What Is the Trigger for Sexual Climax?

A model is proposed to consider sexual climax in men, women, and animals as a unitary phenomenon. Sexual climax is a stereotyped rhythmic pattern of spinally generated neural activity in the autonomic and somatic nerves innervating pelvic organs. A column of neurons in the spinal cord of the male rat is strongly activated by ejaculation (sexual climax in the male). These neurons project to the thalamus and are therefore called lumbar spinothalamic cells (LSt cells). Comprehensive studies have demonstrated that the LSt cells constitute a central pattern generator of ejaculation. These findings have been extended to female animals. Further studies identified LSt cells in the lumbar spinal cord of men and women. Strong evidence indicates that the LSt cells mediate ejaculation in men. The climax model generalizes and extends these studies. It postulates that LSt cells in the lumbar spinal cord of humans and animals of both sexes generate climax. The LSt cells generate the neural activity driving the pelvic contractions and other responses of climax. The activity is transmitted to supraspinal sites to activate orgasm. The LSt cells receive excitatory and inhibitory projections from supraspinal sites. The descending projections reflect subjective arousal and inhibitions. Spinal sensory neurons from the genitals provide excitatory and inhibitory innervation to the LSt cells. These represent pleasurable and noxious sensations. The supraspinal and spinal excitatory and inhibitory inputs are integrated by the LSt. When the sum of the excitatory inputs, minus the sum of the inhibitory inputs reaches a threshold, the LSt cells generate sexual climax.

Role of PAR2 in the Development of Lower Urinary Tract Dysfunction.

PURPOSE: Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome. We previously reported that the mast cell-tryptase-PAR2 (protease activated receptor 2) axis has a critical role in the development of chronic pain in experimental autoimmune prostatitis, a mouse model of chronic prostatitis/chronic pelvic pain syndrome. Therefore, we examined whether PAR2 activation mediates lower urinary tract dysfunction. MATERIALS AND METHODS: Functional cystometry was done in male B6 mice along with immunoblotting and immunohistochemistry for the expression of COL1A1 (collagen type I α I) and α-SMA (α-smooth muscle actin). Flow cytometry analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen. RESULTS: Experimental autoimmune prostatitis resulted in increased urinary voiding frequency and decreased bladder capacity 30 days after initiation. Concurrently, there was increased expression of COL1A1 and α-SMA in the prostates and bladders. In contrast, induction of experimental autoimmune prostatitis in PAR2 knockout mice did not result in altered urodynamics or increased markers of fibrosis in the prostate or the bladder. Single cell suspensions of the prostate, bladder, lymph nodes and spleen demonstrated that in the absence of PAR2 cellular inflammatory mechanisms were still initiated in experimental autoimmune prostatitis but PAR2 expression may be required to maintain chronic inflammation. Finally, antibody mediated PAR2 neutralization normalized urinary voiding frequency and bladder capacity, and attenuated chronic pelvic pain. CONCLUSIONS: PAR2 activation in the prostate may contribute to the development of lower urinary tract dysfunction through proinflammatory as well as profibrotic pathways.

Subungual Congenital Nevus with Recurrent Nevus Phenomenon.

Melanonychia is uncommon. We report the first case of histopathologic recurrence of a completely excised subungual congenital nevus that presented as congenital melanonychia.

Multipotent bone marrow cell-seeded polymeric composites drive long-term, definitive urinary bladder tissue regeneration.

To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies, including urinary diversion and bladder augmentation enterocystoplasty (BAE), utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist that need to be overcome in order to advance tissue-engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utility of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of an appropriate animal model for testing. In this study, we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold coseeded with autologous bone marrow-derived mesenchymal stem cells and CD34+ hematopoietic stem/progenitor cells support robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem-cell-seeded small-intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem-cell synergism promoted functional trilayer bladder tissue regeneration, including whole-graft neurovascularization, in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem-cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.

A pivotal role of lumbar spinothalamic cells in the regulation of ejaculation via intraspinal connections.

INTRODUCTION: A population of lumbar spinothalamic cells (LSt cells) has been demonstrated to play a pivotal role in ejaculatory behavior and comprise a critical component of the spinal ejaculation generator. LSt cells are hypothesized to regulate ejaculation via their projections to autonomic and motor neurons in the lumbosacral spinal cord. AIM: The current study tested the hypothesis that ejaculatory reflexes are dependent on LSt cells via projections within the lumbosacral spinal cord. METHODS: Male rats received intraspinal injections of neurotoxin saporin conjugated to substance P analog, previously shown to selectively lesion LSt cells. Two weeks later, males were anesthetized and spinal cords were transected. Subsequently, males were subjected to ejaculatory reflex paradigms, including stimulation of the dorsal penile nerve (DPN), urethrogenital stimulation or administration of D3 agonist 7-OH-DPAT. Electromyographic recordings of the bulbocavernosus muscle (BCM) were analyzed for rhythmic bursting characteristic of the expulsion phase of ejaculation. In addition, a fourth commonly used paradigm for ejaculation and erections in unanesthetized, spinal-intact male rats was utilized: the ex copula reflex paradigm. MAIN OUTCOME MEASURES: LSt cell lesions were predicted to prevent rhythmic bursting of BCM following DPN, urethral, or pharmacological stimulation, and emissions in the ex copula paradigm. In contrast, LSt cell lesions were not expected to abolish erectile function as measured in the ex copula paradigm. RESULTS: LSt cell lesions prevented rhythmic contractions of the BCM induced by any of the ejaculatory reflex paradigms in spinalized rats. However, LSt cell lesions did not affect erectile function nor emissions determined in the ex copula reflex paradigm. CONCLUSIONS: These data demonstrate that LSt cells are essential for ejaculatory, but not erectile reflexes, as previously reported for mating animals. Moreover, LSt cells mediate ejaculation via projections within the spinal cord, presumably to autonomic and motor neurons.

Ciprofloxacin-induced phototoxicity in an adult cystic fibrosis population.

The incidence of phototoxicity as a side effect of ciprofloxacin appears to be increased in patients with cystic fibrosis compared to the general population (approximately 2.4%). We used an interview-based questionnaire to determine the incidence of such phototoxic skin reactions in cystic fibrosis patients. Results from 105 respondents revealed the incidence of ciprofloxacin-induced phototoxicity in the adult cystic fibrosis population in Northern Ireland to be 48.4% with only 66% of the patients recalling being given sun care information beforehand. We concluded that the incidence of phototoxicity is increased in patients with cystic fibrosis and that it is important for all to receive good sun care information prior to taking ciprofloxacin given the high risk of developing phototoxic rash.

Peptide amphiphile nanofiber delivery of sonic hedgehog protein to reduce smooth muscle apoptosis in the penis after cavernous nerve resection.

INTRODUCTION: Erectile dysfunction (ED) is a serious medical condition that affects 16-82% of prostate cancer patients treated by radical prostatectomy and current treatments are ineffective in 50-60% of prostatectomy patients. The reduced efficacy of treatments makes novel therapeutic approaches to treat ED essential. The secreted protein Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle and apoptosis that is decreased in cavernous nerve (CN) injury and diabetic ED models. Past studies using Affi-Gel beads have shown SHH protein to be effective in suppressing apoptosis caused by CN injury. AIM: We hypothesize that SHH protein delivered via novel peptide amphiphile (PA) nanofibers will be effective in suppressing CN injury-induced apoptosis. METHODS: Adult Sprague Dawley rats (n=50) were used to optimize PA injection in vivo. PA with SHH protein (n=16) or bovine serum albumin (BSA) (control, n=14) was injected into adult rats that underwent bilateral CN cut. Rats were sacrificed at 2, 4, and 7 days. Alexa Fluor-labeled SHH protein was used to determine the target of SHH signaling (n=3). MAIN OUTCOME MEASURES: Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and semiquantitative immunohistochemical analysis for SHH protein and cluster differentiation protein three (CD3) were performed. RESULTS: SHH-PA caused a 25% and 16% reduction in apoptosis at 4 and 7 days after CN injury and a 9.3% and 19% increase in SHH protein at 4 and 7 days after CN injury. CD3 protein was not observed in SHH-PA-treated penis. In vitro, 73% of SHH protein diffused from PA within 6 days. Labeled SHH was observed in smooth muscle. CONCLUSIONS: PA technology is effective in delivering SHH protein to the penis and SHH is effective in suppressing CN injury-induced apoptosis. These results suggest substantial translational potential of this methodology and show that only a short duration of SHH treatment is required to impact the apoptotic index.

Activation of NMDA receptors in lumbar spinothalamic cells is required for ejaculation.

INTRODUCTION: The sexual reflex ejaculation is controlled by a spinal ejaculation generator located in the lumbosacral spinal cord. A population of spinothalamic (LSt) neurons forms a key component of this generator, as manipulations of LSt cells either block or trigger ejaculation. However, it is currently unknown which afferent signals contribute to the activation of LSt cells and ejaculation. AIM: The current study tested the hypothesis that glutamate, via activation of N-Methyl-D-aspartic acid (NMDA) receptors in LSt cells, is a key regulator of ejaculation. METHODS: Expression of phosphorylated NMDA receptor subunit 1 (NR1) was investigated following mating, or following ejaculation induced by electrical stimulation of the dorsal penile nerve (DPN) in anesthetized, spinalized male rats. Next, the effects of intraspinal delivery of NMDA receptor antagonist AP-5 on DPN stimulation-induced ejaculation were examined. Moreover, the ability of intraspinal delivery of NMDA to trigger ejaculation was examined. Finally, the site of action of NMDA was determined by studying effects of NMDA in male rats with LSt cell-specific lesions. MAIN OUTCOME MEASURES: Expression of NR1 and phosphorylated NR1 in LSt cells was analyzed. Electromyographic recordings of the bulbocavernosus muscle (BCM) were recorded in anesthetized, spinalized rats following stimulation of the DPN and delivery of AP-5 or NMDA. RESULTS: Results indicate that the NR1 receptors are activated in LSt cells following ejaculation in mating animals or induced by DPN stimulation in anesthetized, spinalized animals. Moreover, NR1 activation in LSt cells is an essential trigger for rhythmic BCM bursting, as DPN stimulation-induced reflexes were absent following administration of NMDA receptor antagonist in the L3-L4 spinal area, and were triggered by NMDA. NMDA effects were dependent on intact LSt cells and were absent in LSt-lesioned males. CONCLUSION: These results demonstrate that glutamate, via activation of NMDA receptors in LSt cells, is a key afferent signal for ejaculation.

Activation of MAP kinase in lumbar spinothalamic cells is required for ejaculation.

INTRODUCTION: Ejaculation is a reflex controlled by a spinal ejaculation generator located in the lumbosacral spinal cord responsible for the coordination of genital sensory with autonomic and motor outputs that regulate ejaculation. In the male rat, a population of lumbar spinothalamic cells (LSt cells) comprises an essential component of the spinal ejaculation generator. LSt cells are activated with ejaculation, but the nature of the signal transduction pathways involved in this activation is unknown. Moreover, it is unknown if LSt cell activation is required for expression of ejaculation. AIM: The current study tested the hypothesis that ejaculatory reflexes are triggered via activation of the mitogen-activated protein (MAP) kinase signaling pathway in the LSt cells. METHODS: Expression of phosphorylated extracellular signal-related kinases 1 and 2 (pERK) was investigated following mating behavior, or following ejaculation induced by electrical stimulation of the dorsal penile nerve (DPN) in anesthetized, spinalized male rats. Next, the effects of intrathecal or intraspinal delivery of Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor U0126 on DPN stimulation-induced ejaculation was examined. MAIN OUTCOME MEASURES: Expression of pERK in LSt cells and associated areas was analyzed. Electromyographic recordings of the bulbocavernosus muscle were recorded in anesthetized, spinalized rats. RESULTS: Results indicate that the MAP kinase signaling pathway is activated in LSt cells following ejaculation in mating animals or induced by DPN stimulation in anesthetized, spinalized animals. Moreover, ERK activation in LSt cells is an essential trigger for ejaculation, as DPN stimulation-induced reflexes were absent following administration of MEK inhibitor in the L3-L4 spinal area. CONCLUSION: These data provide insight into the nature of the signal transduction pathways involved in the activation of ejaculation through LSt cells. The data demonstrate that ERK activation in LSt cells is essential for ejaculation and contribute to a more detailed understanding of the spinal generation of ejaculation.

Effect of Onabotulinum Toxin A on Substance P and Receptor Neurokinin 1 in the Rat Ventral Prostate.

INTRODUCTION: The objective of this work is to examine if sensory innervation impacts lower urinary tract symptoms (LUTS). Onabotulinum toxin A (BoNTA) has been used for the treatment of overactive and neurogenic bladder and as a treatment for LUTS secondary to benign prostatic hyperplasia (BPH). The mechanism of how BoNTA impacts LUTS/BPH is unclear. In rats, BoNTA injection causes prostate denervation, apoptosis and atrophy. In clinical trials reduced prostate size and LUTS are observed inconsistently, suggesting a neurologic component. We will examine if BoNTA treatment inhibits substance P production in sensory nerve fibers in the rat prostate. METHODS: Twenty Sprague Dawley rats were divided into four groups including 1X PBS (control, n=6), 2.5 units Onabotulinum toxin A (BoNTA, n=6), 5 units BoNTA (n=6) injected into both lobes of the ventral prostate (VP) and sham surgery (n=2). Rats were Euthanized after one week. Substance P and its receptor neurokinin 1 localization and quantification were performed by counting the number of stained neurons and nerve bundles, by semi-quantitative immunohistochemical analysis and by western analysis. RESULTS: Substance P was localized in neuronal axons and bundles in the stroma of the VP but not in the epithelium. Receptor neurokinin 1 was identified in neuronal bundles of the stroma and in columnar epithelium of the VP ducts. Substance P decreased ~90% after BoNTA treatment (p=0.0001) while receptor neurokinin 1 did not change by IHC (p=0.213) or Western (p=0.3675). CONCLUSIONS: BoNTA treatment decreases substance P in the rat VP.

Central regulation of ejaculation.

Ejaculation is a reflex mediated by a spinal control center, referred to as a spinal ejaculation generator. This spinal ejaculation generator coordinates sympathetic, parasympathetic and motor outflow to induce the two phases of ejaculation, i.e., emission and expulsion. In addition, the spinal ejaculation generator integrates this outflow with inputs that are related to the summation of sexual activity prior to ejaculation that are required to trigger ejaculation. Recently, a group of spinothalamic neurons in the lumbar spinal cord (LSt cells) were demonstrated to comprise an integral part of the spinal ejaculation generator. Specifically, lesions of LSt cells completely ablate ejaculatory function. Moreover, LSt cells are activated following ejaculation, but not following other components of sexual behavior. Furthermore, based on their relationship with autonomic nuclei, motoneurons and genital sensory inputs, LSt cells are also in the ideal anatomical position to integrate sensory inputs and autonomic and motor outflow. Additionally, the spinal ejaculation generator is under inhibitory and excitatory influence of supraspinal sites, including the nucleus paragigantocellularis (nPGi), the paraventricular nucleus of the hypothalamus (PVN) and the medial preoptic area (MPOA). Finally, sensory information related to ejaculation is processed in the spinal cord and brain, possibly contributing to the rewarding properties of ejaculation. One candidate pathway for relay of ejaculation-related cues consists of LSt cells and their projections to the parvocellular subparafascicular thalamic nucleus. Moreover, neural activation specifically related to ejaculation is observed in the brain and may reflect of processing of ejaculation-related sensory cues.

PDE-5 inhibition and sexual response: pharmacological mechanisms and clinical outcomes.

Phosphodiesterase type-5 (PDE-5) inhibitors are a new class of vasoactive drugs that have been developed for treatment of erectile dysfunction (ED). The mechanism of action involves active inhibition of the PDE-5 enzyme and resulting increase in cyclic guanosine monophosphate (cGMP) and smooth muscle relaxation in the penis. Sildenafil citrate (Viagra) is a potent and selective PDE-5 inhibitor, which is the first drug in this class to be approved for treatment of ED. More than 10 million men worldwide have been treated with this drug. Sildenafil has been shown to be generally effective in the treatment of ED, although the degree of efficacy varies according to the etiology and severity of the disorder. The drug is well tolerated, with relatively few contraindications (e.g., nitrates) and safety risks. The cardiovascular effects of sildenafil, in particular, have been extensively investigated. The results of recent studies suggest that sildenafil may have an additional role in the treatment of other male and female sexual disorders, such as premature ejaculation and female sexual arousal disorder, although results to date are inconclusive. Two additional agents in this class (tadalafil [Cialis], vardenafil [Levitra]) have been developed recently and are under regulatory review. Tadalafil is a long-acting PDE-5 inhibitor, which is effective for up to 36 hr in the majority of men. Vardenafil has a similar duration of action to sildenafil, but is more potent and selective biochemically. Both drugs appear to be generally safe and well tolerated, with a similar side-effect profile to sildenafil. There are no controlled comparison studies to date. Despite the overall effectiveness of PDE-5 inhibitors in the treatment of ED, significant psychological and interpersonal issues need to be addressed in their clinical use. The potential impact on societal attitudes toward sexuality and sexual dysfunction also warrants consideration.

Systemic leptin produces a long-lasting increase in respiratory motor output in rats.

Leptin decreases food intake and increases energy expenditure. Leptin administration into the CNS of mice or rats increases alveolar ventilation and dysfunction in leptin signaling has been implicated in the hypoventilation that can accompany obesity. An increase in CO(2) chemosensitivity has been implicated in this response but it is unclear whether ventilation is augmented when PCO(2) is maintained constant. We examined the effects of intravenous leptin to test the hypothesis that systemic leptin administration in isoflurane anesthetized, mechanically ventilated and vagotomized rats would lead to a sustained increase in respiratory motor output that was independent of changes in end-tidal PCO(2), body temperature or lung inflation pressure (an indicator of overall lung and chest wall compliance). In anesthetized Sprague-Dawley rats with end-tidal PCO(2), lung compliance and rectal temperature maintained constant, injection of a bolus of leptin (0.25 mg, 0.5 mg/ml, i.v.), followed over the next 1 h by the intravenous infusion of an additional 0.25 mg, elicited a progressive increase in the peak amplitude of integrated phrenic nerve discharge lasting at least 1 h beyond the end of the infusion. The increase peaked at 90 min at 58.3 ± 5.7% above baseline. There was an associated increase in the slope of the phrenic response to increasing inspired CO(2). There was also a moderate and sustained decrease in arterial pressure 9 ± 1.3 mmHg at 120 min, with no associated change in heart rate. These data indicate that leptin elicits a sustained increase in respiratory motor output that outlasts the administration leptin via a mechanism that does not require alterations in arterial PCO(2), body temperature, or systemic afferent feedback via the vagus nerves. This stimulation may help to prevent obesity-related hypoventilation.

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent.

Benign prostatic hyperplasia (BPH) is a serious health concern and is an underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected men, LUTS/BPH is believed to result from benign proliferation of the prostate resulting in bladder outlet obstruction. Postnatal growth of the prostate is controlled via growth factor and endocrine mechanisms. However, little attention had been given to the function of the autonomic nervous system in prostate growth and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a trophic role in autonomic sensory end organ interaction. In this study, we examine how the autonomic nervous system influences prostate growth as a function of age by quantifying NGF in the rat ventral prostate (VP) after pelvic ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days 30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n=39). Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for NGF were performed on denervated, intact (contralateral side) and sham control VP 7 days after surgery. Ngf RNA expression was significantly increased in the denervated and intact hyperplastic VP. Western blotting showed age-dependent increases in NGF protein at P60 in the contralateral intact VP. NGF was localized in the nerves, basal cells and columnar epithelium of the prostatic ducts. Denervation causes age-dependent increases in NGF in the VP, which is a potential mechanism by which the autonomic nervous system may regulate prostate growth and lead to BPH/LUTS.

Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers.

SHH plays a significant role in peripheral nerve regeneration and has clinical potential to be used as a regenerative therapy for the CN in prostatectomy patients and in other patients with neuropathy of peripheral nerves. Efforts to regenerate the cavernous nerve (CN), which provides innervation to the penis, have been minimally successful, with little translation into improved clinical outcomes. We propose that, Sonic hedgehog (SHH), is critical to maintain CN integrity, and that SHH delivered to the CN by novel peptide amphiphile (PA) nanofibers, will promote CN regeneration, restore physiological function, and prevent penile morphology changes that result in erectile dysfunction (ED). We performed localization studies, inhibition of SHH signaling in the CN, and treatment of crushed CNs with SHH protein via linear PA gels, which are an innovative extended release method of delivery. Morphological, functional and molecular analysis revealed that SHH protein is essential to maintain CN architecture, and that SHH treatment promoted CN regeneration, suppressed penile apoptosis and caused a 58% improvement in erectile function in less than half the time reported in the literature. These studies show that SHH has substantial clinical application to regenerate the CN in prostatectomy and diabetic patients, that this methodology has broad application to regenerate any peripheral nerve that SHH is necessary for maintenance of its structure, and that this nanotechnology method of protein delivery may have wide spread application as an in vivo delivery tool in many organs.

Regulation of cavernous nerve injury-induced apoptosis by sonic hedgehog.

Thirty to eighty-seven percent of patients treated by radical prostatectomy experience erectile dysfunction (ED). The reduced efficacy of treatments in this population makes novel therapeutic approaches to treat ED essential. We propose that abundant apoptosis observed in penile smooth muscle when the cavernous nerve (CN) is cut (mimicking the neural injury which can result from prostatectomy) is a major contributing factor to ED development. We hypothesize that decreased Sonic hedgehog (SHH) signaling is a cause of ED in neurological models of impotence by increasing apoptosis in penile smooth muscle. We examined this hypothesis in a bilateral CN injury model of ED. We found that the active form of SHH protein was significantly decreased 1.2-fold following CN injury, that SHH inhibition causes a 12-fold increase in smooth muscle apoptosis in the penis, and that SHH treatment at the time of CN injury was able to decrease CN injury-induced apoptosis (1-3-fold) in a dose-dependent manner. These results show that SHH stabilizes the alterations of the corpora cavernosal smooth muscle following nerve injury.

Spinal cord control of ejaculation.

Ejaculation is a reflex mediated by a spinal control center, referred to as a spinal ejaculation generator. During intercourse, the spinal ejaculation generator integrates the sensory inputs that are necessary to trigger ejaculation. At the time of ejaculation, it coordinates the sympathetic, parasympathetic, and somatic outflow to induce the two phases of ejaculation, i.e. emission and expulsion. It also provides the brain with signals related to the occurrence of ejaculation. Experimental and clinical data evidenced that these functions were devoted to neurons located in the lumbosacral cord. We recently characterized a population of spinothalamic neurons in the lumbar spinal cord of male rats (LSt cells) that constitutes an integral part of the spinal ejaculation generator. LSt cells send projections to the autonomic nuclei and motoneurons involved in the emission and expulsion phase, and they receive sensory projections from the pelvis. LSt cells are activated with ejaculation, but not following other components of sexual behavior, and lesions of LSt cells completely ablate ejaculatory function. These data support a pivotal role for the LSt cells in the control of ejaculation.

The neural control of female sexual function.

Recent basic research on the neural control of female sexual function is reviewed with an emphasis on the pathways controlling the genitalia. Sexual responses require the coordination of sympathetic, parasympathetic and somatic nervous system. This coordination is performed by interneuronal systems within the lower spinal cord. Sexual responses can be reflexively elicited by genital stimulation. The excitability of the spinal cord can be positively or negatively modulated by descending pathways from supraspinal sites. These supraspinal areas are extensively interconnected and also receive pelvic sensory information. Several of them are modulated by gonadal hormones, allowing for a hormonal control of sexual behavior. Successful restoration of function following neural injury requires an understanding of these neural pathways.

The neurophysiology of female sexual function.

Recent research on the neural control of female sexual function is reviewed. The control of female genital responses has not been extensively studied and significant gaps in our knowledge remain. Sexual arousal is largely the product of spinal level reflexes. A network of interneurons processes the sensory information and generate complex patterns of activities that are then distributed to the autonomic and somatic efferents. The spinal reflexive systems are under inhibitory and excitatory control from the brainstem and hypothalamic sites. Further research is necessary to identify the mechanisms underlying female sexual function, the pathogenesis of sexual dysfunctions and their possible treatment.