The proximodistal aggravation of colitis depends on substance P released from TRPV1-expressing sensory neurons

Engel, Matthias; Khalil, Mohammad; Mueller-Tribbensee, Sonja M.; Becker, Christoph; Neuhuber, Winfried; Neurath, Markus F.; Reeh, Peter W.

doi:10.1007/s00535-011-0495-6

Cited by 79 publications

(75 citation statements)

References 43 publications

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“…In mice, capsaicin-and acid-induced SP and CGRP release from the inflamed distal colon in DSS-induced colitis was significantly higher than that from the noninflamed colon (56). During DSS-induced colitis, the proportions of TRPV1 expressed in DRGs neurons and the relative content of TRPV1 mRNA were significantly increased in DRGs projecting to the inflamed distal colon compared to those receiving vehicle treatment.…”

Section: Roles Of Tks In Chemically Induced Inflammatory Colitismentioning

confidence: 85%

Tachykinin: recent developments and novel roles in health and disease

Onaga

2014

Biomolecular Concepts

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Over 80 years has passed since the discovery of substance P (SP), and a variety of peptides of the tachykinin (TK) family have been found and investigated. SP, neurokinin A (NKA), and neurokinin B (NKB) are representative peptides in mammalian species. SP and NKA are major excitatory neurotransmitters in the peripheral nervous system, while NKB is primarily involved in the central nervous system (CNS). Moreover, TK peptides play roles not only as neurotransmitters but also as local factors and are involved in almost all aspects of the regulation of physiological functions and pathophysiological processes. The role of SP as a mediator of pain processing and inflammation in peripheral tissues in coordination with transient receptor potential channels is well established, while novel aspects of TKs in relation to hematopoiesis, venous thromboembolism, tendinopathy, and taste perception have been clarified. In the CNS, the NKB signaling system in the hypothalamus has been shown to play a crucial role in the regulation of gonadotropin hormone secretion and the onset of puberty, and molecular biological studies have elucidated novel prophylaxic activities of TKs against neurogenic movement disorders based on their molecular structure. This review provides an overview of the novel aspects of TKs reported around the world in the last 5 years, with particular focus on nociception, inflammation, hemopoiesis, gonadotropin secretion, and CNS diseases.

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Section: Roles Of Tks In Chemically Induced Inflammatory Colitismentioning

confidence: 85%

Tachykinin: recent developments and novel roles in health and disease

Onaga

2014

Biomolecular Concepts

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“…Upon activation, these neuronal TRPs may give rise to neurogenic inflammation, which implies the release of proinflammatory neuropeptides, such as substance P and CGRP [46,87]. However, TRP channels are also expressed by non-neuronal cells (table 3), among which are immune and epithelial cells [70,124], thus contributing to acute inflammatory responses in the lung in response to CS or one of its components.…”

Section: Interaction Between Trp Channels and Cs In The Lungmentioning

confidence: 99%

“…The channel TRPV1, belonging to the vanilloid subfamily, is found in extrinsic spinal and vagal primary afferent sensory neurons in the myenteric plexus (table 2), as shown in the mouse, rat and guinea-pig [11,36,37,38,39,40,41,42,43,44,45,46]. The amount of TRPV1-expressing neurons depends on the gut region, higher in visceral than somatic afferent neurons [41,47,48,49].…”

Section: Localization Of Trp Channels In the Gutmentioning

confidence: 99%

Transient Receptor Potential Channels in Intestinal Inflammation: What Is the Impact of Cigarette Smoking?

Allais

Smet²,

Verschuere³

et al. 2016

Pathobiology

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Inflammatory bowel disease (IBD) is characterized by severe gastrointestinal inflammation and results from a complex interplay between genetic and environmental factors. IBD includes two prominent subtypes: Crohn's disease (CD) and ulcerative colitis (UC). One of the main risk factors for the development of CD is cigarette smoking, while UC is rather a disease of ex-smokers. To date, many of the mechanisms underlying the immune imbalance in IBD and the involvement of cigarette smoke (CS) are incompletely understood. Transient receptor potential (TRP) proteins are non-selective cation channels that, upon activation, lead to plasma membrane depolarization and, in general, to Ca²⁺ influx. TRP channels of the ankyrin and vanilloid family, expressed by sensory neurons in the central and enteric nervous systems, have been extensively studied in the context of intestinal inflammation. Moreover, recent advances made on the role of non-neuronal expressed TRP channels shed light on the involvement of epithelial cells in inflammatory processes. This review focuses on how CS may impact TRP channel function in intestinal inflammation. Firstly, we discuss the current knowledge on neuronal TRP channels, known to be linked to IBD, in health, immune homeostasis and intestinal inflammation. Subsequently, we address how TRP channels are activated by CS and its components in other organ systems and also hypothesize on the potential implications for CS-mediated TRP channel activation in gut inflammation.

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“…Moreover, the releases of neurotransmitters such as substance P and calcitonin generelated peptide (CGRP) [17][18][19], within the dorsal horn play a key role in regulating pain responses [16]. Numerous neurotransmitters and related receptors in the dorsal horn have been targets to understanding of the underlying mechanisms responsible for pain [15,16].…”

Section: Hushan Wangmentioning

confidence: 99%

Blocking Mammalian Target of Rapamycin (mTOR) Alleviates Neuropathic Pain Induced by Chemotherapeutic Bortezomib

Duan

Pang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Bortezomib (BTZ) is largely used as a chemotherapeutic agent for the treatment of cancer. However, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. Drugs preventing and/or treating the painful symptoms induced by BTZ are lacking since the underlying mechanisms leading to neuropathic pain remain largely unclear. The purposes of this study were to examine 1) the effects of blocking mammalian target of rapamycin (mTOR) on mechanical pain and cold hypersensitivity evoked by BTZ and 2) the underlying mechanisms responsible for the role of mTOR in regulating BTZ-induced neuropathic pain. Methods: Behavioral test was performed to determine mechanical pain and cold sensitivity in a rat model. Western blot analysis and ELISA were used to examine expression of mTOR and phosphatidylinositide 3-kinase (p-PI3K) signals, and the levels of substance P and calcitonin gene-related peptide (CGRP). Results: Systemic injection of BTZ significantly increased mechanical pain and cold sensitivity as compared with control animals (P<0.05 vs. control rats). The expression of p-mTOR, mTORmediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4E-binding protein 4 (p-4E-BP1) as well as p-PI3K was amplified in the dorsal horn of spinal cord of BTZ rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated mechanical pain and cold hypersensitivity. Blocking PI3K signal also attenuated activities of mTOR, which was accompanied with decreasing neuropathic pain. Inhibition of either mTOR or PI3K blunted enhancement of the spinal substance P and CGRP in BTZ rats. Conclusions: The data for the first time revealed specific signaling pathways leading to BTZ-induced peripheral neuropathic pain, including the activation of mTOR and PI3K. Inhibition of these signal pathways alleviates pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of peripheral painful neuropathy observed during chemotherapeutic application of BTZ.

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The proximodistal aggravation of colitis depends on substance P released from TRPV1-expressing sensory neurons

Abstract: The spatial correlation among increased colonic innervation density, TRPV1 receptor expression, stimulated SP release, and colitis severity suggested that TRPV1/SP-expressing sensory neurons should be considered as a therapeutic target in human ulcerative colitis.

Cited by 79 publications

References 43 publications

Tachykinin: recent developments and novel roles in health and disease

Tachykinin: recent developments and novel roles in health and disease

Transient Receptor Potential Channels in Intestinal Inflammation: What Is the Impact of Cigarette Smoking?

Blocking Mammalian Target of Rapamycin (mTOR) Alleviates Neuropathic Pain Induced by Chemotherapeutic Bortezomib

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