Visceral Motor Pathways

+, positive effect; −, negative effect; 0, no effect; ±, variable effect.

General Features of Peripheral Visceral Motor Outflow

There are similarities and differences between the neural control of skeletal muscle and visceral effectors such as smooth muscle (Fig. 29-1). As described in Chapter 24, lower motor neurons (alpha motor neurons) function as the final common pathway linking the CNS to skeletal muscle fibers (Fig. 29-1A). Similarly, sympathetic and parasympathetic outflows serve as the final but often dual common neural pathway from the CNS to visceral effectors. However, unlike the somatic motor system, the peripheral visceral motor pathway consists of two neurons (Fig. 29-1B, C). The first, the preganglionic neuron, has its cell body in either the brainstem or the spinal cord. Its axon projects as a thinly myelinated preganglionic fiber to an autonomic ganglion. The second, the postganglionic neuron, has its cell body in the ganglion and sends an unmyelinated axon (postganglionic fiber) to visceral effector cells such as smooth muscle. In general, parasympathetic ganglia are close to the effector tissue and sympathetic ganglia are close to the CNS. Consequently, parasympathetic pathways typically have long preganglionic fibers and short postganglionic fibers, whereas sympathetic pathways more often have short preganglionic fibers and long postganglionic fibers.

Figure 29-1. Comparison of somatic motor outflow (A) with sympathetic (B) and parasympathetic (C) outflow.

Visceral motor neurons and their targets are not organized into discrete motor units like those of the somatic motor system. Recall that an alpha motor neuron makes synaptic contacts with a definite group of skeletal muscle fibers over which it has exclusive control. In contrast, the terminal branches of a postganglionic visceral motor axon typically have a series of swellings containing neurotransmitter vesicles along their length, giving them a beaded (varicose) appearance (Fig. 29-1B, C). The neurotransmitters released from these terminals may act on effector cells at a distance of up to 100 µm. Moreover, unlike skeletal muscle fibers, cardiac muscle fibers and the smooth muscle cells of some organs are electrically coupled by gap junctions. Because of this, neurochemical signaling to a few cells is sufficient to regulate a large group of cells that act as a unit. The main features of sympathetic and parasympathetic divisions are summarized in Table 29-2.

Table 29-2 Comparison of the Sympathetic and Parasympathetic Divisions of Autonomic Outflow

DEVELOPMENT

Preganglionic Visceral Motor Neurons

Cell bodies of these neurons are located in nuclei or cell columns embryologically derived from the visceral efferent cell column. This column arises from neuroblasts in the basal (motor) plate of the brainstem and spinal cord portions of the neural tube.

Postganglionic Visceral Motor Neurons

Cell bodies of these multipolar neurons are located in autonomic ganglia, which may be either well-defined, encapsulated structures, such as the superior cervical ganglion, or clusters of somata found in nerve plexuses or in the walls and capsules of visceral organs. Like most primary sensory neurons, autonomic ganglion cells are derived from neural crest cells that migrate to appropriate locations during development.

One result of this cell migration is the advent, in the adult, of the myenteric (Auerbach) and the submucosal (Meissner) plexuses and the normal muscular and secretory functions of the intestinal wall.

Congenital megacolon, or Hirschsprung disease, results from a failure of these enteric neuronal precursor cells to migrate into the wall of the developing lower gut. As a result, the affected segment of the gut (the portion lacking enteric ganglion cells, the aganglionic segment), usually the colon, is paralyzed in a constricted state, with consequent distention of the proximal and normally innervated portion of the intestine (the portion containing enteric ganglion cells, the ganglionic segment) (Fig. 29-2). This disease is most commonly seen in the very young (newborn to 6 years) but may be seen in adults. Although the presentation of the disease is strikingly characteristic on a radiograph or with magnetic resonance imaging (Fig. 29-2), definitive diagnosis relies on a biopsy and histologic confirmation of a lack of enteric ganglion neurons in the affected segment. The treatment of choice is to resect the aganglionic segment and join the remaining normal portions of the gut.

Figure 29-2. Congenital megacolon in a neonate before (A) and after (B) evacuation. The affected portion of the large bowel is lacking ganglion cells and is in a chronically constricted state; the dilated portion of the bowel contains ganglion cells (A and B).

Development of the autonomic nervous system requires an elaborate sequence of intercellular signaling that involves two major families of neurotrophic factors. One is the glial cell line–derived neurotrophic factor (GDNF) family, which consists of several distinct signaling molecules and their receptors. Mutations of one of these receptors, designated RET, is the underlying cause of some cases of congenital megacolon. The neurotrophins are the other large family of neurotrophic factors. As with the GDNF family, each neurotrophin regulates development and function of specific populations of peripheral nervous system and CNS neurons via binding to specific receptors. The existence of these neuronal growth factors was first demonstrated when the neurotrophin nerve growth factor (NGF) was discovered as a target-derived messenger molecule that is absolutely essential for survival and development of sympathetic postganglionic neurons (Fig. 29-3) as well as those primary sensory neurons that are involved in pain (Fig. 29-3). The pathologic changes in animals deprived of NGF or its high-affinity receptor are similar to those seen in patients with congenital insensitivity to pain with anhidrosis (hereditary sensory and autonomic neuropathy type IV), an autosomal recessive disease. Indeed, mutations that impair the function of the NGF receptor trkA have been identified in patients with this disease.

Figure 29-3. Mechanism by which the neurotrophin nerve growth factor (NGF) regulates the development and function of sympathetic ganglion neurons. trkA, tropomyosin-related kinase (the high-affinity NGF receptor); PKC, protein kinase C; Ras, rat sarcoma (a family of GTPases); MAPK, mitogen-activated protein kinase; CREB, cAMP response element–binding protein (a family of transcription factors).

SYMPATHETIC DIVISION

Sympathetic Preganglionic Neurons

Although the sympathetic outflow influences visceral targets throughout the body, sympathetic preganglionic neurons are found only in spinal cord segments T1 through L2 (sometimes in C8 and L3). These cell bodies are located in Rexed lamina VII, primarily in the intermediolateral nucleus (cell column) of the lateral horn. The axons of these preganglionic cells exit the spinal cord in the ventral root and enter the sympathetic trunk via the white communicating ramus. A preganglionic fiber takes one of three courses after entering the sympathetic chain: (1) it may synapse at that level with postganglionic neurons whose unmyelinated axons join that spinal nerve via a gray communicating ramus; (2) it may ascend or descend in the sympathetic chain to synapse on postganglionic neurons whose axons either join spinal nerves or project to targets in the thoracic cavity or head; or (3) it may pass through the chain ganglion as a preganglionic fiber to form part of a splanchnic nerve (Fig. 29-4).

Figure 29-4. The types of routes that can be taken by peripheral sympathetic pathways. A preganglionic fiber may terminate in the chain ganglion at its level of origin (A), ascend or descend in the chain to terminate in different ganglia (B), or traverse the ganglion to enter a splanchnic nerve and terminate in a prevertebral ganglion (C). Postganglionic neurons that originate in a sympathetic chain ganglion may exit via the gray ramus and spinal nerve (A and B) or directly via a nerve such as the cardiac nerve shown in C.

The sympathetic outflow for the entire body originates from thoracic and upper lumbar spinal cord segments. Although the segmental pattern of innervation is not straightforward, there is a general viscerotopic organization (Figs. 29-5 and 29-6). Neurons of the superior, middle, and inferior cervical ganglia receive input, via the sympathetic trunk, from preganglionic neurons of the upper thoracic spinal segments. Lower lumbar and sacral ganglia are supplied by neurons of the lower thoracic and upper lumbar spinal segments. The ganglia between these regions are supplied by their corresponding spinal levels. Thus visceral targets in the head, neck, and upper extremity as well as the viscera of the thoracic cavity are served by preganglionic sympathetic neurons in the upper thoracic segments. The main abdominal viscera and other targets in the trunk are served by the central and lower thoracic spinal cord segments, whereas the pelvic viscera, the lower trunk, and the lower extremity are served by the lower thoracic and upper lumbar spinal cord segments.

Figure 29-5. Sympathetic pathways to visceral targets in the body wall, limbs, and scalp and neck. Postganglionic sympathetic fibers that distribute to targets of the head are shown in Figure 29-6.

Figure 29-6. Sympathetic and parasympathetic pathways to visceral targets in the head and body cavities. g., ganglion; inf., inferior; m., muscle; mes., mesenteric; n., nucleus; spl. nr., splanchnic nerve; submand., submandibular; sup., superior.

Preganglionic sympathetic neurons also target the adrenal gland (Fig. 29-6). Chromaffin cells of the adrenal medulla are related to sympathetic ganglion neurons in both derivation (neural crest) and function. These cells secrete catecholamines (mostly epinephrine) into the bloodstream in response to signals from preganglionic neurons. Thus the sympathetic system, through this endocrine pathway, regulates functions of cells that are not directly contacted by nerve terminals.

Sympathetic Ganglia

Cell bodies of sympathetic postganglionic neurons are generally grouped into discrete ganglia that are located at some distance from the target tissue. Most of them make up the sympathetic chain (paravertebral) ganglia and the prevertebral ganglia associated with the abdominal aorta or its large branches (the celiac, aorticorenal, superior mesenteric, and inferior mesenteric ganglia; see Fig. 29-6). In addition, small clusters of cell bodies are also scattered among nerve fibers in communicating rami, the sympathetic trunk between chain ganglia, and peripheral plexuses.

The sympathetic chain extends along the full length of the vertebral column, but the number of ganglia does not exactly match the number of spinal nerves. In general, there are 3 cervical, 10 to 11 thoracic, 3 to 5 lumbar, and 3 to 5 sacral sympathetic ganglia on each side and a single coccygeal ganglion (ganglion impar), where the two chains meet caudally (Figs. 29-5 and 29-6). Typically, the inferior cervical ganglion and the first thoracic ganglion fuse to form the stellate ganglion.

The sympathetic chain ganglia are connected to spinal nerves via white and gray communicating rami. The former appear white because they contain myelinated preganglionic fibers, and the latter appear gray because they are composed of unmyelinated postganglionic fibers that serve the limbs and body wall (Fig. 29-4). Consequently, only spinal nerves T1 to L2 have white rami (and contain preganglionic axons), whereas every spinal nerve is connected to the sympathetic trunk by a gray ramus that conveys postganglionic axons (Fig. 29-5).

Sympathetic postganglionic neurons in paravertebral ganglia send their axons in two general directions. First, some postganglionic fibers join the spinal nerve via a gray ramus. These fibers distribute to blood vessels, sweat glands, and arrector pili muscles in the body wall and extremities (Figs. 29-4A, B and 29-5). These structures receive little or no parasympathetic innervation, so they are exceptions to the dual arrangement of visceral innervation. Second, some of the postganglionic fibers that arise from cervical and upper thoracic sympathetic chain ganglia form cervical and thoracic cardiac nerves and pulmonary nerves that emerge directly from the ganglia (Figs. 29-4C and 29-6). These fibers innervate the vascular smooth muscle of the esophagus, heart, and lung; the glandular epithelium of respiratory structures; the smooth muscles of the esophagus; and cardiac muscle. Axons of these sympathetic neurons mingle with parasympathetic fibers of the vagus nerve to form the autonomic plexuses of the thorax.

The largest of the paravertebral (sympathetic chain) ganglia is the superior cervical ganglion. Postganglionic fibers from these cells innervate blood vessels and cutaneous targets of the face, scalp, and neck of the territories supplied by the first four cervical nerves (Figs. 29-5 and 29-6). The superior cervical ganglion also innervates the salivary glands, nasal glands, lacrimal glands, and structures of the eye such as the pupillary dilator muscle and the superior and inferior tarsal muscles (Fig. 29-6). Accordingly, a constellation of signs and symptoms results from interruption (central or peripheral) of the sympathetic pathway through the superior cervical ganglion (Fig. 29-7). These include constriction of the pupil (miosis) caused by the unopposed action of the parasympathetically innervated pupillary constrictor, drooping of the upper eyelid (ptosis) resulting from paralysis of the superior tarsal muscle (of Müller), flushing of the face from loss of sympathetically mediated vascular tone, and diminished or absent sweating (anhidrosis) on the face. Collectively, these signs and symptoms are known as the Horner syndrome (Fig. 29-7).