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Guangda Peng, Makiko Kashio, Tianbang Li, Xiaofeng Dong, Makoto Tominaga, Tatsuhiko Kadowaki
The transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is conserved between many arthropods, and in some has been shown to function as a chemosensor for noxious compounds. Activation of arthropod TRPA1 channels by temperature fluctuations has been tested in only a few insect species, and all of them were shown to be activated by heat. The recent identification of chemosensitive TRPA1 channels from two honey bee ectoparasitic mite species (VdTRPA1 and TmTRPA1) have provided an opportunity to study the temperature-dependent activation and the temperature-associated physiological functions of TRPA1 channels in non-insect arthropods...
2016: Frontiers in Physiology
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Francesco De Logu, Raquel Tonello, Serena Materazzi, Romina Nassini, Camilla Fusi, Elisabetta Coppi, Simone Li Puma, Ilaria M Marone, Laura R Sadofsky, Alyn M Morice, Tommaso Susini, Alessandro Terreni, Gloriano Moneti, Mariarosaria Di Tommaso, Pierangelo Geppetti, Silvia Benemei
Aromatase inhibitors (AI) induce painful musculoskeletal symptoms (AIMSS), which are dependent upon the pain transducing receptor TRPA1. However, since the AI concentrations required to engage TRPA1 in mice are higher than those found in the plasma of patients, we hypothesized that additional factors may cooperate to induce AIMSS. Here we report that the aromatase substrate androstenedione, unique among several steroid hormones, targeted TRPA1 in peptidergic primary sensory neurons in rodent and human cells expressing the native or recombinant channel...
October 6, 2016: Cancer Research
Cassandra E Deering-Rice, Chris Stockmann, Erin G Romero, Zhenyu Lu, Darien Shapiro, Brian L Stone, Bernhard Fassl, Flory Nkoy, Derek A Uchida, Robert M Ward, John M Veranth, Christopher A Reilly
Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of TRPV1 would be uniquely responsive to insoluble coal fly ash compared to the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1 I315M and T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles, due to reduced translation of protein and an apparent role for I585 in activation by particles...
October 7, 2016: Journal of Biological Chemistry
Lovish Marwaha, Yashika Bansal, Raghunath Singh, Priyanka Saroj, Ranjana Bhandari, Anurag Kuhad
Neuropathic pain is a debilitating disease which affects central as well as peripheral nervous system. Transient receptor potential (TRP) channels are ligand-gated ion channels that detect physical and chemical stimuli and promote painful sensations via nociceptor activation. TRP channels have physiological role in the mechanisms controlling several physiological responses like temperature and mechanical sensations, response to painful stimuli, taste, and pheromones. TRP channel family involves six different TRPs (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPA1) which are expressed in pain sensing neurons and primary afferent nociceptors...
October 18, 2016: Inflammopharmacology
Yun Ling, Zhuang-Li Hu, Qing-Li Meng, Peng Fang, Hai-Xia Liu
Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the (R)-(+)-WIN55, 212-2 mesylate salt (WIN), a synthetic cannabinoid on their cell bodies in vitro...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Junjie Luo, Wei L Shen, Craig Montell
Avoidance of noxious ambient heat is crucial for survival. A well-known phenomenon is that animals are sensitive to the rate of temperature change. However, the cellular and molecular underpinnings through which animals sense and respond much more vigorously to fast temperature changes are unknown. Using Drosophila larvae, we found that nociceptive rolling behavior was triggered at lower temperatures and at higher frequencies when the temperature increased rapidly. We identified neurons in the brain that were sensitive to the speed of the temperature increase rather than just to the absolute temperature...
October 17, 2016: Nature Neuroscience
Yao Lu, Honit Piplani, Stacy L McAllister, Carl M Hurt, Eric R Gross
BACKGROUND: Recent evidence suggests that cross talk exists between cellular pathways important for pain signaling and ischemia-reperfusion injury. Here, the authors address whether the transient receptor potential ankyrin 1 (TRPA1) channel, important in pain signaling, is present in cardiac myocytes and regulates cardiac ischemia-reperfusion injury. METHODS: For biochemical analysis of TRPA1, techniques including quantitative polymerase chain reaction, Western blot, and immunofluorescence were used...
September 30, 2016: Anesthesiology
Nicole Kurhanewicz, Rachel McIntosh-Kastrinsky, Haiyan Tong, Allen Ledbetter, Leon Walsh, Aimen Farraj, Mehdi Hazari
Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone...
October 13, 2016: Toxicology and Applied Pharmacology
Bernhard Stenger, Tanja Popp, Harald John, Markus Siegert, Amelie Tsoutsoulopoulos, Annette Schmidt, Harald Mückter, Thomas Gudermann, Horst Thiermann, Dirk Steinritz
Transient receptor potential family channels (TRPs) have been identified as relevant targets in many pharmacological as well as toxicological studies. TRP channels are ubiquitously expressed in different tissues and act among others as sensors for different external stimuli, such as mechanical stress or noxious impacts. Recent studies suggest that one member of this family, the transient receptor potential ankyrin 1 cation channel (TRPA1), is involved in pain, itch, and various diseases, suggesting TRPA1 as a potential therapeutic target...
October 13, 2016: Archives of Toxicology
Linda J Fothergill, Brid Callaghan, Leni R Rivera, TinaMarie Lieu, Daniel P Poole, Hyun-Jung Cho, David M Bravo, John B Furness
TRPA1 is a ligand-activated cation channel found in the intestine and other tissues. Components of food that stimulate TRPA1 receptors (phytonutrients) include allyl isothiocyanate, cinnamaldehyde and linalool, but these may also act at other receptors. Cells lining the intestinal mucosa are immunoreactive for TRPA1 and Trpa1 mRNA occurs in mucosal extracts, suggesting that the TRPA1 receptor is the target for these agonists. However, in situ hybridisation reveals Trpa1 expression in 5-HT containing enteroendocrine cells, not enterocytes...
October 10, 2016: Nutrients
L Buntinx, T Voets, B Morlion, L Vangeel, M Janssen, E Cornelissen, J Vriens, J de Hoon, E Levtchenko
Cystinosis is a rare autosomal recessive disorder characterized by lysosomal cystine accumulation due to loss of function of the lysosomal cystine transporter (CTNS). The most common mutation in cystinosis patients of Northern Europe consists of a 57-kb deletion. This deletion not only inactivates the CTNS gene but also extends into the non-coding region upstream of the start codon of the TRPV1 gene, encoding the capsaicin- and heat-sensitive ion channel TRPV1. To evaluate the consequences of the 57-kb deletion on functional TRPV1 expression, we compared thermal, mechanical and chemical sensitivity of cystinosis patients with matched healthy controls...
October 13, 2016: Scientific Reports
Ji Young Kwon, Hyun Soo Lee, Choun-Ki Joo
PURPOSE: To determine the immunologic functions of TRPA1 or TRPV1 in allergic conjunctivitis (AC). METHODS: Mice were sensitized with ovalbumin (OVA), after which TRPA1 antagonist or TRPV1 antagonist was administered before topical OVA challenge. Expression of TRPV1 or TRPA1 in AC was examined by western blotting and multicolor immunofluorescence. Clinical signs, OVA-specific IgE, infiltration of inflammatory cells into conjunctivae (CJs), and Th2 cytokine in draining lymph nodes (LNs) were evaluated by microscopy, flow cytometry, and ELISA...
October 11, 2016: Ocular Immunology and Inflammation
Frances Corrigan, Kimberley A Mander, Anna V Leonard, Robert Vink
BACKGROUND: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. MAIN BODY: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI...
October 11, 2016: Journal of Neuroinflammation
S A Coavoy-Sánchez, L Rodrigues, S A Teixeira, A G Soares, R Torregrossa, M E Wood, M Whiteman, S K P Costa, M N Muscará
Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved...
October 6, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
József Kun, Anikó Perkecz, Lorenz Knie, György Sétáló, Tamás Tornóczki, Erika Pintér, Ágnes Bán
OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology with antigen-specific and non-specific mechanisms. Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel activated by noxious stimuli such as oxidative stress products evoking pain and release of proinflammatory mediators from sensory nerve endings culminating in neurogenic inflammation. Extraneuronal TRPA1s e.g. on immune cells possess yet unkown functions. SUBJECTS AND METHODS: We studied the buccal mRNA expression (qPCR) and protein localization (immunohistochemistry) of TRPA1 receptors, and key OLP mediator transcripts in oral mucosa samples of healthy volunteers (n=9), OLP patients (n=43) and OLP-like hyperkeratotic diseases (n=12)...
October 8, 2016: Oral Diseases
Takaaki Sokabe, Hsiang-Chin Chen, Junjie Luo, Craig Montell
Drosophila third-instar larvae exhibit changes in their behavioral responses to gravity and food as they transition from feeding to wandering stages. Using a thermal gradient encompassing the comfortable range (18°C to 28°C), we found that third-instar larvae exhibit a dramatic shift in thermal preference. Early third-instar larvae prefer 24°C, which switches to increasingly stronger biases for 18°C-19°C in mid- and late-third-instar larvae. Mutations eliminating either of two rhodopsins, Rh5 and Rh6, wiped out these age-dependent changes in thermal preference...
October 4, 2016: Cell Reports
Man-Kyo Chung, Jennifer Park, Jamila Asgar, Jin Y Ro
BACKGROUND: Chronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptive primary afferents following muscle inflammation or injury contributes to muscle hyperalgesia. It is well known that craniofacial muscle injury or inflammation induces regulation of multiple genes in trigeminal ganglia, which is associated with muscle hyperalgesia. However, overall transcriptional profiles within trigeminal ganglia following masseter inflammation have not yet been determined...
2016: Molecular Pain
Dragana Srebro, Sonja Vučković, Milica Prostran
We previously showed that magnesium sulfate (MS) has systemic antinociceptive and local peripheral pronociceptive effects. The role of transient receptor potential (TRP) channels and acid-sensing ion channels (ASICs) in the mechanism of action of MS has not been investigated in detail. The aim of this study was to explore the participation of TRP channels in the pronociceptive action of MS in rats after its intraplantar injection. The paw withdrawal threshold (PWT) to mechanical stimuli was measured by the electronic von Frey test...
September 28, 2016: Neuroscience
L Buntinx, L Chang, A Amin, B Morlion, J de Hoon
AIM: To develop a non-invasive, safe and reproducible target-engagement biomarker for future TRPA1 antagonists in healthy volunteers. METHODS: Dose Finding (n = 11): 3%, 10%, and 30% cinnamaldehyde (CA) and placebo (=vehicle) was topically applied on the right forearm. One-way ANOVA with post-hoc Bonferroni was used to compare between doses. Reproducibility: 10% CA doses were topically applied during 1 visit on both arms (n = 10) or during 2 visits (n = 23) separated by a washout period of 7 days...
September 29, 2016: British Journal of Clinical Pharmacology
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