TRP Channel Cooperation for Nociception: Therapeutic Opportunities

Bamps, Dorien; Vriens, Joris; Hoon, Jan de; Voets, Thomas

doi:10.1146/annurev-pharmtox-010919-023238

Cited by 63 publications

(52 citation statements)

References 134 publications

(79 reference statements)

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“…TRP channels are non-selective cation channels that act as biosensors for environmental and noxious stimuli, including capsaicin and allicin, in addition to changes in temperature and conditions inside the cell (14,15). The TRPA1 receptor is highly expressed in the intestinal mucosa and can be activated by oxidative stress products, where the cell damage signals can induce oxidative stress (19), which implicates its possible association with intestinal disfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Transient receptor potential ankyrin 1 channel (TRPA1) serves as a key sensor for temperature and is permeable to Ca 2+ (14). In addition, TRPA1 can be activated by mustard oil, cinnamic acid, garlicin, oxidative stress products and inflammatory mediators, such as prostanoids (15,16). TRPA1 is mainly expressed on sensory neurons, afferent nerve endings and some non-neuronal cells, including immune cells, where it is involved in the process of nociception and inflammatory responses (17).…”

Section: Introductionmentioning

confidence: 99%

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Effects of norepinephrine on colonic tight junction protein expression during heat stress

Luo

Niu

et al. 2021

Exp Ther Med

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Stress induced by changes in the internal or external environment in humans and animals leads to intestinal epithelial damage, in a manner that is associated with impaired intestinal barrier function. However, the role of the stress hormone norepinephrine (NE) in impairments in barrier function remains poorly understood. In the present study, a rat heat-exposed model was used to observe changes in the tight junction proteins Occludin and zonula occludens-1 (ZO-1), in addition to those in protease-activated receptor 2 (PAR-2) and transient receptor potential ankyrin 1 channel (TRPA1) in colon. The levels of plasma NE were detected using an ELISA kit. Different concentrations of NE were used to culture the human colon cell line Caco-2 for 6 and 24 h to investigate the cell viability using Cell Counting Kit-8 assay, whilst the expression levels of Occludin, ZO-1, PAR-2 and TRPA1 were examined using western blotting and immunofluorescence in Caco-2 cells and immunohistrochemistry in rat colon tissues. Although there was no clear histological damage to the rat colonic mucosa, there were decreased expression levels of tight junction proteins Occludin and ZO-1 after heat exposure. In addition, PAR-2 expression was increased by heat exposure. It was found that TRPA1 expression was concentrated to the luminal surface of the colon in the heat exposed group compared with that in the control group. After the administration of increasing concentrations of NE for 6 h, treatment did not affect cell viability. Furthermore, after application of NE for 24 h, cell viability gradually increased as the NE concentration was elevated from 10 to 100 µM. However, no significant increase in viability was observed when the cells were treated with 120 and 160 µM NE. Occludin expression was decreased when 10 µM NE was applied for 6 or 24 h. By contrast, 60 µM NE significantly downregulated Occludin expression in the 6 h group, but caused an insignificant decrease in the 24 h group. It was found that ZO-1 expression was upregulated after treatment with 10 µM NE for 6 h, whilst downregulation was observed after treatment with 10 µM NE for 24 h. PAR-2 protein expression was increased after application of NE for both 6 and 24 h, but not after treatment with 60 µM NE. In addition, TRPA1 expression was not affected by the treatment of NE, but increased positive staining was observed on the luminal side of the mucosa, which appeared to be concentrated in the cells of the luminal side in the rat colon after heat exposure. Collectively, the present results suggested that expression of tight junction proteins Occludin and ZO-1, in addition to that of PAR-2, can be regulated by NE, which may contribute to impairments in barrier function observed during heat stress.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of norepinephrine on colonic tight junction protein expression during heat stress

Luo

Niu

et al. 2021

Exp Ther Med

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“…Transient receptor potential (TRP) channels are a large family of ion channels, and most of them are conserved from Drosophila to humans. It has more than 50 subtypes, divided into 7 subfamilies according to their amino acid sequence homology, which includes vanilloid (TRPV1-6), canonical or classic (TRPC1-7), melastatin (TRPM1-8), non-mechanoreceptor potential C (NOMP-like, TRPN1), long TRP ankyrin (TRPA1), polycystins (TRPP1-5) and mucolipins (TRPML1-3) ( Clapham et al, 2001 ; Nilius et al, 2005 , 2012 ; Wu et al, 2010 ; Li, 2017 ; Bamps et al, 2021 ). TRP channels allow an inward cation current to regulate cell function, and have a variety of activation modes by mechanical, thermal and chemical stimuli ( Nilius et al, 2007 ; Nilius and Owsianik, 2011 ).…”

Section: The Role Of Pain-related Genes In Regulating Nociception/painmentioning

confidence: 99%

Drosophila as a Model to Study the Mechanism of Nociception

Han

et al. 2022

Front. Physiol.

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Nociception refers to the process of encoding and processing noxious stimuli, which allow animals to detect and avoid potentially harmful stimuli. Several types of stimuli can trigger nociceptive sensory transduction, including thermal, noxious chemicals, and harsh mechanical stimulation that depend on the corresponding nociceptors. In view of the high evolutionary conservation of the mechanisms that govern nociception from Drosophila melanogaster to mammals, investigation in the fruit fly Drosophila help us understand how the sensory nervous system works and what happen in nociception. Here, we present an overview of currently identified conserved genetics of nociception, the nociceptive sensory neurons responsible for detecting noxious stimuli, and various assays for evaluating different nociception. Finally, we cover development of anti-pain drug using fly model. These comparisons illustrate the value of using Drosophila as model for uncovering nociception mechanisms, which are essential for identifying new treatment goals and developing novel analgesics that are applicable to human health.

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“…Several TRPs are sensitive to thermal transitions. For example, TRPV1-TRPV4, TRPM2 and TRPM3 are sensitive to warmth or noxious heat, whereas TRPM8, TRPA1 and TRPC5 are activated by cooling or by noxious cold temperatures (Bamps et al, 2020;Buijs and McNaughton, 2020;Dhaka et al, 2006;Tan and McNaughton, 2018). The thermal sensing mechanisms of TRPs are yet to be fully understood (Baez et al, 2014;Singh et al, 2019).…”

Section: Activation and Regulation Of Trp Channelsmentioning

confidence: 99%

TRP channels in health and disease at a glance

Yue

2021

Journal of Cell Science

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The transient receptor potential (TRP) channel superfamily consists of a large group of non-selective cation channels that serve as cellular sensors for a wide spectrum of physical and environmental stimuli. The 28 mammalian TRPs, categorized into six subfamilies, including TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin) and TRPP (polycystin), are widely expressed in different cells and tissues. TRPs exhibit a variety of unique features that not only distinguish them from other superfamilies of ion channels, but also confer diverse physiological functions. Located at the plasma membrane or in the membranes of intracellular organelles, TRPs are the cellular safeguards that sense various cell stresses and environmental stimuli and translate this information into responses at the organismal level. Loss- or gain-of-function mutations of TRPs cause inherited diseases and pathologies in different physiological systems, whereas up- or down-regulation of TRPs is associated with acquired human disorders. In this Cell Science at a Glance article and the accompanying poster, we briefly summarize the history of the discovery of TRPs, their unique features, recent advances in the understanding of TRP activation mechanisms, the structural basis of TRP Ca2+ selectivity and ligand binding, as well as potential roles in mammalian physiology and pathology.

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TRP Channel Cooperation for Nociception: Therapeutic Opportunities

Cited by 63 publications

References 134 publications

Effects of norepinephrine on colonic tight junction protein expression during heat stress

Effects of norepinephrine on colonic tight junction protein expression during heat stress

Drosophila as a Model to Study the Mechanism of Nociception

TRP channels in health and disease at a glance

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