INT111416

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Context Info
Confidence 0.70
First Reported 2003
Last Reported 2010
Negated 2
Speculated 0
Reported most in Body
Documents 65
Total Number 66
Disease Relevance 14.62
Pain Relevance 17.13

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
neurons 6
sensory neurons 3
nerves 2
dorsal root ganglia 2
autonomic 1
Trpm8 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
qutenza 838 100.00 Very High Very High Very High
TRP channel 362 100.00 Very High Very High Very High
nociceptor 85 100.00 Very High Very High Very High
agonist 579 99.98 Very High Very High Very High
c fibre 43 99.96 Very High Very High Very High
Thermal hyperalgesia 2 99.86 Very High Very High Very High
Pain 491 99.80 Very High Very High Very High
addiction 32 99.78 Very High Very High Very High
antagonist 80 99.60 Very High Very High Very High
Lasting pain 24 99.32 Very High Very High Very High
Disease Link Frequency Relevance Heat
Hyperalgesia 26 99.86 Very High Very High Very High
Pain 448 99.80 Very High Very High Very High
Increased Venous Pressure Under Development 53 99.72 Very High Very High Very High
Ganglion Cysts 720 99.00 Very High Very High Very High
Nociception 256 98.76 Very High Very High Very High
Nervous System Injury 17 98.48 Very High Very High Very High
Frailty 3 97.56 Very High Very High Very High
Toxicity 124 97.44 Very High Very High Very High
Bladder Disease 46 96.80 Very High Very High Very High
Overactive Bladder 45 96.20 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
RESULTS: We show that activation of TRPM8 in a subpopulation of sensory afferents (by either cutaneous or intrathecal application of specific pharmacological agents or by modest cooling) elicits analgesia in neuropathic and other chronic pain models in rats, thereby inhibiting the characteristic sensitization of dorsal-horn neurons and behavioral-reflex facilitation.
Positive_regulation (activation) of TRPM8 in horn
1) Confidence 0.70 Published 2006 Journal Curr. Biol. Section Body Doc Link 16920620 Disease Relevance 0.10 Pain Relevance 0
The activation of the TRPM8 channel, a member of the large class of TRP ion channels, has been reported to be involved in overactive bladder and painful bladder syndrome, although an endogenous activator has not been identified.
Positive_regulation (activation) of TRPM8 in bladder associated with pain, overactive bladder and bladder disease
2) Confidence 0.70 Published 2008 Journal Am. J. Physiol. Renal Physiol. Section Abstract Doc Link 18562636 Disease Relevance 0.40 Pain Relevance 0.17
The effects of this phospholipid on TRPM8 and TRPV1 are also functionally opposite: PIP(2) is necessary for the activation of TRPM8 but it constitutively inhibits TRPV1.
Positive_regulation (activation) of TRPM8
3) Confidence 0.69 Published 2007 Journal J. Neurochem. Section Abstract Doc Link 17074062 Disease Relevance 0 Pain Relevance 0.09
Since there was little activation of TRPM8 receptors at temperatures above 24°C when cells were near resting membrane potential [28], a basal temperature of 26°C was used in our experiments.
Neg (little) Positive_regulation (activation) of TRPM8
4) Confidence 0.68 Published 2008 Journal Mol Pain Section Body Doc Link PMC2430548 Disease Relevance 0.62 Pain Relevance 0.07
These results would suggest that cooling-induced contraction of the rat fundus is mediated by activation of TRPM8 receptors via a mechanism involving activation of Rho-kinase.
Positive_regulation (activation) of TRPM8 in fundus
5) Confidence 0.67 Published 2005 Journal Clin. Exp. Pharmacol. Physiol. Section Abstract Doc Link 16173944 Disease Relevance 0 Pain Relevance 0.08
The finding that successful completion of the operant task was hindered by menthol in the presence of 10 but not in the presence of 24°C provides evidence that activation of the TRPM8 receptor elicits sensations of cold pain.
Positive_regulation (activation) of TRPM8 receptor associated with pain
6) Confidence 0.67 Published 2006 Journal Mol Pain Section Body Doc Link PMC1764875 Disease Relevance 0.33 Pain Relevance 0.69
Acute activation of both TRPV1 and TRPM8 induced large currents in response to saturating agonist concentration.
Positive_regulation (activation) of TRPM8 associated with agonist
7) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2780724 Disease Relevance 0.15 Pain Relevance 0.56
Although TRPM8 activation mediates similar current densities to TRPV1 (Figure 4), TRPV1 has larger secondary effects on cell function, including interference with endogenous synaptic transmission in the absence of exogenous agonist stimulation (Figure 6) and overt calcium-dependent toxicity with agonist exposure (Figure 5).
Positive_regulation (activation) of TRPM8 associated with toxicity and agonist
8) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2780724 Disease Relevance 0.09 Pain Relevance 0.29
Activation of TRPM8 can result in a large increase of intracellular Ca2+ levels due to the high Ca2+ permeability of this channel [1,2,4,5].
Positive_regulation (Activation) of TRPM8
9) Confidence 0.61 Published 2010 Journal Mol Pain Section Body Doc Link PMC2936373 Disease Relevance 0.59 Pain Relevance 0.21
TRPM8 can also be activated by menthol, an active ingredient of peppermint that produces a cooling sensation [1,2,6,7].
Positive_regulation (activated) of TRPM8
10) Confidence 0.61 Published 2010 Journal Mol Pain Section Body Doc Link PMC2936373 Disease Relevance 0.72 Pain Relevance 0.24
xlTRPM8 was robustly activated by cold, and resultant currents displayed characteristic outward rectification and voltage dependence (Fig. 3A,B).
Positive_regulation (activated) of xlTRPM8 associated with addiction
11) Confidence 0.60 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2683941 Disease Relevance 0 Pain Relevance 0.05
However, while three unique ionic mechanisms of cold transduction have recently been identified (i.e. activation of the transient receptor potential channel M8 [TRPM8] or an epithelial Na(+) channel [ENaC] or inhibition of two pore K(+) channel [TREK-1]), the possibility that these "mechanisms" may be differentially distributed among sensory neurons in a manner consistent with predictions based on in vivo observations has not been investigated.
Positive_regulation (activation) of channel M8 in sensory neurons associated with trp channel
12) Confidence 0.60 Published 2003 Journal Neuroscience Section Abstract Doc Link 12831865 Disease Relevance 0.14 Pain Relevance 0.20
The actions of high micromolar icilin in the present study are more consistent with TRPA1 activation because the enhancement of spinal glutamatergic synaptic transmission by high micromolar icilin is highly correlated to that produced by activation of TRPA1, but not TRPM8 [[29], see also [32]].
Positive_regulation (activation) of TRPM8 in spinal
13) Confidence 0.56 Published 2010 Journal Mol Pain Section Body Doc Link PMC2987996 Disease Relevance 0 Pain Relevance 0.42
The presynaptic actions of menthol and icilin are partly consistent with activation of TRPM8 and TRPA1, respectively [36-38].
Positive_regulation (activation) of TRPM8
14) Confidence 0.56 Published 2010 Journal Mol Pain Section Body Doc Link PMC2987996 Disease Relevance 0 Pain Relevance 0.44
AMTB inhibits icilin-induced TRPM8 channel activation as measured in a Ca(2+) influx assay, with a pIC(50) of 6.23.
Positive_regulation (icilin-induced) of TRPM8
15) Confidence 0.50 Published 2008 Journal Am. J. Physiol. Renal Physiol. Section Abstract Doc Link 18562636 Disease Relevance 0.49 Pain Relevance 0.19
By retrograde labeling afferent neurons that target hindlimb skin, we showed that the skin neurons expressed TRPM8 receptors, that the percentage of menthol-sensitive/cold-sensitive/capsaicin-sensitive neurons increased, and that the menthol- and cold-evoked responses were significantly enhanced in capsaicin-sensitive neurons after CCI.
Positive_regulation (enhanced) of TRPM8 in neurons associated with nervous system injury and qutenza
16) Confidence 0.50 Published 2007 Journal J. Neurosci. Section Abstract Doc Link 18077679 Disease Relevance 0.91 Pain Relevance 0.66
Along with the number of cooling agents that activate TRPM8, several antagonists have been identified, including BCTC, thio-BCTC, capsazepine, and protons [30,34].
Positive_regulation (activate) of TRPM8 associated with antagonist
17) Confidence 0.50 Published 2005 Journal Mol Pain Section Body Doc Link PMC1087877 Disease Relevance 0 Pain Relevance 0.19
It was first reported that icilin can only activate TRPM8 in the presence of extracellular calcium [14], and Chuang et al. have further described the dependence of icilin activation of TRPM8 on calcium [32].
Positive_regulation (activation) of TRPM8 associated with addiction
18) Confidence 0.50 Published 2005 Journal Mol Pain Section Body Doc Link PMC1087877 Disease Relevance 0 Pain Relevance 0.42
Icilin, the peripheral cold channel agonist, activates TRPM8 and TRPA1, localized on dorsal root ganglia and trigeminal neurons in rats.
Positive_regulation (activates) of TRPM8 in neurons associated with agonist
19) Confidence 0.49 Published 2006 Journal Amino Acids Section Abstract Doc Link 16622598 Disease Relevance 0 Pain Relevance 0.28
TRPM8-mediated currents increase with decreasing temperatures and reach maximum currents near 10°C.
Positive_regulation (increase) of TRPM8-mediated
20) Confidence 0.49 Published 2008 Journal Mol Pain Section Body Doc Link PMC2430548 Disease Relevance 0 Pain Relevance 0.11

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