INT101119

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Context Info
Confidence 0.58
First Reported 2002
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 19
Total Number 22
Disease Relevance 8.77
Pain Relevance 13.09

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

mitochondrion (Comt) methyltransferase activity (Comt) plasma membrane (Comt)
Anatomy Link Frequency
brain 2
tail 1
cortex 1
prefrontal 1
Comt (Mus musculus)
Pain Link Frequency Relevance Heat
Catechol-O-methyltransferase 582 100.00 Very High Very High Very High
analgesia 28 99.90 Very High Very High Very High
Nucleus accumbens 208 99.84 Very High Very High Very High
Morphine 360 99.54 Very High Very High Very High
Dopamine 526 99.08 Very High Very High Very High
Opioid 9 98.38 Very High Very High Very High
tail-flick 9 98.12 Very High Very High Very High
noradrenaline 3 97.60 Very High Very High Very High
Catecholamine 48 96.36 Very High Very High Very High
dopamine receptor 29 95.40 Very High Very High Very High
Disease Link Frequency Relevance Heat
Targeted Disruption 49 99.96 Very High Very High Very High
Sprains And Strains 1038 99.88 Very High Very High Very High
Schizophrenia 31 99.76 Very High Very High Very High
Urological Neuroanatomy 70 99.08 Very High Very High Very High
Disease 50 99.04 Very High Very High Very High
Stress 21 98.70 Very High Very High Very High
Cognitive Disorder 53 98.16 Very High Very High Very High
Aggression 23 96.40 Very High Very High Very High
Pain 35 95.00 High High
Affective Disorder 4 86.56 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
For example, Met polymorphisms, which decrease COMT activity, enhance working memory and attention [5], [34], [35], [36], [37], [38], [39].
Negative_regulation (decrease) of COMT associated with catechol-o-methyltransferase
1) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2923157 Disease Relevance 0.43 Pain Relevance 0.53
In fact, amino acid substitution from Leu in mice to Val in monkeys and Met in humans substantially reduces COMT activity.
Negative_regulation (reduces) of COMT associated with catechol-o-methyltransferase
2) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2923157 Disease Relevance 0.39 Pain Relevance 0.51
Individuals homozygous for the Met allele have a 3- to 4-fold reduction in COMT activity and increased prefrontal cortex dopamine levels [8].
Negative_regulation (reduction) of COMT in prefrontal associated with catechol-o-methyltransferase and dopamine
3) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2923157 Disease Relevance 0.39 Pain Relevance 0.80
Consistent with human studies, disruption of Comt in male mice elevates dopamine levels in the prefrontal cortex [2] and enhances working memory [30].
Negative_regulation (disruption) of Comt in cortex associated with dopamine
4) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2923157 Disease Relevance 0.58 Pain Relevance 0.50
We, therefore, can hypothesize that animals, or humans, with elevated Comt levels would experience reduced rewarding effects to drugs of abuse, while animals or humans with decreased levels of Comt may be more sensitive to certain drugs of abuse and perhaps even find them aversive.
Negative_regulation (decreased) of Comt associated with catechol-o-methyltransferase
5) Confidence 0.49 Published 2007 Journal BMC Genomics Section Body Doc Link PMC1851712 Disease Relevance 0.13 Pain Relevance 0.95
A recent report made the observation that individuals with a Met/Met genotype (associated with significantly decreased COMT activity) at the Val158Met polymorphism of the human COMT gene required a significantly reduced dose of morphine to achieve pain relief, as compared to individuals with the Val/Val genotype [10].
Negative_regulation (decreased) of COMT associated with pain and morphine
6) Confidence 0.49 Published 2007 Journal BMC Genomics Section Body Doc Link PMC1851712 Disease Relevance 0.44 Pain Relevance 0.66
A corollary of our hypotheses is that reduction of Comt activity, by the use of Comt inhibitors, may have two important effects.
Negative_regulation (reduction) of Comt associated with catechol-o-methyltransferase
7) Confidence 0.49 Published 2007 Journal BMC Genomics Section Body Doc Link PMC1851712 Disease Relevance 0.09 Pain Relevance 0.93
Under normal conditions, COMT deficiency does not appear to affect significantly brain dopamine and noradrenaline levels in spite of relevant changes in their metabolites.
Negative_regulation (deficiency) of COMT in brain associated with catechol-o-methyltransferase, dopamine and noradrenaline
8) Confidence 0.43 Published 2002 Journal Eur. J. Neurosci. Section Abstract Doc Link 11849292 Disease Relevance 0.17 Pain Relevance 0.75
In this family, Comt expression maps to the location of the Comt gene itself (Fig. 1C and Fig. 1D).
Negative_regulation (location) of Comt
9) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2923157 Disease Relevance 0.50 Pain Relevance 0.07
Intriguingly, both COMT and MAO inhibitors cause significant modulating effects on the clinical manifestations of Parkinson's disease [6], [53].
Negative_regulation (inhibitors) of COMT associated with disease
10) Confidence 0.41 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956650 Disease Relevance 0.73 Pain Relevance 0.32
In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice.
Negative_regulation (decreased) of COMT in tail associated with targeted disruption, stress, catechol-o-methyltransferase, tail-flick, opioid, morphine and analgesia
11) Confidence 0.37 Published 2008 Journal Basic Clin. Pharmacol. Toxicol. Section Abstract Doc Link 18834357 Disease Relevance 0.90 Pain Relevance 2.44
As expected, dopaminergic systems are clearly downstream of Comt, including Maoa in the striatum, DRD1 and DRD2 binding density in multiple brain regions, and the response to the dopamine receptor antagonist haloperidol.
Negative_regulation (downstream) of Comt in brain associated with antagonist and dopamine receptor
12) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2923157 Disease Relevance 0.07 Pain Relevance 0.44
All crosses derived from strains that differed in Comt expression show strong cis-modulation.
Negative_regulation (differed) of Comt associated with sprains and strains
13) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2923157 Disease Relevance 0.49 Pain Relevance 0.04
This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits.


Negative_regulation (differences) of Comt
14) Confidence 0.37 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2923157 Disease Relevance 0.33 Pain Relevance 0.18
While these results might suggest that there is an important molecular interaction between Comt and drugs of abuse, it is important to note that these studies were carried out with less specific, first generation COMT inhibitors.
Negative_regulation (inhibitors) of COMT associated with catechol-o-methyltransferase
15) Confidence 0.36 Published 2007 Journal BMC Genomics Section Body Doc Link PMC1851712 Disease Relevance 0.07 Pain Relevance 0.74
We suggest that inhibition of Comt by pharmacological methods may reduce desire for drugs and perhaps cause them to be more effective in clinical settings and/or less rewarding in non-clinical settings.
Negative_regulation (inhibition) of Comt associated with catechol-o-methyltransferase
16) Confidence 0.36 Published 2007 Journal BMC Genomics Section Body Doc Link PMC1851712 Disease Relevance 0.32 Pain Relevance 0.36
Comt activity was modestly, but significantly, reduced in NAC (p = 0.01) and FC (p = 0.002) of DBA mice, as compared to C57 mice (Figure 2).


Negative_regulation (reduced) of Comt associated with nucleus accumbens, catechol-o-methyltransferase and urological neuroanatomy
17) Confidence 0.36 Published 2007 Journal BMC Genomics Section Body Doc Link PMC1851712 Disease Relevance 0.50 Pain Relevance 1.32
In recent QPCR analyses of striata from four strains of mice, Comt was found to be downregulated in DBA, as compared to C57 [24], consistent with the microarray, QPCR and enzyme activity results presented here.
Negative_regulation (downregulated) of Comt associated with catechol-o-methyltransferase and sprains and strains
18) Confidence 0.36 Published 2007 Journal BMC Genomics Section Body Doc Link PMC1851712 Disease Relevance 0.23 Pain Relevance 0.60
Similarly, decreases in 3-MT concentrations due to central COMT inhibition could significantly diminish the possibility of TAAR1-mediated effects of 3-MT.
Negative_regulation (inhibition) of COMT
19) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956650 Disease Relevance 0.08 Pain Relevance 0.17
As such, inhibitors of COMT lead to dramatic decreases in 3-MT levels while blockade of MAO induces remarkable elevations in 3-MT levels [35], [38], [50], [52].
Negative_regulation (inhibitors) of COMT
20) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956650 Disease Relevance 0.66 Pain Relevance 0.26

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