BARR'S The Human Nervous System: An anatomical viewpoint, 9th Edition

PART 3 - Review of the Major Systems

Chapter 24

Visceral Innervation

Important Facts

  • The control of smooth muscle, cardiac muscle, and secretory tissues by the central nervous system always involves a chain of at least two neurons, preganglionic and postganglionic, with the cell body of the latter being in an autonomic ganglion.
  • Whereas parasympathetic ganglia are near the organs they innervate, most sympathetic ganglia are paravertebral or preaortic. The enteric ganglia are located in the myenteric and submucous plexuses of the alimentary canal.
  • Preganglionic parasympathetic neurons are present in certain nuclei of cranial nerves III, VII, IX, and X and in the intermediolateral cell columns of spinal segments S2, S3, and S4.
  • Parasympathetic ganglia supply the sphincter pupillae and ciliary muscles, the lacrimal and salivary glands, thoracic and abdominal viscera (including the heart), the urinary bladder and other pelvic organs, and the erectile tissue of the genitalia.
  • Preganglionic sympathetic neurons are located in the intermediolateral cell column of spinal segments T1 to L2. Their axons pass through the ventral roots and the white communicating rami into the sympathetic trunk. They reach paravertebral ganglia by way of the sympathetic trunk or preaortic ganglia by way of splanchnic nerves.
  • Gray communicating rami carry postganglionic sympathetic axons into mixed nerves to supply blood vessels, sweat glands, and piloarrector muscles. Postganglionic fibers to the head travel along the carotid arteries and their branches. Cardiac sympathetic nerves arising in the cervical ganglia supply the heart. Mesenteric and similar nerve plexuses carry postganglionic sympathetic fibers from preaortic ganglia to abdominal organs. The adrenal medulla is a modified sympathetic ganglion with neurons that release their transmitters directly into the blood.
  • The enteric nervous system can work independently, but its activities are modulated by preganglionic parasympathetic and postganglionic sympathetic axons. The enteric plexuses contain sensory neurons, interneurons, and cells that provide excitatory and inhibitory innervation to the gut.
  • Acetylcholine is the principal neurotransmitter of all preganglionic neurons and all parasympathetic postganglionic neurons. Noradrenaline is the principal transmitter of all postganglionic sympathetic neurons except those that supply sweat glands, which are cholinergic. Several peptides also occur in autonomic neurons.
  • The activities of the autonomic nervous system are subject to control by descending central pathways from the medial prefrontal cortex, amygdala, septal area, hypothalamus, and reticular formation. The descending pathway mediating sympathetic effects in the eye and face passes ipsilaterally through the lateral part of the medulla and then in the medial part of the lateral funiculus of the spinal cord.
  • Fibers for visceral pain have cell bodies in dorsal root ganglia and axons that accompany the preganglionic and postganglionic sympathetic fibers. Pain is often referred to somatic structures supplied by the same spinal segments as the affected organ. The central pathway to the cerebral cortex is the spinothalamic system.
  • Most sensory neurons for visceral reflexes (and for conscious sensation of fullness) have cell bodies in the inferior ganglion of the vagus nerve and axons that accompany the preganglionic parasympathetic fibers. The sensory neurons project centrally to the solitary nucleus, which is connected with preganglionic autonomic neurons, the hypothalamus, various regions of the reticular formation, and the amygdala. There are indirect projections to the mediodorsal thalamic nucleus and to the insular and medial prefrontal cortex.

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In neurobiology, the adjective visceral is applied to innervated smooth and cardiac muscle and secretory cells in all parts of the body. The primary role of visceral innervation is to maintain optimal homeostasis. This end is attained through regulation of the organs and structures concerned with digestion, circulation, respiration, maintenance of normal body temperature, excretion, and reproduction. In addition to the regulating role of visceral reflexes, the activities of smooth muscles, glandular elements, and cardiac muscle can be altered by influences from the highest levels of the brain, especially in response to emotion and to the external environment.

Afferent signals of visceral origin reach the central nervous system (CNS) through primary sensory neurons similar to those for general sensation. Under normal conditions, these impulses elicit reflex responses in viscera and feelings of fullness of hollow organs such as the stomach, large intestine, and urinary bladder. Visceral sensation also contributes to feelings of well-being or malaise. In the presence of abnormal function and disease, visceral afferents transmit impulses for pain. The painful sensation often is referred to a part of the body wall or a limb supplied by the same segmental nerves as the affected organ.

The motor or efferent supply of smooth muscle cells (SMC), cardiac muscle, and gland cells differs from that of voluntary muscles in that the connection between the CNS, and the viscus consists of a succession of at least two neurons rather than a single motor neuron (see Fig. 3-2). The cell body of the first neuron is in the brain stem or the spinal cord; its axon terminates on a neuron in an autonomic ganglion, and the axon of the latter neuron ends either on effector cells or on a third neuron. The first and second neurons are calledpreganglionic and postganglionic neurons, respectively. The third neuron, when present, is part of the plexuses within the wall of the alimentary canal. In 1898, J.N. Langley assigned the term autonomic nervous system to the visceral efferents. He later (1921) subdivided the autonomic system into the parasympathetic, sympathetic, and entericdivisions, and this classification is still in use.

Visceral Efferent or Autonomic System

The SMCs, secretory cells of viscera, and also cardiac muscle come under the dual influence of the sympathetic and parasympathetic divisions of the autonomic nervous system. In some organs, these are functionally antagonistic, and a delicate balance between the two systems maintains a more or less constant level of visceral activity. Autonomic innervation extends beyond the organs in the major body cavities to include the muscles of the iris and ciliary body in the eye, smooth muscles in the orbit, the lacrimal and salivary glands, sweat glands and arrector pili muscles of the skin, and blood vessels everywhere. In addition, the alimentary canal contains its own intrinsic nerve supply, the enteric nervous system, which is able to control at least the simpler forms of gastrointestinal (GI) motility.

AUTONOMIC GANGLIA

An autonomic ganglion receives thin, myelinated (group B) afferent fibers from the brain stem or spinal cord. Its efferent fibers, which supply visceral structures, are the axons of the principal cells of the ganglion. They are unmyelinated (group C) and are more numerous than the preganglionic fibers. Thus, the synapses in the ganglion provide for divergence in the efferent pathway so that relatively small numbers of neurons in the CNS control large numbers of smooth muscle and gland cells in the periphery. The divergence is enhanced by preterminal branching of the postganglionic fibers and, in the alimentary canal, by further synapses with the neurons of the enteric nervous system.

Divergence cannot be the sole reason for the existence of autonomic ganglia; the same effect could be more simply achieved by further branching of axons. Evidence for integration and comparison of neural inputs is seen in the synaptic organization of the ganglion (Fig. 24-1). Each principal cell is inhibited at the dendrodendritic synapses with nearby principal cells and from the small intrinsic neurons of the ganglion. These interneurons, whose only cytoplasmic processes are short dendrites, are excited

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by branches of the preganglionic axons. In at least some autonomic ganglia, sensory fibers that are passing through give off branches that synapse with the principal cells. This arrangement may provide for reflexes that do not involve the CNS.

 

FIGURE 24-1 Synaptic organization of an autonomic ganglion, showing the principal transmitters and their excitatory (1) or inhibitory (2) actions.

NEUROTRANSMITTERS

The preganglionic neurons are invariably cholinergic. The principal cells are all cholinergic in parasympathetic ganglia, but only a small proportion of them are cholinergic in sympathetic ganglia. Most of the principal cells of sympathetic ganglia are noradrenergic at their peripheral synapses. The intrinsic neurons of the ganglia contain dopamine, which they are believed to use as a transmitter. All the neurons in autonomic ganglia also contain two or more peptides, which may serve as additional neurotransmitters or as neuromodulators. Several clinically valuable drugs selectively enhance or inhibit both the synthesis and the metabolism of acetylcholine, dopamine, and noradrenaline. Other drugs imitate or block the actions of these transmitters at postsynaptic sites. Information about synaptic connections in autonomic ganglia is therefore valuable in understanding some of the physiological effects of these drugs.

PARASYMPATHETIC DIVISION

The actions of the parasympathetic system include a decrease in the rate and force of the heart beat, augmentation of the activity of the digestive system (promoting propulsion and secretion), emptying of the urinary bladder, and tumescence of the genital erectile tissue. As previously stated, acetylcholine is the chemical mediator at the synapses between preganglionic and postganglionic neurons and at the contacts between postganglionic terminals and effector cells, with various peptides also being released. The parasympathetic system is therefore cholinergic. It acts in localized and discrete regions rather than causing effects throughout the body. The discrete nature of the response is a result of the fact that there is less divergence than there is in the sympathetic system. Acetylcholine is rapidly inactivated by acetylcholinesterase; each parasympathetic discharge is, consequently, of short duration.

Preganglionic parasympathetic neurons, which have long axons, are located in the brain

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stem and in the middle three sacral segments (S2-S4) of the spinal cord (Fig. 24-2). The preganglionic parasympathetic nuclei and the sites of the corresponding postganglionic neurons are as follows:

  1. Edinger-Westphal nucleusof the oculomotor complex and the ciliary ganglion behind the eyeball
  2. Superior salivatory nucleusof the facial nerve and submandibular ganglion beneath the floor of the mouth
  3. Lacrimal nucleusof the facial nerve and pterygopalatine ganglion beneath the base of the skull
  4. Inferior salivatory nucleusof the glossopharyngeal nerve and otic ganglion beneath the base of the skull
  5. Dorsal nucleus of the vagus nerveand ganglia in the pulmonary plexus, cells in the myenteric and submucosal plexuses of the GI tract (the enteric nervous system), and postganglionic neurons at other sites

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  1. Nucleus ambiguusand cardiac ganglia. The cardiac parasympathetic ganglia are most numerous in the atria, around the entering great veins. Ganglionated plexuses are formed by numerous slender nerves that interconnect the ganglia.
  2. Sacral parasympathetic nucleusand postganglionic neurons in and near the pelvic viscera.
 

FIGURE 24-2 Plan of the parasympathetic nervous system. Preganglionic neurons are red, and postganglionic neurons are blue.

The locations of the cranial nerve nuclei are described and illustrated in Chapters 7 and 8, and the sacral parasympathetic nucleus is described in Chapter 5.

SYMPATHETIC DIVISION

Paravertebral ganglia are associated with all the spinal nerves, although at the cervical levels, eight segments share three ganglia. The sympathetic outflow originates in theintermediolateral cell column (lateral horn) of all thoracic spinal segments and the upper two or three lumbar segments (Figs. 24-3 and 24-4). The axons of preganglionic neurons reach the sympathetic trunk by way of the corresponding ventral roots and white communicating rami (see Fig. 24-3). With respect to the sympathetic supply of structures in the head and thorax, the preganglionic fibers terminate in the ganglia of the sympathetic trunk. For smooth muscles and glands in the head, the synapses between preganglionic and postganglionic neurons are mainly located in the superior cervical ganglion of the sympathetic trunk, and the postganglionic axons are located in the carotid plexus, which accompanies the carotid artery and its branches. In the case of thoracic viscera, the synapses are located in the three cervical sympathetic ganglia (superior, middle, and inferior) and the upper five ganglia of the thoracic portion of the sympathetic trunk.

 

FIGURE 24-3 Visceral efferent and afferent neurons associated with a thoracic segment of the spinal cord. Preganglionic neurons are red, and postganglionic neurons are green. A sensory (pain) neuron supplying an internal organ of the abdomen is shown in blue. Visceral sensory axons pass through autonomic ganglia, but their cell bodies are located in dorsal root ganglia.

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FIGURE 24-4 Plan of the sympathetic nervous system. Preganglionic neurons are red, postganglionic neurons are blue, and enteric neurons are green.

Preganglionic fibers for abdominal and pelvic viscera proceed without interruption through the sympathetic trunk and into the splanchnic nerves. The axons terminate on postganglionic neurons located in preaortic ganglia (also known as collateral ganglia), which are situated in the plexuses that surround the main branches of the abdominal aorta. The largest are the celiac plexus and the superior and inferior mesenteric plexuses. The sympathetic supply to the adrenal medulla is exceptional. The secretory cells of the medulla, which are derived from the neural crest, are postganglionic sympathetic neurons that lack axons or dendrites. The adrenal medulla is, consequently, supplied directly by preganglionic sympathetic neurons. The alimentary canal is chiefly supplied by the ganglia in the celiac and mesenteric plexuses; the postganglionic fibers do not terminate directly on SMCs and gland cells but on neurons of the enteric nervous system.

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For the body wall and the limbs, preganglionic fibers terminate in all ganglia of the sympathetic trunk, from which postganglionic fibers are distributed by way of gray communicating rami (see Fig. 24-3) and spinal nerves to blood vessels, arrector pili muscles, and sweat glands. Gray communicating rami are gray because the postganglionic axons are unmyelinated (group C) fibers; white rami contain thin (group B) myelinated axons.

The sympathetic system stimulates activities that are accompanied by an expenditure of energy. These include acceleration of the heart and increase in force of the heartbeat, increase in arterial pressure, and direction of blood flow to skeletal muscles at the expense of visceral and cutaneous circulation. Sympathetic responses are most dramatically expressed during stress and emergency situations (the fight-or-flight reaction). The neurotransmitter substance between preganglionic and postganglionic neurons is acetylcholine, as in the parasympathetic system. In the case of the sympathetic system, noradrenaline (also known as norepinephrine) is the transmitter released by most postganglionic axons. The sympathetic system is therefore said to be noradrenergic. The sympathetic supply to sweat glands is cholinergic, constituting an exception to the general rule. Cutaneous areas lack parasympathetic fibers; the cholinergic sudomotor neurons are anatomically sympathetic but are functionally similar to those of parasympathetic ganglia.

Noradrenaline has different actions in different tissues, according to the type of receptor molecule on the responding cells. Alpha receptors occur on the surfaces of smooth muscle cells in the dilator pupillae muscle and in the blood vessels of the skin and internal organs. These cells contract when noradrenaline is bound by their alpha receptors, with consequent pupillary dilatation and cutaneous and visceral vasoconstriction. The enteric neurons that cause closure of sphincters also bear alpha receptors. The beta receptors occur on cardiac muscle cells in the atrial pacemaker tissue and in the ventricles, on smooth muscle cells in the bronchioles, in blood vessels of skeletal muscle, and on enteric neurons that inhibit propulsive movements of the alimentary tract. SMCs with beta receptors relax in response to noradrenaline so dilatation of the bronchioles and vasodilation in skeletal muscles take place. The rate and force of contraction of the heart are increased, and propulsion along the gut is inhibited. Several clinically important drugs act by stimulating or blocking the alpha or beta receptors.

Strong sympathetic stimulation produces diffuse effects because of the following factors, which are the converse of those present in the parasympathetic system. Each sympathetic preganglionic neuron synapses with many postganglionic neurons, and each of the latter supplies numerous effector cells or enteric neurons. Hence, there is much divergence. Noradrenaline liberated at postganglionic terminals is deactivated by being taken up into the axonal terminals from which it was released, and this is a slower process than the enzyme-catalyzed hydrolysis of acetylcholine.

ENTERIC NERVOUS SYSTEM

From the esophagus to the rectum, the walls of the human alimentary canal contain some 108 neurons, a population comparable to the number of neurons in the spinal cord. The cell bodies occur in two zones. The myenteric plexus (Auerbach's plexus) lies between the longitudinal and circular muscle layers, and the submucosal plexus (of Meissner) lies in the connective tissue between the circular muscle layer and the muscularis mucosae. Each plexus consists of small enteric ganglia, joined to one another by thin nerves in which all the axons are unmyelinated. Similar nerves connect the two plexuses across the circular muscle layer and carry branches from the plexuses into the smooth muscle layers and the lamina propria of the mucosa. Most of the neurons are multipolar, but there are also many bipolar and unipolar ones, especially in the submucous plexus. In addition to neurons, the enteric nervous system contains neuroglial cells, which ensheath the neurons and their processes. The nervous tissue is avascular and receives its nutrients by diffusion from capillary vessels outside the glial sheath.

The synaptic organization of the enteric nervous system (Fig. 24-5) is not simple. Several types of neuron are found in the plexuses. The bipolar and unipolar cells are presumed to have sensory functions, especially in initiating the peristaltic reflex. Neurons of two types have

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axons that end on smooth muscle and gland cells; the excitatory neurons are cholinergic. The nonadrenergic, noncholinergic inhibitory neurons may use a peptide, a nucleotide, or nitric oxide. Some enteric neurons send axons centripetally in the nerves that accompany the mesenteric and other abdominal arteries to the celiac and mesenteric sympathetic ganglia. Enteric neurons have been shown to contain many different peptides with pharmacologically demonstrable actions on the gut, and it is considered probable that at least some of these substances serve as neurotransmitters.

 

FIGURE 24-5 Organization of the enteric nervous system. For simplification, the myenteric and submucosal plexuses have been combined. The sites of some known transmitters are shown, as are sites of excitation (+) and inhibition (-). The inhibitory transmitter to smooth muscle may be adenosine triphosphate or nitric oxide or both of these compounds. Arrows indicate directions of axonal conduction. Cholinergic neurons are red, the noradrenergic neuron is green, the sensory enteric neuron is blue, the neuron inhibitory to smooth muscle is magenta, and intrinsic enteric neurons (interneurons) are black. ACh, acetylcholine; NA, noradrenaline.

CLINICAL NOTE

Hirschsprung's Disease

In about one in 5,000 infants, 80% of them male, cells of the neural crest fail to migrate into the most caudal part of the large intestine. Intrinsic enteric neurons are absent from the distal rectum and for a variable distance rostrally, often to the sigmoid colon. In the absence of intrinsic neurons, there is no peristalsis, and the circular smooth muscle is tonically contracted, creating a functional obstruction to the movement of feces. The proximal parts of the colon, which have normal innervation, become greatly distended, giving the condition its alternative name of congenital megacolon. Preganglionic cholinergic nerve fibers are present in abnormally high numbers in the rectum. The presence of these fibers in biopsies of the rectal mucosa confirms the diagnosis of Hirschsprung's disease. The condition is treated by surgical removal of the aganglionic segment.

Acquired megacolon in adults can have a variety of causes—disease such as diabetes mellitus, scleroderma, or amyloidosis that can interfere with smooth muscle and its innervation. Chagas' disease (South American trypanosomiasis) is a parasitic infection in which enteric neurons are destroyed by an autoimmune mechanism. This occasionally results in megacolon, but more frequently, the aganglionic region is above the junction of the esophagus with the stomach, and the esophagus becomes greatly distended.

The fibers afferent to the enteric nervous system are of two types. Cholinergic axons of preganglionic parasympathetic neurons

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terminate on the dendrites and cell bodies of interneurons and of neurons that supply smooth muscle and secretory cells and glands. The noradrenergic axons of sympathetic neurons terminate in axoaxonal synapses on both parasympathetic and intrinsic fibers. They are believed to mediate presynaptic inhibition of the cholinergic neurons that stimulate contraction of the musculature and glandular secretion.

Central Control of the Autonomic Nervous System

The hypothalamus has a diverse afferent input, and its efferent connections include projections to neurons that constitute the autonomic outflow. It is therefore an important controlling and integrating center for the autonomic system.

Through afferent connections described in Chapter 11, the hypothalamus is influenced by the neocortex, hippocampal formation, amygdala and septal area, and olfactory areas. Ascending pathways from the spinal cord and brain stem convey information of visceral and gustatory origin. In addition, hypothalamic neurons respond directly to changes in the temperature, osmolarity, and concentrations of various substances (including hormones) in the circulating blood. Depending on specific sensitivities, these neurons are related either to the autonomic system or to the pituitary gland.

Signals that originate in the hypothalamus reach autonomic nuclei in the brain stem and spinal cord directly and through relays in the reticular formation. Direct projections from the amygdala and septal area to preganglionic autonomic neurons have also been described. The autonomic neurons are also influenced by visceral “centers” and by visceral afferent nuclei, notably the solitary nucleus, in the medulla. The autonomic outflow therefore comes under a wide range of influences: visceral (including taste and smell), emotional (both basic drives and moods), and even mental processes at the neocortical level. Cortical areas that are functionally active at the same time as the sympathetic nervous system include the medial prefrontal cortex and the anterior parts of the insula and cingulate gyrus.

CENTRAL SYMPATHETIC PATHWAY FOR THE EYE AND FACE

Central pathways that control the sympathetic innervation of the head can be interrupted by lesions in the brain stem. Horner's syndrome (see Chapter 7) and loss of thermoregulatory sweating of facial skin can occur after the development of ipsilateral lesions in the medulla, dorsal to the inferior olivary nucleus. The sympathetic dysfunction is part of Wallenberg's syndrome, and the position of the lesion (see Fig. 7-17) indicates that nuclei or descending fibers essential for pupillary dilation and facial vasomotor control descend through the lateral part of the medullary reticular formation. Lateral medullary lesions prevent thermally induced but not emotionally induced facial sweating, indicating the existence of more than one descending pathway to the preganglionic sympathetic neurons. In the human spinal cord, descending fibers that originate in or pass through the lateral medulla are deeply located in the lateral funiculus of the spinal white matter just lateral to the ventral horn.

Visceral Afferents

The unipolar cell bodies of general visceral afferent neurons are situated in the inferior ganglia of the glossopharyngeal and vagus nerves and in the ganglia of spinal nerves. The peripheral processes of visceral afferent neurons traverse autonomic ganglia and plexuses without interruption to reach the organs they supply. These neurons are functionally of two kinds: physiological afferents and afferents for pain. Most physiological afferents accompany fibers of the parasympathetic division of the autonomic nervous system. The afferents for pain accompany the fibers of the sympathetic division (see Fig. 24-3).

PHYSIOLOGICAL AFFERENTS

Visceral afferents of special physiological importance are associated with the parasympathetic division of the autonomic system. The

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following examples illustrate the reflex arcs of which they form the afferent limbs.

Cardiovascular System

Terminals of sensory fibers in the aortic arch and carotid sinus (at the bifurcation of the common carotid artery) serve as baroreceptors, signaling changes in arterial blood pressure (BP). Whereas the cell bodies of neurons supplying the aortic arch are located in the inferior (nodose) ganglion of the vagus nerve, those for the carotid sinus are in the inferior ganglion of the glossopharyngeal nerve. The central processes terminate in the solitary nucleus in the medulla, from which fibers pass to regions of the reticular formation commonly called cardiovascular “centers.” Axons from the solitary nucleus and the reticular formation project to the nucleus ambiguus and intermediolateral cell column of the spinal cord. Through the reflex pathways thereby established, a rapid increase in arterial pressure causes a decrease in heart rate (vagus nerve) and vasodilation through inhibition of the vasoconstrictor action of the sympathetic outflow. A decrease in arterial pressure, such as occurs after hemorrhage, initiates reflex responses that are the reverse of those caused by an increase in arterial pressure. Visceral afferents in the glossopharyngeal and vagus nerves therefore participate in the maintenance of normal arterial BP.

The cardiac output is also regulated by the Bainbridge reflex, which is triggered by vagally innervated receptors in the right atrium; these monitor the central venous pressure. The central connections provide for stimulation of the sympathetic nervous system and inhibition of the vagal slowing of the heart. Thus, the cardiac output is increased as the volume of the venous return increases.

Respiratory System

Three respiratory “centers” are present in the brain stem for automatic control of respiratory movements. Two such regions are situated in the reticular formation of the medulla: an inspiratory center medially and an expiratory center laterally. In addition, a pneumotaxic center in the parabrachial area, at the level of the pontine isthmus, regulates the rhythmicity of inspiration and expiration. The inspiratory and expiratory “centers,” as well as those for the cardiovascular system, are probably fields within the network of long dendrites in the reticular formation rather than compact collections of cell bodies. Inspiration is initiated by stimulation of neurons in the inspiratory center by carbon dioxide of the circulating blood. The chemosensory neurons, by means of reticulospinal connections, stimulate the motor neurons that supply the diaphragm and intercostal muscles.

Respiratory movements are also influenced by signals conducted centrally from the carotid bodies situated near the bifurcation of each common carotid artery and from small aortic bodies adjacent to the aortic arch. These bodies serve as chemoreceptors that respond to decreased oxygen concentration in the blood. The resulting signals are sent to the solitary nucleus through neurons with cell bodies in the inferior ganglia of the glossopharyngeal and vagus nerves. Further connections with respiratory “centers” in the brain stem bring about increased rate and depth of respiratory movements. This reflex operates in vigorous exercise, when a person is exposed to a lowered oxygen tension (as at high altitudes), or in any circumstances that produce asphyxia.

Sensory neurons in the vagus nerve constitute the afferent limb of the Hering-Breuer reflex, through which expiration is initiated. Sensory endings in the bronchial tree, especially the smaller branches, discharge at an increasing rate as the lungs are inflated. These signals reach the expiratory center through a relay in the solitary nucleus. Neurons in the expiratory center then inhibit those of the inspiratory center. Expiration ensues as a passive (elastic) process when the inspiratory muscles relax.

Other Systems

Sensory axons in the vagus nerve are distributed to the GI tract at least as far as the junction of the transverse and descending parts of the colon (the splenic flexure). The nerve terminals are stimulated by distention of the stomach and intestine, contraction of the smooth musculature, and irritation of the mucosa. Although motility and secretion are not dependent on the extrinsic nerves, they are modified by reflex action involving vagal afferent and efferent neurons. The

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distal colon, rectum, and urinary bladder are supplied by splanchnic branches of the second, third, and fourth sacral nerves. Reflexes in these segments of the spinal cord and the sacral component of the parasympathetic system stimulate emptying of the large bowel and urinary bladder, subject to voluntary control.

ASCENDING PATHWAYS FOR FULLNESS

Some ascending visceral pathways are distinct from those for pain (described in the next section). One such pathway originates in the solitary nucleus in the medulla, which receives general visceral afferents from the vagus nerve predominantly. A second pathway originates in segments T1 to L2 and S2 to S4 of the spinal cord. These ascending fibers are included in the spinoreticular and spinothalamic tracts. Through the pathways from the medulla and spinal cord, signals of visceral origin reach the reticular formation of the brain stem, hypothalamus, and the lateral division of the ventral posterior nucleus (VP1) of the thalamus. A thalamocortical projection provides for a conscious feeling of fullness when the stomach is distended and a feeling of hunger when the stomach is empty. Feelings of fullness in the distal colon and urinary bladder are also mediated by these spinoreticular and spinothalamic connections.

CLINICAL NOTE

Pain From Internal Organs

The heart is supplied with pain fibers by the middle and inferior cervical cardiac nerves and by the thoracic cardiac branches of the left sympathetic trunk. Central processes of the primary sensory neurons enter segments T1 to T5. Pain of cardiac origin is therefore referred to the center of the chest and the inner aspect of the left arm. Deviations from this zone of reference are common and are probably attributable to variations in the laterality and segmental levels of the cardiac innervation.

Pain from the gallbladder or bile ducts passes centrally in the right greater splanchnic nerve, entering the spinal cord through dorsal roots T7 and T8. The pain is referred to the upper quadrant of the abdomen and the infrascapular region on the right side. Disease of the liver or gallbladder may irritate the peritoneum covering the diaphragm. The resulting pain is referred to the top of the shoulder because the diaphragm is supplied with sensory (as well as motor) fibers by the phrenic nerve, which originates from segments C3, C4, and C5.

Pain of gastric origin is felt in the epigastrium because the stomach is supplied with pain afferents that reach segments T7 and T8 by way of the left and right greater splanchnic nerves. Pain from the duodenum, as in duodenal ulcer, is referred to the anterior abdominal wall just above the umbilicus, with both this area and the duodenum being supplied by nerves T9 and T10. Afferent fibers from the appendix are included in the lesser splanchnic nerve, which contains axons from the T10 dorsal root ganglion. The pain of appendicitis is initially referred to the region of the umbilicus, which lies in the T10 dermatome. The pain shifts to the lower right quadrant of the abdomen when the parietal peritoneum becomes involved in the inflammatory process. (The parietal peritoneum and pleura are supplied by segmental somatic nerves in a distribution similar to that of the skin of the trunk.) Pain fibers from the renal pelvis and ureter are included in the least splanchnic nerve; they enter segments L1 and L2 of the spinal cord, and the pain is referred to the loin and the groin.

There is no entirely satisfactory explanation for the referral of pain. An early proposal was that afferent fibers for visceral and somatic pain synapse with the same tract cells in the spinal cord, with these cells being excited by subliminal somatic stimuli when receiving impulses of visceral origin. A more recent hypothesis is that both visceral and somatic pain from regions served by a specific segment of the spinal cord are relayed to the same group of cells in the ventral posterior nucleus of the thalamus. The topographic representation of the body in the thalamus and cerebral cortex allows recognition of the sources of ordinary somatic sensations. Localization may be in error when pain originates internally, perhaps because pain of somatic origin is a more common experience than pain caused by visceral malfunction or disease. It is of interest that more than 230 years ago, John Hunter called referred pain a “delusion of the mind.”

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PAIN AFFERENTS

The sensory endings for pain arising in internal organs are stimulated in various ways in the presence of abnormal function or disease. The pain is most commonly caused by distention of a hollow viscus such as the intestine. This may occur proximal to localized and forcible contraction of the smooth muscle. Similarly, distention of a bile duct or a ureter occurs when the lumen is obstructed by a stone. Visceral pain also results from rapid stretching of the capsule of a solid organ, such as the liver or spleen. Peritoneal or pleural irritation contributes to the pain of inflammatory disease. In the case of angina and the pain of myocardial infarction, the effective stimulus is anoxia of cardiac muscle.

The sensory neurons for pain arising in thoracic and abdominal organs are associated only with the sympathetic nervous system. The cell bodies of the primary sensory neurons are located in the dorsal root ganglia of the thoracic and upper lumbar nerves (see Fig. 24-4). The peripheral processes of these neurons reach the sympathetic trunk by way of white communicating rami (see Fig. 24-3); they run in the sympathetic trunk for variable distances and then continue to the viscera by way of the cardiac, pulmonary, and splanchnic nerves. The corresponding dorsal root fibers probably enter the dorsolateral tract of Lissauer along with somatic pain fibers and end similarly in the dorsal horn of the spinal cord. The ascending pathway for visceral pain corresponds, in part, with the pathway for somatic pain (see Chapter 19), through crossed fibers in the spinothalamic tract. There are also bilateral spinoreticular fibers and relays in the reticular formation, as in the pathway for pain from somatic structures.

REFERRED PAIN

Visceral pain has characteristics that distinguish it from pain arising in somatic structures, notably diffuse localization and radiation to somatic areas (i.e., referred pain). The zone of reference of the pain from an internal organ coincides with the part of the body served by somatic sensory neurons associated with the same segments of the spinal cord. The principle of referred pain is illustrated by the examples in the Clinical Note on page 363. The reader should compare the areas of reference with the distribution of segmental innervation of the skin (see Fig. 5-13).

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