The dorsal nerve of the penis, a sensory branch of the pudendal nerve, carries impulses to thoracic, lumbar, and sacral segments of the spinal cord from sensory receptors harbored in the penile skin, prepuce, and glans [39, 77]. Encapsulated receptors (Krause-Finger corpuscles) have been found in the glans but the majority of afferent terminals are represented by free nerve endings [32]. Stimulation of the Krause-Finger corpuscles, which can be potentiated by sensory information coming from various peripheral areas such as penile shaft, perineum, and testes, facilitates the ejaculatory reflex. In various mammalian species, a relatively sparse sensory innervation of ductus deferens, prostate, and urethra has been evidenced which reaches the lumbosacral spinal cord via the pudendal nerve [40, 81]. A second afferent pathway is constituted by fibers travelling along the hypogastric nerve and, after passing through the paravertebral lumbosacral sympathetic chain, enters the spinal cord via thoracolumbar dorsal roots [8]. Sensory afferents terminate in the medial dorsal horn and the dorsal grey column of the spinal cord [62, 102].

The soma of the preganglionic sympathetic neurons are located in the intermediolateral cell column and in the central autonomic region (dorsal gray column) of the lower thoracic and upper lumbar segments of the spinal cord [69, 75]. The sympathetic fibers, emerging from the spinal column via the ventral roots, relay in the paravertebral sympathetic chain. In the majority of mammalian species, the fibers then proceed whether directly via the splanchnic nerves or after relaying in the celiac superior mesenteric ganglia via the intermesenteric nerves to the inferior mesenteric ganglia [79] or superior hypogastric plexus in humans. Emanating from the inferior mesenteric ganglia are the hypogastric nerves that form, after joining the parasympathetic pelvic nerve, the pelvic plexus from which arise fibers innervating the anatomical structures involved in ejaculation.

The cell bodies of the preganglionic parasympathetic neurons are located in the intermediolateral cell column of the sacral (lumbosacral in rodents) segments of the spinal cord, i.e., sacral parasympathetic nucleus (SPN) [74]. The SPN neurons send projections, travelling in the pelvic nerve, to the postganglionic cells located in the pelvic plexus (or inferior hypogastric plexus). Postganglionic parasympathetic neurons fibers follow the course of the blood vessels to reach the pelvic organs participating in ejaculation.

Efferents of somatic motoneurons, cell bodies of which are found at the lumbosacral spinal level (sacral level in the human male) in the Onuf’s nucleus, exit the ventral horn of the medulla and proceed via the motor branch of the pudendal nerve to the pelvic floor striated muscles, including bulbospongiosus and ischiocavernosus muscles [87].

Sensory inputs have been shown sufficient to elicit expulsion reflex or even complete ejaculatory response (forceful expulsion of semen). In an experimental paradigm developed in anesthetized rats with complete transection of the spinal cord at T8 level, urethral distension by accumulating liquid infused into the urethra elicited rhythmic contractions of bulbospongiosus muscles [63]. In anesthetized and intact rats, pudendal nerve (motor branch innervating bulbospongiosus and ischiocavernosus muscles) firing was elicited in response to electrical stimulation of the dorsal nerve of the penis and pelvic nerve which convey sensory information from penis and urethrogenital tract, respectively [38].

In humans also, contractions of bulbospongiosus muscles identified with electromyographic electrodes were evidenced following electrostimulation of the penile dorsal nerve, mechanical distension of the posterior urethra, and magnetostimulation of the sacral roots [76, 78, 90]. These procedures can be used to evaluate the integrity of the reflex arc controlling expulsion and have also served as a basis for developing a method that produces ejaculation in patient with neurogenic anejaculation. This method, namely penile vibratory stimulation, consists in placing a vibration-delivering device on the glans of the penis, either the dorsum or frenulum, and applying 2.5 mm amplitude vibrations at an optimal frequency of 100 Hz for 5–15 min [13, 94]. Penile vibratory stimulation leads to complete ejaculatory response in a significant number of men with spinal cord injury [13].

The importance of the autonomic nervous system in regulating the ejaculatory response is well documented. All of the organs participating in ejaculation receive a dense autonomic innervation composed of sympathetic and parasympathetic axons mainly originating in the pelvic plexus. The ganglia of the pelvic plexus, that are dispersed in amongst the pelvic organs in most animal species, contain fibers from both pelvic and hypogastric nerves and from the caudal paravertebral sympathetic chain [42]. In addition to adrenergic and cholinergic mechanisms of regulation of ejaculation, non-adrenergic/non-cholinergic (NANC) factors including ATP [4, 36, 70], neuropeptide Y (NPY; [31, 109], vasoactive intestinal peptide (VIP; [24, 25], and NO [16, 25] have been shown to have a direct participation in the peripheral control of ejaculation.

Both sympathetic and parasympathetic tones act in a synergistic fashion to initiate seminal emission by activating respectively smooth muscle contraction and epithelial secretion throughout the seminal tract.

From experimental studies carried out in different animal species, it has been demonstrated that activation of the sympathetic nervous system, whether by stimulating sympathetic nerves (hypogastric or splanchnic) or using sympathomimetic agents, elicited strong contractile responses in the ducti deferens [43, 45], seminal vesicle [27, 100], prostate [47, 105], and urethra [47]. Contractions induced by sympathetic nerve stimulation were blocked, only partially in ducti deferens and seminal vesicle [96], by α1 adrenergic antagonists [45]. The functional role of parasympathetic cholinergic fibers conveyed by the pelvic nerves is still not fully defined likely because of the differences in gross and microscopic anatomy of the prostate among species that do not allow straightforward extrapolation between animals.

Contractions of the ductus deferens in rodents [45, 48], prostate [105], and urethra [23] in dogs were elicited by electrical stimulation of the pelvic nerves, although no appreciable emission of fluid was observed [105]. Pharmacological evidence relating to a cholinergic mechanism for both contraction and secretion of prostate and seminal vesicle exist [71, 92, 100]. Essentially, these glands were activated by cholinomimetic compounds acting on muscarinic receptors [50]. Altogether, the results of pelvic nerve stimulation and pharmacological cholinergic activation led to suggest—and converse to the conventional view of the organization of pelvic autonomic pathways—that sympathetic innervation to the prostate includes both adrenergic and cholinergic components.

In addition to adrenergic and cholinergic commands, peptidergic and purinergic regulations have been demonstrated in laboratory animals although the precise mechanisms remain to be clarified. Several lines of evidence have shown that VIP and NPY participate in contraction and secretion of prostate and seminal vesicle [71, 93, 96] by apparently modulating noradrenaline release [97]. The same regulatory role has been reported for NPY in ductus deferens contractions [97]. Finally, ATP, the main endogenous purine, was found to act as a cotransmitter with noradrenaline to produce prostatic [103], seminal vesicle [65], and ductus deferens [2] contractions.

In humans, disruption of sympathetic pathways supplying the bladder neck, ductus deferens, and prostate is widely accepted to be the cause of postoperative anejaculation or retrograde ejaculation [61, 106]. The essential role of sympathetic innervation is best illustrated by surgical strategies that, by sparing sympathetic efferents, successfully preserve normal ejaculatory function in patients who have undergone retroperitoneal lymphadenectomy for testicular cancer or resection for rectal cancer [84, 99]. In addition, in paraplegic men whose ability to ejaculate is commonly severely impaired, semen was obtained upon electrical stimulation of the hypogastric plexus [15]. As far as we know, there is no clear clinical evidence for a functional role of parasympathetic innervation in the ejaculatory process.

The expulsion phase of ejaculation is commanded by the somatic nervous system though it is a reflex mechanism with no voluntary control. Forceful propulsion of semen out of the urethra via the glans meatus is caused by rhythmic contractions of pelvi perineal muscles. Owing to the fact that relatively non invasive measurement of pelvi perineal muscle activity is possible in humans, the expulsion phase has been shown to be characterized by synchronous activation of ischiocavernosus, bulbospongiosus and levator ani muscles, anal and urethral external sphincters [11, 28]. The contractions are regular, with an interburst interval starting at approx. 0.6 s and increasing by about 100 ms for each subsequent interburst interval. The typical number of bursts of contractions varies from 10 to 15 depending on the subject although each subject’s pattern of contractions is reproducible [11]. In case of lesion of the pudendal nerves, as it may occur after trauma [30] or neuropathy related to diabetes [104], retrograde and/or dribbling ejaculation is observed. Besides being important for the expulsion of sperm, rhythmic contractions of pelviperineal muscles seem associated with the orgasmic feeling inseparable from ejaculation (except in rare pathophysiological conditions like anorgasmia).

The initial phase of ejaculation (emission) develops as autonomic pathways are activated due to increasing sexual arousal and peripheral sex-related stimuli. What triggers the expulsion phase is unclear, however. The “pressure chamber” hypothesis by Marberger [54] states that accumulation of seminal emission within the proximal penile urethra (bulbous urethra), because of closed urethral proximal and distal sphincters, until a threshold level is reached triggers pelvi perineal striated muscle contractions which, together with external (distal) urethral sphincter episodic relaxation and continuous bladder neck (proximal sphincter) contraction, propels sperm anterogradely. This hypothesis has however to be reassessed in view of the large body of contradictory data collected in laboratory animals and men (for review see [52]. The major argument is the observation that pharmacological inhibition of emission by adrenergic blockers or lack of emission following selective nerve injury or radical prostatectomy does not prevent pelvi perineal muscle contractions with a similar pattern than in the normal condition [9, 10, 28]. The occurrence of expulsion in absence of emission (known as dry ejaculation) clearly indicates that other mechanisms not related to the pressure chamber concept can trigger the expulsion phase of ejaculation. These mechanisms involve specific spinal cord and brain elements.

The soma of the neurons controlling the peripheral events of ejaculation are distributed in the thoracolumbar and sacral (lumbosacral in rodents) spinal cord as described in Sect. 3.3 (Fig. 3.2). Another spinal structure characterized in the male rat plays the role of a spinal generator for ejaculation (SGE) [101]. SGE is composed of cells that are located around the central canal, in laminae X and VII (medial part) of the lumbar segments 3 and 4 and that contain galanin, cholecystokinin, and enkephalin [22]. One component of the SGE, referred to lumbar spinothalamic (LSt) cells, connects to the parvicellular subparafascicular nucleus of the thalamus (SPFp). SGE neurons expressing galanin and/or neurokinin-1 receptors (SP preferential receptor) also project to the sympathetic and parasympathetic preganglionic neurons innervating the prostate as well as to the motoneurons of the dorsomedial nucleus innervating the bulbospongiosus muscle (Fig. 3.3; [107, 108]). In addition, fibers of the sensory branch of the pudendal nerve terminate close to LSt cells [62], although a direct connection remains to be demonstrated and their nature is unknown. One question still to be answered is about brain influence on SGE. Direct supraspinal projections onto SGE neurons have not been described to date although functional investigations provide evidence of brain outputs triggering ejaculation, likely by activating SGE (Clement et al. [18, 19, 44]. Finally, investigations in anesthetized male rats have demonstrated that electrical stimulation of SGE elicits a complete ejaculatory response allowing the collection of motile spermatozoa [12]. Altogether these data support a crucial role for LSt cells in orchestrating autonomic and somatic spinal centers. A plausible mechanism is that both peripheral and brain stimulatory and inhibitory outputs are summated in SGE and, once an excitatory threshold is reached, a programed sequence is generated and activates autonomic and somatic spinal centers to produce ejaculation. Integrity of these spinal nuclei is necessary and sufficient for the expression of ejaculation as demonstrated by the induction of ejaculation after peripheral, spinal, or pharmacological stimulation in animals with spinal cord transection and men suffering from spinal cord injury [12, 13, 63, 95].

As a centrally integrated and highly coordinated process, ejaculation involves cerebral sensory areas and motor centers which are tightly interconnected.