Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic pancreatitis (CP) is characterized by progressive fibrosis, pain and/or loss of exocrine and endocrine functions. With the identification and characterization of pancreatic stellate cells (PSCs), the pathogenesis of CP and pancreatic fibrosis is now better understood. Molecular mediators shown to regulate the pathogenesis include transforming growth factor-beta, platelet-derived growth factor, and proinflammatory cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha. Besides these, the roles of cyclooxygenase (COX)-2 and apoptosis-related proteins have also been implicated in the pathogenesis. Furthermore, molecular pathways involving mitogen-activated protein kinases, phosphatidylinositol 3-kinase, Ras superfamily G proteins, serine threonine protein kinase Raf-1 and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) have been elucidated. Newer pathobiologic concepts concerning pain generation have also been put forward. Understanding the pathogenesis has led to the identification of novel molecular targets and the development of newer potential therapeutic agents. Those found to retard the progression of experimental CP and fibrosis in animal models include antioxidants, a Japanese herbal medicine called Saiko-keisi-to (TJ 10), the PPAR-gamma ligand troglitazone, the protease inhibitor Camostat mesilate, and Lovastatin.
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PMID:Chronic pancreatitis: evolving paradigms. 1684 81

Camostat mesilate, an orally available proteinase inhibitor, is clinically used for treatment of pancreatitis. Given recent evidence that pancreatic proteinases including trypsin and/or proteinase-activated receptor-2 (PAR2) might be involved in pancreatic pain, we examined if camostat mesilate could suppress spinal Fos expression, a marker for neuronal activation, following specific application of trypsin to the pancreas, and pancreatitis-related referred allodynia. Trypsin, administered into the pancreatic duct, caused delayed expression of Fos proteins in the superficial layer of the bilateral T8 and T9 spinal dorsal horns in rats. The trypsin-induced spinal Fos expression was completely abolished by oral pre-administration of camostat mesilate at 300 mg/kg. After hourly repeated (6 times in total) administration of caerulein, mice showed typical symptoms of pancreatitis, accompanied by mechanical allodynia in the upper abdomen (i.e., referred hyperalgesia/allodynia), as assessed by use of von Frey filaments. Camostat mesilate at 100-300 mg/kg, given orally twice before the 1st and 4th doses of caerulein, abolished the pancreatitis-related abdominal allodynia, while it partially prevented the inflammatory signs. The same doses of camostat mesilate, when administered once after the final dose of caerulein, also revealed significant anti-allodynic effect. These data suggest that camostat mesilate prevents and/or depresses pancreatitis-induced pain and/or referred hyperalgesia/allodynia, in which proteinases including trypsin would play a critical role.
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PMID:The proteinase inhibitor camostat mesilate suppresses pancreatic pain in rodents. 1743 71