TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model

Li, Qian; Guo, Chenghao; Chowdhury, Mohammed Ali; Dai, Taoli; Han, Wei

doi:10.2147/jpr.s118581

Cited by 12 publications

(7 citation statements)

References 40 publications

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“…Hypersensitive VMR, and the release of substance P and CGRP, are reduced in Trpa1 KO mice and in mice with reduced TRPA1 expression on the DRG neurons that innervate the colon. Additionally, the TNBS-or AITC-induced VH is accompanied by higher TRPA1 mRNA, protein levels, and currents in colonic DRG neurons of mouse and rat (144,162,239,392,418,468,501,560,922). Moreover, TNBS-induced colonic inflammation in rats increases the H 2 O 2 levels and VH.…”

Section: E Trpa1 In Gastrointestinal Tract Diseasesmentioning

confidence: 91%

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Talavera

Startek

Alvarez‐Collazo

et al. 2020

Physiological Reviews

274

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The transient receptor potential ankyrin (TRPA) channels are Ca2+-permeable nonselective cation channels remarkably conserved through the animal kingdom. Mammals have only one member, TRPA1, which is widely expressed in sensory neurons and in non-neuronal cells (such as epithelial cells and hair cells). TRPA1 owes its name to the presence of 14 ankyrin repeats located in the NH2 terminus of the channel, an unusual structural feature that may be relevant to its interactions with intracellular components. TRPA1 is primarily involved in the detection of an extremely wide variety of exogenous stimuli that may produce cellular damage. This includes a plethora of electrophilic compounds that interact with nucleophilic amino acid residues in the channel and many other chemically unrelated compounds whose only common feature seems to be their ability to partition in the plasma membrane. TRPA1 has been reported to be activated by cold, heat, and mechanical stimuli, and its function is modulated by multiple factors, including Ca2+, trace metals, pH, and reactive oxygen, nitrogen, and carbonyl species. TRPA1 is involved in acute and chronic pain as well as inflammation, plays key roles in the pathophysiology of nearly all organ systems, and is an attractive target for the treatment of related diseases. Here we review the current knowledge about the mammalian TRPA1 channel, linking its unique structure, widely tuned sensory properties, and complex regulation to its roles in multiple pathophysiological conditions.

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Section: E Trpa1 In Gastrointestinal Tract Diseasesmentioning

confidence: 91%

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Talavera

Startek

Alvarez‐Collazo

et al. 2020

Physiological Reviews

274

View full text Add to dashboard Cite

show abstract

“…TRPA1 stimulation induces the Ca 2+ -mediate secretion of substance P (SP) and calcitonin gene-related peptide (CGRP) and other transmitters from afferent nerve fiber, which eventually results in inflammation and VH [76]. Several murine models of IBS present increased TRPA1 function in sensory ganglia and colon [77]. The same applies to humans, where the upregulation of TRPA1 in biopsies of IBD patients has been observed [78].…”

Section: Expression and Pathophysiological Roles Of Trp Channels Imentioning

confidence: 99%

The Pivotal Role of TRP Channels in Homeostasis and Diseases throughout the Gastrointestinal Tract

Alaimo

Rubert

2019

IJMS

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The transient receptor potential (TRP) channels superfamily are a large group of proteins that play crucial roles in cellular processes. For example, these cation channels act as sensors in the detection and transduction of stimuli of temperature, small molecules, voltage, pH, and mechanical constrains. Over the past decades, different members of the TRP channels have been identified in the human gastrointestinal (GI) tract playing multiple modulatory roles. Noteworthy, TRPs support critical functions related to the taste perception, mechanosensation, and pain. They also participate in the modulation of motility and secretions of the human gut. Last but not least, altered expression or activity and mutations in the TRP genes are often related to a wide range of disorders of the gut epithelium, including inflammatory bowel disease, fibrosis, visceral hyperalgesia, irritable bowel syndrome, and colorectal cancer. TRP channels could therefore be promising drug targets for the treatment of GI malignancies. This review aims at providing a comprehensive picture of the most recent advances highlighting the expression and function of TRP channels in the GI tract, and secondly, the description of the potential roles of TRPs in relevant disorders is discussed reporting our standpoint on GI tract–TRP channels interactions.

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“…In this experiment, a colonic hyperalgesia model was established by injection of TNBS (Sigma-Aldrich, MO, USA), as previously described [ 34 , 35 ]. Briefly, the rats were anesthetized with 2% isoflurane and fasten in a supine position.…”

Section: Methodsmentioning

confidence: 99%

Blockade of Erythropoietin-Producing Human Hepatocellular Carcinoma Receptor B1 in Spinal Dorsal Horn Alleviates Visceral Pain in Rats

Sun

et al. 2021

Pain Research and Management

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Objective. This experiment was designed to determine whether erythropoietin-producing human hepatocellular carcinoma (Eph) receptors were involved in the development of visceral pain. Methods. Adult male Sprague-Dawley rats were randomly divided into three groups receiving different treatments (n = 16 per group): intracolonic vehicle (control group), intracolonic 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) (TNBS group), and intracolonic TNBS and intrathecal EphB1 receptor blocking reagent (TNBS + EphB2-Fc group). Visceral hyperalgesia was evaluated with quantification of visceral pain threshold induced by colorectal distention. The spinal expressions of EphB1 and ephrinB2 and levels of their phosphorylated forms (p-EphB1 and p-ephrinB2) were assessed by Western blotting and immunohistochemistry. Results. The TNBS-treated rats developed significant visceral hyperalgesia. The spinal expressions of EphB1, p-EphB1, ephrinB2, and p-ephrinB2 were significantly increased in the TNBS group compared with the control group, but visceral hyperalgesia and elevation of spinal EphB1 and p-EphB1 expressions were evidently alleviated by intrathecal administration of EphB2-Fc in the TNBS + EphB2-Fc group. The number of EphB1- and p-EphB1-immunopositive cells, the average optical (AO) value of EphB1, and its phosphorylated form in the spinal dorsal horn were significantly increased in the TNBS group than in the control group, but they were obviously reduced by intrathecal administration of EphB2-Fc. There were no significant differences in the number of ephrinB2- and p-ephrinB2-immunopositive cells and the AO value of ephrinB2 and its phosphorylated form between the TNBS and TNBS + EphB2-Fc groups. Conclusion. EphB1 receptors in the spinal dorsal horn play a pivotal role in the development of visceral pain and may be considered as a potential target for the treatment of visceral pain.

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TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model

Cited by 12 publications

References 40 publications

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

The Pivotal Role of TRP Channels in Homeostasis and Diseases throughout the Gastrointestinal Tract

Blockade of Erythropoietin-Producing Human Hepatocellular Carcinoma Receptor B1 in Spinal Dorsal Horn Alleviates Visceral Pain in Rats

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