Sensory TRP Channels

Mickle, Aaron D.; Shepherd, Andrew J.; Mohapatra, Durga P.

doi:10.1016/bs.pmbts.2015.01.002

Cited by 125 publications

(79 citation statements)

References 271 publications

(377 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of these channels turn out to be polymodal, in terms of their activation. The exhaustive list of exogenous and endogenous activators of nociceptive TRP channels and their underlying structure-functional mechanisms have recently been detailed [11]. Here we summarize only the endogenous or pathophysiological activators of nociceptive TRP channels (Figure 1).…”

Section: Nociceptive Trp Channelsmentioning

confidence: 99%

“…Significant expression of several nociceptive TRP channels has also been shown in the CNS and other tissue and cell types, such as keratinocytes, vascular endothelial cells, bladder epithelial cells and fibroblasts. Furthermore, TRPV1-3 have also been shown to be expressed in human dental pulp [9,11]. TRPV1 protein expression has been detected in peptidergic sensory afferents innervating bones [77], although expression of other nociceptive TRP channels there remains unexplored.…”

Section: Nociceptive Trp Channelsmentioning

confidence: 99%

“…Most of these mediators activate specific G protein-coupled receptors (GPCRs) and growth factor receptors (GFRs) on sensory nerves, leading to downstream activation (or inhibition) of several protein kinases and phosphatases. These cellular signal transduction effectors induce post-translational modifications on multiple nociceptive channel proteins, leading to an increase in the activation of these channels (Figure 1), which results in an increase in nociceptor firing [9,11,13]. Specifically, modification of TRPV1 by protein kinases A and C (PKA & PKC), cyclin-dependent kinase-5 (Cdk5), Src kinase, and phosphoinositide kinases (PI3/4/5Ks) have all been shown to enhance activation of the channel by: (a) decreasing the temperature threshold of channel activation to physiological temperatures (~35 °C to 37 °C); (b) activating the channel at mildly/moderately acidic pH; and/or (c) enhancing plasma membrane delivery of the channel protein (Figure 1) [11,45,85,86,89,90,91,92,93,94,95,96,97].…”

Section: Modulation Of Nociceptive Trp Channel Activity and Expresmentioning

confidence: 99%

“…Conversely, PKA phosphorylation of calcineurin-sensitive residues on TRPV1 protein has been shown to reverse this desensitization, thereby leading to sustained channel opening following activation [97]. All these changes culminate in constitutive activation of TRPV1 under pathophysiological conditions, thereby resulting in sustained nociceptor firing [9,11,13]. In contrast, GABA release from sensory afferents, downstream of TRPV1-mediated Ca 2+ influx, has been shown to activate GABA B receptors, leading to attenuation of NGF/serotonin/bradykinin-PKC-modulation of TRPV1 channel activity [101].…”

Section: Modulation Of Nociceptive Trp Channel Activity and Expresmentioning

confidence: 99%

“…In addition, modifications in channel function and trafficking properties, as well as changes in gene expression of nociceptive TRP channels are considered to be highly critical for peripheral nociceptive and pain processing under a wide variety of pathological conditions. Since in-depth studies have already been conducted to characterize the role of nociceptive TRP channels in multiple pain and migraine pathologies, they constitute attractive targets for new-generation analgesics and anti-migraine drug developments [8,9,10,11,12,13]. This review summarizes a comprehensive knowledge on the molecular characterization of nociceptive TRP channels, their constitutive and modulatory functions, expression and tissue distribution, as well as how these channels and their specific properties are critically involved in various pain conditions.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies

2016

View full text Add to dashboard Cite

Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these TRP channels are also expressed in neurons of the central nervous system, and in non-neuronal cells that communicate with sensory nerves. Nociceptive TRPs are activated by specific physico-chemical stimuli to provide the excitatory trigger in neurons. In addition, decades of research has identified a large number of immune and neuromodulators as mediators of nociceptive TRP channel activation during injury, inflammatory and other pathological conditions. These findings have led to aggressive targeting of TRP channels for the development of new-generation analgesics. This review summarizes the complex activation and/or modulation of nociceptive TRP channels under pathophysiological conditions, and how these changes underlie acute and chronic pain conditions. Furthermore, development of small-molecule antagonists for several TRP channels as analgesics, and the positive and negative outcomes of these drugs in clinical trials are discussed. Understanding the diverse functional and modulatory properties of nociceptive TRP channels is critical to function-based drug targeting for the development of evidence-based and efficacious new generation analgesics.

show abstract

Section: Nociceptive Trp Channelsmentioning

confidence: 99%

Section: Nociceptive Trp Channelsmentioning

confidence: 99%

Section: Modulation Of Nociceptive Trp Channel Activity and Expresmentioning

confidence: 99%

Section: Modulation Of Nociceptive Trp Channel Activity and Expresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies

2016

View full text Add to dashboard Cite

show abstract

Impact of 60‐GHz millimeter waves on stress and pain‐related protein expression in differentiating neuron‐like cells

Haas

Page

Boriskin

et al. 2016

Bioelectromagnetics

View full text Add to dashboard Cite

Millimeter waves (MMW) will be increasingly used for future wireless telecommunications. Previous studies on skin keratinocytes showed that MMW could impact the mRNA expression of Transient Receptor Potential cation channel subfamily Vanilloid, member 2 (TRPV2). Here, we investigated the effect of MMW exposure on this marker, as well as on other membrane receptors such as Transient Receptor Potential cation channel subfamily Vanilloid, member 1 (TRPV1) and purinergic receptor P2X, ligand-gated ion channel, 3 (P2 × 3). We exposed the Neuroscreen-1 cell line (a PC12 subclone), in order to evaluate if acute MMW exposures could impact expression of these membrane receptors at the protein level. Proteotoxic stress-related chaperone protein Heat Shock Protein 70 (HSP70) expression level was also assessed. We used an original high-content screening approach, based on fluorescence microscopy, to allow cell-by-cell analysis and to detect any cell sub-population responding to exposure. Immunocytochemistry was done after 24 h MMW exposure of cells at 60.4 GHz, with an incident power density of 10 mW/cm(2) . Our results showed no impact of MMW exposure on protein expressions of HSP70, TRPV1, TRPV2, and P2 × 3. Moreover, no specific cell sub-populations were found to express one of the studied markers at a different level, compared to the rest of the cell populations. However, a slight insignificant increase in HSP70 expression and an increase in protein expression variability within cell population were observed in exposed cells, but controls showed that this was related to thermal effect. Bioelectromagnetics. 37:444-454, 2016. © 2016 Wiley Periodicals, Inc.

show abstract

Chemical Constituents and Anti‐Gastric Ulcer Activity of Essential Oils of Alpinia officinarum (Zingiberaceae), Cyperus rotundus (Cyperaceae), and Their Herbal Pair

et al. 2021

Chemistry & Biodiversity

View full text Add to dashboard Cite

The essential oil (EO) of the herbal pair (HP), Alpinia officinarum‐Cyperus rotundus (HP G‐X) has been conventionally used in traditional Chinese medicine (TCM) for ‘warming the stomach’ and relieving pain. However, its pharmacologically active compounds, as well as the mechanism of its anti‐gastric ulcer properties remain unclear. In this study, the EOs obtained from HP G‐X and its corresponding single herbs were analyzed using GC/MS. A total of 74, 56, and 85 compounds were detected in A. officinarum (GLJ), C. rotundus (XF), and HP G‐X, accounting for 93.2 %, 89.5 %, and 92.0 % of the total content, respectively. GLJ mainly contains 1,8‐cineol (22.0 %) and α‐terpineol (11.8 %), whereas cyperenone (22.4 %) and cyperene (12.3 %) were the major constituents in XF. These four compounds were also detected in the HP G‐X with relatively high composition as 11.8 %, 5.5 %, 11.8 %, and 10.6 %, respectively. Although no new compounds were detected in HP G‐X, the relative concentration of some compounds increased, while others decreased or even disappeared. HP G‐X showed the lowest toxicity (TC50 >800 μg/mL) against human gastric mucosal epithelial cells (GES‐1) and had the best protective effect against ethanol‐induced GES‐1 cell damage compared to the individual herbs. In vitro studies demonstrated that HP G‐X and the corresponding single herbs significantly reduced IL‐6, TNF‐α, and COX‐2. In addition, in vivo investigations indicated that HP G‐X can protect the gastric mucosa of mice from ethanol‐induced damage by inhibiting the inflammatory reaction and providing analgesia. It can also inhibit the expression of NF‐κBp65, COX‐2, and TRPV1 protein, reduce the concentrations of IL‐6 and TNF‐α, and relieve heat‐induced pain. This study further substantiated the traditional application of HP G‐X against gastric ulcers through both in vivo and in vitro investigations.

show abstract

Sensory TRP Channels

Cited by 125 publications

References 271 publications

Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies

Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies

Impact of 60‐GHz millimeter waves on stress and pain‐related protein expression in differentiating neuron‐like cells

Chemical Constituents and Anti‐Gastric Ulcer Activity of Essential Oils of Alpinia officinarum (Zingiberaceae), Cyperus rotundus (Cyperaceae), and Their Herbal Pair

Contact Info

Product

Resources

About