Central lateral thalamic neurons receive noxious visceral mechanical and chemical input in rats.

Thalamic intralaminar and medial nuclei participate mainly in affective and motivational aspects of pain processing. Unique to the present study were identification and characterization of spontaneously active neurons in the central lateral nucleus (CL) of the intralaminar thalamus, which were found to respond only to viscerally evoked noxious stimuli in animals under pentobarbital anesthesia. Responses to noxious colorectal distention, intrapancreatic bradykinin, intraperitoneal dilute acetic acid, and greater splanchnic nerve electrical stimulation were characterized. Electrophysiological recordings revealed activity in most CL neurons (93%) was excited (69%) or inhibited (31%) in response to noxious visceral stimulation of visceral nerves. Expression of c-Fos observed in CL nucleus after intensive visceral stimulation confirmed the activation. However, excited CL neurons did not have somatic fields, except in 3 of 43 (7%) CL neurons tested for responses to somatic stimulation (innocuous brush and noxious pinch). Intrathecal administration of morphine significantly reduced the increased responses of CL neurons to colorectal and pancreatic stimuli and was naloxone reversible. High-level thoracic midline dorsal column (DC) myelotomy also dramatically reduced responses, identifying the DC as a major route of travel from the spinal cord for CL input, in addition to input traveling ventromedially in the spinothalamic tract identified anatomically in a previous study. Spinal cord and lower brain stem cells providing input to medial thalamus were mapped after stereotaxic injections of a retrograde dye. These data combined with our previous data suggest that the CL nucleus is an important component of a medial visceral nociceptive system that may mediate attentional, affective, endocrine, motor, and autonomic responses to noxious visceral stimuli.

Pancreatic duct secretion: experimental methods, ion transport mechanisms and regulation

The pancreatic ductal tree conveys enzymatic acinar products to the duodenumand secretes the fluid and ionic components of pancreatic juice. The physiology ofpancreatic duct cells has been widely studied, but many questions are still unansweredconcerning their mechanisms of ionic transport. Differences in the transportmechanisms operating in the ductal epithelium has been described both among differentspecies and in the different regions of the ductal tree. In this review we summarizethe methods developed to study pancreatic duct secretion both in vivo and invitro, the different mechanisms of ionic transport that have been reported to date inthe basolateral and luminal membranes of pancreatic ductal cells and the regulationof pancreatic duct secretion by nervous, endocrine and paracrine influences(AU)

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Pancreatic duct secretion: experimental methods, ion transport mechanisms and regulation.

The pancreatic ductal tree conveys enzymatic acinar products to the duodenum and secretes the fluid and ionic components of pancreatic juice. The physiology of pancreatic duct cells has been widely studied, but many questions are still unanswered concerning their mechanisms of ionic transport. Differences in the transport mechanisms operating in the ductal epithelium has been described both among different species and in the different regions of the ductal tree. In this review we summarize the methods developed to study pancreatic duct secretion both in vivo and in vitro, the different mechanisms of ionic transport that have been reported to date in the basolateral and luminal membranes of pancreatic ductal cells and the regulation of pancreatic duct secretion by nervous, endocrine and paracrine influences.

Pancreatobiliary afferent recordings in the anaesthetised Australian possum.

The sensory innervation to the pancreatobiliary system is poorly characterized. Afferent signals from the gastrointestinal tract and biliary tree are transmitted to the central nervous system via the vagus and spinal nerves. We aimed to record afferent discharge in order to characterize the vagal and splanchnic afferent signals from the possum upper gastrointestinal tract, biliary tree and pancreas. In 21 anaesthetised possums nerve fibres were teased from the vagus or splanchnic nerve for multi-unit recording. Mechanical stimuli consisted of balloon distension of the gallbladder and duodenum (2-7 ml) and fluid distension (0-20 mm Hg) of the bile or pancreatic ducts. Approximately 60% of fibres from all nerves displayed spontaneous discharge. Spinal afferent responses to mechanical stimuli were infrequent (n=13). Increased discharge occurred in response to duodenal (12/99 fibres) or gallbladder (7/96 fibres) distension, but not to bile duct (0/73 fibres) or pancreatic duct (0/51 fibres) distension. Vagal afferent responses to distension of the duodenum or stomach (5-30 ml) were more common (n=8). Increased discharge was recorded in response to duodenal (49/134 fibres), or gastric (22/70 fibres) distension. Responses to gallbladder distension were less frequent (6/99 fibres) and as with the spinal afferent no response to bile duct (0/66) or pancreatic duct (0/70) distension were recorded. We conclude that mechanosensitive afferents in the pancreatobiliary system are relatively rare, particularly within the ducts, and/or that they are adapted to monitor stimuli other than luminal distension.

Adrenergic and cholinergic innervation of the chicken pancreas.

The distribution, as well as the morphological characteristics of adrenergic and cholinergic nerve fibres was studied in the pancreas of the hen and the cock. The presence of numerous adrenergic and moderately numerous cholinergic structures was revealed in the organ. They were seen as nerve fibre bundles or single nerve fibres located in the vicinity of blood vessels and exocrine ducts, as well as the cells of the exocrine and endocrine pancreas. Single TH- and ChAT-positive nerve cell bodies were also found in the organ under study.

Autonomic nerve changes in the mouse pancreas after pancreatic duct ligation.

INTRODUCTION: The mouse pancreas exhibits distinct atrophy of the exocrine tissue following pancreatic duct ligation. AIM: To investigate changes of innervation in the whole pancreas after pancreatic duct ligation. METHODOLOGY: The mouse pancreatic duct was ligated at 6 weeks of age. Pancreatic tissues were removed 7 days and 14 days after the ligation, fixed by perfusion and immersion with Zamboni solution, and embedded in gelatin. The whole organ was serially sectioned at a thickness of 100 microm, histochemically stained for cholinesterase, and observed by light microscopy. The number and volume of intrapancreatic ganglia, number of ganglion cells, and volume of each ganglion cell in the whole pancreas were quantitated. Some sections were analyzed using transmission electron microscopy after histochemically staining for cholinesterase. RESULTS: In the normal pancreas, ganglia were often situated on the outer surface of the islets of Langerhans. Thick nerve bundles ran along the arteries and emanated thin nerve fibers that surrounded the arterioles. In the atrophied pancreas following pancreatic duct ligation, ganglia remained on the islets of Langerhans as in normal mice, while the nerve fibers appeared dense, bending and curling in a more complex manner. The thin nerves also crossed each other in a complex network. Using morphometry in the pancreas following pancreatic duct ligation, the total ganglion cell number was found to decrease from normal levels. The mean ganglion cell volume in the ligated pancreas was significantly smaller than that in normal mice. As observed by transmission electron microscopy, some ganglion cells in the ligated pancreas were negative for cholinesterase activity but were surrounded by positive staining around the surface. CONCLUSIONS: These results suggest that the function of pancreatic ganglion cells changes with organ atrophy after pancreatic duct ligation.

Pituitary adenylate cyclase-activating polypeptide in intrinsic and extrinsic nerves of the rat pancreas.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is the latest member of the vasoactive intestinal polypeptide (VIP) family of neuropeptides present in nerve fibres in many peripheral organs. Using double immunohistochemistry, with VIP as a marker for intrinsic innervation and calcitonin-gene related peptide (CGRP) as a marker for mainly extrinsic innervation, the distribution and localization of PACAP were studied in the rat pancreas. PACAP was demonstrated in nerve fibres in all compartments of the pancreas and in a subpopulation of intrapancreatic VIP-containing ganglion cells. PACAP and VIP were co-stored in intra- and interlobular nerve fibres innervating acini, blood vessels, and in nerve fibres within the islets of Langerhans. No PACAP immunoreactivity was observed in the islet cells. Another population of PACAP-immunoreactive nerve fibres co-localized with CGRP innervated ducts, blood vessels and acini. PACAP/CGRP-positive nerve fibres were also demonstrated within the islets. Neonatal capsaicin reduced the PACAP-38 concentration by approximately 50%, and accordingly a marked reduction in PACAP/CGRP-immunoreactive nerve fibres in the exocrine and endocrine pancreas was observed. Bilateral subdiaphragmatic vagotomy caused a slight but significant decrease in the PACAP-38 concentration compared with controls. In conclusion, PACAP-immunoreactive nerve fibres in the rat pancreas seem to have dual origin: extrinsic, most probably sensory fibres co-storing CGRP; and intrinsic, constituting a subpopulation of VIP-containing nerve cell bodies and fibres innervating acinar cells and islet cells. Our data provide a morphological basis for the reported effects of PACAP in the pancreas and suggest that PACAP-containing nerves in the rat pancreas may have both efferent and sensory functions.

Blood pressure reflexes following activation of capsaicin-sensitive afferent neurones in the biliopancreatic duct of rats.

1. Inflammatory diseases of the pancreas or diseases which cause obstruction within the biliary or within the biliary or pancreatic duct system are associated with severe pain. Although neuropeptides such as substance P are present in the biliary tree, only few capsaicin-sensitive, substance P-positive nerve fibres have been found in the ducts. In order to obtain functional evidence whether capsaicin-sensitive afferent neurones transmit nociceptive information arising from the biliopancreatic duct, blood pressure reflexes following electrical stimulation of the duct or increases in intraductal pressure were determined in barbiturate-anaesthetized rats. 2. Electrical stimulation of neurones in the biliopancreatic duct was carried out at 30 V, 3 ms, 50 Hz for 20s. In untreated animals the electrical stimulation resulted in rises in blood pressure by up to 25 mmHg, but in about a quarter of all animals tested this response was absent. Following the administration of phentolamine (7 mumol kg-1, i.p.) the blood pressure responses were changed to pronounced and reproducible depressor reflexes of -5 to -30 mmHg. Retrograde injections into the biliopancreatic duct of 300 microliters of a 154 mM sodium chloride solution produced increases in intraductal pressure of approximately 10 mmHg. This elicited shortlasting falls in blood pressure of 3-15 mmHg. Phentolamine significantly augmented the fall in blood pressure to 8-30 mmHg. 3. The depressor reflexes observed in both models after the administration of phentolamine were abolished by morphine (1 mumol kg-1, i.v.). The inhibition by morphine was reversed by naloxone (3 mumol kg-1, i.v.). Naloxone given before morphine did not affect the depressor reflex but prevented the inhibitory action of subsequently injected morphine.4. Acute s.c. injection of capsaicin (30 mg kg-1) abolished the depressor reflexes in response to both types of nociceptive stimulation in phentolamine-treated rats. The initial pressor effects of electrical stimulation were only partly inhibited by capsaicin whereas the basal depressor reflexes in response to elevation of intraductal pressure were abolished. In rats which had received capsaicin on the day before the experiment or had been treated with capsaicin as neonates, only minor rises in blood pressure were induced by electrical stimulation at the beginning of the experiment and no changes in blood pressure occurred after the administration of phentolamine. After adult or neonatal pretreatment with capsaicin the depressor reflexes in response to increased intraductal pressure were only small and were unchanged by phentolamine.5. The depressor reflexes following either electrical stimulation or increases in intraductal pressure were abolished by the unselective Beta-blocker, (-)-propranolol (3 micromol kg-1, i.p.), and greatly reduced by the Beta 1-blocker, metoprolol (6 micromol kg- 1, i.p.). The Beta2-preferring adrenoceptor antagonist, butoxamine(3 micromol kg-1, i.p.), had no effect on the depressor responses. The reflex falls in blood pressure were also abolished by hexamethonium (10 micromol kg-1, i.p.) but not by atropine (3 micromol kg-1, i.p.).6. Both models of stimulation of nociceptive afferents caused identical patterns of blood pressure responses following adrenalectomy or chemical sympathectomy. In adrenalectomized rats, the initial responses consisted of depressor reflexes which were not augmented but significantly reduced by phentolamine and further inhibited by metoprolol. In rats that had been pretreated with 6-hydroxydopamine(total dose 0.6 mmol kg-1) to accomplish chemical sympathectomy, nociceptive stimulation caused rises in blood pressure. Phentolamine treatment abolished these pressor effects but revealed only minor, if any, depressor responses that were unaffected by metoprolol.7. In summary, the hypotensive effects in both models constitute nociceptive reflexes since they are abolished by morphine and restored by naloxone. The afferent part of the reflex is mediated by nerve fibres sensitive to capsaicin. Both experimental procedures seem to elicit two, presumably separate, reflex mechanisms. Firstly, catecholamines released from the adrenal medulla elevate blood pressure or limit hypotensive responses via activation of vascular alpha receptors. Secondly, the reflex inhibition of the sympathetic nerve activity in the heart and the vasculature causes the nociceptive depressor reflexes.

Study of innervation of the pancreatic duct of Lepus europaeus, using the cholinesterase technique.

The innervation of the pancreatic duct was studied in the European Hare (Lepus europaeus) by the cholinesterase technique. The duct was accompanied by thick myelinated and thin non-myelinated nerve fibres, which subsequently formed a plexi. The plexi were associated with the fibres of the plexi of the islet of Langerhans, or with ganglia, blood vessels or neural networks. No chain of ganglia was observed on or near the duct and the ductules.

The nerves of the accessory pancreatic ducts of the common starling (Sturnus vulgaris): an ultrastructural and light microscopic study.

An ultrastructural and light microscopic study was undertaken to examine the nerves of the accessory pancreatic ducts of the starling (Sturnus vulgaris), previously noted (Vinnicombe, 1982) to have a particularly dense innervation. Large numbers of nerves were found in the ducts, predominantly in the lamina propria, and all contained exclusively unmyelinated axons. Probable neuron cell bodies were observed in the smooth muscle layer, but not in the lamina propria. Schwann cells invested all the axons, and these displayed terminal swellings in a 'synapse en passage' arrangement. The nerves of the lamina propria were most numerous in the region immediately beneath the epithelium and were present in the epithelial folds. One axon was observed to have penetrated the epithelial basal lamina and to lie between two epithelial cells. Examination of the terminal profiles and their contained synaptic vesicles showed the innervation to have probable pain afferent, cholinergic, adrenergic and perhaps peptidergic components. The results of this study were compared with reports on pancreatic duct innervation in other species, mostly as parts of wider studies on pancreatic innervation.

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.

The occlusive competence of the duodenal orifice of the canine pancreatic duct.

Observations by scanning electron microscopy indicate that the mucosa of the terminal part of the major pancreatic duct of the dog is organized into numerous, highly convoluted folds. The individual mucosal cells are tall, columnar and studded with numerous microvilli. These folds are highly vascularized. The intraluminal administration of bethanechol and norepinephrine is associated with subsequent increases and decreases of mean opening pressures. Mean opening pressures were not observed to be associated with autonomic nervous activity that was unaccompanied by changes in systemic arterial pressure. It is concluded that the terminal portion of the canine major pancreatic duct probably acts as a passive valve, the occlusive competence of which is influenced by the status of the vasculature of the lining mucosa in this region.

[Development of the neural and tissue components of the excretory ducts of the liver, pancreas and Odd's sphincter in human embryogeny]. / Razvitie nervnykh i tkanevykh komponentov vyvodnykh protokov pecheni, podzheludochnoi zhelezy i sfinktera Oddi v émbriogeneze

The development of pancreatic, hepatic, cystic, common bile ducts, the Oddi's sphincter and their nervous apparatus were studied during prenatal human ontogenesis of fetuses and newborns. The process of formation of the nervous apparatus corresponds to the development of tissue structures of the ducts and the sphincter. The distinctions in the organization of nervous elements which are noted in adult humans are laid in the process of embryogenesis. These distinctions are especially pronounced in the structure of nervous plexuses and receptory endings. The nervous apparatus of the Oddi's sphincter region has a complex arrangement. This is the site of concentration of nerve nodules and receptory endings as well as abundant nervous connections between plexuses of the pancreatic head, duodenum and orifice zones of the both ducts. The receptors in nerve nodules and pericellular apparatuses on the bodies of ganglionic neurons were revealed.