejaculatory dysfunction in SCL men: Penile vibratory stimulation (PVS) to induce ejaculation is recommended as first treatment choice. If PVS fails, SCL men should be referred for electroejaculation (EEJ). Semen characteristics: Impaired semen profiles with low motility rates are seen in the majority of SCL men. Recently reported data gives evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few weeks) an acute SCL. It is suggested that some factors in the seminal plasma and/or disordered storage of spermatozoa in the seminal vesicles are mainly responsible for the impaired semen profiles in men with chronic SCL. Fertility: Home insemination with semen obtained by PVS and introduced intravaginally in order to achieve successful pregnancies may be an option for some SCL men and their partners. The majority of SCL men will further enhance their fertility potential when using either PVS or EEJ combined with assisted reproduction techniques such as intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection.

Alterations in the nitric oxide (NO)/cGMP levels in hypothalamic nuclei, including the medial preoptic area (MPOA), regulate critical aspects of sexual behavior and penile reflexes. However, the effects of altered central nervous system (CNS) NO/cGMP levels at the end organ level, that is, on the magnitude/quality of the erection so achieved [intracavernous pressure (ICP) response], has yet to be evaluated. The goal of this report was to evaluate the effects of intrathecal administration of modulators of NO and cGMP levels on ICP responses to stimulation of the MPOA and cavernous nerve in rats in vivo. In all cases, intrathecal administration of compounds that increase and decrease cGMP and NO levels, respectively, was associated with corresponding increases and decreases in the MPOA-stimulated ICP response. Specifically, sodium nitroprusside (SNP), 8-bromo-cGMP, and sildenafil increased the MPOA-stimulated ICP response, whereas N(omega)-nitro-L-arginine methyl ester reduced it. None of the intrathecal treatments had detectable effects on blood pressure or the cavernous nerve-stimulated ICP response, although intravenous sildenafil increased the latter. These data clearly indicate that intrathecal drug administration affects central and not peripheral neural mechanisms and, moreover, documents that CNS NO/cGMP levels can affect erectile capacity per se (i.e., ICP) in the rat model.

Central regulation of the erectile process involves several transmitters, including dopamine, serotonin, noradrenaline, and nitric oxide, and peptides, such as oxytocin and ACTH/alpha-MSH. These systems may be targets for future drugs designed to treat erectile dysfunction. Peripherally, the different steps involved in neurotransmission, impulse propagation, and intracellular transduction of neural signals in penile smooth muscles need further investigation. Continued studies of the interactions between different transmitters/modulators may reveal new combination therapies. Increased knowledge of the changes in penile tissues associated with erectile dysfunction may explain the pathogenetic mechanisms and help to prevent the disorder.

Neurologic erectile dysfunction presents a diagnostic and treatment challenge to the internist and urologist. Multiple chronic disease modalities and traumatic etiologies exist. Education regarding these conditions and a detailed and thorough history and office work-up are the best resources for the clinician. Treatment can follow the model of proceeding from the least to most invasive procedure (process of care), taking into account patient and partner satisfaction. Because the psychology of grief and loss may enter into treatment of some neurologic conditions (e.g., erectile dysfunction after radical retropubic prostatectomy, spinal cord injury, or chronic diseases), a whole-patient approach encompassing psychotherapy is warranted.

The functional state of the penis, flaccid or erect is governed by smooth muscle tone. Sympathetic contractile factors maintain flaccidity whilst parasympathetic factors induce smooth muscle relaxation and erection. It is generally accepted that nitric oxide (NO) is the principal agent responsible for relaxation of penile smooth muscle. NO is derived from two principal sources: directly from non-adrenergic non-cholinergic parasympathetic nerves and indirectly from the endothelium lining cavernosal sinusoids and blood vessels in response to cholinergic stimulation. The generation of NO from L-arginine is catalysed by nitric oxide synthase (NOS). There has been controversy over the relative prevalence of endothelial or neuronal NOS within the penis of different animal species. This review examines the role of NO in the penis in detail. Established and new treatments for erectile dysfunction whose effects are mediated via manipulation of the NO pathway are also described.

Penile erection occurs in response to tactile, visual, and imaginative stimuli in humans. In animals olfactory and auditory cues are particularly important. The participation of multiple sites with the brain and spinal cord, and coordination of somatic and autonomic pathways make sexual behavior in general, and erection in particular, vulnerable to neurologic injury and disease. Sites within the brain and spinal cord act in concert to process, coordinate, then distribute the neural inputs necessary for sexual behavior including erection. Activation of neurons in some of these regions either pharmacologically or by electrical stimulation has been associated with penile tumescence. This review will provide a geographic framework for understanding the neuroanatomical basis of penile erection based primarily on animal data. Following discussion of the anatomical substrates, a clinical correlation is then provided to confirm and reinforce these experimental observations.

Penile erection is caused by a change of the activity of efferent autonomic pathways to the erectile tissues and of somatic pathways to the perineal striated muscles. The spinal cord contains the cell bodies of autonomic and somatic motoneurons that innervate the peripheral targets. The sympathetic outflow is mainly antierectile, the sacral parasympathetic outflow is proerectile, and the pudendal outflow, through contraction of the perineal striated muscles, enhances an erection already present. The shift from flaccidity to erection suggests relations among these neuronal populations in response to a variety of informations. Spinal neurons controlling erection are activated by information from peripheral and supraspinal origin. Both peripheral and supraspinal information is capable of eliciting erection, or modulating or inhibiting an erection already present. One can hypothesize a spinal network consisting of primary afferents from the genitals, spinal interneurons and sympathetic, parasympathetic and somatic nuclei. This system is capable of integrating information from the periphery and eliciting reflexive erections. The same spinal network, eventually including different populations of spinal interneurons, would be the recipient of supraspinal information. Premotor neurons that project directly onto spinal sympathetic, parasympathetic or somatic motoneurons, are present in the medulla, pons and diencephalon. Several of these premotor neurons may in turn be activated by sensory information from the genitals. Aminergic and peptidergic descending pathways in the vicinity of spinal neurons, exert complex effects on the spinal network that control penile erection. This is caused by the potential interaction of a great variety of receptors and receptor subtypes present in the spinal cord. Brainstem and hypothalamic nuclei (among the latter, the paraventricular nucleus and the medial preoptic area) may not necessarily reach spinal neurons directly. However they are prone to regulate penile erection in more integrated and coordinated responses of the body, such as those occurring during sexual behavior. Finally, the central and spinal role of regulatory peptides (oxytocin, melanocortins, endorphins) has only recently been elucidated.

Smooth muscle relaxation of the corpus cavernosum is the key mechanism of erection. It depends on a cascade of consecutive regulatory systems starting in the central nervous system, and proceeding via peripheral neurotransmission to intracellular signal transmission within the cavernous smooth muscle cells. Knowledge of these interacting mechanisms of erection is fundamental for understanding of the mode of action of new and possibly selective pharmacological agents that are presently available or under evaluation for treatment of erectile dysfunction.

To examine the effects of altered nitric oxide (NO) levels in the paraventricular nucleus (PVN) on copulatory behavior and reflexive erections in male rats.

Extracellular nitrite (NO2-) and nitrate (NO3-) levels were measured in the PVN following administration of the NO precursor L-arginine (L-arg, 10 mM), the NO synthase inhibitor N(G)-monomethyl L-arginine (L-NMMA, 10 mM), or Ringer's solution via a dialysis probe to the PVN. The effects of alterations in extracellular NO on reflexive erections and copulatory behavior were assessed.

L-arg administration was associated with significant elevations of extracellular NO2- and NO3- in the PVN, while L-NMMA significantly reduced NO2- and NO3- levels. A corresponding increase in reflexive erections was noted during infusion of L-arg in the PVN, with a corresponding decrease in reflexive erections observed during administration of L-NMMA into the PVN (Student's t test for paired samples, p <0.05). Mount rate was unaffected by infusion of the either L-arg or L-NMMA.

Altered NO levels in the PVN affected the frequency of reflexive erections, but not the mount rate. These studies contrast with previous observations of the effects of altered NO levels in the MPOA, and support the hypothesis that physiological specificity in the actions of NO on discrete brain nuclei may have important implications to erectile physiology and dysfunction.

Erectile dysfunction is a common complication of spinal cord injury. This double-blind, placebo-controlled, two-way crossover study assessed the efficacy and safety of oral sildenafil in men with erectile dysfunction caused by traumatic spinal cord injury. A total of 178 men (mean age, 38 years) received placebo or sildenafil 1 hour before sexual activity for 6 weeks; after a 2-week washout period, the men received the alternate treatment for 6 weeks. The 50-mg starting dose could be adjusted to 100 or 25 mg based on efficacy and tolerability. Efficacy was assessed by using global efficacy questions, the International Index of Erectile Function (IIEF), and a patient log of erectile activity. Of 143 men with residual erectile function at baseline, 111 (78%) reported improved erections and preferred sildenafil to placebo. For all men (including those who reported no residual erectile function at baseline), 127 of 168 (76%) reported improved erections and preferred sildenafil to placebo. For all men, 132 of 166 (80%) reported that sildenafil improved sexual intercourse compared with 17 of 166 men (10%) reporting improvement with placebo. IIEF questions assessing the ability to achieve and maintain erections and satisfaction with sexual intercourse demonstrated significant improvement with sildenafil. Sildenafil was well tolerated, with a low rate of discontinuation because of treatment-related adverse events (2% vs 1% for placebo). Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction caused by spinal cord injury.

To better understand the similarities and differences in the neural control of penile erection occurring in different contexts, we recorded intracavernous pressure (ICP) in conscious rats using a miniaturized telemetric device. ICP changes during reflexive, noncontact, and apomorphine-induced erections were characterized by a plateau increase surmounted by peaks. Plateaus were also elicited by cavernous nerve stimulation in anesthetized rats, suggesting that the cavernous nerve represents the final common proerectile autonomic pathway in these contexts and that it responds similarly to information originating in the periphery or in supraspinal nuclei. During reflexive, noncontact, and apomorphine-induced erections, activation of spinal autonomic nuclei, considered the spinal generators of erection, would take place first, representing a prerequisite for the occurrence of peaks. Suprasystolic peaks would result from the addition of pudendal motoneuron activity. In contrast, only peaks were recorded during copulation. In this context, the convergence of peripheral and supraspinal information apparently elicits the best temporal arrangement of autonomic and somatic outflows, reflecting a highly organized and integrated spinal activity.

This study was designed to determine the extent to which Fos immunoreactivity (induced either by mating or noncontact sociosexual interaction) and androgen receptor (AR) immunoreactivity are colocalized in brain and spinal cord of male rats. Some males (Mated) were allowed to mate to ejaculation; others (Social Controls) were placed with females but physical contact was prevented by a wire mesh screen; remaining males (Isolated) were placed alone in the test jar for the duration of the test period. After testing, brains and spinal cords were examined for AR and Fos immunoreactivity (ir). PG21 anti-AR and anti-c-fos primary antibodies were visualized by fluorescence microscopy using cyanine-conjugated and fluorescein-conjugated secondary antibodies. In both brain and spinal cord, the number of Fos-ir neurons varied according to group: Mated males > Social Controls > Isolated males. Fos was highly localized in subsets of AR-ir neurons within the medial preoptic nucleus, bed nucleus of the stria terminalis, dorsomedial nucleus of the amygdala, and central tegmental field. Fos was also localized in subsets of AR-ir neurons within the L5, L6, and S1 segments of the spinal cord. Spinal cord concentrations of AR-ir and Fos-ir neurons were greatest in Lamina X, and the vast majority of Fos-ir neurons in the dorsal part of Lamina X were also AR-ir. Thus, in both brain and spinal cord, androgen-sensitive neurons are active during mating, and transmission of sexually relevant information from cord to brain is probably accomplished via hormone-sensitive spinal neurons.