scholarly journals Transient Receptor Potential Channels and Botulinum Neurotoxins in Chronic Pain

2021 ◽  
Vol 14 ◽  
Author(s):  
Eun Jin Go ◽  
Jeongkyu Ji ◽  
Yong Ho Kim ◽  
Temugin Berta ◽  
Chul-Kyu Park
Keyword(s):  
Chronic Pain ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Analgesic Effects ◽  
Botulinum Neurotoxins ◽  
Potential Channels ◽  
Transient Receptor ◽  
And Function

Pain afflicts more than 1.5 billion people worldwide, with hundreds of millions suffering from unrelieved chronic pain. Despite widespread recognition of the importance of developing better interventions for the relief of chronic pain, little is known about the mechanisms underlying this condition. However, transient receptor potential (TRP) ion channels in nociceptors have been shown to be essential players in the generation and progression of pain and have attracted the attention of several pharmaceutical companies as therapeutic targets. Unfortunately, TRP channel inhibitors have failed in clinical trials, at least in part due to their thermoregulatory function. Botulinum neurotoxins (BoNTs) have emerged as novel and safe pain therapeutics because of their regulation of exocytosis and pro-nociceptive neurotransmitters. However, it is becoming evident that BoNTs also regulate the expression and function of TRP channels, which may explain their analgesic effects. Here, we summarize the roles of TRP channels in pain, with a particular focus on TRPV1 and TRPA1, their regulation by BoNTs, and briefly discuss the use of BoNTs for the treatment of chronic pain.

Transient receptor potential channels in the context of nociception and pain – recent insights into TRPM3 properties and function

2019 ◽  
Vol 400 (7) ◽  
pp. 917-926 ◽  
Author(s):  
Marc Behrendt
Keyword(s):  
Chronic Pain ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Mechanical Pressure ◽  
Noxious Heat ◽  
Potential Channels ◽  
Transient Receptor ◽  
Basic Features ◽  
And Function

Abstract Potential harmful stimuli like heat, mechanical pressure or chemicals are detected by specialized cutaneous nerve fiber endings of nociceptor neurons in a process called nociception. Acute stimulation results in immediate protective reflexes and pain sensation as a normal, physiological behavior. However, ongoing (chronic) pain is a severe pathophysiological condition with diverse pathogeneses that is clinically challenging because of limited therapeutic options. Therefore, an urgent need exists for new potent and specific analgesics without afflicting adverse effects. Recently, TRPM3, a member of the superfamily of transient receptor potential (TRP) ion channels, has been shown to be expressed in nociceptors and to be involved in the detection of noxious heat (acute pain) as well as inflammatory hyperalgesia (acute and chronic pain). Current results in TRPM3 research indicate that this ion channel might not only be part of yet unraveled mechanisms underlying chronic pain but also has the potential to become a clinically relevant pharmacological target of future analgesic strategies. The aim of this review is to summarize and present the basic features of TRPM3 proteins and channels, to highlight recent findings and developments and to provide an outlook on emerging directions of TRPM3 research in the field of chronic pain.

Does serotonin deficiency lead to anosmia, ageusia and dysfunctional chemesthesis in COVID-19?

2021 ◽  
Author(s):  
Amarnath Sen
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Taste Receptor ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Host Cells ◽  
Potential Channels ◽  
Transient Receptor

Anosmia, ageusia and impaired chemesthetic sensations are quite common in coronavirus patients. Different mechanisms have been proposed to explain the anosmia and ageusia of COVID-19 patients, though for reversible anosmia and ageusia, which are resolved quickly, the proposed mechanisms seem to be incomplete. In addition, the reason behind the impaired chemesthetic sensations of some coronavirus patients remains unknown. It is proposed that in coronavirus patients, there is depletion of tryptophan (an essential amino acid), as ACE2, a key element in the process of absorption of tryptophan from food, is significantly reduced due to the attack of coronavirus which use ACE2 as the receptor for its entry into the host cells. Incidentally, the depletion of tryptophan should lead to deficiency of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency not only explains fast resolved anosmia and ageusia, but also dysfunctional chemesthesis, given the fact that 5-HT is an important neuromodulator in the olfactory neurons and taste receptor cells and 5-HT also enhances the nociceptor activity of transient receptor potential channels (TRP channels) responsible for chemesthetic sensations. The female predominance of olfactory and gustatory dysfunctions can also be explained by considering low 5-HT levels in women. In addition, 5-HT deficiency worsens silent hypoxemia and explains why hypoxic pulmonary vasoconstriction is nearly absent in coronavirus patients leading to poor outcome. Hence, clinical trials should be conducted on coronavirus patients to find out how different selective serotonin reuptake inhibitors (SSRIs) and serotonin agonists work out in eliminating or improving the olfactory, gustatory and chemesthetic dysfunctions as well as hypoxemia.

Transient receptor potential channels and vascular function

2010 ◽  
Vol 119 (1) ◽  
pp. 19-36 ◽  
Author(s):  
Scott Earley ◽  
Joseph E. Brayden
Keyword(s):  
Vascular Function ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Receptor Activation ◽  
Transient Receptor Potential Channels ◽  
No Production ◽  
Control Mechanisms ◽  
Potential Channels ◽  
Transient Receptor

TRP (transient receptor potential) channels play important roles in the regulation of normal and pathological cellular function. In the vasculature, TRP channels are present both in ECs (endothelial cells) and vascular SMCs (smooth muscle cells) and contribute to vasomotor control mechanisms in most vascular beds. Vascular TRP channels are activated by various stimuli, such as mechanical perturbation, receptor activation and dietary molecules. Some of the specific roles of these channels in normal and impaired vascular function have emerged in recent years and include participation in vascular signalling processes, such as neurotransmission, hormonal signalling, NO production, myogenic tone and autoregulation of blood flow, thermoregulation, responses to oxidative stress and cellular proliferative activity. Current research is aimed at understanding the interactions of TRP channels with other vascular proteins and signalling mechanisms. These studies should reveal new targets for pharmacological therapy of vascular diseases, such as hypertension, ischaemia and vasospasm, and vascular proliferative states.

scholarly journals Does serotonin deficiency lead to anosmia, ageusia and dysfunctional chemesthesis in COVID-19?

2021 ◽  
Author(s):  
Amarnath Sen
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Taste Receptor ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Host Cells ◽  
Potential Channels ◽  
Transient Receptor

Anosmia, ageusia and impaired chemesthetic sensations are quite common in coronavirus patients. Different mechanisms have been proposed to explain the anosmia and ageusia of COVID-19 patients, though for reversible anosmia and ageusia, which are resolved quickly, the proposed mechanisms seem to be incomplete. In addition, the reason behind the impaired chemesthetic sensations of some coronavirus patients remains unknown. It is proposed that in coronavirus patients, there is depletion of tryptophan (an essential amino acid), as ACE2, a key element in the process of absorption of tryptophan from food, is significantly reduced due to the attack of coronavirus which use ACE2 as the receptor for its entry into the host cells. Incidentally, the depletion of tryptophan should lead to deficiency of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency not only explains fast resolved anosmia and ageusia, but also dysfunctional chemesthesis, given the fact that 5-HT is an important neuromodulator in the olfactory neurons and taste receptor cells and 5-HT also enhances the nociceptor activity of transient receptor potential channels (TRP channels) responsible for chemesthetic sensations. The female predominance of olfactory and gustatory dysfunctions can also be explained by considering low 5-HT levels in women. In addition, 5-HT deficiency worsens silent hypoxemia and explains why hypoxic pulmonary vasoconstriction is nearly absent in coronavirus patients leading to poor outcome. Hence, clinical trials should be conducted on coronavirus patients to find out how different selective serotonin reuptake inhibitors (SSRIs) and serotonin agonists work out in eliminating or improving the olfactory, gustatory and chemesthetic dysfunctions as well as hypoxemia.

scholarly journals Transient receptor potential channels: current perspectives on evolution, structure, function and nomenclature

2020 ◽  
Vol 287 (1933) ◽  
pp. 20201309
Author(s):  
Nathaniel J. Himmel ◽  
Daniel N. Cox
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Phylogenetic Analyses ◽  
Receptor Potential ◽  
Original Description ◽  
Transient Receptor Potential Channels ◽  
Wide Range ◽  
History Of ◽  
Potential Channels ◽  
Transient Receptor

The transient receptor potential superfamily of ion channels (TRP channels) is widely recognized for the roles its members play in sensory nervous systems. However, the incredible diversity within the TRP superfamily, and the wide range of sensory capacities found therein, has also allowed TRP channels to function beyond sensing an organism's external environment, and TRP channels have thus become broadly critical to (at least) animal life. TRP channels were originally discovered in Drosophila and have since been broadly studied in animals; however, thanks to a boom in genomic and transcriptomic data, we now know that TRP channels are present in the genomes of a variety of creatures, including green algae, fungi, choanoflagellates and a number of other eukaryotes. As a result, the organization of the TRP superfamily has changed radically from its original description. Moreover, modern comprehensive phylogenetic analyses have brought to light the vertebrate-centricity of much of the TRP literature; much of the nomenclature has been grounded in vertebrate TRP subfamilies, resulting in a glossing over of TRP channels in other taxa. Here, we provide a comprehensive review of the function, structure and evolutionary history of TRP channels, and put forth a more complete set of non-vertebrate-centric TRP family, subfamily and other subgroup nomenclature.

scholarly journals TRPs in Tox: Involvement of Transient Receptor Potential-Channels in Chemical-Induced Organ Toxicity—A Structured Review

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 98 ◽  
Author(s):  
Dirk Steinritz ◽  
Bernhard Stenger ◽  
Alexander Dietrich ◽  
Thomas Gudermann ◽  
Tanja Popp
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Specific Interaction ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Organ Systems ◽  
Organ Specific ◽  
Specific Organ ◽  
Potential Channels ◽  
Transient Receptor

Chemicals can exhibit significant toxic properties. While for most compounds, unspecific cell damaging processes are assumed, a plethora of chemicals exhibit characteristic odors, suggesting a more specific interaction with the human body. During the last few years, G-protein-coupled receptors and especially chemosensory ion channels of the transient receptor potential family (TRP channels) were identified as defined targets for several chemicals. In some cases, TRP channels were suggested as being causal for toxicity. Therefore, these channels have moved into the spotlight of toxicological research. In this review, we screened available literature in PubMed that deals with the role of chemical-sensing TRP channels in specific organ systems. TRPA1, TRPM and TRPV channels were identified as essential chemosensors in the nervous system, the upper and lower airways, colon, pancreas, bladder, skin, the cardiovascular system, and the eyes. Regarding TRP channel subtypes, A1, M8, and V1 were found most frequently associated with toxicity. They are followed by V4, while other TRP channels (C1, C4, M5) are only less abundantly expressed in this context. Moreover, TRPA1, M8, V1 are co-expressed in most organs. This review summarizes organ-specific toxicological roles of TRP channels.

scholarly journals Regulation of TRP channels: a voltage–lipid connection

2007 ◽  
Vol 35 (1) ◽  
pp. 105-108 ◽  
Author(s):  
B. Nilius ◽  
F. Mahieu ◽  
Y. Karashima ◽  
T. Voets
Keyword(s):  
Transient Receptor Potential ◽  
Voltage Dependence ◽  
Trp Channels ◽  
Receptor Potential ◽  
Binding Pocket ◽  
Transient Receptor Potential Channels ◽  
C Terminus ◽  
Potential Channels ◽  
Transient Receptor ◽  
Phosphatidylinositol Phosphates

TRP (transient receptor potential) channels respond to a plethora of stimuli in a fine-tuned manner. We show here that both membrane potential and the level of PI (phosphatidylinositol) phosphates are efficient regulators of TRP channel gating. Recent work has shown that this regulation applies to several members of the TRPV (TRP vanilloid) subfamily (TRPV1 and TRPV5) and the TRPM (TRP melastatin) subfamily (TRPM4/TRPM5/TRPM7/TRPM8), whereas regulation of members of the TRPC subfamily is still disputed. The mechanism whereby PIP2 (PI 4,5-bisphosphate) acts on TRPM4, a Ca2+- and voltage-activated channel, is shown in detail in this paper: (i) PIP2 may bind directly to the channel, (ii) PIP2 induces sensitization to activation by Ca2+, and (iii) PIP2 shifts the voltage dependence towards negative and physiologically more meaningful potentials. A PIP2-binding pocket seems to comprise a part of the TRP domain and especially pleckstrin homology domains in the C-terminus.

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