INT119098

Context Info Confidence 0.68 First Reported 2004 Last Reported 2008 Negated 0 Speculated 0 Reported most in Abstract Documents 20 Total Number 25 Disease Relevance 10.12 Pain Relevance 9.01

Anatomy Link Frequency nerve 3 peripheral nerves 2 keratinocytes 2 embryonic kidney 2 sensory neurons 1 TRPV3 (Homo sapiens)

Pain Link Frequency Relevance Heat Pain 503 100.00 TRP channel 118 100.00 qutenza 363 99.98 dorsal root ganglion 192 99.28 Spinal cord 102 98.72 Nerve growth factor 137 96.92 Analgesic 44 96.44 nociceptor 44 94.80 Dorsal horn 12 94.68 agonist 130 93.04

Disease Link Frequency Relevance Heat Pain 477 100.00 Nervous System Injury 58 99.88 Increased Venous Pressure Under Development 37 99.84 Injury 120 99.72 Ganglion Cysts 210 99.28 Neuropathic Pain 94 94.12 Diabetes Mellitus 150 93.64 INFLAMMATION 90 92.80 Diabetic Neuropathy 48 92.56 Macromastia 20 90.48

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs.

Positive_regulation (activators) of TRPV3

1) Confidence 0.68 Published 2006 Journal Mol. Cell. Neurosci. Section Abstract Doc Link 16829128 Disease Relevance 0.08 Pain Relevance 0.18

However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3.

Positive_regulation (activates) of TRPV3

2) Confidence 0.68 Published 2006 Journal Mol. Cell. Neurosci. Section Abstract Doc Link 16829128 Disease Relevance 0.09 Pain Relevance 0.18

In this study we have shown that both TRPV3 and TRPV1 are increased in peripheral nerve proximal to the site of injury in accord with our previous study of human DRG, [4].

Positive_regulation (increased) of TRPV3 in peripheral nerve associated with dorsal root ganglion and injury

3) Confidence 0.64 Published 2007 Journal BMC Neurol Section Body Doc Link PMC1892784 Disease Relevance 0.68 Pain Relevance 0.18

Here, we demonstrate that 2-aminoethoxydiphenyl borate (2-APB), a compound used to inhibit store-operated Ca2+ channels and IP3 receptors, produces robust activation of recombinant TRPV3 in human embryonic kidney 293 cells with an EC50 of 28 microm. 2-APB also sensitizes TRPV3 to activation by heat, even at subthreshold concentrations.

Positive_regulation (activation) of TRPV3 in embryonic kidney

4) Confidence 0.64 Published 2004 Journal J. Neurosci. Section Abstract Doc Link 15175387 Disease Relevance 0.09 Pain Relevance 0.09

However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3.

Positive_regulation (activates) of TRPV3

5) Confidence 0.49 Published 2006 Journal Mol. Cell. Neurosci. Section Abstract Doc Link 16829128 Disease Relevance 0.09 Pain Relevance 0.18

In inside-out membrane patches from TRPV3-expressing cells, 2-APB increases the open probability of TRPV3.

Positive_regulation (increases) of TRPV3

6) Confidence 0.46 Published 2004 Journal J. Neurosci. Section Abstract Doc Link 15175387 Disease Relevance 0.08 Pain Relevance 0.08

Here, we demonstrate that 2-aminoethoxydiphenyl borate (2-APB), a compound used to inhibit store-operated Ca2+ channels and IP3 receptors, produces robust activation of recombinant TRPV3 in human embryonic kidney 293 cells with an EC50 of 28 microm. 2-APB also sensitizes TRPV3 to activation by heat, even at subthreshold concentrations.

Positive_regulation (sensitizes) of TRPV3 in embryonic kidney

7) Confidence 0.46 Published 2004 Journal J. Neurosci. Section Abstract Doc Link 15175387 Disease Relevance 0.09 Pain Relevance 0.08

TRPV1 and TRPV3 were significantly increased in injured brachial plexus nerves, and TRPV1 in hypersensitive skin after nerve repair, whilst TRPV4 was unchanged.

Positive_regulation (increased) of TRPV3 in nerve

8) Confidence 0.43 Published 2007 Journal BMC Neurol Section Abstract Doc Link PMC1892784 Disease Relevance 1.32 Pain Relevance 0.48

We previously reported that human dorsal root ganglion (DRG) sensory neurons co-expressed TRPV1 and TRPV3, and that these were increased in injured human DRG.

Positive_regulation (increased) of TRPV3 in sensory neurons associated with ganglion cysts and dorsal root ganglion

9) Confidence 0.43 Published 2007 Journal BMC Neurol Section Abstract Doc Link PMC1892784 Disease Relevance 0.80 Pain Relevance 0.36

The accumulation of TRPV1 and TRPV3 in peripheral nerves after injury, in spared axons, matches our previously reported changes in avulsed DRG.

Positive_regulation (accumulation) of TRPV3 in peripheral nerves associated with dorsal root ganglion and injury

10) Confidence 0.43 Published 2007 Journal BMC Neurol Section Abstract Doc Link PMC1892784 Disease Relevance 1.14 Pain Relevance 0.63

Short duration (1h) exposure of dissociated sensory neurons to NTFs increased numbers of TRPV1-positive neurons, but not of TRPV3, Nav 1.8 and IK1 and the morphological size-distribution remained similar to intact post-mortem DRG neurons.

Positive_regulation (increased) of TRPV3 in neurons

11) Confidence 0.42 Published 2006 Journal Neurosci. Lett. Section Abstract Doc Link 16481104 Disease Relevance 0 Pain Relevance 0.44

Both TRPV3 and TRPV4 were significantly increased in keratinocytes in breast pain tissues; TRPV3, median [range] – no pain group, n = 6, 0.75 [0–2]; pain group, n = 11, 2 [1-3], p = 0.008; TRPV4, median [range] – no pain group, n = 6, [0–1]; pain group, n = 11, 1 [0.5–2], p = 0.014).

Positive_regulation (increased) of TRPV3 in keratinocytes associated with pain

12) Confidence 0.41 Published 2005 Journal BMC Womens Health Section Abstract Doc Link PMC554997 Disease Relevance 1.00 Pain Relevance 1.44

The recently discovered vanilloid thermoreceptors TRPV3 and TRPV4, which are also expressed by sensory fibres and activated by warmth, were also studied [17,18].

Positive_regulation (activated) of TRPV3 associated with increased venous pressure under development

13) Confidence 0.41 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC554997 Disease Relevance 1.08 Pain Relevance 0.98

It may be speculated that increased TRPV3 and TRPV4 in observed in keratinocytes may alter keratinocyte expression of NGF and other molecules, which in turn may sensitise nociceptors.

Positive_regulation (increased) of TRPV3 in nociceptors associated with nerve growth factor and nociceptor

14) Confidence 0.41 Published 2005 Journal BMC Womens Health Section Body Doc Link PMC554997 Disease Relevance 0.62 Pain Relevance 0.97

After nerve injury both TRPV3 (Fig. 3D) and TRPV1 (Fig 3B) – immunoreactive fibres appeared to be increased in both number and intensity but there was no change for TRPV4 (Fig 3F).

Positive_regulation (increased) of TRPV3 in nerve associated with nervous system injury

15) Confidence 0.38 Published 2007 Journal BMC Neurol Section Body Doc Link PMC1892784 Disease Relevance 0.51 Pain Relevance 0.07

Both TRPV3 and TRPV4 were significantly increased in keratinocytes in breast pain tissues; TRPV3, median [range] – no pain group, n = 6, 0.75 [0–2]; pain group, n = 11, 2 [1-3], p = 0.008; TRPV4, median [range] – no pain group, n = 6, [0–1]; pain group, n = 11, 1 [0.5–2], p = 0.014).

Positive_regulation (increased) of TRPV3 in keratinocytes associated with pain

16) Confidence 0.35 Published 2005 Journal BMC Womens Health Section Abstract Doc Link PMC554997 Disease Relevance 1.00 Pain Relevance 1.43

Immunoreactivities for both TRPV3 and TRPV1 (% area immunoreactive nerve) were significantly increased after injury [median (range) TRPV3: control 5.25 (0.9–6.9), injured 15.0 (5.8–20.1) p < 0.001; TRPV1; control 17.6 (12.1–20.6), injured 24.1 (18.6–32.0) p < 0.001; Fig 4A,C] and although image analysis of the nerve marker peripherin showed no change, % ratios of TRPV3 or TRPV1 to peripherin were significantly increased also [median (range) % TRPV3:PPN, control 17.6 (2.9–19.4), injured 50.1 (25.0–67.9), p < 0.001; % TRPV1:PPN, control 55.7 (31.9–82.3), injured 89.8 (63.4–100.0), p < 0.001; Fig 4B,D].

Positive_regulation (increased) of TRPV3 in nerve associated with injury

17) Confidence 0.19 Published 2007 Journal BMC Neurol Section Body Doc Link PMC1892784 Disease Relevance 0.47 Pain Relevance 0

However, this compound also activates other TRP channels, including TRPV1, TRPV3 and TRPA1.

Positive_regulation (activates) of TRPV3 associated with trp channel

18) Confidence 0.15 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645550 Disease Relevance 0 Pain Relevance 0.05

The natural compound camphor (Cinnamomum camphora tree, (see above)), which modulates sensations of warmth in humans [29], proved to be an activator of TRPV3 [73].

Positive_regulation (activator) of TRPV3 associated with increased venous pressure under development

19) Confidence 0.15 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645550 Disease Relevance 0.22 Pain Relevance 0.16

Vanillin, the active ingredient of vanilla (Vanilla planifolia), weakly activates TRPV3, whereas the more potent synthetic vanillin much more potently activates TRPV3.

Positive_regulation (activates) of TRPV3

20) Confidence 0.15 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2645550 Disease Relevance 0.17 Pain Relevance 0.07

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