Nerve Endings

NERVE ENDINGS, sites of connection between nerve fibers and elements of various tissues of the organism. Formations connecting nerve cells to one another, the so-called pericellular apparatuses, may also be categorized as nerve endings (see Asthenic theory). Physiologically, a nerve ending represents that region of the nerve and innervated tissue where the transition of excitation from the nerve fiber to the innervated tissue occurs—effector nerve endings (motor, secretory, trophic)—or where the transition of excitation from the tissue to the nerve fiber occurs—sensory nerve endings. The doctrine of the structure and function of nerve endings, as a chapter of the doctrine of nervous tissue, reflected all the trends of scientific thought concerning cell theory, in particular the neuron theory, and criticisms of these theories. The conception of cells as elements or even elementary organisms, the sum of which yields a tissue, required a sharp demarcation of both cells and individual tissues. Therefore, connections between tissues were conceived solely as the juxtaposition of some elements with others. Regarding nervous tissue, its connection with others was described as contact (contiguity). In this connection, a crude analogy with electrical installations was frequently used. Kühne was the first to clearly demonstrate that nerve endings in muscle fibers do not fit the conception of contact, since the branches of nerve fibers penetrate directly into the protoplasm of the muscle fiber. Through the works of Apáthy, Kolmer, Heringa, and others, it was shown that such close relationships of nerve fibers to innervated tissues can also be demonstrated in a number of other nerve endings (epithelium, sense organs epithelium, connective tissue). Thus, it was elucidated that nerve endings represent an organic whole that cannot be reduced to a sum: nerve plus muscle, or nerve plus epithelium, either morphologically or physiologically. This qualitative peculiarity of nerve endings was subsequently established both by physiological methods (irreiprocal conduction, the "receptive substance" of Langley) and by morphological methods. With ordinary staining methods of histological preparations, nerve endings are mostly undetectable. Nerve endings were discovered and described in detail only with the advent of special methods for staining nervous tissue (methylene blue, silver impregnation and gold gilding of Golgi, Cajal, and Bielschowsky). Nerve endings possess certain general structural features. Approaching a nerve ending, the nerve fiber usually loses its myelin sheath and becomes non-medullated for some distance. The Schwann and Henle sheaths often merge with the capsules of the nerve endings or the sheaths of the organ. The existence of so-called naked axial cylinders in the region of nerve endings is contested by many at the present time. In the region of the nerve endings of the autonomic nervous system, the presence of elements of the Schwann syncytium, having the character of multipolar cells (so-called "interstitial" cells), is characteristic. The axial cylinder forming part of the nerve ending often branches. The number of branches can be very large. Characteristic of many nerve endings is the disaggregation of neurofibrils (see Nerve fibers) and the resulting expansion or swelling of the nerve fiber (so-called varicosities). Sometimes these expansions can reach a very large size and in such cases are described as plates (sensory nerve endings). Many nerve endings are provided with special cells with which the nerve fibers enter into the closest connection (so-called sensory cells, tactile cells, etc.). The origin of these cells has not been sufficiently elucidated. Classification of nerve endings. Physiologically, nerve endings are usually divided into effector and sensory. Morphologically, determining the affiliation of nerve endings to these two categories is not always possible, especially with regard to nerve endings located in connective tissue. The classification of nerve endings in relation to special types of sensitivity (pain, tactile, thermal) is not established at the present time, and while the pathways for conducting various types of sensitivity in the central nervous system are known, with respect to the periphery we currently possess extremely scant data. Effector nerve endings. These include motor endings on smooth and striated muscles and secretory endings on the cells of internal and external secretion glands. Those endings of nerve fibers of the autonomic nervous system to which a trophic function is ascribed must also be classified here. Motor nerve endings in voluntary musculature. Motor endings in the skeletal striated musculature of mammals have a complex structure [see separate table (pp. 607–608), fig. 5]. The nerve fiber approaching the muscle fiber loses its myelin sheath. The Schwann sheath merges with the sarcolemma of the muscle fiber, and the axial cylinder enters the sarcoplasm of the muscle fiber. At this site, the sarcoplasm may have a protrusion in the form of a more or less noticeable tubercle (strongly developed in some insects and birds). Entering the sarcoplasm, the axial cylinder divides into branches, the number of which in different muscles and in different animals can vary greatly. The branches of the axial cylinder frequently terminate in lamellar expansions with a reticular or fan-shaped arrangement of neurofibrils (Fig. 1). Around the ramifications of the axial cylinder, there is an accumulation of nuclei. According to Tello's data, they originate from ordinary nuclei of the muscle fiber. The sarcoplasm in the region of the nerve ending has a fine-grained character and contains large rod-shaped chondrioconts. The entire formation, including the axial cylinder, sarcoplasm, and nuclei, has been named the motor plaque. This complex is also called the "sole." Boeke, using modern methodology for demonstrating neurofibrils, described a delicate network penetrating the sarcoplasm of the motor plaque; this network is connected on one hand with the neurofibrils of the axial cylinder, and on the other hand closely approaches the myofibrils. It has been named the "periterminal network." Its existence in fixed and stained preparations is currently confirmed by most investigators. Its physiological significance remains unclear. In some cases, during the formation of motor plaques,

Figure L. Motor plate on striated muscle: 1—nuclei; 2—terminal branches; 3—periterminal network.

one of the branches of the axon extends beyond the limits of the plaque and runs to another muscle fiber, where it forms a secondary motor plaque. Such branches were named ultra-terminal fibers. From the secondary motor plaques, a branch may depart and form a tertiary motor plaque, and so on. In some cases, the number of ultra-terminal fibers is so great that the entire muscle appears penetrated by a continuous network of nerve fibers, with motor plaques inserted into this network at certain sections (figure 2). Such relations were found in amphibians and reptiles (mainly in the tongue) by Stefanelli, Ruffini (Stefanelli, Ruffini), and Lavrentiev. The physiological significance of this phenomenon has not been elucidated. According to Stefanelli's hypothesis, such a structure facilitates maximum synchronicity of contraction of all muscle fibers of the organ. In addition to spinal nerve fibers forming the motor plaque of a muscle fiber, thin, mostly unmyelinated nerve fibers enter the same plaque, observed for the first time in amphibians and reptiles by Bremer and Gemelli and described in detail by Boeke for mammals. Through a series of experiments, Boeke established that these fibers belong to the autonomic nervous system. Physiologically, these data were confirmed by Orbeli and his pupils. Nerve endings in striated skeletal muscles of amphibians are constructed more primitively. The "sole" is usually absent, and the branches of the axon lie in the form of long threads along the length of the muscle fiber. In some muscles, predominantly in amphibians and reptiles, nerve endings have the appearance of clusters, or bunches. Such endings were described for the first time by Chiriev and received the name of grape-like endings (terminaisons en grappe). Plurisegmental nerve endings of striated voluntary muscles. For some striated muscles of mammals, the presence of several motor plaques on one and the same muscle fiber is characteristic. Agduhr experimentally proved that in such cases the muscle fiber is innervated simultaneously from several segments of the spinal cord; for example, the flexor digitorum sublimis muscle of the cat is innervated from three cervical segments, and the muscle fibers here have three plaques, each of which belongs to a neighboring segment. Plurisegmental innervation is also encountered in lower vertebrates. Physiologically it was discovered in the frog by Beritov and de Boer and recently confirmed morphologically by Lavrentiev. The physiological significance of this phenomenon remains unelucidated. Motor nerve endings on smooth muscles have the appearance of very dense plexuses of thin unmyelinated nerve fibers; the terminal ramifications of these fibers are extremely thin and apparently form a terminal reticulum. Varicose thickenings occur on the fiberlets. Free button-like terminal apparatuses are possible, which perhaps penetrate inside the cells. It must be noted that on smooth muscles nerve endings are located rarely, and far from every fiber is supplied with them. Trophic nerve endings. A whole series of physiological observations, showing the influence of the nervous system on tissue metabolism, made it necessary to assume the existence of special trophic nerve fibers and their endings. Studies concerning the sympathetic innervation of striated muscles showed that sympathetic nerve endings in muscles are important mainly as an apparatus influencing the metabolism of the muscle fiber (Orbeli).

₃fibers

influence of the nervous system on tissue

tissue metabolism is connected with the innervation not only of muscle tissue and glandular organs, but also with the innervation of so-called passive tissues, which include epithelium and the group of connective tissue substances (connective tissue, cartilage, bone). Until the very last time, the innervation of "passive" tissues in the effector sense was denied. The existence of strictly effector nerve endings on chromatophores (cells of pigmented connective tissue) of some lower vertebrates was considered an exception. In 1930–1931, works appeared establishing the effector innervation of connective tissue elements. Indications of the possibility of such innervation are given in the work of Akkeringa. In 1931, de Castro showed that osteoblasts, taking part in the formation of perichondral and endochondral bone, are supplied with special nerve endings. These endings have the appearance of small loops located in direct proximity to the nucleus of the osteoblast. It is highly probable that these nerve endings lie inside the protoplasm of the osteoblasts. To the same author

Figure 2. Ruffini corpuscle (after Dogel). It was possible to ascertain that the indicated endings belong to the postganglionic fibers of the superior cervical sympathetic ganglion. Nerve endings of the same appearance were discovered by Calderón on the odontoblasts of a growing tooth. Upon the transition of osteoblasts into bone cells, their innervation ceases, and the corresponding nerve endings and the accompanying nerve fiber degenerate. Effector nerve endings on the nerve cells of the central and peripheral nervous system are described in the form of so-called pericellular apparatuses (Ehrlich, Aronson). They are described in detail in the central nervous system by Held, Cajal and his school, Lenhossék (Held, Cajal, Lenhossek), and in the autonomic nervous system by Arnstein, Dogel, Timofeev, Leontovich, and others. Pericellular apparatuses physiologically represent the site of transition of excitation from one nerve cell or even many nerve cells to another. The nature of these formations was interpreted differently depending on the development of the critique of the neuron theory. A number of physiological and morphological data suggest the great importance of this apparatus in the processes of conduction of excitation and inhibition in nerve tissue. The structure of pericellular apparatuses is extremely diverse. In the simplest case, a nerve ending may have the appearance of a small button or plaque located on the body of the nerve cell or on its processes. Thus, pericellular apparatuses on the cells of the anterior horns of the spinal cord have the appearance of numerous small buttons (Endknöpfchen) located on the body and dendrites of nerve cells. In reptiles and birds, pericellular apparatuses are described that have the appearance of massive thickenings encompassing the nerve cell like a cap or hood. In some cases, pericellular apparatuses have the appearance of the finest nerve threads that accompany the dendrites of the nerve cell right up to their terminal branches, as if spreading over them (climbing fibers on Purkinje cells of the cerebellum). In other cases, the neurites of one nerve cell and the dendrites of another cell enter into connection, forming tangles of varying complexity equipped with special elements of neuroglia. Such tangles are found in the olfactory bulb and in the cerebellum ("mossy fibers"). Often the nerve threads of the pericellular apparatus encompass the dendrites of the nerve cell, forming true spirals. Especially often this phenomenon is encountered in the autonomic nervous system (the so-called "spiral process" in amphibians). In the autonomic nervous system, pericellular apparatuses are described that have the appearance of complex tangles or baskets encompassing the body of the nerve cell. In some cases, the pericellular apparatus has the appearance of plaques or clusters strikingly similar to endings in striated muscles (Timofeev, Serebryakov). In elderly individuals and in a number of pathological cases, an overgrowth of the threads of the pericellular apparatus is described (alcoholism — Cajal, de Castro). Sensory nerve endings. In connective tissue, especially subcutaneous tissue, as well as in mucous and serous membranes, near joints, etc., there are many nerve endings of a very diverse form. Apparently, all of them have the character of receptor endings, and the majority of them belong to cerebrospinal sensory fibers. Morphologically, they can be divided into free apparatuses and encapsulated ones. Free nerve endings represent numerous branchings of the nerve fiber — telodendria — forming a more or less dense plexus concentrated in one place or distributed over a wide space, developed in one plane in the form of a plate or penetrating the connective tissue in various directions. Individual thin branches often bear varicose thickenings. Some branches sometimes end in swellings. Sometimes all branches form terminal plates — yielding so-called arborescent nerve endings (A. S. Dogel). In the connective-tissue part of the skin directly beneath the epidermis, there are plexuses of thin nerve fibers, more or less abundant in different parts of the body. Thin branches depart from these fibers, penetrating between the epithelial cells of the epidermis and, sometimes branching, reaching in the form of the finest threads to its superficial layers. These tiny threads end freely, or they are lost between keratinized cells, or they form button-like thickenings near or (according to Boeke) inside the cells. These intraepithelial endings are developed very differently in different parts of the body and are especially strongly expressed in places with the most developed sensitivity (for example, lips, animal muzzles). Encapsulated nerve endings. Many nerve endings are clothed in sheaths consisting of thin connective-tissue plates arranged in a greater or lesser number of rows. Flat connective-tissue cells are located between the plates. Bridges sometimes extend from the sheath into the interior of the sheath-formed "bulb." There are many varieties of encapsulated nerve endings, which is due to the varying size, shape, thickness of the capsule, and the endless diversity of the terminal plexuses of the nervous apparatus proper. In the skin of the mole snout, nerve endings form complex so-called Eimer organs (Eimer, 1871). The latter consist of a series of epithelial cells arranged in columns one above another throughout the entire thickness of the epidermis. Nerve fibers pass through such columns, forming intracellular fibrillar networks. Merkel cells (Merkel, 1875) are large, clear, vesicular epithelial cells found in the lower layers of the epidermis, usually in a group. A medullated fiber approaches them, breaking down into branches that form a fibrillar plexus at the base of each cell — a tactile meniscus or plate. According to Boeke, there is a periterminal cytoplasmic network in Merkel cells. Botezat, Dogel, and also Kadanov described additional innervation of Merkel cells from another nerve fiber in the form of varicose threads wreathing them. A type of more complex encapsulated nerve ending is Meissner's (synonym Wagner's) tactile corpuscles (Figure 3); Meissner's corpuscles are located in the tips of skin papillae, mainly on the palm and...

Figure 3. Meissner's corpuscle (after Dogel). endings. These are elongated structures measuring up to 40-180 µ. Their capsule consists of several rows of connective tissue lamellae. The Henle and Schwann sheaths of the medullated nerve fiber approaching the corpuscle merge with it. Inside the capsule, there are flattened cells (tactile cells) lying transversely across it. Ramifications of the nerve fiber with thickenings wind intricately between the cells. According to recent data (Botezat, Heringa), the nerve fibrils form delicate fibrillar networks inside the tactile cells. In addition to the medullated nerve fiber, unmedullated fibers also take part in the plexus inside the corpuscle (Timofeev, Dogel). More simply arranged encapsulated nerve endings consist of a glomerulus of nerve fibrillae covered by sheaths. To this category belong the end-bulbs of Krause, found in connective tissue, and the genital corpuscles of Dogel and Martynov, located in the skin of the genital organs. Vater-Pacini corpuscles (Vater, Pacini) are distinguished by their regular ovoid shape, large size (up to 4 mm in length), and complex capsule structure (see vol. XIII, col. 221, figure 3). The capsule of the Vater-Pacini corpuscle consists of a large number (up to 60) of regularly arranged, superimposed connective tissue lamellae. Tissue fluid is located between these lamellae. The capsule is called the outer bulb. The space inside the capsule is called the inner bulb; it is apparently also filled with fluid. Within it lies the nerve ending proper in the form of a flattened ribbon-like axial cylinder, running along the axis of the corpuscle and terminating in a button-like thickening or a network. In addition to the thick medullated nerve fiber, which gives rise to the main lamella or glomerulus within the inner bulb, a thin medullated or unmedullated nerve fiber takes part in the formation of many Pacinian corpuscles. This fiber loses its sheaths upon entering the inner bulb and entwines the main lamella with its ramifications. This structure was first described by Timofeev and was named Timofeev's apparatus. According to data obtained by Yuryeva, Timofeev's apparatus is formed by sympathetic nerve fibers. Along with the nerve fiber, blood vessels enter the corpuscle, forming a capillary network in the basal part of the corpuscle and between the layers of the capsule. Vater-Pacini corpuscles are very widespread in the organism; they are found in the loose connective tissue of the skin and in the connective tissue of many internal organs, blood vessels, and organs of movement. Their function has not yet been sufficiently elucidated. Analogous structures or a variety of Vater-Pacini corpuscles are Herbst corpuscles (figure 4) in birds. They are distinguished by a smaller size, a smaller number of lamellae in the outer bulb, and a series of "tactile cells" located in the inner bulb on the sides of the nerve fiber. To this same group belong Golgi-Mazzoni corpuscles (Golgi, Mazzoni); they are distinguished by a small size, sometimes an irregular shape, and lesser lamination of their outer bulb, and are found in the submucosal and subserous tissues. A special type of complex encapsulated nerve ending is represented by Grandry corpuscles (Grandry) (figure 5), found in the skin of the beak and in the mucous membrane of the oral cavity in birds (₁

Figure 4. Herbst corpuscle (after Dogel). (ducks, geese); they represent complexly structured tactile cells surrounded by a capsule. Their size is from 10 to 50 µ. Usually, they consist of two hemispherical, somewhat elongated cells put together by their flat surfaces. A medullated fiber approaches the corpuscle, loses its myelin, enters the interior, and forms a reticular lamellar plexus of fibrils between the cells—the tactile meniscus. The fibrils are in close union (Dogel, Botezat, Heringa) with the intracytoplasmic network of the tactile cells. An educational structure (corpusculum tactus) is produced, analogous to the periterminal network of motor endplates (Botezat). If there are more than two tactile cells, the tactile menisci are located between every two cells. Sometimes the cells are arranged in a stack, sometimes single tactile cells are encountered, and then they resemble Merkel cells. The question of the origin of tactile cells from connective tissue or epithelium remains unresolved. Hairs are richly supplied with nerve endings. In animals, nerve endings are particularly numerous in the so-called sinus hairs. The nerve fibers approaching the hair break up into branches that form a dense plexus surrounding the hair below the site of the sebaceous glands [see separate table (col. 607-608), figure 6]. Other fibrillae extend pro

Fig. 5. Grandry corpuscle Figure 6. Neuro-muscular (after Botezat). spindle (after Dogel).

long and form a wreath of thinning, sometimes dichotomously dividing threads around the neck of the hair. These nerve plexuses are located on the outer epithelial sheath, into which thin branches penetrate not very deeply. There appear to be no nerve endings in the hair papilla. Usually, several medullated nerve fibers approach the hair, which, dividing into branches, encompass the connective tissue follicle of the hair somewhat below the level of the sebaceous glands. Thin branches penetrate to the outer part of the outer root sheath, where they form several circular spiral turns. Other branches, also lying at the periphery of the outer root sheath, are located parallel to the long axis of the hair and cross the previous ones at a right angle. The resulting lattice is thus called the "palisade apparatus of the hair." In a number of mammals, special nerve endings have been found in the so-called "sinus hairs." The shaft of the sinus hair, together with the root sheaths, is surrounded on all sides by cavities containing lymph and blood. Along the walls of these cavities and along their connective tissue septa runs a huge number of nerve fibers. Thus, the slightest vibration of the hair changes the pressure in the cavities and acts on the nerve receptors located in the connective tissue. In addition, sinus hairs are equipped with a typical "palisade apparatus." Sensory nerve endings in striated muscles are called neuro-muscular spindles (Figure 6). Among the muscle fibers, very thin transversely striated fibers rich in sarcoplasm stand out by their structure. One or several such fibers are enclosed over a considerable extent by a special connective tissue capsule having the form of a sleeve. Between the capsule and the muscle fibers, there is a significant amount of lymph. Thick medullated nerve fibers, piercing the capsule, enter the lymphatic space and break down in it into a series of branches. The latter spirally envelop the muscle fibers, forming expansions, varicosities, or plates, and closely adjoining the sarcolemma. In addition to sensory nerve fibers, motor nerve fibers also approach this apparatus, forming typical motor end-plates in the muscle fibers. Experiments have established that neuro-muscular spindles are organs of muscle sense. The spirals of the nerve endings are irritated both upon contraction of the muscle fiber and upon its stretch. Similar endings are also present on tendon fibers; these are the so-called neuro-tendinous spindles. Nerve endings in individual organs. In arteries, there are fine plexuses of non-medullated fibers in the tunica media; in the tunica adventitia, nerve endings of the free plexus type and nerve endings of the Vater-Pacini corpuscle type. In veins, in the tunica media, plexuses of non-medullated fibers and treelike nerve endings. In large veins, Vater-Pacini corpuscles. Capillaries are often accompanied by thin non-medullated fibers; proper nerve endings on them have been little described. Stern the Younger saw the finest anastomosing branches on the capillaries of the heart, which he considers the terminal apparatus. He also described button-like endings on the capillaries of the meninges. In the heart, plexuses have been described in the epicardium. In the myocardium, there are plexuses of thin nerve fibers; small networks are sometimes apparently formed between the muscle fibers. Regarding nerve endings in the heart muscle fibers themselves, it is definitely known that endings analogous to the terminal plates of skeletal musculature are not present here. Some authors (Cajal, Retzius, Smirnov, Mikhailov) describe button-like nerve endings on the fibers; Ranvier, Boeke describe intracytoplasmic nerve endings. Some authors could not find such endings. In the endocardium, a great variety of nerve endings have been described, both free, in the form of tufts, glomeruli, etc., and encapsulated (Dogel, Mikhailov, Smirnov). In the pericardium, there are plexuses and encapsulated nerve endings of the Vater-Pacini corpuscle type. In lymph glands and the spleen, delicate nerve plexuses are encountered along the vessels and in the trabeculae. In the kidneys, nerve branches form plexuses in the walls of the pelvices; many nerve branches accompany the vessels; closely connected with them are nerve threads spreading between and around the cells of the tubules, and perhaps also inside them. The mucosa of the respiratory tract is richly supplied with all types of sensory endings; there are free nerve endings in the epithelium and subepithelially lying plexuses and glomeruli, both free and encapsulated. In the bronchi, a perichondral plexus between the cartilage and the lung parenchyma and a subchondral plexus in the connective tissue of the submucosa between the cartilage and the muscle coat are distinguished. From the latter, thin branches go, ending in a plexus at the glandular tissue and in the smooth musculature. In the parietal (Dogel) pleura, there are encapsulated bodies of the Vater-Pacini-Golgi-Mazzoni type and free endings in the form of tufts. In the pulmonary pleura, free endings in the form of plexuses and branches with a thickening. In the submucosal connective tissue of the tongue, there is a dense plexus formed by medullated and non-medullated fibers. Branches depart from it into the papillae. Thin branches terminate in free endings in the epithelium and in the taste buds. In the dental pulp, there is a dense plexus with thicker branches in the center and thinner ones at the periphery. Nerve endings have not been found in the dentin. In the gums, there are all sorts of free and encapsulated nerve endings of the Vater-Pacini, Merkel, Krause types, etc. In all glands—salivary, gastric, intestinal, etc.—nerve endings have the appearance of plexuses around the lobules with button-like thickenings at the ends of the branches or arranged bead-like on them (Figure 7). In the liver, only fine nerve fibrils in the connective tissue are known with certainty. The peritoneum has many both free endings and encapsulated endings of the Vater-Pacini corpuscle type and others. The membranes of the brain are abundantly supplied with nerve endings. Here there are plexuses and tuft-like nerve endings. Encapsulated nerve endings have been described in the pia mater and in the tela chorioidea. Both after nerve transection (Boeke) and during intoxication (J. M. Villa-Verde), nerve endings undergo degeneration. This has been especially studied in detail on motor nerve endings in striated muscles. At the same time, the staining reaction changes first; then the nerve ending breaks down into clumps and lumps and then completely disappears. Upon regeneration of the corresponding nerve fiber, the nerve ending also regenerates (Tello, Boeke). The new fiber penetrates through the sarcolemma and first forms thin, delicate loops, then networks, and a new terminal plate is formed. Sensory nerve endings regenerate in the same order. Recent experimental works have shown that these nerve endings can whimsically hypertrophy under the influence of external

Figure 7. Nerve plexus around the glandular cells of the pancreas (after Pensa).

stimuli, e.g., radium rays, X-rays, ultraviolet rays (Luterstein, Rakhmanov, Shinkarenko, Meissel).