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Capsaicin and TRPV1 in the Study of Pain and Organ Pathologies

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2019) | Viewed by 30747

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Special Issue Editor

Prof. Dr. Gábor Jancsó

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Guest Editor

Department of Physiology, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary

Special Issue Information

Dear Colleagues,

Capsaicin, a selective nociceptor excitant and a unique neurotoxic agent affecting C-fiber nociceptive primary sensory neurons, has become an indispensable tool in pain research and in studies concerned with the role of sensory nerves in various organ functions. Capsaicin/TRPV1 receptor-expressing chemosensitive afferent nerves are widely distributed in the body and play important roles in various organ functions. This Special Issue focuses on the mechanism(s) of action of vanilloid compounds and the involvement of sensory nerves expressing capsaicin/TRPV1 receptor (and other TRP receptors, such as TRPA1 co-expressed with TRPV1) in the function of the pain system and in (patho)physiological processes affecting different organ systems.

Possible topics may include: 1) the cellular mechanism(s) of the sensory excitatory, sensitizing, desensitizing, and neurotoxic actions of capsaicin, 2) the use of capsaicin as a specific research tool to investigate the involvement of capsaicin/TRPV1/TRPA1 receptor-expressing chemosensitive sensory nerves in pathophysiological processes such as pain, inflammation, nerve and tissue injury, metabolism, tumor development, etc., and, 3) the possible therapeutic perspectives of vanilloid agonists and antagonists in the management of pain and inflammation.

Prof. Gábor Jancsó
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

Capsaicin
TRPV1
TRPA1
Primary sensory neurons
Neurotoxicity
Pain
Peripheral nerve injury
Sensory neuropeptides
Organ pathology

Published Papers (6 papers)

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Research

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23 pages, 8018 KiB

Open AccessArticle

Reciprocal Regulatory Interaction between TRPV1 and Kinin B1 Receptor in a Rat Neuropathic Pain Model

by Veronica Cernit, Jacques Sénécal, Rahmeh Othman and Réjean Couture

Int. J. Mol. Sci. 2020, 21(3), 821; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030821 - 27 Jan 2020

Cited by 19 | Viewed by 3432

Abstract

Kinins are mediators of pain and inflammation and evidence suggests that the inducible kinin B1 receptor (B1R) is involved in neuropathic pain (NP). This study investigates whether B1R and TRPV1 are colocalized on nociceptors and/or astrocytes to enable regulatory interaction either directly or through the cytokine pathway (IL-1β, TNF-α) in NP. Sprague Dawley rats were subjected to unilateral partial sciatic nerve ligation (PSNL) and treated from 14 to 21 days post-PSNL with antagonists of B1R (SSR240612, 10 mg·kg⁻¹, i.p.) or TRPV1 (SB366791, 1 mg·kg⁻¹, i.p.). The impact of these treatments was assessed on nociceptive behavior and mRNA expression of B1R, TRPV1, TNF-α, and IL-1β. Localization on primary sensory fibers, astrocytes, and microglia was determined by immunofluorescence in the lumbar spinal cord and dorsal root ganglion (DRG). Both antagonists suppressed PSNL-induced thermal hyperalgesia, but only SB366791 blunted mechanical and cold allodynia. SSR240612 reversed PSNL-induced enhanced protein and mRNA expression of B1R and TRPV1 mRNA levels in spinal cord while SB366791 further increased B1R mRNA/protein expression. B1R and TRPV1 were found in non-peptide sensory fibers and astrocytes, and colocalized in the spinal dorsal horn and DRG, notably with IL-1β on astrocytes. IL-1β mRNA further increased under B1R or TRPV1 antagonism. Data suggest that B1R and TRPV1 contribute to thermal hyperalgesia and play a distinctive role in allodynia associated with NP. Close interaction and reciprocal regulatory mechanism are suggested between B1R and TRPV1 on astrocytes and nociceptors in NP. Full article

(This article belongs to the Special Issue Capsaicin and TRPV1 in the Study of Pain and Organ Pathologies)

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19 pages, 5215 KiB

Open AccessArticle

Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons

by Yuanyuan Li, Chengyu Yin, Xiaojie Li, Boyu Liu, Jie Wang, Xiaoli Zheng, Xiaomei Shao, Yi Liang, Junying Du, Jianqiao Fang and Boyi Liu

Int. J. Mol. Sci. 2019, 20(23), 5917; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20235917 - 25 Nov 2019

Cited by 87 | Viewed by 6450

Abstract

Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during chemotherapy and in cancer survivors. Conventional therapies are usually ineffective and possess adverse effects. Here, we examined the effects of electroacupuncture (EA) on a rat model of paclitaxel-induced neuropathic pain and related mechanisms. EA robustly and persistently alleviated paclitaxel-induced pain hypersensitivities. Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression. Ca²⁺ imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA’s effect. Spinal astrocytes and microglia were activated in paclitaxel-treated rats, whereas EA reduced the activation. These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation. Our work supports EA as a potential alternative therapy for paclitaxel-induced neuropathic pain. Full article

(This article belongs to the Special Issue Capsaicin and TRPV1 in the Study of Pain and Organ Pathologies)

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Review

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23 pages, 965 KiB

Open AccessReview

Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies

by Tamara Szabados, Kamilla Gömöri, Laura Pálvölgyi, Anikó Görbe, István Baczkó, Zsuzsanna Helyes, Gábor Jancsó, Péter Ferdinandy and Péter Bencsik

Int. J. Mol. Sci. 2020, 21(12), 4472; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124472 - 23 Jun 2020

Cited by 20 | Viewed by 6304

Abstract

Cardiovascular diseases, including coronary artery disease, ischemic heart diseases such as acute myocardial infarction and postischemic heart failure, heart failure of other etiologies, and cardiac arrhythmias, belong to the leading causes of death. Activation of capsaicin-sensitive sensory nerves by the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor and other receptors, as well as neuropeptide mediators released from them upon stimulation, play important physiological regulatory roles. Capsaicin-sensitive sensory nerves also contribute to the development and progression of some cardiac diseases, as well as to mechanisms of endogenous stress adaptation leading to cardioprotection. In this review, we summarize the role of capsaicin-sensitive afferents and the TRPV1 ion channel in physiological and pathophysiological functions of the heart based mainly on experimental results and show their diagnostic or therapeutic potentials. Although the actions of several other channels or receptors expressed on cardiac sensory afferents and the effects of TRPV1 channel activation on different non-neural cell types in the heart are not precisely known, most data suggest that stimulation of the TRPV1-expressing sensory nerves or stimulation/overexpression of TRPV1 channels have beneficial effects in cardiac diseases. Full article

(This article belongs to the Special Issue Capsaicin and TRPV1 in the Study of Pain and Organ Pathologies)

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18 pages, 685 KiB

Open AccessReview

Modulation of Sensory Nerve Function by Insulin: Possible Relevance to Pain, Inflammation and Axon Growth

by Bence András Lázár, Gábor Jancsó and Péter Sántha

Int. J. Mol. Sci. 2020, 21(7), 2507; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072507 - 04 Apr 2020

Cited by 5 | Viewed by 4699

Abstract

Insulin, besides its pivotal role in energy metabolism, may also modulate neuronal processes through acting on insulin receptors (InsRs) expressed by neurons of both the central and the peripheral nervous system. Recently, the distribution and functional significance of InsRs localized on a subset of multifunctional primary sensory neurons (PSNs) have been revealed. Systematic investigations into the cellular electrophysiology, neurochemistry and morphological traits of InsR-expressing PSNs indicated complex functional interactions among specific ion channels, proteins and neuropeptides localized in these neurons. Quantitative immunohistochemical studies have revealed disparate localization of the InsRs in somatic and visceral PSNs with a dominance of InsR-positive neurons innervating visceral organs. These findings suggested that visceral spinal PSNs involved in nociceptive and inflammatory processes are more prone to the modulatory effects of insulin than somatic PSNs. Co-localization of the InsR and transient receptor potential vanilloid 1 (TRPV1) receptor with vasoactive neuropeptides calcitonin gene-related peptide and substance P bears of crucial importance in the pathogenesis of inflammatory pathologies affecting visceral organs, such as the pancreas and the urinary bladder. Recent studies have also revealed significant novel aspects of the neurotrophic propensities of insulin with respect to axonal growth, development and regeneration. Full article

(This article belongs to the Special Issue Capsaicin and TRPV1 in the Study of Pain and Organ Pathologies)

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17 pages, 347 KiB

Open AccessReview

Role of Gangliosides in Peripheral Pain Mechanisms

by Péter Sántha, Ildikó Dobos, Gyöngyi Kis and Gábor Jancsó

Int. J. Mol. Sci. 2020, 21(3), 1005; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031005 - 03 Feb 2020

Cited by 21 | Viewed by 3241

Abstract

Gangliosides are abundantly occurring sialylated glycosphingolipids serving diverse functions in the nervous system. Membrane-localized gangliosides are important components of lipid microdomains (rafts) which determine the distribution of and the interaction among specific membrane proteins. Different classes of gangliosides are expressed in nociceptive primary sensory neurons involved in the transmission of nerve impulses evoked by noxious mechanical, thermal, and chemical stimuli. Gangliosides, in particular GM1, have been shown to participate in the regulation of the function of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1), a molecular integrator of noxious stimuli of distinct nature. Gangliosides may influence nociceptive functions through their association with lipid rafts participating in the organization of functional assemblies of specific nociceptive ion channels with neurotrophins, membrane receptors, and intracellular signaling pathways. Genetic and experimentally induced alterations in the expression and/or metabolism of distinct ganglioside species are involved in pathologies associated with nerve injuries, neuropathic, and inflammatory pain in both men and animals. Genetic and/or pharmacological manipulation of neuronal ganglioside expression, metabolism, and action may offer a novel approach to understanding and management of pain. Full article

(This article belongs to the Special Issue Capsaicin and TRPV1 in the Study of Pain and Organ Pathologies)

23 pages, 1269 KiB

Open AccessReview

TRP Channels in the Focus of Trigeminal Nociceptor Sensitization Contributing to Primary Headaches

by Mária Dux, Judit Rosta and Karl Messlinger

Int. J. Mol. Sci. 2020, 21(1), 342; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010342 - 04 Jan 2020

Cited by 38 | Viewed by 5732

Abstract

Pain in trigeminal areas is driven by nociceptive trigeminal afferents. Transduction molecules, among them the nonspecific cation channels transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), which are activated by endogenous and exogenous ligands, are expressed by a significant population of trigeminal nociceptors innervating meningeal tissues. Many of these nociceptors also contain vasoactive neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P. Release of neuropeptides and other functional properties are frequently examined using the cell bodies of trigeminal neurons as models of their sensory endings. Pathophysiological conditions cause phosphorylation, increased expression and trafficking of transient receptor potential (TRP) channels, neuropeptides and other mediators, which accelerate activation of nociceptive pathways. Since nociceptor activation may be a significant pathophysiological mechanism involved in both peripheral and central sensitization of the trigeminal nociceptive pathway, its contribution to the pathophysiology of primary headaches is more than likely. Metabolic disorders and medication-induced painful states are frequently associated with TRP receptor activation and may increase the risk for primary headaches. Full article

(This article belongs to the Special Issue Capsaicin and TRPV1 in the Study of Pain and Organ Pathologies)

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