Study on the nerve endings in the pancreas of Rattus rattus refescens and Gallus domsticus as revealed by the cholinesterase technique.

An investigation was undertaken to study the nerve endings in the pancreas of Rattus rattus rufescens and Gallus domesticus by cholinesterase technique. Bulb-like nerve ending in the connective tissue (negatively stained) and dot-like nerve ending in the lobular cells were recorded in Rattus. Dot-like nerve ending on the periphery of the lobular cells and bulb like nerve endings connected with nerve bundle, were recorded in Gallus. Nerve endings were AChE-positive in nature in both Rattus and Gallus.     

A histochemical study of the neuro-muscular spindles in the tongue of some rodents.

An investigation was undertaken to study the Neuro-muscular spindles in the tongue (Rattus rattus rufescens and Suncus murinus) by cholinesterase technique, under maintained pH of 5.2, incubation period 20 h., and temperature 38 degrees C (Rattus) and 39 degrees C (Suncus). Neuro-muscular spindles were observed frequently distributed from anterior to posterior of the tongue and took a little darker stain than the ordinary muscle fibres (negatively stained) while the nerve fibres and ganglia took still darker stain. Nerve fibres (myelinated, non-myelinated and tortuous) were seen penetrating and embracing the muscle spindles and most of them ran parallel to the spindles. Ganglia of various shapes (oval, irregular, elongated and rounded) and sizes (large, Rattus and medium and small, Suncus) were AChE-positive. Ganglia small and medium in size, rounded and elongated in shape were arranged in chain-like fashion on the muscle spindles in Suncus (Fig. 9, 10). The blood vessels (artery, vein, and capillary) were recorded either in close association with the muscle spindles or lying parallel to it. In all cases they were closely related and deeply associate either with the nerve fibres of the plexus of the muscle spindles or with the nerve fibres of the neural network of vessel. Perivascular and perimuscular ganglia with pre- and postganglionic nerve fibres were closely related to each other. Nerve endings, dot-like (Rattus) and bulb-like (Suncus) were occasionally recorded. AChE activity was found randomly in the muscle spindles (Fig. 2, 5.) and in the form of dark brown patches in the ordinary muscle fibres.     

Nerve endings in the heart of teleosts

The nerve endings in the heart of fishes were studied using silver impregnation techniques. The heart chambers are profusely innervated by the sympathetic, parasympathetic (vagal) and postganglionic fibers of the intracardiac ganglia situated at the sinuatrial and the atrioventricular junctions. The plexuses are composed of medullated and nonmedullated fibers. The nerve fibers generally end freely and are slightly branched or unbranched terminations of myelinated and unmyelinated fibers. Moreover, a few nerve fibers end redundant in the form of end-rings, bulb-like, bush-like, club-shaped end end-coil like structures. The complex unencapsulated types of endings are also found in the myocardium of the atrium and the ventricle. The encapsulated endings (Vater-Pacinian; Krause end-bulb) could not be observed.     

Morphometric analysis of hypoxia-induced synaptic activity in intrapulmonary neuroepithelial bodies

Summary A morphometric analysis has demonstrated ultrastructural changes induced by hypoxia in the epithelial cells and the intracorpuscular nerve endings of the presumed chemoreceptive intrapulmonary neuroepithelial bodies (NEB) of neonatal rabbits.Acute hypoxia stimulates an exocytosis of epithelial dense-core vesicles (DCV) at the level of the morphologically afferent or sensory (type 1 a) intracorpuscular nerve endings of the NEB. Assuming the epithelial cells to be chemoreceptive, this phenomenon could represent a transduction of sensory stimuli.In the morphologically efferent or motor (type 2 and type 1 b) intracorpuscular nerve endings of the NEB, acute hypoxia causes a depletion of synaptic vesicles and an increase in the amount of membrane-bounded cisternae and multivesicular bodies, suggestive of an enhanced synaptic activity of these nerve endings. It is proposed that the chemoreceptor cells could thus in turn be modulated centrifugally by their efferent-like intracorpuscular nerve endings.It has been proposed in our earlier studies that the NEB probably are intrapulmonary chemoreceptors with local secretory activities, reacting to the composition of the inhaled air. By the release of serotonin and peptide substances they may produce a local vasoconstriction in hypoxically aerated lung areas, enabling an intrapulmonary regulation of the V/Q ratio. The present study provides evidence that, in addition to this local effect, NEB could generate centripetal nerve impulses via exocytosis of epithelial DCV at the afferent-like intracorpuscular nerve endings. At the same time they could be modulated by the CNS via their efferent-like intracorpuscular nerve endings.With respect to their innervation, numerous similarities appear to exist morphologically and functionally between the carotid body and the intrapulmonary NEB.     

Light-evoked somatosensory perception of transgenic rats that express channelrhodopsin-2 in dorsal root ganglion cells

In vertebrate somatosensory systems, each mode of touch-pressure, temperature or pain is sensed by sensory endings of different dorsal root ganglion (DRG) neurons, which conducted to the specific cortical loci as nerve impulses. Therefore, direct electrical stimulation of the peripheral nerve endings causes an erroneous sensation to be conducted by the nerve. We have recently generated several transgenic lines of rat in which channelrhodopsin-2 (ChR2) transgene is driven by the Thy-1.2 promoter. In one of them, W-TChR2V4, some neurons were endowed with photosensitivity by the introduction of the ChR2 gene, coding an algal photoreceptor molecule. The DRG neurons expressing ChR2 were immunohistochemically identified using specific antibodies to the markers of mechanoreceptive or nociceptive neurons. Their peripheral nerve endings in the plantar skin as well as the central endings in the spinal cord were also examined. We identified that ChR2 is expressed in a certain population of large neurons in the DRG of W-TChR2V4. On the basis of their morphology and molecular markers, these neurons were classified as mechanoreceptive but not nociceptive. ChR2 was also distributed in their peripheral sensory nerve endings, some of which were closely associated with CK20-positive cells to form Merkel cell-neurite complexes or with S-100-positive cells to form structures like Meissner's corpuscles. These nerve endings are thus suggested to be involved in the sensing of touch. Each W-TChR2V4 rat showed a sensory-evoked behavior in response to blue LED flashes on the plantar skin. It is thus suggested that each rat acquired an unusual sensory modality of sensing blue light through the skin as touch-pressure. This light-evoked somatosensory perception should facilitate study of how the complex tactile sense emerges in the brain.     

Ultrastructure of Merkel corpuscles and so-called "transitional" cells in the white Leghorn chicken

In the chicken Merkel corpuscles are located in the dermis and consist of specialized Merkel cells, discoid nerve endings and lamellar cells. Merkel cells contain characteristic membrane-bound dense-core granules and bundles of microfilaments. Asymmetric junctions, synapse like, with thickened membranes and clusters of dense-core vesicles were observed between the Merkel cells and the nerve endings. The nerve ending is derived from myelinated nerves and sometimes contains clusters of clear vesicles. A laminar system formed by lamellar cells of the Schwann cell type encloses the Merkel cells and the nerve endings. So called "transitional" cells, showing some of the morphological features of both keratinocytes and Merkel cells, were observed in the basal layer of the epidermis. One was located partly in the epidermis and partly in the dermis. The structure of Merkel corpuscles is compared with that of Merkel cells in other tetrapods. The developmental significance of "transitional" cells and the origin of Merkel cells are discussed.     

Mephedrone does not damage dopamine nerve endings of the striatum,but enhances the neurotoxicity of methamphetamine,amphetamine, and MDMA

Mephedrone (4‐methylmethcathinone) is a β‐ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re‐uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine‐induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4‐methylenedioxymethamphetamine on DA nerve endings. In contrast, nomifensine protected against methamphetamine‐induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co‐abused with it, leading to heightened neurotoxicity.     

Ultrastructural and immunocytochemical studies of neuromuscular junctions in oviduct of Locusta migratoria

The ultrastructure of nerve endings in the oviduct visceral muscles of Locusta migratoria was studied by electron microscopy and by immunogold labeling for two kinds of neuromodulators, the pentapeptide proctolin and FMRFamide-related peptides. Nerve endings contained electron-lucent round vesicles and two kinds of granules (round and avoid), and formed two types of synapses or release sites with the muscle. The morphologically distinct nerve endings were classified into three different categories based on the composition of synaptic vesicles and granules. Type-I nerve endings were dominated by electron-lucent round vesicles and contained only a few round electron-dense granules. Type-II nerve endings contained mostly electron-dense round granules and electron-lucent round vesicles. A few electron-dense ovoid granules were also present. Electron-dense ovoid granules dominated the type-III nerve endings, which usually contained less electron-lucent vesicles than either type-I or II nerve endings. Both proctolin and FMRFamide-like immunoreactivity was associated with electron-dense round granules. However, FMRFamide-like immunoreactivity was only found in the type-II nerve endings, while proctolin immunoreactivity was found within type-I nerve endings as well as in some type-II nerve endings. Immunological results therefore allow us to further divide type-II nerve endings into type-IIa (immunonegative for proctolin) and type-IIb (immunopositive for proctolin). Type-III nerve endings show no immunolabeling to either proctolin or FMRFamide.     

Activity-dependent plastic changes in the motor nerve terminals of the adult rat

Summary— Small and short-lasting physiologic variations in the locomotor activity of normal adult rats can induce remodelling in the motor nerve endings of the fast extensor digitorum longus muscle. The specificity and relative importance of the different plastic adaptations occurring in the presynaptic axonal tree have been studied, in silver impregnated nerve endings, by using an automatic image analysis treatment of the nerve terminals' geometric properties and a discriminant analysis of the morphometric parameters. Changes observed, like selective length variations in certain terminal segments and positional rearrangements, agree with a mechanism of neural connectivity regulation in the adult that arises as a consequence of normal neuromuscular activity.     

Identification of Different Types of Spinal Afferent Nerve Endings That Encode Noxious and Innocuous Stimuli in the Large Intestine Using a Novel Anterograde Tracing Technique

In mammals, sensory stimuli in visceral organs, including those that underlie pain perception, are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRG). One of the major challenges in visceral organs has been how to identify the different types of nerve endings of spinal afferents that transduce sensory stimuli into action potentials. The reason why spinal afferent nerve endings have been so challenging to identify is because no techniques have been available, until now, that can selectively label only spinal afferents, in high resolution. We have utilized an anterograde tracing technique, recently developed in our laboratory, which facilitates selective labeling of only spinal afferent axons and their nerve endings in visceral organs. Mice were anesthetized, lumbosacral DRGs surgically exposed, then injected with dextran-amine. Seven days post-surgery, the large intestine was removed. The characteristics of thirteen types of spinal afferent nerve endings were identified in detail. The greatest proportion of nerve endings was in submucosa (32%), circular muscle (25%) and myenteric ganglia (22%). Two morphologically distinct classes innervated myenteric ganglia. These were most commonly a novel class of intraganglionic varicose endings (IGVEs) and occasionally rectal intraganglionic laminar endings (rIGLEs). Three distinct classes of varicose nerve endings were found to innervate the submucosa and circular muscle, while one class innervated internodal strands, blood vessels, crypts of lieberkuhn, the mucosa and the longitudinal muscle. Distinct populations of sensory endings were CGRP-positive. We present the first complete characterization of the different types of spinal afferent nerve endings in a mammalian visceral organ. The findings reveal an unexpectedly complex array of different types of primary afferent endings that innervate specific layers of the large intestine. Some of the novel classes of nerve endings identified must underlie the transduction of noxious and/or innocuous stimuli from the large intestine.     

Functional topography and ultrastructure of periarticular mechanoreceptors in the lateral elbow region of the rat

The distribution and ultrastructure of sensory nerve endings were investigated in the deep lateral elbow region of the rat. Three zones of distribution of mechanoreceptors were distinguished, each in relation to the functional architecture of the connective and muscular tissue in that area: (1) a zone with muscle spindles, Golgi tendon organs, free nerve endings and single small lamellated corpuscles ('muscle-tendon spectrum'), situated in the middle third of the supinator muscle and its superficial aponeurosis; (2) a zone with small lamellated corpuscles and free nerve endings, situated pericapsularly to the humeroradial joint capsule ('shearing spectrum'): this moderately dense, irregular connective tissue is covered by the proximal continuation of the supinator's aponeurosis, and muscle fibers insert from beneath this aponeurosis, which displays, as a part of the joint capsule, a strong collagenous tissue plate; (3) a zone with only free nerve endings within the tendon-like, most proximal part of the supinator's aponeurosis, inserting into the periosteal layer of the lateral humeral epicondyle ('endotenonial spectrum'): it is part of the joint capsule. The ultrastructure of these sensory endings is described and the distribution pattern of the mechanoreceptors observed is discussed in relation to the classification into 'muscle receptors' and 'joint receptors'.     

Structure of the sensory innervation of the anal canal in the pig. A light- and electron-microscopical study

The sensory innervation of the anal canal of the pig was investigated by light and electron microscopy. The distribution of the different types of sensory nerve endings correlates with the histology of different zones: (1) After the rectal mucosa there was a zone lined with nonkeratinized stratified squamous epithelium. (2) A middle zone was lined with keratinized stratified squamous epithelium. Here the dermis already showed a papillary and reticular layer. (3) The last zone showed hairy skin with a high hair density. The following nerve endings were found: Free nerve endings reached the stratum superficiale in nonkeratinized squamous epithelium and the stratum granulosum in the keratinized squamous epithelium. Dermal free nerve endings were found in all zones near the epithelium and two different types were identified as those derived from C-fibers and those from A-delta-fibers. Merkel nerve endings showed different features depending on their location. Few Merkel-like cells were found in the epithelium of the anal crypts. Typical Merkel Tastscheiben were located at the base of epithelial ridges or pegs in zones 2 and 3. The number of Merkel cells varied up to 200. The myelinated afferent fiber supplied 10-15 Merkel cells. Merkel cells were also found regularly in the outermost layer of the external rooth sheath of hair follicles at about the same level as perifollicular nerve endings. Lamellated corpuscles were found in the dermis of all zones except the cranial part of zone 1, where the anal crypts are located. Generally they consisted of a central nerve terminal which may be branched. Each terminal was surrounded by an inner core of concentrically arranged lamellae of the terminal Schwann cell and one or several inner cores were included in a capsule of perineural cells. The size of the corpuscle, the regularity of the inner core and the number of capsular layers depended on the location of the corpuscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurohistological and histochemical observations on the lung of Francolinus pondicerianus (gray partridge or safed teeter) as revealed by the cholinesterase technique.

An investigation was undertaken to demonstrate the neural elements of the lung of Francolinus pondicerianus, from the point of view of neurohistology and histochemistry. The staining of the neural elements was done by the cholinesterase technique with a maintained pH of 5.2, temperature 40 degrees C and incubation period of 19 h. Distribution of nerves in association with bronchial cartilage, pulmonary vessels and bronchi has been described and discussed. The distribution of the ganglia in association with blood vessels, bronchi, cartilage, various plexuses and the neural terminal terminal network has also been described. The innervation of the bronchi and their branches, and formation of the neural terminal network has been studied, as well as the distribution of cholinesterase in bronchi, blood vessels, muscles, ganglia, and nerve fibres.     

Nerves and nerve endings in the skin of tropical cattle.

The nerves and nerve endings in the skin of tropical cattle were studied using histological and histochemical techniques. Many nerve trunks and fibres were present in the reticular and papillary dermis in both hairy and non-hairy skin sites. In non-hairy skin locations such as the muzzle and lower lip, encapsulated endings akin to Krause and Ruffini end bulbs, which arise from myelinated nerve trunks situated lower down the dermis were observed at the upper papillary layer level. Some fibre trunks seen at this level extended upwards to terminate within dermal papillae as bulb-shaped longitudinally lamellated Pacinian-type endings, while other onion-shaped lamellated nerve structures were located either within dermal papillae or near the dermo-epidermal area. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. On hairy skin sites, however, organized nerve endings or intraepidermal nerve endings were not readily identifiable.     

Comparative neurohistological observations on the pancreatic duct in certain birds and mammals as revealed by cholinesterase technique

A comparative study of pancreatic duct innervation of Francolinus pondicerianus (grey partridge or safed teeter) and Suncus murinus (Indian musk shrew) as revealed by cholinesterase technique has been done for investigation. In Suncus pancreas, the AChE-positive ganglia, elongated and irregularly shaped, medium and large-sized, were recorded either on the periphery of the excretory duct or on the wall of the duct. No ganglia were recorded on the periphery, although the fibres of the ganglia were in close association with the periductular plexus and the fibres of the peri-insular plexus in Francolinus. In Suncus, multipolar and AChE-positive ganglia of various shapes, arranged in chain-like fashion on the duct, were recorded, whereas in Francolinus the multipolar ganglia of AChE-positive nature and of various shapes, arranged in chain-like fashion, were observed in the duct region.     

Quantitative evaluation of sensory nerve endings in hypertrophy of labia minora pudendi in women.

The authors studied the types of sensory nerve endings in hypertrophic labia minora pudendi in women aged between 18 and 69. The nervous tissue was impregnated with silver nitrate by Lavrentyev's modification of the Bielschowski-Gross method. The sensory nerve endings were divided into the following groups: free endings and arborizations, spray-like endings, seven types of clew-like nerve endings, and Pacinian corpuscles. It is the clew-like endings that absolutely predominate, they were 2,027 in number. The arborizations and spray-like endings found were 105 in number and only 4 of Pacinian corpuscles were found. As compared with normal labia there are no principal differences among the types of sensory nerve endings. The main difference consists in the rate of occurrence (89.6 as against 57.8) and in the thickness of the capsule, while the nerve clew proper does not grow in diameter. Therefore, we are of theopinion that a more frequent occurrence and larger size of the capsule is associated with local changes in the organ (especially with hypertrophy of the connective tissue). We observed no differences due to age either in the occurrence of the individual types or in the thickness of the capsule. Great individual variability in both directions was seen. The findings corroborated again the rare occurrence of meissner's endings in the labia minora in woman. Therefore it may be assumed that it is rather a random finding and that it is a type of clew-like nerve ending. Finally, we presume that the individually varying rate of occurrence of the nerve endings in the external genitals could also affect general sensitivity in this region, including sexual sensitivity.     

Postnatal maturation of neuroepithelial bodies and carotid body innervation: A quantitative investigation in the rabbit

The intrapulmonary airways contain oxygen-sensitive chemoreceptors which may be analogous to the arterial chemoreceptors: the neuroepithelial bodies (NEB). While the NEB are prominent in the neonatal lung, physiological studies indicate that the carotid bodies are still relatively inactive at birth. This points to an unequal degree of development of both during the early neonatal period. As a reflexogenic chemoreceptor function depends on a well-developed innervation, we undertook a comparative investigation of the development of the NEB and the carotid body glomus cell innervation. Two morphological aspects of the innervation of NEB and carotid body glomus cells were quantified in rabbits of different age groups. The total sectional area of intracorpuscular and intraglomerular nerve endings per NEB or glomus cell group, respectively, was measured and the area percentage of mitochondria and synaptic vesicles was determined. In the NEB, no significant difference in total sectional area of the nerve endings between the age groups was observed, while in the carotid body there was a significant increase in the adult age group. In addition, the area percentage of mitochondria and synaptic vesicles of the nerve endings did not change significantly with age in the NEB, while in the carotid body these increased and decreased, respectively, with age. These observations point to a shift from morphologically efferent nerve endings, rich in synaptic vesicles, to morphologically afferent nerve endings, rich in mitochondria. Our interpretation of these findings is that, at birth, the NEB innervation is more mature than the carotid body glomus cell innervation and that the latter matures at a later time than the former. These findings support the theory that the NEB may act as complementary chemoreceptors to the carotid body during the early postnatal period.     

Identification and characterization of telocytes in the uterus of the oviduct in the Chinese soft‐shelled turtle,Pelodiscus sinensis: TEM evidence

Telocytes (Tcs) are cells with telopodes (Tps), which are very long cellular extensions with alternating thin segments (podomers) and dilated bead‐like thick regions known as podoms. Tcs are a distinct category of interstitial cells and have been identified in many mammalian organs including heart, lung and kidney. The present study investigates the existence, ultrastructure, distribution and contacts of Tcs with surrounding cells in the uterus (shell gland) of the oviduct of the Chinese soft‐shelled turtle, Pelodiscus sinensis. Samples from the uterine segment of the oviduct were examined by transmission electron microscopy. Tcs were mainly located in the lamina propria beneath the simple columnar epithelium of the uterus and were situated close to nerve endings, capillaries, collagen fibres and secretory glands. The complete morphology of Tcs and Tps was clearly observed and our data confirmed the existence of Tcs in the uterus of the Chinese soft‐shelled turtle Pelodiscus sinensis. Our results suggest these cells contribute to the function of the secretory glands and contraction of the uterus.     

Fine structure of nervous elements in the pancreas of some vertebrates

Summary The innervations of the exocrine and endocrine pancreas of some vertebrate animals were studied by electron microscopy. The pancreas of the bat and monkey contained ganglion cells in the interlobular connective tissue or between acinar cells. Unmyelinated nerve fibers ran through the interlobular connective tissue and reached the exocrine and endocrine parts, and terminated there as the endings. The nerve endings within the pancreas could be divided into four types: 1. Type 1-a of the nerve ending contained only agranular synaptic vesicles of about 500 Å in diameter. 2. Type 1-b characterized by containing agranular synaptic vesicles and some large cored vesicles (1,000 Å diameter). These two types of nerve endings might belong to the cholinergic (parasympathetic) endings. 3. Type 2-a contained small cored vesicles and agranular synaptic vesicles along with a few large cored vesicles. 4. Type 2-b was characterized by containing vesicles of the same size as those of agranular synaptic vesicles, and a majority of these vesicles contained bar-shaped crystalloids. This ending also contained a few large cored vesicles. These nerve endings of Type 2-a and 2-b might be the adrenergic (sympathetic) endings.     

Immunohistochemical demonstration of calbindin-containing nerve endings in the rat esophagus

Immunoreactivity for calbindin was found in nerve endings with irregular laminar shapes in the rat esophagus. In the myenteric ganglia, laminar endings of a range of sizes formed a complex network and appeared to lie at the surface of the ganglion. The myenteric ganglia that contained nerve endings were most abundant in the upper portion of the eosphagus, their number decreasing orally to anally. Calbindin-immunoreactive nerve cell bodies were scattered throughout the esophagus. Laminar terminals were found in the connective tissue of the lamina propria immediately beneath the epithelium and in the muscularis mucosae. Occasional nerve branches formed a network of aborizing endings that surrounded part of the submucosal arterioles. Immunoreactive nerve endings in the mucosa and submucosa were present only in the upper part of the cervical esophagus. Unilateral vagotomy caused a remarkable decrease in the number of the myenteric ganglia containing the calbindin-immunoreactive laminar endings after 15 days or survival; in some of ganglia, the laminar structures disappeared and nerve endings showing weak immunoreactivity had an indistinct appearance, so that the outline of the ganglia became obscure. In operated rats at 24 days, the number of innervated ganglia was about half that in normal rats. However, there was no change in the morphology and the occurrence of the immunoreactive laminar structures in the mucosa and submucosa after denervation. The results show that many of the laminar endings that are immunoreactive for calbindin in the myenteric ganglia are derived from the vagus nerve. Thus, the calbindin-immunoreactive nerve endings with laminar expansions that are found in the rat eosphageal wall could be sensory receptors.