Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain is the major symptom in chronic pancreatitis. Its intensity frequently necessitates partial or complete pancreatectomy. The mechanisms of pain are not yet fully understood and, thereby, the therapeutic management is still controversial. Possible causes of pain include outflow obstruction with increased ductal and parenchymal pressure within the pancreas, and inflammatory involvement of intrapancreatic nerve fibres. Possible extrapancreatic causes are common bile duct and duodenal stenosis. The first theory has recently been substantiated by the demonstration of a definite relationship between intrapancreatic pressure, as measured intraoperatively, and intensity of pain. Infiltration of inflammatory cells around the nerves together with an increase in the number of nerve fibres in the fibrotic pancreatic tissue has been proposed as a possible cause of pain in chronic pancreatitis. Moreover, immunohistological studies have shown that the amount of neurotransmitters, such as substance P, is increased in afferent pancreatic nerves. Stenosis of the common bile duct and duodenum has been reported to be associated with severe abdominal pain. Common bile duct and duodenal stenosis in chronic pancreatitis may be caused by extension of fibrosis and active inflammation of the pancreas within the wall of duodenum and bile duct. This article updates the different pathogenetic mechanisms in pancreatic pain and the current therapeutic possibilities with their advantages and shortcomings.
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PMID:[Pain in chronic pancreatitis: recent pathogenetic findings]. 129 36

We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.
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PMID:Changes in peptidergic innervation in chronic pancreatitis. 137 38

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic pancreatitis and diabetes mellitus: plasma and gastroduodenal mucosal profiles of regulatory peptides (gastrin, motilin, secretin, cholecystokinin, gastric inhibitory polypeptide, somatostatin, VIP, substance P, pancreatic polypeptide, glucagon, enteroglucagon, neurotensin). 246 85

The distribution and concentration of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) immunoreactivities in the pancreas of cats with experimentally induced chronic pancreatitis and of age- and sex-matched controls were investigated. By narrowing the main pancreatic duct between the head and the body to approximately 25% of its normal diameter, we induced within 5 weeks chronic pancreatitis restricted to the body and tail. In control animals, peptide immunoreactive nerves were distributed to the islets, acini, and ducts; the latter were predominantly innervated by fibers immunoreactive for NPY, VIP, or CGRP. The vasculature received an abundant supply of NPY-, CGRP-, and, to a lesser extent, SP-containing axons. Within intrapancreatic ganglia, peptide immunoreactivities were identified in fibers and ganglion cells, with the exception of CGRP and SP immunostaining, which could be visualized only in fibers. In animals with chronic pancreatitis, the innervation pattern of each peptidergic system was comparable to that described in controls. However, there was a remarkable increase in the density and staining intensity of VIP and NPY immunoreactive fibers in the exocrine parenchyma and fibrous septa of the body and tail, where chronic pancreatitis developed. Fibers immunoreactive for CGRP and SP also were moderately denser than in controls, whereas those containing GRP immunoreactivity did not show any detectable changes. In addition, a marked increase of the immunostaining for VIP and, to a much lesser extent, for NPY and GRP, was observed in neurites supplying the head of the pancreas, which appeared devoid of histologically detectable pathological alterations. Radioimmunoassay analysis confirmed the immunohistochemical observations. The increased density of distinct peptidergic nerves in the pancreas with induced chronic pancreatitis might be the result of compensatory phenomena in response to the inflammatory process.
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PMID:Differential effects of experimentally induced chronic pancreatitis on neuropeptide immunoreactivities in the feline pancreas. 750 19

Pain is a leading symptom in chronic pancreatitis (CP) and often its management necessitates surgical intervention. Nevertheless the presence of different hypotheses, the pathophysiology of pain is not understood, thus the indications for therapy remain controversial. Increased pressure within the ductal system and/or the parenchyma has been suggested to be one of the causes of pain. This controversial theory has been substantiated by the demonstration of a relationship between intrapancreatic pressure and intensity of pain. On the other hand, recent studies have shown the inflammatory involvement of intrapancreatic nerve fibres in a so called "neuroimmune interaction". In fact, infiltration of inflammatory cells around the nerves together with an increase in the number of nerve fibres in the fibrotic pancreatic tissue have been proposed as a possible cause of pain in chronic pancreatitis. Moreover, immunohistological studies have shown that the amount of neurotransmitters, such as substance P and calcitonin gene related peptide, is increased in afferent pancreatic nerves and a close interrelationship between pain and immune cell infiltration of the nerves has been reported in CP. In addition to these hypothesis, extrapancreatic causes such as common bile duct obstruction and duodenal stenosis are discussed. This article review points to the different pathogenic mechanisms of pancreatic pain in CP.
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PMID:Mechanisms of pain in chronic pancreatitis. 1082 18

Recent theories of pathogenesis of pain in chronic pancreatitis (CP) are neuroimmune interactions of intrapancreatic nerves and inflammatory cells and increase in levels of pain neurotransmitters such as substance P (SP). This study analyzed the expression and localization of neurokinin 1 receptor (NK-1R), which binds SP, and its association with pain and inflammation in CP. Pancreatic tissues from 31 patients (22 males, nine females; mean age 45.9+/-9.4 years) with CP were evaluated. Nine normal pancreases (five males, four females; mean age 42.9+/-9.5 years) served as controls. Quantitative PCR was used to determine the NK-1R mRNA expression levels and in situ hybridization and immunohistochemistry were used to localize expression sites of NK-1R mRNA and protein, respectively. We also analyzed whether an association exists between NK-1R mRNA expression and pain and inflammation. In CP samples, in situ hybridization and immunohistochemistry localized NK-1R mRNA expression and protein mainly in the nerves, ganglia, blood vessels, inflammatory cells and occasionally in fibroblasts. In patients with mild to moderate and strong intensity of pain, NK-1R mRNA levels were increased 14- and 30-fold over controls, respectively. There was a significant relationship between NK-1R mRNA levels and intensity of pain (r=0.46, P=0.03), NK-1R mRNA and the frequency of pain (r=0.51, P=0.04), and NK-1 mRNA and duration of pain (r=0.46, P=0.01) in CP patients, but not with the degree of tissue inflammation. NK-1R signaling may be involved in the pain syndrome of CP. The expression of NK-1R in inflammatory cells and blood vessels also points to an interaction of immunoreactive substance P nerves, inflammatory cells and blood vessels, and further supports the existence of a neuroimmune interaction that probably influences the pain syndrome and chronic inflammatory changes so characteristic of CP.
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PMID:NK-1 receptor gene expression is related to pain in chronic pancreatitis. 1127 76

The pathophysiology of pain in chronic pancreatitis (CP) is incompletely understood. Several hypotheses have been advanced, including pancreatic and extrapancreatic causes. The existence of different hypotheses to explain the genesis of pain in CP also reflects the different therapeutic approaches to pain in these patients. Increased intraductal pressure as a result of single or multiple strictures and/or calculi is believed to be a common cause of pain in CP patients with a dilated main pancreatic duct. Other suggested causes include pancreatic fibrosis, interstitial hypertension and pancreatic ischemia. Additionally, extrapancreatic causes like duodenal and common bile duct stenosis with scarring due to pancreatic inflammation are suggested as factors causing pain in CP. The 'neurogenic inflammation' hypothesis is a fascinating theory which is supported by different studies. Immunohistological reports have shown that the amount of neurotransmitters, such as substance P and its receptor, calcitonin gene-related peptide and other neurotransmitters, are increased in afferent pancreatic nerves and a correlation between pain and immune cell infiltration of the nerves has been reported in CP. In this review we will discuss the different pain hypotheses and will present the perspective that neuroimmune interaction is an important factor for pain generation in CP.
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PMID:Pathogenesis of pain in chronic pancreatitis. 1575 9

The approach to the management of painful chronic pancreatitis has been empirical, primarily due to the lack of information about biological mechanisms producing pain. To facilitate research into pain mechanisms, our aim was to assess a rat model of chronic pancreatitis induced by pancreatic infusion of trinitrobenzene sulfonic acid as a model of painful pancreatitis. Nociception was assessed by measuring mechanical sensitivity of the abdomen and by recording the number of nocifensive behaviors in response to electrical stimulation of the pancreas. Expression of neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) in the thoracic dorsal root ganglia receiving input from the pancreas and nerve growth factor (NGF) in the pancreas were measured. Rats with pancreatitis exhibited marked increase in sensitivity to mechanical probing of the abdomen and increased sensitivity to noxious electrical stimulation of the pancreas. There were significant increases in NGF protein in the pancreas and in expression of neuropeptides CGRP and SP in the sensory neurons from dorsal root ganglia receiving input from the pancreas. We have established quantitative measures of referred nociception and pancreatic hyperalgesia in a rat model of chronic pancreatitis that bears histological similarities to the human disease. This model has considerable construct, face and predictive validity for the human condition. It is of importance for the study of the pathogenesis of pain in this condition and can facilitate the development of new therapeutic options.
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PMID:Molecular and behavioral changes in nociception in a novel rat model of chronic pancreatitis for the study of pain. 1609 67

Increase in the number of intrapancreatic sensory nerve fibers has been implicated in the generation of pain in chronic pancreatitis. Because some sensory neurotransmitters (e.g., substance P) are known to have proinflammatory effects, we hypothesized that denervation of intrapancreatic nerves might influence not only pain generation but also inflammation. Neonatal Lewis rats were injected with capsaicin (50 mg/kg or 0 mg/kg), a neurotoxin, to induce denervation of primary sensory neurons. When rats reached 170-190 g body weight, experimental pancreatitis was induced by a single administration of dibutyltin dichloride (7 mg/mg). The severity of pancreatitis was evaluated in both groups in the acute phase (at 3 and 7 days) and chronic phase (at 28 days). At day 7, the sensory denervation induced by neonatal capsaicin administration inhibited pancreatic inflammation on both histological (determination of interstitial edema, expansion of interlobular septa and intercellular spaces, and inflammatory cell infiltration) and biochemical (intrapancreatic myeloperoxidase activity) evaluation. Furthermore, at day 28, glandular atrophy, pseudotubular complexes, and rate of fibrosis were each significantly lower in the capsaicin-pretreated group than in the vehicle-pretreated group. Our findings provide in vivo evidence that primary sensory neurons play important roles in both acute pancreatitis and chronic pancreatic inflammation with fibrosis.
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PMID:Effects of sensory denervation by neonatal capsaicin administration on experimental pancreatitis induced by dibutyltin dichloride. 1787 46