INT134597

Context Info Confidence 0.48 First Reported 2006 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 21 Total Number 23 Disease Relevance 9.41 Pain Relevance 9.74

transport (Trpa1) transmembrane transport (Trpa1)

Anatomy Link Frequency sensory neurons 2 Plasma 1 spinal cord 1 nociceptors 1 tear 1 Trpa1 (Mus musculus)

Pain Link Frequency Relevance Heat Spinal cord 27 100.00 opioid receptor 11 100.00 antagonist 132 99.96 IPN 9 99.92 Cold hyperalgesia 25 99.68 TRP channel 49 99.64 chronic construction injury 29 99.54 qutenza 129 99.32 nociceptor 182 99.20 Cannabinoid 7 99.16

Disease Link Frequency Relevance Heat Inflammatory Pain 21 99.92 Injury 94 99.54 Hyperalgesia 169 99.48 INFLAMMATION 229 98.52 Ganglion Cysts 143 98.52 Pain 345 96.52 Neurogenic Inflammation 9 95.44 Nociception 160 93.76 Cancer 14 92.56 Diabetic Neuropathy 3 91.60

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Here we use click chemistry to show that derivatives of two such compounds, mustard oil and cinnamaldehyde, covalently bind mouse TRPA1.

TRPA1 Binding (bind) of

1) Confidence 0.48 Published 2007 Journal Nature Section Abstract Doc Link 17237762 Disease Relevance 0.24 Pain Relevance 0.08

In native sensory neurons, TRPA1 is likely part of a macromolecular complex where it may interact intimately with other transmembrane proteins.

TRPA1 Binding (interact) of in sensory neurons

2) Confidence 0.48 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2922334 Disease Relevance 0.18 Pain Relevance 0.14

The true concentration of PGJ2 in the cell that interacts with TRPA1 is difficult to know.

TRPA1 Binding (interacts) of

3) Confidence 0.42 Published 2008 Journal Mol Pain Section Body Doc Link PMC2515828 Disease Relevance 0 Pain Relevance 0.06

We observed that most compounds known to activate TRPA1 are able to covalently bind cysteine residues.

TRPA1 Binding (bind) of

4) Confidence 0.37 Published 2007 Journal Nature Section Abstract Doc Link 17237762 Disease Relevance 0.26 Pain Relevance 0.09

Interestingly, both TRPA1 protein expression and mRNA were over-expressed in spinal cord and dorsal root ganglia (DRG) of mice treated with CFA, an effect that was fully prevented by the pre-treatment with the TRPA1 antagonist HC-030031.

TRPA1 Binding (were) of in dorsal root ganglia associated with antagonist and spinal cord

5) Confidence 0.37 Published 2010 Journal Pain Section Abstract Doc Link 20056530 Disease Relevance 0.76 Pain Relevance 1.10

Combined with the lack of clear evidence of direct mechanical activation of the recombinant mammalian TRPA1, these data raise the possibility that TRPA1 is not intrinsically mechanically sensitive, but instead serves as an amplifier or a signal integrator that is downstream of the bona fide mechanoreceptor(s).

TRPA1 Binding (integrator) of

6) Confidence 0.37 Published 2009 Journal Mol Pain Section Body Doc Link PMC2681449 Disease Relevance 0 Pain Relevance 0.21

We report a major role for TRPV4, which detects osmotic pressure and arachidonic acid metabolites, and TRPA1, which responds to 4-hydroxynonenal and cyclopentenone prostaglandins, in pancreatic inflammation and pain in mice.

TRPA1 Binding (responds) of associated with pain and inflammation

7) Confidence 0.37 Published 2010 Journal Am. J. Physiol. Gastrointest. Liver Physiol. Section Abstract Doc Link 20539005 Disease Relevance 0.81 Pain Relevance 0.73

TRPA1 is also targeted by environmental irritants, such as acrolein, that account for toxic and inflammatory actions of tear gas, vehicle exhaust, and metabolic byproducts of chemotherapeutic agents.

TRPA1 Binding (targeted) of in tear associated with inflammation

8) Confidence 0.37 Published 2006 Journal Cell Section Abstract Doc Link 16564016 Disease Relevance 0.58 Pain Relevance 0.54

Structurally unrelated cysteine-modifying agents such as iodoacetamide (IA) and (2-aminoethyl)methanethiosulphonate (MTSEA) also bind and activate TRPA1.

TRPA1 Binding (bind) of

9) Confidence 0.36 Published 2007 Journal Nature Section Abstract Doc Link 17237762 Disease Relevance 0.22 Pain Relevance 0.12

mice may be due to a direct contribution of TRPA1 channel activation to mechanically-gated SA currents or to alteration or downregulation of other associated proteins that normally form a structure/function complex with TRPA1.

TRPA1 Binding (complex) of

10) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2922334 Disease Relevance 0 Pain Relevance 0.10

TRPA1 Mediates Mechanical Currents in the Plasma Membrane of Mouse Sensory Neurons Mechanosensitive channels serve as essential sensors for cells to interact with their environment.

TRPA1 Binding (interact) of in Plasma

11) Confidence 0.35 Published 2010 Journal PLoS ONE Section Title Doc Link PMC2922334 Disease Relevance 0.17 Pain Relevance 0.21

In further experiments, individual L4 and L5 ganglia were dissected from control and CCI rats and processed as above for qRT-PCR of TRPM8, TRPA1 and GAPDH mRNA.

TRPA1 Binding (above) of in ganglia associated with chronic construction injury

12) Confidence 0.35 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2753652 Disease Relevance 0.16 Pain Relevance 0.08

While its role in cold and mechanical sensation remains unclear, there is a growing body evidence that TRPA1 is a key chemical sensor and is directly activated by diverse chemicals and the products of cell and tissue injury [66].

TRPA1 Binding (activated) of in body associated with injury

13) Confidence 0.35 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 1.42 Pain Relevance 0.85

These results suggest that TRPA1 and TRPV1 mediate slow-SNAP+ and fast-SNAP+ responses, respectively, demonstrating that native TRPV1 and TRPA1 are each required for normal NO sensing.

TRPA1 Binding (native) of

14) Confidence 0.33 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2764051 Disease Relevance 0 Pain Relevance 0.35

To verify our calcium imaging results, and to address whether NO-activation is membrane delimited, we next used electrophysiological methods to directly determine whether SNAP could activate recombinant TRPA1 and TRPV1.

TRPA1 Binding (recombinant) of associated with imagery

15) Confidence 0.33 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2764051 Disease Relevance 0 Pain Relevance 0.20

Although other TRP ion channels were not tested, these results suggest that 15d-PGJ2 is specific for TRPA1 among three TRP channels tested.

TRPA1 Binding (specific) of associated with trp channel

16) Confidence 0.32 Published 2008 Journal Mol Pain Section Body Doc Link PMC2515828 Disease Relevance 0 Pain Relevance 0.14

Activation of Mu and Kappa opioid receptors antagonized the stimulant action of icillin on TRPA1 [232], suggesting a central mechanism of interaction between opioid receptors and TRPA1.

TRPA1 Binding (interaction) of associated with kappa opioid receptor and opioid receptor

17) Confidence 0.25 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645548 Disease Relevance 0.68 Pain Relevance 0.67

TRPA1 was sensitized by PLC activator m-3M3FBS (1 ?

TRPA1 Binding (sensitized) of

18) Confidence 0.20 Published 2009 Journal Mol Pain Section Body Doc Link PMC2672059 Disease Relevance 0 Pain Relevance 0.25

For example, specific pharmacological inhibition strongly suggests a role of TRPA1 in the sensitization of nociceptors to mechanical stimuli, but compensatory mechanisms completely mask this role in TRPA1 deficient mice [100] 'Modality-specific' peripheral sensory neurons also express transduction molecules for different stimuli

TRPA1 Binding (role) of in sensory neurons associated with nociceptor

19) Confidence 0.19 Published 2008 Journal Mol Pain Section Body Doc Link PMC2386863 Disease Relevance 0.30 Pain Relevance 0.43

Hence, cannabinoid mechanisms may play an important role by interacting with the TRPA1 component in these nociceptors.

TRPA1 Binding (interacting) of in nociceptors associated with nociceptor and cannabinoid

20) Confidence 0.19 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645548 Disease Relevance 0.68 Pain Relevance 0.64

General Comments

This test has worked.