TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons

Anand, Uma; Otto, W; Facer, P.; Zebda, Noureddine; Selmer, Inger S; Gunthorpe, Martin J.; Chessell, Iain P.; Sinisi, Marco; Birch, Rolfe; Anand, Praveen

doi:10.1016/j.neulet.2008.04.007

Cited by 167 publications

(121 citation statements)

References 19 publications

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“…In the sciatic nerve, FKN-induced production of ROS from CX3CR1-expressing macrophages in the vicinity of sensory axons could result in a pronociceptive effect through the activation of TRPA1 receptors that are functionally located at axonal level (39)(40)(41). Thus, we demonstrated that 2 TRPA1 antagonists, AP-18 and A967079, repeatedly administered during the first VCR cycle, significantly prevented the development of VCR-induced allodynia by approximately 20% (Supplemental Figure 9).…”

Section: Figurementioning

confidence: 65%

“…Indeed, lidocaine desensitizes murine TRPA1 channel, thereby suggesting that this mechanism, in combination with sodium channel blockade, underlies lidocaine efficacy in treating neuropathic pain (39). This is a plausible suggestion, as TRPA1-immunoreactive fibers are expressed in human peripheral nerves (41). Chemotherapeutic drugs increase oxidative stress, which may result in pain hypersensitivity following activation of TRPA1 and TRPV4 channels located on sensory neurons (36,43,44).…”

Section: Animalsmentioning

confidence: 99%

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Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain

Old

Nadkarni²,

Grist³

et al. 2014

J. Clin. Invest.

149

185

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A major dose-limiting side effect associated with cancer-treating antineoplastic drugs is the development of neuropathic pain, which is not readily relieved by available analgesics. A better understanding of the mechanisms that underlie pain generation has potential to provide targets for prophylactic management of chemotherapy pain. Here, we delineate a pathway for pain that is induced by the chemotherapeutic drug vincristine sulfate (VCR). In a murine model of chemotherapy-induced allodynia, VCR treatment induced upregulation of endothelial cell adhesion properties, resulting in the infiltration of circulating CX3CR1 + monocytes into the sciatic nerve. At the endothelial-nerve interface, CX3CR1 + monocytes were activated by the chemokine CX3CL1 (also known as fractalkine [FKN]), which promoted production of reactive oxygen species that in turn activated the receptor TRPA1 in sensory neurons and evoked the pain response. Furthermore, mice lacking CX3CR1 exhibited a delay in the development of allodynia following VCR administration. Together, our data suggest that CX3CR1 antagonists and inhibition of FKN proteolytic shedding, possibly by targeting ADAM10/17 and/or cathepsin S, have potential as peripheral approaches for the prophylactic treatment of chemotherapy-induced pain.

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Section: Figurementioning

confidence: 65%

Section: Animalsmentioning

confidence: 99%

Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain

Old

Nadkarni²,

Grist³

et al. 2014

J. Clin. Invest.

149

185

View full text Add to dashboard Cite

show abstract

“…Furthermore, TRPV1 is a high-threshold thermo-TRP channel that opens in transfected cells in vitro at ϳ43°C (Caterina et al, 1997;Tominaga et al, 1998), which would be considered a very high T b . Both in rodents Kobayashi et al, 2005;Hjerling-Leffler et al, 2007) and in humans (Anand et al, 2008), high-threshold heat-sensitive TRPV1 channels are largely coexpressed with high-threshold cold-sensi-TRPV1 IN BODY TEMPERATURE REGULATION tive TRPA1 channels, and roles for both TRPV1 and TRPA1 gene polymorphisms in cold-pain and heat-pain sensitivity in humans have been proposed (Kim et al, 2004(Kim et al, , 2006. All these data make TRPV1-expressing neurons good candidates for detecting noxious thermal stimuli of both "modalities" (i.e., heat and cold) rather than innocuous thermal stimuli that would trigger thermoeffector responses of a particular modality (e.g., heatdefense responses).…”

Section: A Afferent Nervesmentioning

confidence: 99%

The Transient Receptor Potential Vanilloid-1 Channel in Thermoregulation: A Thermosensor It Is Not

et al. 2009

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“…It has been shown that components of urban PM, such as diesel exhaust PM (DEP), activate airway neurons that express transient receptor potential (TRP) ankyrin-1 (TRPA1) and TRP vanilloid-1 (TRPV1) (1)(2)(3)(4)(5)(6)(7)(8). TRPA1 and TRPV1 are members of the TRP family of ion channels.…”

mentioning

confidence: 99%

Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

Deering-Rice

Shapiro

Romero

et al. 2015

Am J Respir Cell Mol Biol

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Inhaled irritants activate transient receptor potential ankyrin-1 (TRPA1), resulting in cough, bronchoconstriction, and inflammation/edema. TRPA1 is also implicated in the pathogenesis of asthma. Our hypothesis was that particulate materials activate TRPA1 via a mechanism distinct from chemical agonists and that, in a cohort of children with asthma living in a location prone to high levels of air pollution, expression of uniquely sensitive forms of TRPA1 may correlate with reduced asthma control. Variant forms of TRPA1 were constructed by mutating residues in known functional elements and corresponding to single-nucleotide polymorphisms in functional domains. TRPA1 activity was studied in transfected HEK-293 cells using allyl-isothiocynate, a model soluble electrophilic agonist; 3,5-ditert butylphenol, a soluble nonelectrophilic agonist and a component of diesel exhaust particles; and insoluble coal fly ash (CFA) particles. The N-terminal variants R3C and R58T exhibited greater, but not additive, activity with all three agonists. The ankyrin repeat domain-4 single nucleotide polymorphisms E179K and K186N exhibited decreased response to CFA. The predicted N-linked glycosylation site residues N747A and N753A exhibited decreased responses to CFA, which were not attributable to differences in cellular localization. The pore-loop residue R919Q was comparable to wild-type, whereas N954T was inactive to soluble agonists but not CFA. These data identify roles for ankyrin domain-4, cell surface N-linked glycans, and selected pore-loop domain residues in the activation of TRPA1 by insoluble particles. Furthermore, the R3C and R58T polymorphisms correlated with reduced asthma control for some children, which suggest that TRPA1 activity may modulate asthma, particularly among individuals living in locations prone to high levels of air pollution.

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TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons

Cited by 167 publications

References 19 publications

Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain

Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain

The Transient Receptor Potential Vanilloid-1 Channel in Thermoregulation: A Thermosensor It Is Not

Activation of Transient Receptor Potential Ankyrin-1 by Insoluble Particulate Material and Association with Asthma

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