INT134596

Context Info Confidence 0.62 First Reported 2006 Last Reported 2010 Negated 3 Speculated 1 Reported most in Body Documents 32 Total Number 33 Disease Relevance 18.78 Pain Relevance 17.02

transport (Trpa1) transmembrane transport (Trpa1)

Anatomy Link Frequency neurons 7 nerve 2 nociceptors 2 sensory neurons 1 tear 1 Trpa1 (Mus musculus)

Pain Link Frequency Relevance Heat antagonist 69 100.00 bradykinin 59 99.98 agonist 105 99.96 IPN 8 99.92 Inflammation 174 99.76 calcitonin gene related peptide 33 99.76 nociceptor 213 99.68 unmyelinated 27 99.44 induced neuropathy 80 99.16 dorsal root ganglion 337 99.12

Disease Link Frequency Relevance Heat Hypersensitivity 205 99.92 Inflammatory Pain 28 99.92 INFLAMMATION 172 99.76 Neuropathic Pain 599 99.16 Ganglion Cysts 635 99.12 Sprains And Strains 140 99.04 Pain 521 98.96 Nociception 227 98.70 Nervous System Injury 204 98.16 Hyperalgesia 388 97.16

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Given the broad range of molecules that can affect TRPA1 activity, a variety of possibilities, including local increases in intracellular calcium concentration [19,32,33], could explain how TRPA1 responds to activity of a mechanoreceptor.

Regulation (affect) of TRPA1

1) Confidence 0.62 Published 2009 Journal Mol Pain Section Body Doc Link PMC2681449 Disease Relevance 0 Pain Relevance 0.22

In this study, we selected miogadial (MD), miogatrial (MT), and polygodial (PG) from the terpenoids with an alpha,beta-unsaturated 1,4-dialdehyde moiety and examined the effects of these 3 terpenoids on TRPA1 or TRPV1.

Spec (examined) Regulation (effects) of TRPA1

2) Confidence 0.61 Published 2009 Journal Life Sci. Section Abstract Doc Link 19409911 Disease Relevance 0.09 Pain Relevance 0.04

In order to study the regulation of TRPA1 mRNA in another model, we also examined its expression during inflammatory pain.

Regulation (regulation) of TRPA1 mRNA associated with eae

3) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2753652 Disease Relevance 0.55 Pain Relevance 0.40

However, we and others [39] detected no up-regulation of TRPA1 in either injured or uninjured neurons after nerve injury, but were still able to measure robust cold allodynia.

Regulation (regulation) of TRPA1 in nerve associated with nervous system injury and allodynia

4) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2753652 Disease Relevance 0.74 Pain Relevance 0.35

Cisplatin induced significant up-regulation of TRPV1 and TRPA1 mRNA (3-fold) in cultured DRG neurons at 6 h (Figure 2A and 2C).

Regulation (regulation) of TRPA1 mRNA in neurons associated with dorsal root ganglion

5) Confidence 0.58 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.47 Pain Relevance 0.27

We also illustrate that up-regulation of TRPV1 and TRPA1 mRNA reflects increases in TRPV1 and TRPA1 responsiveness in the nociceptors that contribute to the molecular mechanisms of the thermal hyperalgesia and mechanical allodynia observed in cisplatin-treated mice.

Regulation (regulation) of TRPA1 mRNA in nociceptors associated with allodynia, thermal hyperalgesia and nociceptor

6) Confidence 0.58 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.86 Pain Relevance 0.67

While our results illustrate that changes in the relative levels of TRPV1 and TRPA1 mRNA in vivo were similar to those observed in vitro (Figure 2), the increase in TRPM8 mRNA that was observed in oxaliplatin-treated mice was less than that seen in vitro.

Regulation (changes) of TRPA1 mRNA

7) Confidence 0.58 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.78 Pain Relevance 0.61

Overall, the regulation of Trpa1 did not correlate significantly with any of the pain parameters considered.

Regulation (regulation) of Trpa1 associated with pain

8) Confidence 0.57 Published 2009 Journal Mol Pain Section Body Doc Link PMC2649910 Disease Relevance 1.09 Pain Relevance 0.31

More importantly, we show that the shRNA and miRNA sequences targeting trpV1 have no effect on the expression levels of the closely related trpA1 gene or stat1, which is another gene involved in the INF response, when expressed in neurons in vivo.

Neg (no) Regulation (effect) of trpA1 in neurons

9) Confidence 0.50 Published 2008 Journal Nucleic Acids Research Section Body Doc Link PMC2504301 Disease Relevance 0.28 Pain Relevance 0.11

TRPA1 antagonist alters mechanically-evoked firing in mouse C fibers, but not in TRPA1-deficient littermates

Regulation (firing) of TRPA1 associated with antagonist

10) Confidence 0.45 Published 2009 Journal Mol Pain Section Body Doc Link PMC2681449 Disease Relevance 0 Pain Relevance 0.67

The effects of TRPV4 and TRPA1 agonists on [Ca(2+)](i), pain and inflammation were markedly diminished or abolished in trpv4 and trpa1 knockout mice.

Regulation (effects) of TRPA1 associated with targeted disruption, pain, inflammation and agonist

11) Confidence 0.45 Published 2010 Journal Am. J. Physiol. Gastrointest. Liver Physiol. Section Abstract Doc Link 20539005 Disease Relevance 1.52 Pain Relevance 1.40

The present study focused on the effects of TRPA1 activation on contractile responses in isolated mouse intestine preparations.

Regulation (effects) of TRPA1 in intestine

12) Confidence 0.45 Published 2007 Journal Eur. J. Pharmacol. Section Abstract Doc Link 17825279 Disease Relevance 0 Pain Relevance 0.13

Menthol-induced cold hypersensitivity is dependent on TRPA1 but not TRPM8

Neg (not) Regulation (dependent) of TRPA1 associated with hypersensitivity

13) Confidence 0.44 Published 2010 Journal Mol Pain Section Body Doc Link PMC2822744 Disease Relevance 0.84 Pain Relevance 0.13

However, using the same model, another study reported down-regulation of both TRPA1 and TRPM8 in injured neurons and no change in expression in the uninjured ganglion [39].

Regulation (regulation) of TRPA1 in neurons associated with ganglion cysts

14) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2753652 Disease Relevance 0.95 Pain Relevance 0.64

Intriguingly the reduction in TRPA1 expression was seen exclusively in the IB4-positive neurons, with no change in the number of TRPA1 plus CGRP or TRPA1 plus NF200 positive cells (Table 2).

Neg (no) Regulation (change) of TRPA1 in IB4 associated with calcitonin gene related peptide

15) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2753652 Disease Relevance 0.48 Pain Relevance 0.41

First, we demonstrate that treatment with platinum drugs results in the up-regulation of TRPV1, TRPA1, and TRPM8 mRNA in cultured dorsal root ganglion (DRG) neurons and that a similar up-regulation occurs with TRPV1 and TRPA1 following in vivo treatment with cisplatin although cisplatin-treated mice had no change in the proportion of TRPV1-immunopositive TG neurons.

Regulation (regulation) of TRPA1 in neurons associated with ganglion cysts and dorsal root ganglion

16) Confidence 0.42 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.90 Pain Relevance 0.60

Cisplatin and oxaliplatin induced up-regulation of TRPV1, TRPM8 and TRPA1 mRNA in vitro

Regulation (regulation) of TRPA1 mRNA

17) Confidence 0.42 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.98 Pain Relevance 0.64

Oxaliplatin treatment results in up-regulation of only TRPA1 in vivo.

Regulation (regulation) of TRPA1

18) Confidence 0.42 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.84 Pain Relevance 0.67

The most parsimonious explanation of these results is that NO's behavioral consequences is due to direct activation of these thermoTRPs; however, it cannot be ruled out that NO also targets TRPV1 and TRPA1 in vivo through indirect mechanisms.

Regulation (targets) of TRPA1

19) Confidence 0.40 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2764051 Disease Relevance 0.42 Pain Relevance 0.37

Regardless, BH4-induced intracellular calcium increase in primary cultured DRG neurons is partly dependent on NOS [19], and essentially dependent on TRPV1 and TRPA1 (Fig. 5).

Regulation (dependent) of TRPA1 in neurons

20) Confidence 0.40 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2764051 Disease Relevance 0.59 Pain Relevance 0.33

General Comments

This test has worked.