INT117601

Context Info Confidence 0.70 First Reported 2004 Last Reported 2010 Negated 14 Speculated 9 Reported most in Abstract Documents 174 Total Number 184 Disease Relevance 72.41 Pain Relevance 71.90

transport (Trpa1) transmembrane transport (Trpa1)

Anatomy Link Frequency neurons 18 nociceptors 6 sensory neurons 5 tear 3 neuronal 2 Trpa1 (Mus musculus)

Pain Link Frequency Relevance Heat qutenza 1563 100.00 nociceptor 1059 100.00 TRP channel 592 100.00 bradykinin 260 100.00 c fibre 223 100.00 Nerve growth factor 205 100.00 Kappa opioid receptor 10 100.00 Morphine 586 99.98 agonist 1114 99.92 addiction 89 99.92

Disease Link Frequency Relevance Heat Nociception 1729 99.92 Diabetic Neuropathy 22 99.84 Nervous System Injury 253 99.72 INFLAMMATION 1073 99.52 Ganglion Cysts 1535 99.46 Pain 2675 99.36 Injury 596 99.36 Hypersensitivity 725 99.32 Stress 136 99.30 Hyperalgesia 1353 98.96

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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

Positive_regulation (activate) of TRPA1

1) Confidence 0.70 Published 2007 Journal Nature Section Abstract Doc Link 17237762 Disease Relevance 0.22 Pain Relevance 0.12

Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines.

Positive_regulation (activate) of TRPA1 associated with pain

2) Confidence 0.70 Published 2007 Journal Nature Section Title Doc Link 17237762 Disease Relevance 0.28 Pain Relevance 0.29

TRPA1 is activated by a variety of noxious stimuli, including cold temperatures, pungent natural compounds, and environmental irritants.

Positive_regulation (activated) of TRPA1

3) Confidence 0.70 Published 2007 Journal Nature Section Abstract Doc Link 17237762 Disease Relevance 0.29 Pain Relevance 0.09

How such diverse stimuli activate TRPA1 is not known.

Positive_regulation (activate) of TRPA1

4) Confidence 0.70 Published 2007 Journal Nature Section Abstract Doc Link 17237762 Disease Relevance 0.27 Pain Relevance 0.09

In excised patches, reactive compounds activated TRPA1 currents that were maintained at least 10 min after washout of the compound in calcium-free solutions.

Positive_regulation (activated) of TRPA1

5) Confidence 0.70 Published 2007 Journal Nature Section Abstract Doc Link 17237762 Disease Relevance 0.20 Pain Relevance 0.13

TRPA1, a TRP ion channel expressed in chemosensory C-fibers, is activated by almost all oxidizing and electrophilic chemicals, including chlorine, acrolein, tear gas agents, and methyl isocyanate, the highly noxious chemical released in the Bhopal disaster.

Positive_regulation (activated) of TRPA1 in tear associated with c fibre

6) Confidence 0.70 Published 2010 Journal Proc Am Thorac Soc Section Abstract Doc Link 20601631 Disease Relevance 0.64 Pain Relevance 0.46

Chemicals likely activate TRPA1 through covalent protein modification.

Positive_regulation (activate) of TRPA1

7) Confidence 0.70 Published 2010 Journal Proc Am Thorac Soc Section Abstract Doc Link 20601631 Disease Relevance 0.64 Pain Relevance 0.47

TRPA1 antagonists camphor and gadolinium, and a general TRP blocker ruthenium red inhibited TRPA1 activation by acetaldehyde.

Positive_regulation (activation) of TRPA1 associated with antagonist

8) Confidence 0.70 Published 2007 Journal Eur. J. Neurosci. Section Abstract Doc Link 17970723 Disease Relevance 0.39 Pain Relevance 0.38

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).

Positive_regulation (activation) of TRPA1

9) Confidence 0.70 Published 2009 Journal Mol Pain Section Body Doc Link PMC2681449 Disease Relevance 0 Pain Relevance 0.22

Cysteine-reducing agents suppressed H(2)O(2)-induced TRPA1 activation, whereas cysteine-oxidizing agents activated TRPA1.

Positive_regulation (activation) of TRPA1

10) Confidence 0.69 Published 2008 Journal Eur. J. Neurosci. Section Abstract Doc Link 18364033 Disease Relevance 0.25 Pain Relevance 0.33

Cysteine-reducing agents suppressed H(2)O(2)-induced TRPA1 activation, whereas cysteine-oxidizing agents activated TRPA1.

Positive_regulation (activated) of TRPA1

11) Confidence 0.69 Published 2008 Journal Eur. J. Neurosci. Section Abstract Doc Link 18364033 Disease Relevance 0.25 Pain Relevance 0.33

H(2)O(2) activated mouse TRPA1 to induce Ca(2+) influx and elicit non-selective cation currents.

Positive_regulation (activated) of TRPA1

12) Confidence 0.69 Published 2008 Journal Eur. J. Neurosci. Section Abstract Doc Link 18364033 Disease Relevance 0.28 Pain Relevance 0.34

Pronociceptive response elicited by TRPA1 receptor activation in mice.

Positive_regulation (activation) of TRPA1 associated with analgesic

13) Confidence 0.69 Published 2008 Journal Neuroscience Section Title Doc Link 18272293 Disease Relevance 0.28 Pain Relevance 1.05

Collectively, the present findings demonstrate that the TRPA1 agonist allyl isothiocyanate produces a consistent nociceptive response when injected into the mouse paw, an effect that seems to be mediated via activation of TRPA1 receptor and dependent on the capsaicin-sensitive fibers, release of histamine by mast cells and participation of tachykinins.

Positive_regulation (activation) of TRPA1 in paw associated with nociception, qutenza and agonist

14) Confidence 0.69 Published 2008 Journal Neuroscience Section Abstract Doc Link 18272293 Disease Relevance 0.49 Pain Relevance 0.76

We further show that phospholipase C is an important signaling component for TRPA1 activation.

Positive_regulation (activation) of TRPA1

15) Confidence 0.69 Published 2004 Journal Neuron Section Abstract Doc Link 15046718 Disease Relevance 0.18 Pain Relevance 0.44

Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.

Positive_regulation (activation) of TRPA1 associated with pain and burning pain

16) Confidence 0.69 Published 2004 Journal Neuron Section Abstract Doc Link 15046718 Disease Relevance 0.28 Pain Relevance 0.46

We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1).

Positive_regulation (activate) of ANKTM1

17) Confidence 0.69 Published 2004 Journal Neuron Section Abstract Doc Link 15046718 Disease Relevance 0.17 Pain Relevance 0.43

We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1).

Positive_regulation (activate) of TRPA1

18) Confidence 0.69 Published 2004 Journal Neuron Section Abstract Doc Link 15046718 Disease Relevance 0.17 Pain Relevance 0.43

Heavy metals zinc, cadmium, and copper stimulate pulmonary sensory neurons via direct activation of TRPA1.

Positive_regulation (activation) of TRPA1 in sensory neurons

19) Confidence 0.69 Published 2010 Journal J. Appl. Physiol. Section Title Doc Link 20133428 Disease Relevance 0.16 Pain Relevance 0.30

In summary, our results suggest that activation of TRPA1 in pulmonary C-fiber sensory nerves may contribute to the respiratory toxicity induced by airway exposure to these three heavy metals.

Positive_regulation (activation) of TRPA1 in respiratory associated with c fibre and toxicity

20) Confidence 0.69 Published 2010 Journal J. Appl. Physiol. Section Abstract Doc Link 20133428 Disease Relevance 0.25 Pain Relevance 0.32

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