INT134379

Context Info Confidence 0.48 First Reported 2006 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 13 Total Number 14 Disease Relevance 7.16 Pain Relevance 7.27

transmembrane transport (Trpa1)

Anatomy Link Frequency spinal nerve 2 dendrites 1 dorsal root ganglia 1 Trpa1 (Rattus norvegicus)

Pain Link Frequency Relevance Heat agonist 128 100.00 Eae 49 100.00 Cold hyperalgesia 8 100.00 Neuropathic pain 41 99.64 Pain 101 99.52 cannabis 1 98.76 c fibre 78 97.12 nociceptor 54 94.60 Cancer pain 41 94.40 bradykinin 14 92.96

Disease Link Frequency Relevance Heat Hyperalgesia 29 100.00 Targeted Disruption 11 99.82 Neuropathic Pain 89 99.64 Pain 111 99.52 Bladder Cancer 5 98.56 Hypersensitivity 75 97.84 Cancer 81 97.00 Nociception 79 94.96 Bone Cancer 28 94.80 Cancer Pain 12 93.88

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Immunoreactivity for TRPA1 was also occasionally observed in postsynaptic dendrites.

TRPA1 Binding (Immunoreactivity) of in dendrites

1) Confidence 0.48 Published 2010 Journal J. Comp. Neurol. Section Abstract Doc Link 20034057 Disease Relevance 0.38 Pain Relevance 0.38

Next, a possible role for TRPA1 in spinal nerve ligation induced neuropathic pain was investigated using HC-030031.

TRPA1 Binding (ligation) of in spinal nerve associated with eae and neuropathic pain

2) Confidence 0.48 Published 2008 Journal Mol Pain Section Body Doc Link PMC2584039 Disease Relevance 0.49 Pain Relevance 0.38

Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats.

TRPA1 Binding (ligation) of in spinal nerve associated with targeted disruption, hyperalgesia, cold hyperalgesia and eae

3) Confidence 0.47 Published 2006 Journal Exp. Neurol. Section Title Doc Link 16546170 Disease Relevance 1.21 Pain Relevance 0.83

Given that there are functional interactions between TRPA1 and TRPV1 in vitro and in vivo (Bandell et al., 2004; Bautista et al., 2006; Jeske et al., 2006; Akopian et al., 2007; Ruparel et al., 2007), it is interesting to speculate that a TRPA1/TRPV1 interaction may be responsible for the lower heat thresholds seen in the polymodal C-fibres that express TRPA1 in comparison to those that do not.

TRPA1 Binding (interaction) of associated with c fibre

4) Confidence 0.47 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2658012 Disease Relevance 0.61 Pain Relevance 0.58

Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.

TRPA1 Binding (interacting) of associated with pain, cannabis and cancer

5) Confidence 0.44 Published 2008 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 18354058 Disease Relevance 0.19 Pain Relevance 0.30

In addition, it was shown that TRPA1 can be gated through another mode of activation involving its N-terminal EF-hand calcium binding domain.

TRPA1 Binding (gated) of

6) Confidence 0.37 Published 2008 Journal Mol Pain Section Body Doc Link PMC2584039 Disease Relevance 0.68 Pain Relevance 0.45

There are known interactions between TRPV1 and TRPA1 (Bandell et al., 2004; Bautista et al., 2006; Jeske et al., 2006; Akopian et al., 2007; Ruparel et al., 2008), and cinnamaldehyde-evoked heat sensitisation is initiated by TRPA1 but affected by TRPV1 (Bandell et al., 2004).

TRPA1 Binding (interactions) of

7) Confidence 0.37 Published 2010 Journal Neuroscience Section Body Doc Link PMC2860241 Disease Relevance 0 Pain Relevance 0.74

The functional interaction between B2R and TRPA1, as well as the modulation mechanism, was also observed in rat dorsal root ganglia neurons.

TRPA1 Binding (interaction) of in dorsal root ganglia

8) Confidence 0.37 Published 2008 Journal Brain Section Abstract Doc Link 18356188 Disease Relevance 0.55 Pain Relevance 0.78

Given that there are functional interactions between TRPA1 and TRPV1 in vitro and in vivo (Bandell et al., 2004; Bautista et al., 2006; Jeske et al., 2006; Akopian et al., 2007; Ruparel et al., 2007), it is interesting to speculate that a TRPA1/TRPV1 interaction may be responsible for the lower heat thresholds seen in the polymodal C-fibres that express TRPA1 in comparison to those that do not.

TRPA1 Binding (interactions) of associated with c fibre

9) Confidence 0.36 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2658012 Disease Relevance 0.62 Pain Relevance 0.62

Aldehydes are known to covalently bind to TRPA1, so sections were postfixed with Zamboni's fixative rather than 4% paraformaldehyde, as preliminary data suggested that paraformaldehyde fixation resulted in poor TRPA1 staining.

TRPA1 Binding (bind) of

10) Confidence 0.36 Published 2008 Journal The European Journal of Neuroscience Section Body Doc Link PMC2658012 Disease Relevance 0.27 Pain Relevance 0.16

These results suggest that activations of TRPA1 receptors by cyclooxygenase metabolites and P2X receptors by ATP are both necessary for the ROS-mediated stimulation of CSLVA fibers by CS in rats.

TRPA1 Binding (receptors) of

11) Confidence 0.33 Published 2010 Journal J. Appl. Physiol. Section Abstract Doc Link 20167675 Disease Relevance 0.06 Pain Relevance 0.17

We have shown that citral acts as a partial agonist of TRPV1, TRPV3, TRPM8, and TRPA1.

TRPA1 Spec (partial) Binding (agonist) of associated with agonist

12) Confidence 0.25 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2346451 Disease Relevance 0 Pain Relevance 0.54

Formaldehyde induces pain responses via TRPV1 and/or TRPA1

TRPA1 Binding (/) of associated with pain

13) Confidence 0.23 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858155 Disease Relevance 1.75 Pain Relevance 0.97

Menthol has been found to interact with TRPA1 in heterologous expression systems that express mouse and human TRPA1 [29,31], raising a possibility that menthol responses in some cells may be mediated by TRPA1 in our study.

TRPA1 Binding (interact) of

14) Confidence 0.19 Published 2010 Journal Mol Pain Section Body Doc Link PMC2936373 Disease Relevance 0.34 Pain Relevance 0.38

General Comments

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