A THIRTEENTH CRANIAL NERVE: THE CLOACAL NERVE
B. Graber.. Omaha, Nebraska PO Box 540788 68154

ABSTRACT

The completion by vertebrates of micturition, defecation, and copulation via the cloaca or its derivatives is hypothesized to be best explained by the existence of a thirteenth cranial nerve, the cloacal nerve, which, similar to the facial and trigeminal nerves, functions as a mixed cranial nerve containing both general and special components.

INTRODUCTION

Much of the confusion that persists about the neural control of urination, defecation, and sexual function is the result of attempts to reconcile the anatomy and physiology of the relevant organ systems with currently accepted models of the nervous system. In this article, I propose that a complete explanation of the complex viscerosomatic integration necessary for these evacuative functions requires a concep- tual reunification of rostrocaudal innervation. Further, I propose that a parsimonious approach to such a reunification is the postulation of a cloacal nerve. This nerve, while exiting the central nervous system from the spinal cord is, by virtue of its functional character- istic and its intimate control of somatovisceral evacuative functions, most accurately described as a cranial nerve. A comparison will be made between the innervation of cloacal derivatives and the cranial nerve pathways innervating those branchiomeric derivatives involved in swallowing.

Cloacal Specialization, Innervation, and Function

The cloaca is the common emptying chamber for the urogenital and alimentary systems found at the caudal end of all vertebrates either during embryogenesis or adult life (1). Cloacal derivatives include part or all of the external genitalia, the perineal musculature and supporting tissue, the actual openings of the urethra and anus, and the vagina in the female, as well as a portion of the linings of these openings (2,3). Other pelvic structures, including musculature and supporting tissues, the bladder, portions of the urethra, and the internal genitalia and adnexa, are functionally integrated with the cloacal derivatives, especially with respect to their sphincteric functions. The cloacal derivatives are caudal, and/or external, to the bladder, internal genitalia, and adnexa. Their location is consistent with the sphincteric role they serve in the evacuation of the products of the urogenital and gastrointestinal systems.

Recent textbook descriptions (4,5) of the innervation of perineal/ pelvic structures involved in elimination do not differ greatly from the early explanations of Sherrington (6) and Langley (7). The external genitalia and perineal and pelvic muscles are supplied with a variety of afferent end organs (8,9). One major pathway of pelvtc/ perineal innervation, the pudendal nerve, originates in the sacral spinal cord and provides somatic afferents and efferents, primarily general somatic afferents and efferents. The penis and clitoris contain a pair of terminal nerves, the dorsal nerves. The remainder of the cavernous/vascular components of the external genitalia receive additional innervation from the cavernous plexus. This plexus, together with similar plexi on or near the prostate, seminal vesicles, and other male accessory glands, and their homologs/analogs in the female, are conduits for presynaptic and postsynapttc general visceral afferents and efferents innervating these perineal and pelvic structures. These pelvic plexi and nerves are part of a continuous net of innervation that extends rostrally into structures such as the inferior hypogastric, superior hypogastric (presacral) and coeliac ganglia. Some of these more rostral neural elements, in addition to their possible distribution to the perineal cloacal derivatives, provide some of the innervation to the pelvic viscera including the bladder, proximal urethra, internal genitalia and adnexa including the seminal organs in the male and the uterus in the female (3-5,10). The crux of these representations is that urination, copulation, and defecation are controlled by spinal reflex mechanisms that are only modulated by supraspinal neural centers.

The Cloacal Nerve Hypothesis

The hypothesis presented here is that cloacally derived structures are, under normal physiological conditions, controlled by a thirteenth cranial nerve complex, whose afferent and efferent nuclei lie in the lower brain stem and mesencephalon. The complex somatovisceral inte- gration involved in the vital functions mediated by these structures cannot be completely explained by general somatic and visceral spinal cord reflex pathways. At least some cloacal derivatives are unique sphincteric structures of ancient phylogenetic origin. The cloacal nerve hypothesis postulates SPECIAL visceral pathways for these structures. One rationale for hypothesizing a new cranial nerve is that special visceral and somatic pathways as currently described are only associated with cranial nerves (10,11).

Spinal nerves are named and numbered according to their corre- sponding embryological segment or somite. Cranial nerves are numbered anatomically by their rostral-caudal location and named by their specialized function or their target organ (10,11). The cloacal nerve hypothesis states that the evacuative functions that occur at the caudal end of vertebrates are controlled by a thirteenth cranial nerve, labeled the cloacal nerve because of its distributions to the derivatives of the cloaca. These structures are not derived from a specific somite and are highly specialized structures whose functions require complex ectodermal/endodermal interactions in a fashion analogous to the specialized derivatives of the branchial arches. The crux of the cloacal nerve hypothesis is that the control of midline viscerosomatic integration is by rostral (cephalic) neural centers.

Branchiomeric - Cloacal Similarities

Some cranial nerves are labelled as mixed, in that they are com- posed of general and special afferents (GSA, SSA, GVA, SVA) from the alar lamina of the neural tube and/or general and special efferents (GSE, GVE, SVE) from the basal lamina (10,11). Cranial innervation of sphincter mechanisms involved with swallowing and its integration with and separation from air intake provides an excellent model for the hypothesized cloacal nerve. Embryogenesis of structures associated with the oropharyngeal plate occurs at an early phase of development and is integrated with the early development of the nervous system (12). Swallowing mechanisms for food ingestion and the prevention of aspiration involve a unique form of striated musculature that receives special visceral motor innervation from cranial nerves V, VII, IIIX-XIIII (10-12). These structures are derived from the pharyngeal or branchial arches and related mesenchyme. The embryological development of caudal/cloacal structures and their innervation are similar and parallel in context and time to that of oropharyngeal development (1,3).

Neurons from the cranial nerve nuclei that innervate branchiomeric structures are special or distinct in more than name. One important difference from spinal motor innervation is the lack of recurrent collaterals which activate inhibitory interneurons (10,12). The negative feedback from such circuitry presumably is inconsistent with the coordination requisite for the rhythmic propulsive movements of the special pharyngeal branchiomeric muscle sphincters and the smooth muscles and related structures of the lower esophagus. A cloacal cranial motor nucleus, that provides special visceral efferent innerva- tion that lacks recurrent inhibition can explain how the cloacally derived external sphincters are coordinated with the viscera involved in urination, defecation and sexual function.

Not all cranial special visceral motor innervation is involved in swallowing. Other examples of branchiomeric derivatives that receive special innervation are the muscles of facial expression, e.g. the platysma (10,11). Similarly, there are other cloacally derived nonsphincteric muscles, including the ischiocavernosus and bulbo- cavernosus, which probably also receive special visceral motor inner- vation that may explain the actions of these muscles during copulation, including the rhythmic contractions reported with orgasm in the human (13-16).

As noted, the cranial nerves associated with swallowing are mixed cranial nerves with multiple functions and end organs. Thus, some of the branchiomeric muscles, such as those involved with mastication are innervated by general somatic afferents and efferents (GSA/ GSE) that project through cranial nerve pathways. These muscles participate in the voluntary processes that occur during ingestion (17). Similar voluntary participation in elimination is possible in adult verte- brates. This voluntary control, as described at least for micturition and defecation, involves alteration of the angular orientation of the discharging pelvic organ and its cloacally derived outlet (18,19). As with volitional modulation of branchiomeric functions, volitional facilitation or inhibition of cloacal functions would be best labeled by current convention as general somatic afferent or efferent inner- vation.

Doty (12) describes another feature of deglutition, namely that it is not subject to significant proprioceptive modification or control. Thus, the afferents to the cranial motor nuclei for these sphincteric branchiomeric muscles do not arise from the muscles themselves, which usually lack muscle spindles (12). The afferents to these nuclei are instead from central areas including the medial reticular formation. Associated with swallowing, there are afferent end organs found in the mucocutaneous surfaces of the oropharynx. These peripheral afferents (GSA) project to the brain stem mostly in the glossopharyngeal nerve and are distributed to central neural areas, while the special motor fibers (SVE) to the sphincters project through a different path, the vagus (11,12). Again, parallelism with the cloacal nerve can be noted. Specialized nerve end organs exist in the ectodermal mucocutaneous surfaces of cloacal derivatives. In the past these end organs have received a number of specific names (8,9); however, Winkelman (20) concluded that there is only one mucocutaneous end organ. Like their rostral counterparts involved in deglutition, these mucosal and submucosal end organs are not found in the muscles involved in the sphincteric process. And again, it is most likely that they project to the central nervous system through pathways distinct from those of the special efferent neurons. Thus, the afferent innervation to motor nuclei of the cloacal nerve may be via other central neural structures, perhaps the same sensory medial reticular formation that is afferent to the motor nuclei of other mixed cranial nerves (12).

Cloacal Specialization, Innervation, and Function - Revisited

The relevant scientific data needed to understand the innervation of cloacal functions must be culled from diverse fields of inquiry including nociception, sexual function, micturition, and defecation. An area in the lower brain stem involved with micturition was first described by Barrington (21) through the use of both lesion and stimulation techniques. Further studies employing these techniques and additional tracing studies have been done by Bradley (22) and DeGroat (23), relating lower brain stem and other cephalic neural centers to the functions of cloacal derivatives and related pelvic viscera. Mackel, stimulating pontine-medullary sites, elicited responses from both the external urinary and anal sphincters. Of particular significance to the proposed cranial nerve hypothesis, Mackel found “surprisingly” that these sphincter motor neurons did not show recurrent inhibition and had paradoxically short spike after polarization (24).

Significant information about urogenital and alimentary functions has been derived from the study of the dysfunctions that are the result of pathologic or experimental intervention. From these studies it is evident that with lesions at the diencephalic/mesencephalic brain stem levels, the cloacal functions are severely impaired (25,26). Depending on the level of the lesion, individual components of bladder, bowel, or sexual function may be elicited but are pathological variations due to the denervated condition that creates increased spasm or decreased tonus (10,27-29). Chordotomy results in a variety of sexual dys- functions reflecting disruption of, among other connections, specific ascending tracts, including those to the medial portion of the reticular formation (30-32). All of the complex behavior patterns associated with male and female sexual function can be elicited or impaired by a variety of manipulations directed at cephalic neural areas (33). In most studies lesion and stimulation only affect single components of the complete behavioral patterns (34-37), but studies employing centrally placed neurochemical agents have elicited almost the entire array of sexual responses seen in the laboratory rodent (38). Reflexes in spinal preparations (39,40), while similar to those seen in intact animals, are not identical (41).

Several authors have attempted to integrate the data relevant to the neurophysiology of sexual function. Komisaruk (42) has described most of the complex somatovisceral interrelationships seen in the reproductive functions of cloacal derivatives. He and Gillman (43) have noted the close relationship between the pathways and mechanisms involved in nociception and copulation. Davidson (44), having studied complex neuroendocrine and other neurochemical relationships both at peripheral and central levels, has attempted to integrate the accumulated viscerosomatic/rostralcaudal information into a “bipolar theory of orgasm.”

Of all the cloacal derivatives, the external urinary sphincter complex is probably the most highly specialized structure, especially in the male (45,46). During perinatal development and again at puberty, this structure undergoes changes reflecting an androgen controlled sexually dimorphic specialization (45). In both sexes, the histologic structure of this muscle is different from that of other surrounding skeletal muscles in that its fibers are smaller and are almost exclusively Type I tonic muscle fibers (24,25). These muscles have a high concentration of golgi bodies and lack muscle spindles (47). The connective tissue intramuscular matrix is characteristic neither of striated nor of smooth muscle (45). Hence the external urinary muscle sphincter appears to be an ideal candidate for the type of special visceral innervation compatible with the cloacal nerve hypothesis presented here.

A sexually dimorphic nucleus, closely related to, or identical with, Onufs nucleus has been identified in a number of species (48.49). The structural alterations of the male external urinary sphincter and its dimorphic innervation are compatible with the differences that occur during the culmination of copulation in males and females (46). Physiologically, the external urinary sphincter is maintained in a tonic resting state in both males and females, apparently controlled by a central monoaminergic locus (50). Gillan and Brindley (14) have identified a “tonic glandipudendal reflex” in human females using vibratory stimulation. Such stimulation, if prolonged, eventually elicits phasic contractions in perineal/pelvic structures, similar to those seen in orgasm (13,15,16). In the male, these phasic contrac- tions are accompanied by anterograde ejaculation of semen that has been deposited in the prostatic urethra at the level of the vermonatum and seminal colliculus. Clonidine centrally inhibits the EMG activity seen in the external urinary sphincter (50). Repetitive peripheral stimula- tion ascending to the sensory portion of the reticular formation could trigger phasic disinhibition (as seen by the alternating periods of electrical silence) (51) in the external urinary sphincter, allowing the release of the ejaculate.

In addition to, or possibly related to, the role the mucocutaneous end organs and their afferent nerves play in the control of sphincter muscles, they may also constitute a special afferent pathway related to the tumescence/detumescence involved in sexual function. In fact, these afferent signals may represent a new special visceral afferent or even special somatic afferent pathway. The former category is currently exclusively used for the afferents associated with smell and taste, while the latter is used only for sight and hearing (10). There is clearly a difference in sensory experience involved in tumescent versus flaccid cloacal structures and thus the afferents associated may be different as well. Kitchell (52) and Campbell (53) suggested that tumescence might alter conductivity in the epithelial filaments seen originating in genital end organs and Sachs (30) has demonstrated involvement of cloacal perineal muscles in tumescence in male rodents. The conduction times from the proximal urethra to the CNS and back to the perineal musculature are consistent with a longer pathway such as the hypothesized cloacal cranial nerve (22).

CONCLUSIONS

It is proposed that the conventional explanations of the mechanisms of neural control of urination, defecation and sexual func- tion are inadequate and fail to explain existing data. A thirteenth cranial nerve, the cloacal nerve, is postulated as a simple yet com- plete solution to the problem of how to unify the diverse data. Existing work from several fields has already provided descriptions of the components of the pathways of the cloacal nerve but its ultimate verification must be determined by direct in vivo experimentation. In addition to any theoretical extensions of this hypothesis, its verifi- cation could have major implications for clinical research and treatment of pelvic/perineal disease.

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