INT117113

Context Info Confidence 0.45 First Reported 2004 Last Reported 2010 Negated 4 Speculated 1 Reported most in Body Documents 28 Total Number 32 Disease Relevance 16.71 Pain Relevance 11.99

mitochondrion (Mapk14) cell morphogenesis (Mapk14) response to stress (Mapk14) cytoplasm (Mapk14) cytosol (Mapk14) nucleus (Mapk14)

Anatomy Link Frequency macrophages 2 embryo 1 bone marrow 1 CPu 1 osteoclast 1 Mapk14 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 539 100.00 Pain 17 100.00 Arthritis 109 99.90 Sciatic nerve 6 99.68 qutenza 10 99.20 midbrain 2 99.20 Neuropathic pain 5 99.18 Nucleus accumbens 18 98.76 long-term potentiation 209 98.66 Ventral tegmentum 5 98.08

Disease Link Frequency Relevance Heat INFLAMMATION 583 100.00 Arthritis 117 99.90 Targeted Disruption 128 99.74 Stress 185 99.24 Neuropathic Pain 15 99.18 Apoptosis 73 99.12 Hyperglycemia 220 98.64 Lung Injury 58 98.44 Osteogenic Sarcomas 6 98.08 Syndrome 25 97.56

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Role of p38 mitogen activated protein kinase in a model of osteosarcoma-induced pain.

Regulation (Role) of p38 associated with pain and osteogenic sarcomas

1) Confidence 0.45 Published 2008 Journal Pharmacol. Biochem. Behav. Section Title Doc Link 18584857 Disease Relevance 1.11 Pain Relevance 0.70

Capsaicin decreased the activation of extracellular signal-regulated kinases (ERK) without markedly affecting p38 kinases.

Neg (without) Regulation (affecting) of p38 associated with qutenza

2) Confidence 0.45 Published 2010 Journal J. Toxicol. Environ. Health Part A Section Abstract Doc Link 20954075 Disease Relevance 0.50 Pain Relevance 0.85

To date, our studies have focused on defining the role of the p38 MAPK pathway during preimplantation development. p38 MAPK regulates actin filament formation through the downstream kinases MAPKAPK2/3 (MAPK-activated protein kinase 2/3) or MAPKAPK5 [PRAK (p38 regulated/activated kinase)] and subsequently through HSP25/27 (heat-shock protein 25/27).

Regulation (role) of p38 MAPK in filament associated with shock

3) Confidence 0.41 Published 2005 Journal Biol. Cell Section Abstract Doc Link 15850458 Disease Relevance 0.25 Pain Relevance 0.11

We next determined if the p38 MAPK pathway was affected in STZ treated mice in association with the oxidative stress.

Regulation (affected) of p38 MAPK associated with stress

4) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956689 Disease Relevance 0.22 Pain Relevance 0

The levels of total p38 MAPK protein, however, did not significantly differ in the four groups of mice, Figure 4B.

Neg (not) Regulation (differ) of p38 MAPK protein

5) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956689 Disease Relevance 0.27 Pain Relevance 0

In the present study, we investigated whether a state of neuropathic pain induced by sciatic nerve ligation could change the activities of the extracellular signal-regulated kinase (ERK) and p38 in the mouse lower midbrain area including the ventral tegmental area (VTA), and these changes could directly affect the development of the morphine-induced rewarding effect in mice.

Regulation (change) of p38 in sciatic nerve associated with ventral tegmentum, neuropathic pain, midbrain, sciatic nerve and morphine

6) Confidence 0.38 Published 2004 Journal J. Neurochem. Section Abstract Doc Link 15009639 Disease Relevance 0.34 Pain Relevance 1.03

Either of these possibilities would require further study, as very little is currently known about the translational regulation of CCM2 protein, nor is it clear how CCM2-p38 MAPK interactions may be regulated in general.

Spec (may) Regulation (regulated) of p38 MAPK

7) Confidence 0.27 Published 2007 Journal BMC Dev Biol Section Body Doc Link PMC1781062 Disease Relevance 0.05 Pain Relevance 0

We have discovered that p38 MAPK activity is regulated by exposure to hyperosmotic stimuli, and that the response to hyperosmotic stress in the early embryo includes increased CCM2 levels.

Regulation (regulated) of p38 MAPK in embryo associated with stress

8) Confidence 0.27 Published 2007 Journal BMC Dev Biol Section Body Doc Link PMC1781062 Disease Relevance 0.10 Pain Relevance 0

(iv) The relationship of exogenous NO and nNOS inhibition with mitoKATP channels and p38MAPK

Regulation (relationship) of p38MAPK

9) Confidence 0.24 Published 2010 Journal BMC Physiol Section Body Doc Link PMC2927582 Disease Relevance 1.40 Pain Relevance 0.17

Our WB data did not exhibit any alteration in the level of p38 MAPK protein itself.

Neg (not) Regulation (alteration) of p38 MAPK protein

10) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956689 Disease Relevance 1.24 Pain Relevance 0.03

The changes in the phosphorylated levels of p38 MAPK can be ascribed to the alteration of activation status of the kinase at 1-week of hyperglycemia.

Regulation (changes) of p38 MAPK associated with hyperglycemia

11) Confidence 0.24 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956689 Disease Relevance 0.94 Pain Relevance 0.07

However, the activities of other protein kinases in the MAPK pathway, including p38 and JNK, showed no changes in FrA, Acb and CPu of the mice during the chronic morphine dependence and withdrawal phases.

Regulation (activities) of p38 in Acb associated with addiction, nucleus accumbens, withdrawal and morphine

12) Confidence 0.22 Published 2010 Journal Neurosci. Lett. Section Abstract Doc Link 19922770 Disease Relevance 0.79 Pain Relevance 1.77

In contrast to the effects of the p38 MAPK inhibitor, celecoxib treatment had no obvious effect on the cathepsin and MMP signals in any paw region.

Regulation (effects) of p38 MAPK in paw

13) Confidence 0.18 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911895 Disease Relevance 0.41 Pain Relevance 0.23

In vivo activation of p38MAPK has been observed in the inflamed synovial membrane of arthritis and deregulation of p38MAPK increases osteoclast formation and promotes a more severe destructive phenotype of arthritis [22].

Regulation (deregulation) of p38MAPK in osteoclast associated with arthritis

14) Confidence 0.18 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1860063 Disease Relevance 0.61 Pain Relevance 0.30

, IL-6, and IL-10 exclusively through TTP phosphorylation such as in murine bone marrow-derived macrophages [126].These above studies and others offer strong evidence for the p38 MAPK regulation of ARE-mRNA stability and the association with loss of TTP function.

Regulation (regulation) of p38 MAPK in macrophages

15) Confidence 0.17 Published 2010 Journal Cell Mol Life Sci Section Body Doc Link PMC2921490 Disease Relevance 0.41 Pain Relevance 0.14

Then we tested the effects of JNK or p38 inhibitor on the induction of cingulate LTP, because the MAPK signaling pathways include extracellular signal-regulated (ERK), c-Jun N-terminal kinase (JNK), p38 and ERK5 [17].

Regulation (regulated) of p38 associated with long-term potentiation

16) Confidence 0.16 Published 2007 Journal Mol Pain Section Body Doc Link PMC2245920 Disease Relevance 0 Pain Relevance 0.29

Then we tested the effects of JNK or p38 inhibitor on the induction of cingulate LTP, because the MAPK signaling pathways include extracellular signal-regulated (ERK), c-Jun N-terminal kinase (JNK), p38 and ERK5 [17].

Regulation (effects) of p38 associated with long-term potentiation

17) Confidence 0.16 Published 2007 Journal Mol Pain Section Body Doc Link PMC2245920 Disease Relevance 0 Pain Relevance 0.30

We found that LPS significantly increased the concentrations of TLR-4, NF-kappaB and MAPKs, including extracellular regulated kinase (ERK), c-jun N-terminal kinase (JNK) and p38 MAPK, in activated macrophages.

Regulation (concentrations) of p38 MAPK in macrophages

18) Confidence 0.16 Published 2008 Journal Clin. Exp. Pharmacol. Physiol. Section Abstract Doc Link 18505446 Disease Relevance 0.13 Pain Relevance 0.39

Several ongoing clinical trials targeting cell-signaling molecules such as p38MAPK and TNF-a appear promising [26, 27].

Regulation (targeting) of p38MAPK

19) Confidence 0.14 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902105 Disease Relevance 0.73 Pain Relevance 0.14

These results are important because studies have determined that ELAVL1, ZFP36 and KHSRP RBPs are downstream targets of p38 MAPK ?

Regulation (targets) of p38 MAPK

20) Confidence 0.14 Published 2008 Journal Molecular Human Reproduction Section Body Doc Link PMC2639449 Disease Relevance 0.32 Pain Relevance 0

General Comments

This test has worked.