INT139580

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Context Info
Confidence 0.58
First Reported 2005
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 19
Total Number 22
Disease Relevance 3.80
Pain Relevance 6.26

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

Anatomy Link Frequency
sensory neurons 1
poly 1
neurons 1
DRG 1
Trpm8 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
agonist 206 100.00 Very High Very High Very High
alcohol 50 99.04 Very High Very High Very High
Inflammatory mediators 5 98.60 Very High Very High Very High
Analgesic 16 98.32 Very High Very High Very High
Potency 42 98.24 Very High Very High Very High
TRP channel 270 98.22 Very High Very High Very High
dorsal root ganglion 116 98.04 Very High Very High Very High
qutenza 379 97.80 Very High Very High Very High
antagonist 9 96.16 Very High Very High Very High
allodynia 22 95.24 Very High Very High Very High
Disease Link Frequency Relevance Heat
Nervous System Injury 8 98.88 Very High Very High Very High
INFLAMMATION 26 98.60 Very High Very High Very High
Ganglion Cysts 332 98.04 Very High Very High Very High
Nociception 90 97.40 Very High Very High Very High
Neuropathic Pain 23 95.24 Very High Very High Very High
Intractable Pain 1 88.16 High High
Toxicity 19 86.24 High High
Bladder Disease 3 83.20 Quite High
Pain 59 82.88 Quite High
Loss Of Sense Of Smell 16 82.64 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Conversely, intracellular dialysis with anti-PIP(2) antibody or with the PIP(2) scavenger, poly L-lysine, enhanced the ethanol-induced inhibition of TRPM8.
Negative_regulation (inhibition) of TRPM8 in poly
1) Confidence 0.58 Published 2007 Journal J. Neurochem. Section Abstract Doc Link 17074062 Disease Relevance 0 Pain Relevance 0.10
These findings suggest that ethanol inhibits TRPM8 by weakening the PIP(2)-TRPM8 channel interaction; a similar mechanism may contribute to the ethanol-mediated modulation of some other PIP(2)-sensitive TRP channels.
Negative_regulation (inhibits) of TRPM8 associated with trp channel
2) Confidence 0.58 Published 2007 Journal J. Neurochem. Section Abstract Doc Link 17074062 Disease Relevance 0 Pain Relevance 0.10
A previous study performed on HEK cells expressing TRPM8 showed that 8-Br-cAMP and forskolin, two PKA activators, inhibited TRPM8 activity induced by menthol [23].
Negative_regulation (inhibited) of TRPM8
3) Confidence 0.52 Published 2010 Journal Mol Pain Section Body Doc Link PMC2936373 Disease Relevance 0.14 Pain Relevance 0.05
Indeed, mice deficient in TRPM8 [8]–[10] display pronounced defects in responses to pharmacological “cooling” agents and cold at both cellular and behavioral levels, illustrating that, in mammals, this channel plays a physiologically relevant role in the detection of environmental temperature.
Negative_regulation (deficient) of TRPM8
4) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2683941 Disease Relevance 0 Pain Relevance 0.11
Ethanol has opposite effects on two members of the transient receptor potential (TRP) family of ion channels: it inhibits the cold-menthol receptor TRPM8, whereas it potentiates the activity of the heat- and capsaicin-gated vanilloid receptor TRPV1.
Negative_regulation (inhibits) of TRPM8 associated with qutenza
5) Confidence 0.43 Published 2007 Journal J. Neurochem. Section Abstract Doc Link 17074062 Disease Relevance 0 Pain Relevance 0.10
AMTB inhibits icilin-induced TRPM8 channel activation as measured in a Ca(2+) influx assay, with a pIC(50) of 6.23.
Negative_regulation (inhibits) of TRPM8
6) Confidence 0.43 Published 2008 Journal Am. J. Physiol. Renal Physiol. Section Abstract Doc Link 18562636 Disease Relevance 0.49 Pain Relevance 0.19
We found that cold allodynic response in the CCI animals was significantly attenuated by capsazepine, a blocker for both TRPM8 and TRPV1 (transient receptor potential vanilloid 1) receptors, but not by the selective TRPV1 antagonist I-RTX (5-iodoresiniferatoxin).
Negative_regulation (blocker) of TRPM8 associated with nervous system injury and antagonist
7) Confidence 0.43 Published 2007 Journal J. Neurosci. Section Abstract Doc Link 18077679 Disease Relevance 1.13 Pain Relevance 0.66
Both TRPV1 and TRPM8 currents were reduced but not eliminated by 4 hr incubation in saturating agonist concentration.
Neg (not) Negative_regulation (reduced) of TRPM8 associated with agonist
8) Confidence 0.40 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2780724 Disease Relevance 0.16 Pain Relevance 0.18
Gene expression analysis for various thermo-sensitive transient receptor potential (TRP) channels indicated marked reductions in the mRNA levels of TRPV1 (70%), TRPM8 (46%) and TRPA1 (64%), but not of TRPV2, in the DRG of capsaicin-treated rats compared with those in the control rats.
Negative_regulation (reductions) of TRPM8 in DRG associated with dorsal root ganglion and qutenza
9) Confidence 0.38 Published 2008 Journal J. Biochem. Section Abstract Doc Link 18079164 Disease Relevance 0.28 Pain Relevance 0.68
Therefore, it is unclear if the reduction of TRPM8 functions occurs in a similar manner across functionally distinct populations of neurons.
Negative_regulation (reduction) of TRPM8 in neurons
10) Confidence 0.38 Published 2010 Journal Mol Pain Section Body Doc Link PMC2936373 Disease Relevance 0.15 Pain Relevance 0.32
Desensitization of TRPM8 channels could also be induced by inflammatory mediators that activate PLC to deplete PIP2 [20].
Negative_regulation (Desensitization) of TRPM8 associated with inflammatory mediators
11) Confidence 0.38 Published 2010 Journal Mol Pain Section Body Doc Link PMC2936373 Disease Relevance 0.44 Pain Relevance 0.35
It has been suggested that Ca2+ influx through TRPM8 channels activates a Ca2+-sensitive phospholipase C and the subsequent depletion of PIP2 results in desensitization of TRPM8 channels [16,17,19].
Negative_regulation (desensitization) of TRPM8
12) Confidence 0.38 Published 2010 Journal Mol Pain Section Body Doc Link PMC2936373 Disease Relevance 0.44 Pain Relevance 0.34
Probably the most pharmacologically relevant effect described here is citral's prolonged inhibition of TRPV1–3 and TRPM8 following activation.
Negative_regulation (inhibition) of TRPM8
13) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2346451 Disease Relevance 0 Pain Relevance 0.59
The fact that some of the compounds are alcohols also constrains the potential mechanisms underlying sustained inhibition of TRPV1–3 and TRPM8.
Negative_regulation (inhibition) of TRPM8
14) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2346451 Disease Relevance 0 Pain Relevance 0.09
Sustained inhibition of TRPV1–3, and TRPM8 developed subsequent to channel activation.
Negative_regulation (inhibition) of TRPM8
15) Confidence 0.37 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2346451 Disease Relevance 0 Pain Relevance 0.38
Specifically, lowering of the intracellular pH to below 7 was able to completely block TRPM8 currents elicited by either cold or icilin, but not menthol [34].
Negative_regulation (block) of TRPM8
16) Confidence 0.31 Published 2005 Journal Mol Pain Section Body Doc Link PMC1087877 Disease Relevance 0.11 Pain Relevance 0.20
Citral inhibition of agonist-evoked TRPV1, TRPV2, TRPV3, and TRPM8 currents was essentially irreversible (Fig. 2A, D).
Negative_regulation (inhibition) of TRPM8 associated with agonist
17) Confidence 0.27 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2346451 Disease Relevance 0 Pain Relevance 0.08
Citral is both an activator and inhibitor of TRPV1, TRPV3, TRPM8, and TRPA1, but these opposing actions cannot be attributed to the cis and trans enantiomers.
Negative_regulation (inhibitor) of TRPM8
18) Confidence 0.27 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2346451 Disease Relevance 0 Pain Relevance 0.38
Citral inhibition of TRPV1–4, TRPM8, and TRPA1
Negative_regulation (inhibition) of TRPM8
19) Confidence 0.27 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2346451 Disease Relevance 0 Pain Relevance 0.43
Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1.
Negative_regulation (inhibition) of TRPM8 in sensory neurons associated with trp channel
20) Confidence 0.27 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2346451 Disease Relevance 0.30 Pain Relevance 0.33

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