INT63809

Context Info Confidence 0.69 First Reported 1996 Last Reported 2010 Negated 8 Speculated 10 Reported most in Abstract Documents 110 Total Number 124 Disease Relevance 48.95 Pain Relevance 62.98

mitosis (rl) nucleus (rl) transcription factor binding (rl) cytoplasm (rl)

Anatomy Mention Frequency spinal cord 10 neurons 10 microglia 8 epithelial cells 6 neuronal 6 rl (Drosophila melanogaster)

Pain Term Frequency Confidence Heat Anterior cingulate cortex 37 100.00 withdrawal 11 100.00 Inflammation 220 100.00 Ventral tegmentum 7 100.00 opioid receptor 126 100.00 MU agonist 12 100.00 Spinal cord 55 100.00 Opioid 131 100.00 Enkephalin 17 100.00 Nerve growth factor 16 100.00

Disease Term Frequency Confidence Heat Opiate Addiction 4 100.00 Myocardial Infarction 2 100.00 Neuropathic Pain 115 99.98 Nervous System Injury 87 99.98 Hemophilus Infection 89 99.98 Injury 32 99.98 INFLAMMATION 239 99.96 Pain 223 99.86 Ganglion Cysts 55 99.84 Inflammatory Pain 11 99.84

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Key:

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Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The goal of this study was to determine if mu agonist treatment induced ERK activation acutely or after withdrawal of chronic opioids in one glial and three neuronal cell lines.

Spec (determine) Positive_regulation (induced) of Positive_regulation (activation) of ERK in neuronal associated with agonist, opioid and withdrawal

1) Confidence 0.69 Published 2004 Journal J. Neurochem. Section Abstract Doc Link 15341521 Disease Relevance 0 Pain Relevance 0.91

Our results provide evidence that receptor internalization is not an obligatory requirement for MAPK activation by mu and delta opioid receptors.

Neg (not) Positive_regulation (requirement) of Positive_regulation (activation) of MAPK associated with delta opioid receptors

2) Confidence 0.61 Published 2000 Journal Neuropharmacology Section Abstract Doc Link 10884553 Disease Relevance 0 Pain Relevance 0.43

Additionally, a pronounced instatement of morphine-induced MAPK activation was observed in CA3 hippocampal processes.

Positive_regulation (induced) of Positive_regulation (activation) of MAPK associated with morphine

3) Confidence 0.61 Published 2003 Journal J. Neurosci. Section Abstract Doc Link 12967998 Disease Relevance 0 Pain Relevance 1.86

Activation of MAPK was increased in the anterior cingulate (Acc), somato-sensory and association cortices, and locus ceruleus (LC).

Positive_regulation (increased) of Positive_regulation (Activation) of MAPK in anterior associated with locus ceruleus and anterior cingulate

4) Confidence 0.61 Published 2003 Journal J. Neurosci. Section Abstract Doc Link 12967998 Disease Relevance 0 Pain Relevance 1.26

Locomotor sensitization resulted in sensitization to morphine-induced MAPK activation in the posterior basolateral amygdala.

Positive_regulation (induced) of Positive_regulation (activation) of MAPK in amygdala associated with amygdala and morphine

5) Confidence 0.61 Published 2003 Journal J. Neurosci. Section Abstract Doc Link 12967998 Disease Relevance 0 Pain Relevance 1.96

On the other hand, peripheral inflammation and axotomy also induces p38 MAPK activation in DRG neurons.

Positive_regulation (induces) of Positive_regulation (activation) of MAPK in DRG associated with dorsal root ganglion and inflammation

6) Confidence 0.52 Published 2004 Journal Life Sci. Section Abstract Doc Link 15041446 Disease Relevance 1.47 Pain Relevance 0.79

On the other hand, axotomy induced the activation of ERK mainly in medium-and large-sized DRG neurons and in satellite glial cells.

Positive_regulation (induced) of Positive_regulation (activation) of ERK in satellite glial cells associated with dorsal root ganglion

7) Confidence 0.50 Published 2003 Journal J. Neurosci. Section Abstract Doc Link 12764099 Disease Relevance 1.13 Pain Relevance 0.73

The characterization of cannabinoid- and opioid-induced ERK activation in these two cell-lines enables future studies into possible interactions between these two groups of drugs at the level of MAPK signaling.

Positive_regulation (induced) of Positive_regulation (activation) of ERK associated with cannabinoid and opioid

8) Confidence 0.50 Published 2008 Journal Brain Res. Section Abstract Doc Link 18068691 Disease Relevance 0.05 Pain Relevance 1.06

These findings suggest that opioids may acutely activate ERK in non-neuronal cells, and that the acute ERK activation observed in some brain regions during opioid withdrawal in vivo might be mediated by indirect effects on neuronal cells.

Spec (might) Positive_regulation (mediated) of Positive_regulation (activation) of ERK in neuronal associated with withdrawal and opioid

9) Confidence 0.46 Published 2004 Journal J. Neurochem. Section Abstract Doc Link 15341521 Disease Relevance 0.10 Pain Relevance 1.02

mu and delta-opioid receptor agonists induce mitogen-activated protein kinase (MAPK) activation in the absence of receptor internalization.

Positive_regulation (induce) of Positive_regulation (activation) of mitogen-activated protein kinase associated with agonist and opioid receptor

10) Confidence 0.44 Published 2000 Journal Neuropharmacology Section Title Doc Link 10884553 Disease Relevance 0 Pain Relevance 0.42

mu and delta-opioid receptor agonists induce mitogen-activated protein kinase (MAPK) activation in the absence of receptor internalization.

Positive_regulation (induce) of Positive_regulation (activation) of MAPK associated with agonist and opioid receptor

11) Confidence 0.44 Published 2000 Journal Neuropharmacology Section Title Doc Link 10884553 Disease Relevance 0 Pain Relevance 0.42

Here we report that endocytosis of mu and delta opioid receptors is not required for efficient ligand-induced activation of mitogen-activated protein kinase.

Neg (not) Positive_regulation (required) of Positive_regulation (activation) of mitogen-activated protein kinase associated with delta opioid receptors

12) Confidence 0.44 Published 1999 Journal J. Biol. Chem. Section Abstract Doc Link 10455121 Disease Relevance 0 Pain Relevance 0.05

We investigated the hypotheses that these drugs (A) are less neurotoxic than the prototype local anesthetic, lidocaine (B) are selectively toxic for subcategories of dorsal root ganglion neurons and (C) induce activation of either p38 MAPK or related enzymes, such as the c-jun terminal N-kinase (JNK) and extracellular signal-regulated kinase (ERK).

Positive_regulation (induce) of Positive_regulation (activation) of extracellular signal-regulated kinase in neurons associated with ganglion cysts, root ganglion neuron, lidocaine and local anesthetic

13) Confidence 0.42 Published 2008 Journal Anesth. Analg. Section Abstract Doc Link 18420860 Disease Relevance 0.26 Pain Relevance 0.42

Activation of extracellular signal-regulated kinase (ERK), a mitogen activated-protein kinase (MAPK), in dorsal horn neurons contributes to inflammatory pain by transcription-dependent and -independent means.

Positive_regulation (contributes) of Positive_regulation (Activation) of ERK in neurons associated with ipn and dorsal horn neuron

14) Confidence 0.42 Published 2005 Journal Pain Section Abstract Doc Link 15733640 Disease Relevance 0.33 Pain Relevance 0.79

The principal finding of these studies is demonstration that the activation of CaMKII and PKC is required for ERK stimulation following acute opioid treatment while in a chronic morphine treatment and withdrawal, the up-regulation of PKC and CaMKII pathways seems to be engaged in the ERK inhibition.

Positive_regulation (required) of Positive_regulation (stimulation) of ERK associated with kinase c, withdrawal, opioid and morphine

15) Confidence 0.41 Published 2005 Journal Cell. Mol. Life Sci. Section Abstract Doc Link 16158186 Disease Relevance 0 Pain Relevance 1.17

We also tested whether the increased behavioral response to DHPG following inflammation may be explained by enhanced coupling of the group I mGluRs to ERK activation.

Positive_regulation (enhanced) of Positive_regulation (activation) of ERK associated with inflammation

16) Confidence 0.40 Published 2004 Journal Pain Section Abstract Doc Link 15327816 Disease Relevance 0.59 Pain Relevance 0.67

Arrestins also link GPCRs to several signalling pathways, including activation of the non-receptor tyrosine kinase SRC and mitogen-activated protein kinase.

Positive_regulation (link) of Positive_regulation (activation) of mitogen-activated protein kinase

17) Confidence 0.39 Published 2001 Journal Nat. Rev. Neurosci. Section Abstract Doc Link 11584310 Disease Relevance 0.15 Pain Relevance 0.20

Activation of the delta-, mu-, and kappa-receptors by agonists induced a rapid and transient increase in MAPK activity accompanied by reduced electrophoretic mobility of the 42-kDa isoform of MAPK (p42), probably owing to phosphorylation.

Spec (probably) Positive_regulation (induced) of Spec (probably) Positive_regulation (increase) of MAPK associated with agonist

18) Confidence 0.37 Published 1996 Journal J. Neurochem. Section Abstract Doc Link 8752140 Disease Relevance 0 Pain Relevance 0.38

The intrathecal application of nerve growth factor (NGF) induced an increase in the number of p-ERK-and BDNF-labeled cells, mainly small neurons, and the application of anti-NGF induced an increase in p-ERK and BDNF in some medium-to-large-diameter DRG neurons.

Positive_regulation (induced) of Positive_regulation (increase) of ERK in neurons associated with dorsal root ganglion, nerve growth factor and intrathecal

19) Confidence 0.36 Published 2003 Journal J. Neurosci. Section Abstract Doc Link 12764099 Disease Relevance 1.09 Pain Relevance 0.78

The 5-HT 1E/1F receptor agonist BRL54443 induced contraction, but this was abolished by the 5-HT 2A/2C receptor antagonist ketanserin (10 nM ); contraction was not observed with a different 5-HT 1F receptor agonist, LY344864. 5-HT and alpha-methyl-5-HT produced a concentration-dependent increase in Erk MAPK activity in cultured aortic smooth muscle cells and in aorta contracted with these agonists.

Positive_regulation (produced) of Positive_regulation (increase) of MAPK in smooth muscle cells associated with antagonist and agonist

20) Confidence 0.36 Published 2001 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 11588524 Disease Relevance 0 Pain Relevance 0.56

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