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Trpv1 and cancer pain

Terumasa Chiba, Yusuke Oka, Hiroya Sashida, Toshie Kanbe, Kenji Abe, Iku Utsunomiya, Kyoji Taguchi
The clinical anti-cancer efficacy of vincristine is limited by the development of dose-dependent peripheral neuropathy. Up-regulation of transient receptor potential vanilloid 1 (TRPV1) is correlated with peripheral neuropathy following anti-cancer drug treatment. To analyze the contribution of TRPV1 to the development of vincristine-induced mechanical allodynia/hyperalgesia, TRPV1 expression in the rat dorsal root ganglion (DRG) was analyzed after vincristine treatment. Mechanical allodynia/hyperalgesia was tested with von Frey filaments 14 days after intraperitoneal administration of 0...
March 30, 2017: Journal of Pharmacological Sciences
Shiqi Zhang, Xiaohan Ma, Lei Zhang, Hui Sun, Xiong Liu
Chili peppers exhibit antiobesity, anticancer, antidiabetic, and pain- and itch-relieving effects on animals and humans; these effects are due to capsaicin, which is the main pungent and biologically active component of pepper. Capsiate, a nonpungent capsaicin analogue, is similar to capsaicin in terms of structure and biological activity. In this study, we investigated whether capsaicin and capsiate exhibit the same hypoglycemic effects on rats with type 1 diabetes (T1D). Experimental rats were categorized into four groups: control, model, capsaicin, and capsiate groups...
March 2, 2017: Journal of Agricultural and Food Chemistry
Mi Hwa Heo, Jin Young Kim, Ilseon Hwang, Eunyoung Ha, Keon Uk Park
Background/Aims: Cancer-induced bone pain (CIBP) is one of the most common pains in patients with advanced neoplasms. Because of treatment-associated side effects, more than half of cancer patients are reported to have inadequate and undermanaged pain control. New mechanism-based therapies must be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug. We report a study of the potential analgesic effects of quetiapine in a mouse model of CIBP and examine the mechanism of bone pain by analyzing the expression of various nociceptors...
January 20, 2017: Korean Journal of Internal Medicine
Yener Yazğan, Mustafa Nazıroğlu
Relative 17β-estradiol (E2) deprivation and excessive production of mitochondrial oxygen free radicals (OFRs) with a high amount of Ca(2+) influx TRPA1, TRPM2, and TRPV1 activity is one of the main causes of neurodegenerative disease in postmenopausal women. In addition to the roles of tamoxifen (TMX) and raloxifene (RLX) in cancer and bone loss treatments, regulator roles in Ca(2+) influx and mitochondrial oxidative stress in neurons have not been reported. The aim of this study was to evaluate whether TMX and RLX interactions with TRPA1, TRPM2, and TRPV1 in primary hippocampal (HPC) and dorsal root ganglion (DRG) neuron cultures of ovariectomized (OVX) rats...
November 10, 2016: Molecular Neurobiology
E S Fernandes, A R A Cerqueira, A G Soares, Soraia K P Costa
A significant number of experimental and clinical studies published in peer-reviewed journals have demonstrated promising pharmacological properties of capsaicin in relieving signs and symptoms of non-communicable diseases (chronic diseases). This chapter provides an overview made from basic and clinical research studies of the potential therapeutic effects of capsaicin, loaded in different application forms, such as solution and cream, on chronic diseases (e.g. arthritis, chronic pain, functional gastrointestinal disorders and cancer)...
2016: Advances in Experimental Medicine and Biology
Shaherin Basith, Minghua Cui, Sunhye Hong, Sun Choi
Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions...
July 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
László Pecze, Katalin Jósvay, Walter Blum, György Petrovics, Csaba Vizler, Zoltán Oláh, Beat Schwaller
Vanilloids including capsaicin and resiniferatoxin are potent transient receptor potential vanilloid type 1 (TRPV1) agonists. TRPV1 overstimulation selectively ablates capsaicin-sensitive sensory neurons in animal models in vivo. The cytotoxic mechanisms are based on strong Na(+) and Ca(2+) influx via TRPV1 channels, which leads to mitochondrial Ca(2+) accumulation and necrotic cell swelling. Increased TRPV1 expression levels are also observed in breast and prostate cancer and derived cell lines. Here, we examined whether potent agonist-induced overstimulation mediated by TRPV1 might represent a means for the eradication of prostate carcinoma (PC-3, Du 145, LNCaP) and breast cancer (MCF7, MDA-MB-231, BT-474) cells in vitro...
August 2016: Biochimica et Biophysica Acta
Satoshi Fuseya, Katsumi Yamamoto, Hitoshi Minemura, Satoshi Yamaori, Tomoyuki Kawamata, Mikito Kawamata
BACKGROUND: The aim of this study was to determine whether systemic administration of QX-314 reduces bone cancer pain through selective inhibition of transient receptor potential vanilloid subfamily 1 (TRPV1)-expressing afferents. METHODS: A mouse model of bone cancer pain was used. The authors examined the effects of bolus (0.01 to 3 mg/kg, n = 6 to 10) and continuous (5 mg kg h, n = 5) administration of QX-314 on both bone cancer pain-related behaviors and phosphorylated cyclic adenosine monophosphate response element-binding protein expression in dorsal root ganglion neurons (n = 3 or 6) and the effects of ablation of TRPV1-expressing afferents on bone cancer pain-related behaviors (n = 10)...
July 2016: Anesthesiology
Jennifer Fazzari, Katja Linher-Melville, Gurmit Singh
Chronic pain is a major symptom that develops in cancer patients, most commonly emerging during advanced stages of the disease. The nature of cancer-induced pain is complex, and the efficacy of current therapeutic interventions is restricted by the dose-limiting side-effects that accompany common centrally targeted analgesics. With a growing population of patients receiving inadequate treatment for intractable pain, new targets need to be considered to better address this largely unmet clinical need for improving their quality of life...
May 9, 2016: Current Neuropharmacology
Liang Han, Jiguang Ma, Wanxing Duan, Lun Zhang, Shuo Yu, Qinhong Xu, Jianjun Lei, Xuqi Li, Zheng Wang, Zheng Wu, Jason H Huang, Erxi Wu, Qingyong Ma, Zhenhua Ma
Abdominal pain is a critical clinical symptom in pancreatic cancer (PC) that affects the quality of life for PC patients. However, the pathogenesis of PC pain is largely unknown. In this study, we show that PC pain is initiated by the sonic hedgehog (sHH) signaling pathway in pancreatic stellate cells (PSCs), which is activated by sHH secreted from PC cells, and then, neurotrophic factors derived from PSCs mediate the pain. The different culture systems were established in vitro, and the expression of sHH pathway molecules, neurotrophic factors, TRPV1, and pain factors were examined...
April 5, 2016: Oncotarget
You Wan
In recent years, our serial investigations focused on the role of cancer cells-derived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation process by serine hydroxymethyltransferase (SHMT1 and SHMT2) and lysine-specific histone demethylase 1 (LSD1). When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1 (TRPV1) in the peripheral nerve fibers...
2016: Advances in Experimental Medicine and Biology
Kiichiro Yamaguchi, Kentaro Ono, Suzuro Hitomi, Misa Ito, Tomotaka Nodai, Tetsuya Goto, Nozomu Harano, Seiji Watanabe, Hiromasa Inoue, Kanako Miyano, Yasuhito Uezono, Motohiro Matoba, Kiyotoshi Inenaga
In many patients with cancer, chemotherapy-induced severe oral ulcerative mucositis causes intractable pain, leading to delays and interruptions in therapy. However, the pain mechanism in oral ulcerative mucositis after chemotherapy has not been extensively studied. In this study, we investigated spontaneous pain and mechanical allodynia in a preclinical model of oral ulcerative mucositis after systemic administration of the chemotherapy drug 5-fluorouracil, using our proprietary pain assay system for conscious rats...
May 2016: Pain
Wenjia Zhang, Guanling Yu, Mengyuan Zhang
ARA 290 is an erythropoietin-derived polypeptide that possesses analgesic and tissue protective effect in many diseases such as diabetes and cancer. The analgesic effect of ARA 290 is mediated by its anti-inflammatory and immunomodulatory functions, or more specifically, by targeting the innate repair receptor (IRR) to down-regulate inflammation to alleviate neuropathic pain. However, whether other mechanisms or pathways are involved in ARA 290-mediated analgesic effect remains elusive. In this study, we are particularly interested in whether ARA 290 could directly target peripheral nociceptors by blocking or influencing receptors in pain sensation...
February 2016: Peptides
Jinghui Wang, Yan Li, Yinfeng Yang, Jian Du, Shuwei Zhang, Ling Yang
The transient receptor potential vanilloid type 1 (TRPV1), a non-selective cation channel, is known for its essential role in the pathogenesis of various pain conditions such as nerve damage induced hyperalgesia, diabetic neuropathy and cancer pain. Therefore, TRPV1 is considered as a promising target for the development of new anti-inflammatory and analgesic drugs. In the present study, a theoretical study on the functionalities of the molecular interactions between 236 active ligands and TRPV1 was carried out, using three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking and molecular dynamics (MD) simulation approaches...
November 2015: Molecular BioSystems
Yanju Bao, Gaimei Wang, Yebo Gao, Maobo Du, Liping Yang, Xiangying Kong, Honggang Zheng, Wei Hou, Baojin Hua
Herbal analgesic Xiaozheng Zhitong Paste (XZP) and related modifications are often used in traditional Chinese medicine to manage cancer pain. However, its underlying mechanism remains unknown. To investigate the effects and mechanism of XZP on bone cancer pain in a rat model of breast cancer-induced bone pain, a bone cancer pain model was established by inoculating Walker 256 cells into Wistar rats. Bone cancer-bearing rats were topically treated with different doses of XZP or injected with 5 mg/kg of osteoprotegerin (OPG) as positive control...
September 2015: Oncology Reports
Shivani Ruparel, Michelle Bendele, Ashley Wallace, Dustin Green
BACKGROUND: Pain in the head neck area is an early symptom in oral cancer, supporting the hypothesis that cancer cells control the activities of surrounding nociceptors at the site of the tumor. Several reports implicate TRPV1 and TRPA1 in cancer pain, although there is a large gap in knowledge since the mechanisms for tumor-induced activation of these TRP receptors are unknown. Interestingly, TRP-active lipids such as linoleic acid, arachidonic acid, hydroxyoctadecadienoic acid and hydroxyeicosatetraenoic acid are significantly elevated in the saliva of oral cancer patients compared to normal patients, supporting a possible linkage between these lipids and oral cancer pain...
2015: Molecular Pain
Aaron D Mickle, Andrew J Shepherd, Lipin Loo, Durga P Mohapatra
The neurobiological mechanisms underlying chronic pain associated with cancers are not well understood. It has been hypothesized that factors specifically elevated in the tumor microenvironment sensitize adjacent nociceptive afferents. We show that parathyroid hormone-related peptide (PTHrP), which is found at elevated levels in the tumor microenvironment of advanced breast and prostate cancers, is a critical modulator of sensory neurons. Intraplantar injection of PTHrP led to the development of thermal and mechanical hypersensitivity in both male and female mice, which were absent in mice lacking functional transient receptor potential vanilloid-1 (TRPV1)...
September 2015: Pain
Nicolas Cenac, Tereza Bautzova, Pauline Le Faouder, Nicholas A Veldhuis, Daniel P Poole, Corinne Rolland, Jessica Bertrand, Wolfgang Liedtke, Marc Dubourdeau, Justine Bertrand-Michel, Lisa Zecchi, Vincenzo Stanghellini, Nigel W Bunnett, Giovanni Barbara, Nathalie Vergnolle
BACKGROUND & AIMS: In mice, activation of the transient receptor potential cation channels (TRP) TRPV1, TRPV4, and TRPA1 causes visceral hypersensitivity. These receptors and their agonists might be involved in development of irritable bowel syndrome (IBS). We investigated whether polyunsaturated fatty acid (PUFA) metabolites, which activate TRPs, are present in colon tissues from patients with IBS and act as endogenous agonists to induce hypersensitivity. METHODS: We analyzed colon biopsy samples from 40 patients with IBS (IBS biopsies) and 11 healthy individuals undergoing colorectal cancer screening (controls), collected during colonoscopy at the University of Bologna, Italy...
August 2015: Gastroenterology
Kazue Mizumura, Shiori Murase
Nerve growth factor (NGF) was first identified as a substance that is essential for the development of nociceptive primary neurons and later found to have a role in inflammatory hyperalgesia in adults. Involvement of NGF in conditions with no apparent inflammatory signs has also been demonstrated. In this review we look at the hyperalgesic effects of exogenously injected NGF into different tissues, both human and animal, with special emphasis on the time course of these effects. The roles of NGF in inflammatory and neuropathic conditions as well as cancer pain are then reviewed...
2015: Handbook of Experimental Pharmacology
Hae-Jin Kweon, Soo-Young Yu, Dong-Il Kim, Byung-Chang Suh
Protons are released in pain-generating pathological conditions such as inflammation, ischemic stroke, infection, and cancer. During normal synaptic activities, protons are thought to play a role in neurotransmission processes. Acid-sensing ion channels (ASICs) are typical proton sensors in the central nervous system (CNS) and the peripheral nervous system (PNS). In addition to ASICs, capsaicin- and heat-activated transient receptor potential vanilloid 1 (TRPV1) channels can also mediate proton-mediated pain signaling...
2015: PloS One
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