INT49509

Context Info Confidence 0.42 First Reported 1995 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 53 Total Number 55 Disease Relevance 24.87 Pain Relevance 11.66

signal transduction (Ptger2) plasma membrane (Ptger2) signal transducer activity (Ptger2)

Anatomy Link Frequency PGE2 5 plasma 2 theca 2 cortex 2 macrophages 1 Ptger2 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 550 100.00 bradykinin 19 100.00 aspirin 28 99.98 Pain threshold 1 99.84 cytokine 277 99.74 cINOD 115 99.72 long-term potentiation 59 99.68 Stimulus evoked pain 3 99.58 Pain 84 99.44 Paracetamol 96 98.86

Disease Link Frequency Relevance Heat INFLAMMATION 683 100.00 Pain 91 99.84 Pressure And Volume Under Development 175 99.78 Hypersensitivity 18 99.58 Targeted Disruption 78 99.56 Infection 378 99.48 Cancer 353 99.48 Breast Cancer 117 99.48 Sepsis 36 99.44 Dermatitis 5 99.44

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

To address this question, we have analyzed mice deficient in the EP2 receptor (EP2-/- mice) or in the GlyR alpha3 subunit (GlyR alpha3-/- mice) using the chronic constriction injury (CCI) model of neuropathic pain and the formalin test.

Spec (analyzed) Negative_regulation (deficient) of EP2 receptor associated with eae, injury and neuropathic pain

1) Confidence 0.42 Published 2006 Journal Pain Section Abstract Doc Link 16846696 Disease Relevance 1.56 Pain Relevance 1.07

Recently, theca cells have also been suggested as a target for PGE2 action, with detection of mRNA for EP2, EP3, and EP4 in bovine theca [32] and EP2 mRNA in mouse theca cells [9].

Negative_regulation (detection) of EP2 in theca

2) Confidence 0.41 Published 2010 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2988801 Disease Relevance 0 Pain Relevance 0

EP2 and EP4 are reported to couple exclusively with G?

Negative_regulation (reported) of EP2

3) Confidence 0.41 Published 2010 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2988801 Disease Relevance 0 Pain Relevance 0

Recently, theca cells have also been suggested as a target for PGE2 action, with detection of mRNA for EP2, EP3, and EP4 in bovine theca [32] and EP2 mRNA in mouse theca cells [9].

Negative_regulation (detection) of EP2 mRNA in theca

4) Confidence 0.41 Published 2010 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2988801 Disease Relevance 0 Pain Relevance 0

Here, we report that deletion of the PGE2 EP2 receptor in the APPSwe-PS1DeltaE9 model of familial AD results in marked reductions in lipid peroxidation in aging mice.

Negative_regulation (deletion) of EP2 receptor in PGE2 associated with aging and disease

5) Confidence 0.40 Published 2005 Journal J. Neurosci. Section Abstract Doc Link 16267225 Disease Relevance 1.32 Pain Relevance 0.31

The findings presented in the previous section indicate that infection with virulent Mtb leads to the induction of LXA4 and suppression of PGE2, which results in the necrotic death of infected M?.

Negative_regulation (suppression) of PGE2 associated with mycobacterial infection, death and infection

6) Confidence 0.35 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2585850 Disease Relevance 1.07 Pain Relevance 0

Deficiency of either EP2 or DP1 was associated with increased formalin-evoked flinching responses and c-Fos IR in dorsal horn neurons suggesting facilitated spinal cord pain reflex circuity.

Negative_regulation (Deficiency) of EP2 in spinal cord associated with pain, dorsal horn neuron and spinal cord

7) Confidence 0.34 Published 2009 Journal Eur J Pain Section Abstract Doc Link 18938093 Disease Relevance 1.34 Pain Relevance 1.01

We found that both EP2 and EP3, but not EP1 or EP4, are involved in the LTP in the visual cortex.

Negative_regulation (involved) of EP2 in cortex associated with long-term potentiation

8) Confidence 0.32 Published 2007 Journal Gene Regulation and Systems Biology Section Body Doc Link PMC2759147 Disease Relevance 0.06 Pain Relevance 0.14

The difference may be due to the subcellular location of EP2, i.e. at the presynaptic site in the hippocampus and at the postsynaptic site in visual cortex.

Negative_regulation (location) of EP2 in cortex associated with hippocampus

9) Confidence 0.28 Published 2007 Journal Gene Regulation and Systems Biology Section Body Doc Link PMC2759147 Disease Relevance 0 Pain Relevance 0.16

with 1 nM LXA4, 1 h before infection with H37Ra (MOI 10:1) to decreasing concentrations of PGE2.

Negative_regulation (decreasing) of PGE2 associated with infection

10) Confidence 0.26 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2585850 Disease Relevance 0.18 Pain Relevance 0

When calphostin C (Calp.C), a specific PKC inhibitor, was added to the pipette solution, the effect of PGE2 was almost completely inhibited (0.92 ± 0.15 fold increase, n = 10) (Figure 2F).

Negative_regulation (inhibited) of PGE2

11) Confidence 0.21 Published 2005 Journal Mol Pain Section Body Doc Link PMC1074353 Disease Relevance 0 Pain Relevance 0.16

In our study, however, both PGE2- and PGI2-induced potentiation of TRPV1 activity was completely inhibited by treatments with two kinds of PKC inhibitors.

Negative_regulation (inhibited) of PGE2

12) Confidence 0.21 Published 2005 Journal Mol Pain Section Body Doc Link PMC1074353 Disease Relevance 0.26 Pain Relevance 0.40

A similar potentiating effect of PGE2 was observed for proton (pH 6.2)-evoked TRPV1 current responses (0.91 ± 0.06 fold increase, n = 3 for control; 4.47 ± 1.09 fold, n = 7 for PGE2, p < 0.01) (Figure 2E).

Negative_regulation (effect) of PGE2

13) Confidence 0.21 Published 2005 Journal Mol Pain Section Body Doc Link PMC1074353 Disease Relevance 0 Pain Relevance 0.28

Orally administered OGT prevented or reduced lethality, intestinal lesions, bleeding, increased serum nitrate/nitrite levels, and reduction of mucosal PGE2 induced by indomethacin.

Negative_regulation (reduction) of PGE2 in PGE2 associated with hemorrhage

14) Confidence 0.19 Published 2007 Journal Biol. Pharm. Bull. Section Abstract Doc Link 17329845 Disease Relevance 0.52 Pain Relevance 0.34

Ibuprofen decreased ear swelling at the same time-points as apocynin and inhibited the ex vivo produced PGE2.

Negative_regulation (inhibited) of PGE2 in PGE2 associated with pressure and volume under development

15) Confidence 0.18 Published 2006 Journal Eur. J. Pharmacol. Section Abstract Doc Link 16405885 Disease Relevance 0.68 Pain Relevance 0.34

In response to peripheral inflammatory challenges, mice lacking the ATP-gated P2X4 channel (P2X4R) do not develop pain hypersensitivity and show a complete absence of inflammatory PGE2 in tissue exudates.

Negative_regulation (absence) of PGE2 in PGE2 associated with inflammation, hypersensitivity and stimulus evoked pain

16) Confidence 0.17 Published 2010 Journal EMBO J. Section Abstract Doc Link 20562826 Disease Relevance 1.19 Pain Relevance 0.91

The combinatorial effects of indomethacin/genistein (GEN) and aspirin/GEN were found to be synergistic for PGE2 suppression, while the nimesulide/GEN combination was antagonistic.

Negative_regulation (suppression) of PGE2 associated with aspirin

17) Confidence 0.14 Published 2003 Journal Biosci. Biotechnol. Biochem. Section Abstract Doc Link 12834283 Disease Relevance 0.49 Pain Relevance 0.12

The deficiency of the prostaglandin receptor EP2 gene reduced the size and number of intestinal tumors in APC716 mice, similar to deficiency of the COX-2 gene [69].

Negative_regulation (deficiency) of prostaglandin receptor EP2 gene associated with intestinal cancer

18) Confidence 0.14 Published 2003 Journal Mol Cancer Section Body Doc Link PMC149414 Disease Relevance 1.27 Pain Relevance 0.04

PGE2 receptors are a family of G-protein-coupled receptors, namely, EP1, EP2, EP3, and EP4 [68].

Negative_regulation (family) of EP2

19) Confidence 0.14 Published 2003 Journal Mol Cancer Section Body Doc Link PMC149414 Disease Relevance 1.25 Pain Relevance 0.03

CONCLUSION: Acupuncture has a marked antinociceptive effect in WT mice with visceral pain, which may be related to its effects in increasing hypothalamic beta-EP and decreasing serum PGE2; while in connexin 43 gene knockout mice, all the above-mentioned effects of acupuncture are eliminated, indicating an important role of connexin 43 in the analgesic effect of acupuncture.

Negative_regulation (decreasing) of PGE2 in visceral

20) Confidence 0.13 Published 2008 Journal Zhen Ci Yan Jiu Section Body Doc Link 18386636 Disease Relevance 0 Pain Relevance 0

General Comments

This test has worked.