Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mediators involved in the generation of pain in patients with cancer are poorly understood. Using a combined molecular, pharmacologic, behavioral, and genetic approach, we have identified a novel mechanism of cancer-dependent allodynia induced by protease-activated receptor 2 (PAR2). Here we show that human head and neck carcinoma cells have increased levels of proteolytic activity compared to normal human cell controls. Supernatant from human carcinoma cells, but not controls, caused marked and prolonged mechanical allodynia in mice, when administered into the hindpaw. This nociceptive effect was abolished by serine protease inhibition, diminished by mast cell depletion and absent in PAR2-deficient mice. In addition, non-contact co-culture of trigeminal ganglion neurons with human head and neck carcinoma cells increased the proportion of neurons that exhibited PAR2-immunoreactivity. Our results point to a direct role for serine proteases and their receptor in the pathogenesis of cancer pain. This previously unrecognized cancer pain pathway has important therapeutic implications wherein serine protease inhibitors and PAR2 antagonists may be useful for the treatment of cancer pain.
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PMID:Serine proteases and protease-activated receptor 2-dependent allodynia: a novel cancer pain pathway. 2018 17

Chronic pain is an important health and social problem. Misuse and abuse of opioids in chronic non-cancer pain management seem to be a huge problem, in some countries. This could probably affect the normal use of such analgesics in patients in need of them. Basic and clinical researches should find the solution to mitigate the potential damage. Dysregulation of mast cell and microglia activation plays an important role in the pathogenesis and management of chronic pain. Persistent mast cell activation sensitizes nociceptors and initiates central nervous system inflammatory processes, involving microglial cell activation and sensitization of spinal somatosensory neurons. Exposure of mast cells and microglia to opioids is well known to provoke activation of these non-neuronal immune cell populations, thereby contributing to an exacerbation of pro-inflammatory and pro-nociceptive processes and promoting, over the long-term, opioid-induced hyperalgesia and tolerance. This review is intended to provide the reader with an overview of the role for these non-neuronal cells in opioid-induced chronic pain and tolerance as a consequence of prolonged exposure to these drugs. In addition, we will examine a potential strategy with the aim to modulate opioid-induced over-activation of glia and mast cells, based on endogenous defense mechanisms and fatty acid amide signaling molecules.
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PMID:A Pharmacological Rationale to Reduce the Incidence of Opioid Induced Tolerance and Hyperalgesia: A Review. 2959 72

Cancer pain induced by pancreatic carcinoma is one of the most common symptoms and is difficult to endure, especially in the advanced stage. Evidence suggests that mast cells are recruited and degranulate in enteric disease-related visceral hypersensitivity. However, whether mast cells promote the visceral pain induced by pancreatic carcinoma remains unclear. Here, using toluidine blue staining and western blotting, we observed that mast cells were dramatically recruited to tissues surrounding pancreatic carcinoma, but not inside the carcinoma in patients with severe visceral pain. The levels of mast cell degranulation products, including tryptase, histamine, and nerve growth factor, were significantly increased in pericarcinoma tissues relative to their levels in normal controls, as evidenced by enzyme-linked immunosorbent assay. We determined that systemic administration of mast cell secretagogue compound 48/80 exacerbated pancreatic carcinoma-induced visceral hypersensitivity in a male BALB/c nude mouse model as assessed by measuring the hunching behavior scores and mechanical withdrawal response frequency evoked by von Frey stimulation. In contrast, the mast cell stabilizer ketotifen dose-dependently alleviated pancreatic cancer pain. In addition, we observed incomplete development of abdominal mechanical hyperalgesia and hunching behavior in mast cell-deficient mice with pancreatic carcinoma. However, ketotifen did not further attenuate visceral hypersensitivity in mast cell-deficient mice with carcinoma. Finally, we confirmed that intraplantar injection of pericarcinoma supernatants from BALB/c nude mice but not mast cell-deficient mice caused acute somatic nociception. In conclusion, our findings suggest that mast cells contribute to pancreatic carcinoma-induced visceral hypersensitivity through enrichment and degranulation in pericarcinoma tissues. The inhibition of mast cell degranulation may be a potential strategy for the therapeutic treatment of pancreatic carcinoma-induced chronic visceral pain.
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PMID:Inhibition of Mast Cell Degranulation Relieves Visceral Hypersensitivity Induced by Pancreatic Carcinoma in Mice. 3120 57