Contrôle neurologique de l’éjaculation

The brain control of the genital tract and sexual behaviour remains poorly understood. Clinical results and basic research indicate that the neural control of ejaculation depends on three levels of organization. The first level consists of peripheral autonomic and somatic nerves. Leaving the spinal cord, these nerves control the motility, secretions and blood supply of the genital tract, and contractions of perineal striated muscles. Their path in the abdominal cavity and the effects of their neuro-transmitters on peripheral tissues have been established. These nerves also convey sensory information from the genital tract to the spinal cord. The second level is represented by the spinal cord. The thoracolumbar (sympathetic), and sacral (parasympathetic and pudendal) segments of the cord contain the somata of autonomic and somatic motoneurons, whose axons run in the above nerves. These motoneurons are part of a spinal network that likely organizes the activity of the whole genital tract in a given context such as copulation. The role of the different spinal cord segments in the control of ejaculation is mainly inferred from observations of the deleterious effects of spinal cord injury in human patients. A small population of galaninergic positive neurons has recently been identified in the lumbar segments of the rat spinal cord that plays a major role in ejaculation (Truitt and Coolen, 2003). Selective lesion of this population abolishes in copula ejaculations, but spares erection. Finally, the third level of organization is represented by supraspinal nervous structures. The spinal cord receives direct excitatory and inhibitory information from the brainstem, pons and hypothalamus. In turn, these structures receive sensory information from the genital tract. However, their role in the control of ejaculation remains poorly investigated. Again, it is mainly inferred from the observation of the deleterious effects of pharmacological treatments on brain neurotransmission. Positron emission tomography has recently been used to observe brain areas whose activity is enhanced during ejaculation in humans (Holstege et al., 2003). In this study, several areas of the right side of the cortex and the cerebellum were activated. The targets of future clinical and basic research include: the neural basis of the required coordination between spinal autonomic and somatic nuclei that innervate the genital tract, the role of sensory information from the genital tract in the recruitment and coordination of spinal and supraspinal nuclei, and finally the integration of descending excitatory and inhibitory influences onto the spinal cord. Both the organization during development and the activation at puberty of the spinal neural network that controls the genital tract are dependent on androgens. Future research should identify the regulatory factors that, in response to the action of androgens, provide neurons with the possibility of building their connexions and selecting their neurotransmitters and receptors.     

Vers une approche physiopathologique des troubles de l’éjaculation

Seminal emission and sperm expulsion are under the control of both the sympathetic and parasympathetic outflows and also of the somatic innervation conveyed by the pudendal nerve. The 2 phases of ejaculation are reflexive with the reflexes handled at the thoraco-lumbar and sacral levels of the spinal cord. Such a spinal organization remains widely unknown. The role of various peripheral neurotransmitters has been evidenced including norepinephrine and acetylcholine and also peptidergic, purinergic i.e. ATP and nitric oxide. Stimulation of the seminal tract afferents play a crucial in the onset of ejaculatory mechanisms. Except for the dorsal nerve of the penis, there is a lack of information concerning these afferents. Several supraspinal centers i.e. hypothalamus, medial amygdala, pons and nucleus paragigantocellularis exert descending and ascending inhibitory and excitatory influences on spinal nuclei controlling emission and expulsion of sperm. Central neurotransmission responsible for this supraspinal control could involve serotonin, oxytocin and norepinephrine. In the light of the available anatomical and neurophysiological data, pathophysiological aspects of ejaculatory disorders are futher discussed. Premature ejaculation could be related to a periheral and central hypersentivity. Most of the other ejaculation abnormalities are likely mainly related to an impairment of the central mechanisms.     

Physiology and pharmacology of ejaculation

Ejaculation requires an interplay of peripheral actors comprising, among others, smooth and skeletal fibers, glandular and endothelial cells. These actors are driven by vegetative and somatic innervations, deriving essentially from the spinal cord, in turn controlled by cerebral structures and endocrine factors, mostly steroids; These controls require sensitive afferences and command two steps, emission under autonomic control, and ejaculation per se which further involves somatic motoneurons. This review first describes the peripheral innervation of the part of the genital tract concerned in ejaculation, in which the sympathetic component is predominant and releases noradrenalin and neuropeptides; however parasympathetic and somatic components also play a role. At the spinal level, control circuits are organized into networks influenced by spinal structures, which have been discovered through selective lesions or stimulations, as well as by retrograde trans-synaptic tracing with neurotropic viruses. Among these structures, the median preoptic area and the hypothalamic paraventricular nucleus are major regulation sites. On the other hand, serotoninergic and also dopaminergic and adrenergic systems are implicated as well in the command of ejaculation; the latter constitute priviledged targets for a pharmacological treatment of dysfunctions.     

Apomorphine, systèmes dopaminergiques centraux et contrôle de l’érection

Relaxation of penile erectile tissue and increased blood flow in the penile arteries are the two basic local mechanisms of erection. Relaxation is elicited by several agents released by the nerve terminals of sacral parasympathetic pathways (nitric oxide [NO] and vasoactive intestinal polypeptide [VIP]) and endothelial cells. The increased activity of sacral parasympathetic pathways leads to erection. Other molecules (e.g. noradrenaline) released by the nerve endings of sympathetic pathways contract the penile tissue and arteries. A decrease in sympathetic pathway activity can therefore lead to erection. A better understanding of the local mechanisms of penile erection has led to the production of compounds designed to treat erectile dysfunction via a peripheral target. Such compounds are recognised as initiators if they elicit erectionper se or as conditioners if they potentiate a mechanism already present. The central control of penile erection plays an important role in the optimal functioning of the erectile process. Sympathetic and parasympathetic nerves to the penis originate in the spinal cord. In a sexually relevant context, it is likely that a shift of the balance between sympathetic and parasympathetic activities causes erection. This shift is controlled at the spinal cord level by information from the periphery (reflex pathways) and from supraspinal nuclei. Recent experiments have focused on supraspinal nuclei present in the brainstem, pons, and hypothalamus that directly project onto the sacral spinal cord. Pharmacological approaches have revealed an important role for central dopamine in the control of sexual behavior and the genital tract in males. Central dopamine can therefore regulate both sympathetic and parasympathetic pathways. Levels of DA and its metabolites increase in several brain structures during sexual activity. DA agonists, e.g. the D₁/D₂ agonist apomorphine, affect the sexual behavior, erection and ejaculation in a variety of animal species and in humans. Recent clinical investigations have revealed the benefits of the use of apomorphine in patients suffering from erectile dysfunction. Compounds acting centrally, such as apomorphine, can contribute to reorganize the activity of sympathetic and parasympathetic outflows leading to an appropriate recruitment of the autonomic pathways to the genital tract.     

Activation of Mu or Delta Opioid Receptors in the Lumbosacral Spinal Cord Is Essential for Ejaculatory Reflexes in Male Rats

Ejaculation is controlled by a spinal ejaculation generator located in the lumbosacral spinal cord, consisting in male rats of lumbar spinothalamic (LSt) cells and their inter-spinal projections to autonomic and motor centers. LSt cells co-express several neuropeptides, including gastrin releasing peptide (GRP) and enkephalin. We previously demonstrated in rats that GRP regulates ejaculation by acting within the lumbosacral spinal cord. In the present study, the hypothesis was tested that enkephalin controls ejaculation by acting on mu (MOR) or delta opioid receptors (DOR) in LSt target areas. Adult male rats were anesthetized and spinalized and received intrathecal infusions of vehicle, MOR antagonist CTOP (0.4 or 4 nmol), DOR antagonist (TIPP (0.4, 4 or 40 nmol), MOR agonist DAMGO (0.1 or 10 nmol), or DOR agonist deltorphin II (1.3 or 13 nmol). Ejaculatory reflexes were triggered by stimulation of the dorsal penile nerve (DPN) and seminal vesicle pressure and rhythmic contractions of the bulbocavernosus muscle were analyzed. Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation. Intrathecal infusion of DAMGO, but not deltorphin II triggered ejaculation in absence of DPN stimulation. Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals. Overall, these results support the hypothesis that enkephalin plays a critical role in the control of ejaculation in male rats. Activation of either MOR or DOR in LSt target areas is required for ejaculation, while MOR activation is sufficient to trigger ejaculation in the absence of sensory stimulation.     

Cholinergic mechanisms related to REM sleep. III. Tonic and phasic inhibition of monosynaptic reflexes induced by an anticholinesterase in the decerebrate cat

The depression of the postural activity induced by intravenous injection of eserine sulphate (0.1 mg/kg), an anticholinesterase, has been studied in precollicular decerebrate cats. The extensor and flexor monosynaptic reflexes elicited by single shock stimulation of the GS, P1-FDHL and DP nerves are tonically depressed during the episodes of postural atonia induced by the anticholinesterase. A further phasic depression of the monosynaptic reflexes occurs during the bursts of rapid eye movements (REM) typical of these episodes. These changes in spinal reflex activity closely resemble the tonic depression of the spinal reflexes described in the unrestrained cats during the desynchronized sleep as well as the phasic depression of the spinal reflexes characteristic of the hypnic bursts of REM. Results obtained after spinal cord section indicate that both the tonic and the phasic depression of the spinal reflexes induced by eserine are due to active inhibitory influences originating from supraspinal structures. A complete bilateral destruction of the vestibular nuclei or limited to the medial and descending vestibular nuclei abolishes not only the cholinergically induced bursts of REM, as reported in a previous paper, but also the related phasic depression of the monosynaptic reflexes. These findings can be related with previous observations showing that a bilateral lesion of the vestibular nuclei abolishes the REM bursts of desynchronized sleep, as well as the related phasic inhibition of the spinal reflexes. The tonic depression of the monosynaptic reflexes induced by the anticholinesterase, on the other hand, remains unmodified by this vestibular lesion. This depression, therefore, can be attributed to supraspinal descending inhibitory volleys originating from extravestibular structures.     

Characterization of p-chloroamphetamine-induced penile erection and ejaculation in anesthetized rats

Methodological shortcomings present in elicitation of male sexual reflexes in anesthetized animals. The present study has demonstrated, however, that intraperitoneal (i.p.) injection of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, elicited simultaneously both penile erection and ejaculation in anesthetized rats. PCA (2.5-10.0 mg/kg, i.p.) caused an intermittent cluster of genital responses consisting of penile erection, glans erections, and penile cups, which closely resembles the response observed during the ex copula tests in unanesthetized rats. Measurements of intracavernous penile pressure showed that rhythmic changes in penile pressure were produced by PCA, together with glans erections and penile cups. PCA also caused a frequent ejaculations and the weighing of ejaculate accumulated over 0.5 hr was increased in a bell-shaped pattern, and the maximum effect was observed at 5.0 mg/kg. Pretreatment with p-chlorophenylalanine, a serotonin (5-HT)-synthesis inhibitor, significantly inhibited the expression of PCA-induced penile erection and ejaculation, while acute spinal transection at thoracic level did not affect the sexual responses. These results indicate that PCA-induced penile erection and ejaculation in anesthetized rats are mainly produced by the release of 5-HT, which is limited to the lower spinal cord and/or the peripheral sites. Furthermore, the sexual responses can be easily and reliably elicited by administration of PCA, which may be useful for the study of the mechanisms underlying male sexual functions.     

Monoaminergic Modulation of Spinal Viscero-Sympathetic Function in the Neonatal Mouse Thoracic Spinal Cord

Descending serotonergic, noradrenergic, and dopaminergic systems project diffusely to sensory, motor and autonomic spinal cord regions. Using neonatal mice, this study examined monoaminergic modulation of visceral sensory input and sympathetic preganglionic output. Whole-cell recordings from sympathetic preganglionic neurons (SPNs) in spinal cord slice demonstrated that serotonin, noradrenaline, and dopamine modulated SPN excitability. Serotonin depolarized all, while noradrenaline and dopamine depolarized most SPNs. Serotonin and noradrenaline also increased SPN current-evoked firing frequency, while both increases and decreases were seen with dopamine. In an in vitro thoracolumbar spinal cord/sympathetic chain preparation, stimulation of splanchnic nerve visceral afferents evoked reflexes and subthreshold population synaptic potentials in thoracic ventral roots that were dose-dependently depressed by the monoamines. Visceral afferent stimulation also evoked bicuculline-sensitive dorsal root potentials thought to reflect presynaptic inhibition via primary afferent depolarization. These dorsal root potentials were likewise dose-dependently depressed by the monoamines. Concomitant monoaminergic depression of population afferent synaptic transmission recorded as dorsal horn field potentials was also seen. Collectively, serotonin, norepinephrine and dopamine were shown to exert broad and comparable modulatory regulation of viscero-sympathetic function. The general facilitation of SPN efferent excitability with simultaneous depression of visceral afferent-evoked motor output suggests that descending monoaminergic systems reconfigure spinal cord autonomic function away from visceral sensory influence. Coincident monoaminergic reductions in dorsal horn responses support a multifaceted modulatory shift in the encoding of spinal visceral afferent activity. Similar monoamine-induced changes have been observed for somatic sensorimotor function, suggesting an integrative modulatory response on spinal autonomic and somatic function.     

Spinal proerectile effect of oxytocin in anesthetized rats

The spinal cord contains the neural network that controls penile erection. This network is activated by information from peripheral and supraspinal origin. We tested the hypothesis that oxytocin (OT), released at the lumbosacral spinal cord level by descending projections from the paraventricular nucleus, regulated penile erection. In anesthetized male rats, blood pressure and intracavernous pressure (ICP) were monitored. Intrathecal (it) injection of cumulative doses of OT and the selective OT agonist [Thr(4),Gly(7)]OT at the lumbosacral level elicited ICP rises whose number, amplitude, and area were dose dependent. Thirty nanograms of OT and one-hundred nanograms of the agonist displayed the greatest proerectile effects. Single injections of OT also elicited ICP rises. Preliminary injection of a specific OT-receptor antagonist, hexamethonium, or bilateral pelvic nerve section impaired the effects of OT injected it. NaCl and vasopressin injected it at the lumbosacral level and OT injected it at the thoracolumbar level or intravenously had no effect on ICP. The results demonstrate that OT, acting at the lumbosacral spinal cord, elicits ICP rises in anesthetized rats. They suggest that OT, released on physiological activation of the PVN in a sexually relevant context, is a potent activator of spinal proerectile neurons.     

Locomotion induced by epidural stimulation in a decerebrated cat after spinal cord injury

The effect of partial and complete spinal cord transection (Th7–Th8) on locomotor activity evoked in decerebrated cats by electrical epidural stimulation (segment L5, 80–100 μA, 0.5 ms at 5 Hz) has been investigated. Transection of dorsal columns did not substantially influence the locomotion. Disruption of the ventral spinal quadrant resulted in deterioration and instability of the locomotor rhythm. Injury to lateral or medial descending motor systems led to redistribution of the tone in antagonist muscles. Locomotion could be evoked by epidural stimulation within 20 h after complete transection of the spinal cord. The restoration of polysynaptic components in EMG responses correlated with recovery of the stepping function. The data obtained confirm that initiation of locomotion under epidural stimulation is caused by direct action on intraspinal systems responsible for locomotor regulation. With intact or partially injured spinal cord, this effect is under the influence of supraspinal motor systems correcting and stabilizing the evoked locomotor pattern.     

Tachykinins as modulators of the micturition reflex in the central and peripheral nervous system

In the normal urinary bladder, tachykinins (TKs) are expressed in a population of bladder nociceptors that is sensitive to the excitatory and desensitizing effects of capsaicin (i.e., capsaicin-sensitive primary afferent neurons (CSPANs)). Several endobiotics or xenobiotics excite CSPANs and release TKs and other mediators at both the peripheral and spinal cord level. The peripheral release of TKs determines a set of responses (known as neurogenic inflammation) that includes vasodilatation, plasma protein extravasation, smooth muscle contraction and stimulation of afferent nerves. Following chronic inflammation, both immune cells and capsaicin-resistant sensory neurons can de novo express TKs: whether these pools of TKs are releasable and contribute to inflammatory processes is presently unsettled. At the spinal cord level, the release of TKs contributes in determining an altered pattern of vesicourethral reflexes in response to nociceptive stimulation of the bladder by conveying: (a) the afferent transmission to supraspinal sites, and (b) descending or sensory inputs to the sacral parasympathetic nucleus (SPN). Recent evidence also attribute a synergetic role of TKs in the supraspinal modulation of the sensory arm of the micturition reflex.The overall available information suggests that TK receptor antagonists may affect bladder motility/reflexes which occur during different pathological states, while having little influence on the normal motor bladder function.     

Spinal and supraspinal contributions to central sensitization in peripheral neuropathy

We will focus on spinal cord dorsal horn lamina I projection neurones, their supraspinal targets and involvement in pain processing. These spinal cord neurons respond to tonic peripheral inputs by wind-up and other intrinsic mechanisms that cause central hyper-excitability, which in turn can further enhance afferent inputs. We describe here another hierarchy of excitation - as inputs arrive in lamina I, neurones rapidly inform the parabrachial area (PBA) and periaqueductal grey (PAG), areas associated with the affective and autonomic responses to pain. In addition, PBA can connect to areas of the brainstem that send descending projections down to the spinal cord - establishing a loop. The serotonin receptor, 5HT3, in the spinal cord mediates excitatory descending inputs from the brainstem. These descending excitatory inputs are needed for the full coding of polymodal peripheral inputs from spinal neurons and are enhanced after nerve injury. Furthermore, activity in this serotonergic system can determine the actions of gabapentin (GBP) that is widely used in the treatment of neuropathic pain. Thus, a hierarchy of separate, but interacting excitatory systems exist at peripheral, spinal and supraspinal sites that all converge on spinal neurones. The reciprocal relations between pain, fear, anxiety and autonomic responses are likely to be subserved by these spinal-brainstem-spinal pathways we describe here. Understanding these pain pathways is a first step toward elucidating the complex links between pain and emotions.     

Electromyography of pelvic floor muscles

Pelvic floor muscles (PFM) are intimately involved in function of lower urinary tract, the anorectum and sexual functions, therefore their neural control transcends the primarily important somatic innervation of striated muscle, as they are directly involved in “visceral activity”. Neural control of pelvic organs is affected by a unique co-ordination of somatic and autonomic motor nervous systems. Visceral and somatic sensory fibres supply sensory information from pelvic organs; their input influences through central integrative mechanisms also pelvic floor muscle activity. Anatomically, somatic afferent and efferent nerves of the sacral cord segments, reflexly integrated at the spinal cord and brainstem level, conduct neural control of PFM. The inputs from several higher centres influence the complex reflex control and are decisive for voluntary control, and for socially adapted behaviour related to excretory functions.     

Supraspinal influences on the penile reflexes of the male rat: a comparison of the effects of copulation, spinal transection, and cortical spreading depression.

The penile reflexes of the rat were observed on interruption of the copulatory behavior sequence after intromission and ejaculation in the initial ejaculatory series, after the penultimate series, during sexual exhaustion, and during recovery from sexual exhaustion 24 and 72 hr later. These were compared to the reflexes of the normal rat in control conditions, to those of the male rat after spinal transection, and to those of the sexually rested and sexually exhausted male rat under cortical spreading depression (CSD). It was concluded that (1) the stimuli associated with copulation evoke disinhibition of the penile reflexes, these showing the short reflex latencies observed in the spinal animal. The release of the spinal mechanisms is lost within 30 min of the last copulatory event. CSD further inhibits reflex responsivity. (2) Stimuli associated with intromission provoke acceleration of the normal rhythmic presentation of reflexes seen in the normal and spinal rat, resulting in a decrease in the duration of intervals between reflex clusters and an increase in reflex number. This excitation decays within about 15 min after intromission. (3) The increase in degree of penile extension and percentage of penile flips after spinal transection suggests tonic inhibition of reflex intensity in the normal rat. The decrease in capacity to attain full erection with the approach of sexual exhaustion suggests an increase in this inhibition. This does not recover during a rest period but instead intensifies. CSD effects did not mimic the effects of spinal transection but instead depressed reflex excitability. The relationship of these changes to the copulatory behavior pattern is discussed.     

Exogenous overexpression of nerve growth factor in the urinary bladder produces bladder overactivity and altered micturition circuitry in the lumbosacral spinal cord

Background  

Exogenous NGF or saline was delivered to the detrusor smooth muscle of female rats for a two-week period using osmotic mini-pumps. We then determined: (1) bladder function using conscious cystometry; (2) organization of micturition reflexes using Fos protein expression in lumbosacral (L5-S1) spinal cord neurons; (3) calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) in lumbosacral spinal cord segments.     

Mechanisms of the suprasegmental adjustment of the operation of the generators of cyclical motoric reactions

Concousions Analysis of the problem of the organization and mechanisms of the functioning of the system of suprasegmental control of cyclical movements can be recapitulated in the following manner. The systems of control of the cyclical movements (of the locomotion and scratching type) are adaptive control systems in which there are adaptive mechanisms (regulators) of both the spinal and supraspinal levels. The spinocerebellar loop presents as an important component of the supraspinal regulators. The cerebellum apparently plays the role of an adaptive filter in the adaptational mechanism of the supraspinal level, a filter which accomplishes the spatial-temporal filtration of information arriving along its various afferent inputs. That phase and amplitude modulation of the effectiveness of the influence of the corresponding descending systems on the spinal centers of rhythmic movements is accomplished on this basis, modulation which in the final analysis ensures the achievement of a stable state of the limited interaction of the centers with the supraspinal systems. The systems of control of the locomotor and scratching movements differ above all in the quality (degree) of their adaptedness. A higher degree of adaptedness of the system of control is characteristic for the locomotor movements than for the scratching movements.A. A. Bogomolets Institute of Physiology, Ukrainian Academy of Sciences, Kiev. Translated from Neirofiziologiya, Vol. 24, No. 6, pp. 736–755, November–December, 1992.     

Imaging Serotonergic Fibers in the Mouse Spinal Cord Using the CLARITY/CUBIC Technique

Long descending fibers to the spinal cord are essential for locomotion, pain perception, and other behaviors. The fiber termination pattern in the spinal cord of the majority of these fiber systems have not been thoroughly investigated in any species. Serotonergic fibers, which project to the spinal cord, have been studied in rats and opossums on histological sections and their functional significance has been deduced based on their fiber termination pattern in the spinal cord. With the development of CLARITY and CUBIC techniques, it is possible to investigate this fiber system and its distribution in the spinal cord, which is likely to reveal previously unknown features of serotonergic supraspinal pathways. Here, we provide a detailed protocol for imaging the serotonergic fibers in the mouse spinal cord using the combined CLARITY and CUBIC techniques. The method involves perfusion of a mouse with a hydrogel solution and clarification of the tissue with a combination of clearing reagents. Spinal cord tissue was cleared in just under two weeks, and the subsequent immunofluorescent staining against serotonin was completed in less than ten days. With a multi-photon fluorescent microscope, the tissue was scanned and a 3D image was reconstructed using Osirix software.     

Brain circuits for mating behavior in cats and brain activations and de-activations during sexual stimulation and ejaculation and orgasm in humans

In cats, there exists a descending system that controls the posture necessary for mating behavior. A key role is played by the mesencephalic periaqueductal gray (PAG), which maintains strong specific projections to the nucleus retroambiguus located laterally in the most caudal medulla. The NRA, in turn, has direct access to motoneurons in the lumbosacral cord that produce the mating posture. This pathway is slightly different in males and females, but in females its strength fluctuates strongly depending on whether or not the cat is in heat. This way the PAG determines whether or not mating can take place. Via the PAG many other regions in the limbic system as well as in the prefrontal cortex and insula can influence mating behavior.In humans, the brain also controls responses to sexual stimulation as well as ejaculation in men and orgasm in women. Neuroimaging techniques show activations and de-activations but are not able to verify whether the PAG has a similar effect as in cats. PET-scanning results revealed that there is activation in the upper brainstem and cerebellum, as well as insula in men and in the somatomotor and somatosensory cortex in women. During sexual stimulation, but especially during ejaculation and orgasm there was strong de-activation mainly on the left side in the temporal lobe and ventral prefrontal cortex. These neuroimaging results show the importance of lowering the level of alertness regarding your immediate environment (left hemisphere) to have proper sexual behavior.     

Maternal care effects on the development of a sexually dimorphic motor system: The role of spinal oxytocin

Maternal licking in rats affects the development of the spinal nucleus of the bulbocavernosus (SNB), a sexually dimorphic motor nucleus that controls penile reflexes involved with copulation. Reduced maternal licking results in decreased motoneuron number, size, and dendritic length in the adult SNB, as well as deficits in adult male copulatory behavior. Our previous findings that licking-like tactile stimulation influences SNB dendritic development and upregulates Fos expression in the lumbosacral spinal cord suggest that afferent signaling is changed by differences in maternal stimulation. Oxytocin afferents from the hypothalamus are a possible candidate, given previous research that has shown oxytocin is released following sensory stimulation, oxytocin modulates excitability in the spinal cord, and is a pro-erectile modulator of male sex behavior. In this experiment, we used immunofluorescence and immediate early gene analysis to assess whether licking-like tactile stimulation of the perineum activated parvocellular oxytocinergic neurons in the hypothalamus in neonates. We also used enzyme immunoassay to determine whether this same stroking stimulation produced an increase in spinal oxytocin levels. We found that stroking increased Fos immunolabeling in small oxytocin-positive cells in the paraventricular nucleus of the hypothalamus, in comparison to unstroked or handled control pups. In addition, 60 s of licking-like perineal stimulation produced a transient 89% increase in oxytocin levels in the lumbosacral spinal cord. Together, these results suggest that oxytocin afferent activity may contribute to the effects of early maternal care on the masculinization of the SNB and resultant male copulatory behavior.     

Gentle Mechanical Skin Stimulation Inhibits Micturition Contractions via the Spinal Opioidergic System and by Decreasing Both Ascending and Descending Transmissions of the Micturition Reflex in the Spinal Cord

Recently, we found that gentle mechanical skin stimulation inhibits the micturition reflex in anesthetized rats. However, the central mechanisms underlying this inhibition have not been determined. This study aimed to clarify the central neural mechanisms underlying this inhibitory effect. In urethane-anesthetized rats, cutaneous stimuli were applied for 1 min to the skin of the perineum using an elastic polymer roller with a smooth, soft surface. Inhibition of rhythmic micturition contractions by perineal stimulation was abolished by naloxone, an antagonist of opioidergic receptors, administered into the intrathecal space of the lumbosacral spinal cord at doses of 2–20 μg but was not affected by the same doses of naloxone administered into the subarachnoid space of the cisterna magna. Next, we examined whether perineal rolling stimulation inhibited the descending and ascending limbs of the micturition reflex. Perineal rolling stimulation inhibited bladder contractions induced by electrical stimulation of the pontine micturition center (PMC) or the descending tract of the micturition reflex pathway. It also inhibited the bladder distension-induced increase in the blood flow of the dorsal cord at L5–S1, reflecting the neural activity of this area, as well as pelvic afferent-evoked field potentials in the dorsal commissure at the lumbosacral level; these areas contain long ascending neurons to the PMC. Neuronal activities in this center were also inhibited by the rolling stimulation. These results suggest that the perineal rolling stimulation activates the spinal opioidergic system and inhibits both ascending and descending transmissions of the micturition reflex pathway in the spinal cord. These inhibitions would lead to the shutting down of positive feedback between the bladder and the PMC, resulting in inhibition of the micturition reflex. Based on the central neural mechanisms we show here, gentle perineal stimulation may be applicable to several different types of overactive bladder.