INT87687

Context Info Confidence 0.70 First Reported 2000 Last Reported 2011 Negated 18 Speculated 10 Reported most in Abstract Documents 409 Total Number 430 Disease Relevance 210.24 Pain Relevance 257.59

cytosol (Trpv1) transport (Trpv1) plasma membrane (Trpv1) transmembrane transport (Trpv1) lipid metabolic process (Trpv1)

Anatomy Link Frequency neurons 30 body 12 sensory neurons 12 nociceptors 11 nerve 11 Trpv1 (Mus musculus)

Pain Link Frequency Relevance Heat qutenza 9148 100.00 Pain 4358 100.00 Inflammation 3623 100.00 dorsal root ganglion 3076 100.00 agonist 1817 100.00 nociceptor 1642 100.00 Hyperalgesia 1604 100.00 c fibre 613 100.00 TRP channel 503 100.00 Kinase C 436 100.00

Disease Link Frequency Relevance Heat Ganglion Cysts 4999 100.00 Pain 4672 100.00 INFLAMMATION 3842 100.00 Hyperalgesia 2910 100.00 Nociception 2582 100.00 Cv Unclassified Under Development 131 99.98 Targeted Disruption 1721 99.96 Pruritus 372 99.92 Reperfusion Injury 4 99.90 Hypersensitivity 346 99.84

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Endogenous inflammatory mediators also promote activation of TRPV1.

Positive_regulation (activation) of TRPV1 associated with inflammatory mediators

1) Confidence 0.70 Published 2006 Journal Recent patents on CNS drug discovery Section Abstract Doc Link 18221192 Disease Relevance 0.70 Pain Relevance 0.93

Activation of TRPV1 results in release of neurotransmitters from peripheral and central nerve terminals, resulting in pain and inflammation.

Positive_regulation (Activation) of TRPV1 in nerve associated with pain, neurotransmitter and inflammation

2) Confidence 0.70 Published 2006 Journal Recent patents on CNS drug discovery Section Abstract Doc Link 18221192 Disease Relevance 0.65 Pain Relevance 0.77

Recent advances in pain biology such as the cloning of the transient receptor potential vanilloid 1 (TRPV1) ion channel, exploration of the molecular mechanisms leading to TRPV1 activation and the production of a TRPV1 mutant mouse have defined its role as an integrator of noxious thermal and chemical stimuli.

Positive_regulation (activation) of TRPV1 associated with pain

3) Confidence 0.70 Published 2009 Journal Respir Physiol Neurobiol Section Abstract Doc Link 19450765 Disease Relevance 0.91 Pain Relevance 0.48

Researchers have confirmed that TRPV1 is activated by multiple nociceptive stimuli including protons, noxious heat and some lipids both in the heterologous expression system using the cloned channels and native sensory neurons.

Positive_regulation (activated) of TRPV1 in sensory neurons associated with nociception

4) Confidence 0.70 Published 2008 Journal Brain Nerve Section Abstract Doc Link 18516971 Disease Relevance 0.10 Pain Relevance 0.29

To elucidate the mechanisms underlying the non-pungency of capsiate, we investigated whether capsiate activates the cloned capsaicin receptor, TRPV1 (VR1).

Spec (whether) Positive_regulation (activates) of TRPV1 associated with qutenza

5) Confidence 0.70 Published 2003 Journal Neuropharmacology Section Abstract Doc Link 12726827 Disease Relevance 0.16 Pain Relevance 0.58

To elucidate the mechanisms underlying the non-pungency of capsiate, we investigated whether capsiate activates the cloned capsaicin receptor, TRPV1 (VR1).

Spec (whether) Positive_regulation (activates) of capsaicin receptor associated with qutenza

6) Confidence 0.70 Published 2003 Journal Neuropharmacology Section Abstract Doc Link 12726827 Disease Relevance 0.16 Pain Relevance 0.58

In patch-clamp experiments, capsiate was found to activate TRPV1 expressed transiently in HEK293 cells with a similar potency as capsaicin.

Positive_regulation (activate) of TRPV1 associated with qutenza and potency

7) Confidence 0.70 Published 2003 Journal Neuropharmacology Section Abstract Doc Link 12726827 Disease Relevance 0.17 Pain Relevance 0.60

Electrophysiological recordings demonstrate a novel form of ion channel modulation by which extracellular Na+, Mg2+, and Ca2+ ions sensitize and activate the capsaicin receptor, TRPV1.

Positive_regulation (activate) of TRPV1 associated with qutenza

8) Confidence 0.70 Published 2005 Journal J. Neurosci. Section Abstract Doc Link 15917451 Disease Relevance 0.16 Pain Relevance 0.50

The cloned capsaicin receptor (TRPV1) is a nonselective cation channel with six transmembrane domains, and is activated not only by capsaicin but also by noxious heat (> 43 degrees C) or protons (acidification), both of which cause pain in vivo.

Positive_regulation (activated) of capsaicin receptor associated with pain and qutenza

9) Confidence 0.70 Published 2003 Journal Nihon Shinkei Seishin Yakurigaku Zasshi Section Abstract Doc Link 12884755 Disease Relevance 0.58 Pain Relevance 1.00

In the presence of ATP or bradykinin, the temperature threshold for VR1 activation was reduced from 42 degrees C to 30-35 degrees C, such that normally non-painful normal body temperatures were capable of activating TRPV1, thereby leading to the sensation of pain.

Positive_regulation (activation) of VR1 in body associated with pain and bradykinin

10) Confidence 0.70 Published 2003 Journal Nihon Shinkei Seishin Yakurigaku Zasshi Section Abstract Doc Link 12884755 Disease Relevance 0.64 Pain Relevance 1.32

The cloned capsaicin receptor (TRPV1) is a nonselective cation channel with six transmembrane domains, and is activated not only by capsaicin but also by noxious heat (> 43 degrees C) or protons (acidification), both of which cause pain in vivo.

Positive_regulation (activated) of TRPV1 associated with pain and qutenza

11) Confidence 0.70 Published 2003 Journal Nihon Shinkei Seishin Yakurigaku Zasshi Section Abstract Doc Link 12884755 Disease Relevance 0.58 Pain Relevance 1.00

In addition, sustained morphine increased flinching and plasma extravasation after peripheral stimulation with capsaicin, suggesting an increase in TRPV1 receptor function in the periphery in morphine-treated animals.

Positive_regulation (increase) of TRPV1 in plasma associated with qutenza and morphine

12) Confidence 0.70 Published 2009 Journal J Pain Section Abstract Doc Link 18774343 Disease Relevance 0.94 Pain Relevance 2.06

The release of these neuropeptides from primary afferent (sensory) nerve endings to various stimuli is considered to be induced by activation of the capsaicin (vanilloid) receptor (VR1).

Positive_regulation (activation) of VR1 in nerve associated with qutenza and neuropeptide

13) Confidence 0.70 Published 2003 Journal Neuropeptides Section Abstract Doc Link 12906843 Disease Relevance 0.09 Pain Relevance 0.40

In conclusion, based on the extent of SP and VR1 co-localization in nasal afferent neurons, the present study suggests that, following a peripheral activation of the VR1 receptor on SP afferents, there could be a triggering of SP-mediated phenomena, including those related to inflammation, such as plasma extravasation.

Positive_regulation (activation) of VR1 in plasma associated with inflammation

14) Confidence 0.70 Published 2003 Journal Neuropeptides Section Abstract Doc Link 12906843 Disease Relevance 0.15 Pain Relevance 0.43

It has been reported that extracellular ATP potentiates the TRPV1 currents evoked by capsaicin or protons and reduces the temperature threshold for its activation through metabotropic P2Y receptors in a PKC-dependent pathway, suggesting that TRPV1 activation could trigger the sensation of pain at normal body temperature in the presence of ATP.

Positive_regulation (activation) of TRPV1 in body associated with pain and qutenza

15) Confidence 0.70 Published 2003 Journal J. Neurosci. Section Abstract Doc Link 12853424 Disease Relevance 0.50 Pain Relevance 0.57

The transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel localized on a subset of primary sensory neurons and can be activated by a wide range of stimuli.

Positive_regulation (activated) of TRPV1 in primary sensory neurons

16) Confidence 0.70 Published 2005 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 15831443 Disease Relevance 0.24 Pain Relevance 0.08

In the presence of ATP, the temperature threshold for TRPV1 activation was reduced from 42 degrees C to 35 degrees C, such that normal body temperature could activate TRPV1.

Positive_regulation (activate) of TRPV1 in body

17) Confidence 0.70 Published 2004 Journal Novartis Found. Symp. Section Abstract Doc Link 15469041 Disease Relevance 0.24 Pain Relevance 0.50

In the presence of ATP, the temperature threshold for TRPV1 activation was reduced from 42 degrees C to 35 degrees C, such that normal body temperature could activate TRPV1.

Positive_regulation (activation) of TRPV1 in body

18) Confidence 0.70 Published 2004 Journal Novartis Found. Symp. Section Abstract Doc Link 15469041 Disease Relevance 0.25 Pain Relevance 0.50

The capsaicin receptor TRPV1 (also known as the vanilloid receptor VR1) is a non-selective cation channel and is activated not only by capsaicin but also by noxious heat or protons.

Positive_regulation (activated) of TRPV1 associated with qutenza

19) Confidence 0.70 Published 2004 Journal Novartis Found. Symp. Section Abstract Doc Link 15469041 Disease Relevance 0.28 Pain Relevance 0.40

Capsazepine and Hoe 140 did not further attenuate the already reduced writhing responses of capsaicin-treated mice, suggesting that the acids stimulate the VR1 and the bradykinin B2 receptor in the pathway comprising sensory afferent C-fibers.

Positive_regulation (stimulate) of VR1 associated with c fibre, qutenza and b2 receptor

20) Confidence 0.70 Published 2001 Journal Life Sci. Section Abstract Doc Link 11720094 Disease Relevance 0.22 Pain Relevance 1.10

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