INT144736

Context Info Confidence 0.58 First Reported 2008 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 13 Total Number 13 Disease Relevance 6.47 Pain Relevance 9.28

cytosol (COMT) mitochondrion (COMT) small molecule metabolic process (COMT) plasma membrane (COMT) cytoplasm (COMT)

Anatomy Link Frequency astrocytes 6 white blood cells 2 central nervous system 2 COMT (Homo sapiens)

Pain Link Frequency Relevance Heat Catechol-O-methyltransferase 1330 100.00 Central nervous system 55 99.68 IPN 66 99.36 narcan 2 99.36 Inflammation 89 99.16 Pain 261 98.44 Face pain 22 92.04 Morphine 13 91.84 Glutamate 12 90.88 intrathecal 11 84.96

Disease Link Frequency Relevance Heat Anaplastic Astrocytoma 88 99.84 Inflammatory Pain 66 99.36 INFLAMMATION 111 99.16 Pain 261 98.44 Cancer 35 92.96 Facial Pain 22 92.04 Schizophrenia 16 90.96 Manic Depressive Disorder 12 89.44 Nociception 33 86.72 Acquired Immune Deficiency Syndrome Or Hiv Infection 11 82.40

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Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

-mediated inhibition of COMT expression in astroglioma cells is P2-COMT promoter specific (P < 0.05; Figure 2C).

Negative_regulation (inhibition) of Gene_expression (expression) of COMT associated with anaplastic astrocytoma and catechol-o-methyltransferase

1) Confidence 0.58 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.25 Pain Relevance 0.45

B-dependent inhibition of COMT gene expression.

Negative_regulation (inhibition) of Gene_expression (expression) of COMT associated with catechol-o-methyltransferase

2) Confidence 0.58 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.26 Pain Relevance 0.36

A number of putative regulatory elements have been described in P1- and P2-COMT promoters, including estrogen response (ER) elements [50] that likely mediate estradiol-dependent downregulation of COMT expression in cell culture [55].

Negative_regulation (downregulation) of Gene_expression (expression) of COMT associated with catechol-o-methyltransferase

3) Confidence 0.58 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.36 Pain Relevance 0.47

Our results demonstrating that COMT expression is downregulated in astrocytes under inflammatory conditions are in line with those of other studies showing a positive correlation between astrocyte activation and exaggerated pain responses [24,25,61].

Negative_regulation (downregulated) of Gene_expression (expression) of COMT in astrocyte associated with pain, catechol-o-methyltransferase and inflammation

4) Confidence 0.58 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.47 Pain Relevance 0.59

B activation alone would repress COMT gene expression.

Negative_regulation (repress) of Gene_expression (expression) of COMT associated with catechol-o-methyltransferase

5) Confidence 0.58 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.14 Pain Relevance 0.37

A significant reduction in COMT protein expression was observed beginning at 8 h (Figure 1A) with a 60% maximal decrease relative to untreated control (P < 0.05; Figure 1B).

Negative_regulation (reduction) of Gene_expression (expression) of COMT protein associated with catechol-o-methyltransferase

6) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.85 Pain Relevance 0.96

inhibits endogenous COMT expression in astrocytes

Negative_regulation (inhibits) of Gene_expression (expression) of COMT in astrocytes associated with catechol-o-methyltransferase

7) Confidence 0.43 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 1.02 Pain Relevance 1.02

Collectively, our results provide the first evidence that COMT expression is downregulated in astrocytes via recruitment of the NF-?

Negative_regulation (downregulated) of Gene_expression (expression) of COMT in astrocytes associated with catechol-o-methyltransferase

8) Confidence 0.43 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 1.04 Pain Relevance 1.19

B-mediated decrease in COMT expression is likely to contribute to heightened pain sensitivity under inflammatory conditions.

Negative_regulation (decrease) of Gene_expression (expression) of COMT associated with pain, catechol-o-methyltransferase and inflammation

9) Confidence 0.43 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 1.08 Pain Relevance 1.16

B-mediated inhibition of COMT expression in the central nervous system, suggesting that COMT contributes to the pathogenesis of inflammatory pain states.

Negative_regulation (inhibition) of Gene_expression (expression) of COMT in central nervous system associated with catechol-o-methyltransferase, ipn and central nervous system

10) Confidence 0.43 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2662804 Disease Relevance 0.62 Pain Relevance 0.99

Blots containing COMT protein were blocked with 5% nonfat milk for 30 min at room temperature, incubated with COMT polyclonal primary antibody (1?

Negative_regulation (Blots) of Gene_expression (containing) of COMT protein associated with catechol-o-methyltransferase

11) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2664927 Disease Relevance 0 Pain Relevance 0.22

Furthermore, exposure of white blood cells to 10(-6) M S-nitroso-N-acetyl-DL-penicillamine (SNAP), a nitric oxide (NO) donor, reduced the expression of CYP2D6 and COMT.

Negative_regulation (reduced) of Gene_expression (expression) of COMT in white blood cells

12) Confidence 0.41 Published 2008 Journal Addict Biol Section Abstract Doc Link 17573783 Disease Relevance 0 Pain Relevance 0.97

B activition, significantly decreased P2-COMT reporter expression.

Negative_regulation (decreased) of Gene_expression (expression) of P2-COMT associated with catechol-o-methyltransferase

13) Confidence 0.37 Published 2009 Journal Mol Pain Section Body Doc Link PMC2662804 Disease Relevance 0.39 Pain Relevance 0.53

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