INT11013

Context Info Confidence 0.59 First Reported 1992 Last Reported 2010 Negated 1 Speculated 1 Reported most in Abstract Documents 55 Total Number 57 Disease Relevance 18.74 Pain Relevance 34.66

nucleoplasm (Creb1) mitochondrion (Creb1) nucleolus (Creb1) nucleus (Creb1) DNA binding (Creb1) transcription factor binding (Creb1)

Anatomy Link Frequency neurons 14 spinal cord 12 spinal 4 neuronal 4 chromaffin cells 4 Creb1 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Spinal cord 202 100.00 dorsal root ganglion 78 100.00 withdrawal 49 100.00 Morphine 43 100.00 Dorsal horn neuron 24 100.00 Hyperalgesia 23 100.00 Opioid 13 100.00 Fibrositis 3 100.00 nMDA receptor antagonist 14 99.86 Nucleus accumbens 6 99.84

Disease Link Frequency Relevance Heat Ganglion Cysts 131 100.00 Hyperalgesia 46 100.00 Multiple Sclerosis 11 100.00 Disease 11 99.88 Nociception 194 99.80 INFLAMMATION 46 99.32 Depression 7 99.28 Overdose 8 98.76 Injury 47 97.92 Apoptosis 69 97.64

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Total CREB and phosphorylated CREB in both ipsilateral and contralateral dorsal horn neurons were dramatically reduced in antisense ODN injected PSNL rats 1 week after injection.

Negative_regulation (reduced) of Phosphorylation (phosphorylated) of CREB in neurons associated with dorsal horn neuron

1) Confidence 0.59 Published 2003 Journal Brain Res. Section Abstract Doc Link 14519530 Disease Relevance 0.74 Pain Relevance 1.00

Both formalin-evoked CREB phosphorylation and c-Fos expression in the spinal cord were suppressed by pretreatment with the NMDA receptor antagonist MK-801 (3.5 mg/kg, i.p.) or halothane anesthesia.

Negative_regulation (suppressed) of Phosphorylation (phosphorylation) of CREB in spinal cord associated with anesthesia, nmda receptor antagonist, halothane and spinal cord

2) Confidence 0.59 Published 1997 Journal J. Neurosci. Section Abstract Doc Link 9030636 Disease Relevance 0.56 Pain Relevance 0.81

KN-62 and staurosporine significantly blocked the opioids- induced CREB phosphorylation, while H-89 and PD 98059 had no effect on the actions.

Negative_regulation (blocked) of Phosphorylation (phosphorylation) of CREB

3) Confidence 0.59 Published 2003 Journal Acta Pharmacol. Sin. Section Body Doc Link 14653953 Disease Relevance 0 Pain Relevance 0

Intrathecal treatment with a CaM kinase II inhibitor, KN-93, significantly blocked the increased phosphorylation of CREB, but did not affect the CREB protein itself.

Negative_regulation (blocked) of Phosphorylation (phosphorylation) of CREB associated with intrathecal

4) Confidence 0.58 Published 2005 Journal Neurosci. Lett. Section Abstract Doc Link 15631885 Disease Relevance 0 Pain Relevance 0.53

By contrast, inhibition of protein kinase A (PKA) with 100 microM PKA inhibitor peptide, PKI, blocked A1254-induced CREB phosphorylation.

Negative_regulation (blocked) of Phosphorylation (phosphorylation) of CREB

5) Confidence 0.58 Published 2002 Journal Neuroscience Section Abstract Doc Link 12421622 Disease Relevance 0 Pain Relevance 0.18

Buffering [Ca(2+)](i) with bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl) ester in the absence of extracellular Ca(2+) partially inhibited A1254-induced CREB phosphorylation.

Negative_regulation (inhibited) of Phosphorylation (phosphorylation) of CREB

6) Confidence 0.58 Published 2002 Journal Neuroscience Section Abstract Doc Link 12421622 Disease Relevance 0 Pain Relevance 0.21

Western blot analysis showed that the phosphorylation of CREB in the spinal cord of rats increased significantly at the peak stage of EAE compared with the controls (p<0.05) and declined significantly in the recovery stage (p<0.05).

Negative_regulation (declined) of Phosphorylation (phosphorylation) of CREB in spinal cord associated with multiple sclerosis and spinal cord

7) Confidence 0.58 Published 2007 Journal Brain Res. Section Abstract Doc Link 17617386 Disease Relevance 0.74 Pain Relevance 0.35

We show here, by use of a back phosphorylation and immunoprecipitation procedure, that acute morphine decreases the state of phosphorylation of CREB, an effect that becomes completely attenuated after chronic morphine administration.

Negative_regulation (decreases) of Phosphorylation (phosphorylation) of CREB associated with morphine

8) Confidence 0.58 Published 1992 Journal J. Neurochem. Section Abstract Doc Link 1531356 Disease Relevance 0 Pain Relevance 1.09

In our present study, we found that U0126, a MAP kinase inhibitor, significantly blocked CREB phosphorylation at Ser-133 in response to capsaicin injection.

Negative_regulation (blocked) of Phosphorylation (phosphorylation) of CREB associated with qutenza

9) Confidence 0.57 Published 2005 Journal Mol Pain Section Body Doc Link PMC1224868 Disease Relevance 0.41 Pain Relevance 0.56

In an investigation involving in vitro preparation of cultured striatal neurons, the NMDA- and AMPA/kainate-induced CREB phosphorylation was blocked by MAP kinase inhibitor, U0126 [23].

Negative_regulation (blocked) of Phosphorylation (phosphorylation) of CREB in neurons

10) Confidence 0.57 Published 2005 Journal Mol Pain Section Body Doc Link PMC1224868 Disease Relevance 0.45 Pain Relevance 0.69

Forskolin-stimulated CGRP release and CREB phosphorylation could be mimicked by incubation of the cells with chlorophenylthio-cAMP and blocked by pretreatment with the PKA inhibitor myrPKI(14-22).

Negative_regulation (blocked) of Phosphorylation (phosphorylation) of CREB associated with calcitonin gene-related peptide

11) Confidence 0.57 Published 2001 Journal Mol. Pharmacol. Section Abstract Doc Link 11353815 Disease Relevance 0.09 Pain Relevance 1.02

These experiments indicated that partial inhibition of CREB phosphorylation led to a decrease in the number of of BrdU-immunopositive cells in NMDA plus CREB inhibitor-treated cultures (Figure 4G-I).

Spec (partial) Negative_regulation (inhibition) of Phosphorylation (phosphorylation) of CREB

12) Confidence 0.57 Published 2009 Journal Molecular Vision Section Body Doc Link PMC2666774 Disease Relevance 0.17 Pain Relevance 0.08

The tyrosine kinase (Trk) blocker K252a (2 microg) significantly reduced the CREB phosphorylation elicited either by BDNF or the sciatic ligation.

Negative_regulation (reduced) of Phosphorylation (phosphorylation) of CREB

13) Confidence 0.56 Published 2004 Journal Neurosci. Lett. Section Abstract Doc Link 15135945 Disease Relevance 0.16 Pain Relevance 0.30

These measurements showed that estradiol increased phosphorylation of CREB (cyclic AMP response-element binding protein), which was consistently blocked by the ERK pathway inhibitor PD98059 but not by the inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002. 17beta-Estradiol activation of CREB in DRG neurons was reduced by the ER antagonist, ICI182780.

Negative_regulation (reduced) of Phosphorylation (phosphorylation) of CREB in neurons associated with dorsal root ganglion and antagonist

14) Confidence 0.56 Published 2004 Journal Neuroscience Section Abstract Doc Link 15541884 Disease Relevance 0.91 Pain Relevance 0.43

The spinal ERK inhibition or knockdown also reduced morphine withdrawal-induced phosphorylation of cAMP response element binding protein (CREB), which is one of the important downstream substrates of ERK pathway, and Fos expression.

Negative_regulation (reduced) of Phosphorylation (phosphorylation) of CREB in spinal associated with withdrawal and morphine

15) Confidence 0.50 Published 2005 Journal Pain Section Abstract Doc Link 16289800 Disease Relevance 0.32 Pain Relevance 1.51

Interestingly, CHX itself increased the phosphorylation of CREB, which was abolished by KA administration.

Negative_regulation (abolished) of Phosphorylation (phosphorylation) of CREB

16) Confidence 0.47 Published 2001 Journal Mol. Cells Section Abstract Doc Link 11355693 Disease Relevance 0 Pain Relevance 0.27

The latter scenario gains credence from experiments where immobilizing the Ca2+ channel's C terminus prevented CREB phosphorylation but spared Ca2+ influx (Kobrinsky et al., 2003).

Negative_regulation (prevented) of Phosphorylation (phosphorylation) of CREB

17) Confidence 0.46 Published 2008 Journal The Journal of Cell Biology Section Body Doc Link PMC2592819 Disease Relevance 0 Pain Relevance 0

Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathway in a time-dependent manner after repeated intramuscular acid injections.

Negative_regulation (reversed) of Phosphorylation (Phosphorylation) of CREB associated with hyperalgesia and fibrositis

18) Confidence 0.43 Published 2003 Journal J. Neurosci. Section Title Doc Link 12843242 Disease Relevance 0.51 Pain Relevance 0.60

The extent of reduction of total CREB and phosphorylated CREB containing cells in the dorsal horn ipsilateral to injury was greater than in the contralateral dorsal horn.

Negative_regulation (reduction) of Phosphorylation (phosphorylated) of CREB in dorsal horn associated with injury and dorsal horn

19) Confidence 0.43 Published 2003 Journal Brain Res. Section Abstract Doc Link 14519530 Disease Relevance 0.70 Pain Relevance 0.96

CREB phosphorylation was very rapid and reached peak levels within 10 min of formalin treatment, whereas few pCREB-positive neurons were seen in unstimulated spinal cord.

Negative_regulation (reached) of Phosphorylation (phosphorylation) of CREB in neurons associated with spinal cord

20) Confidence 0.43 Published 1997 Journal J. Neurosci. Section Abstract Doc Link 9030636 Disease Relevance 0.64 Pain Relevance 0.63

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