INT274886

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Context Info
Confidence 0.25
First Reported 2009
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 1
Total Number 17
Disease Relevance 10.54
Pain Relevance 6.65

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

Anatomy Link Frequency
microglia 4
spinal 1
paw 1
Cbr2 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Endocannabinoid 51 99.84 Very High Very High Very High
Antinociceptive 17 99.32 Very High Very High Very High
cytokine 34 99.00 Very High Very High Very High
Peripheral nerve injury 102 98.96 Very High Very High Very High
Inflammation 357 98.82 Very High Very High Very High
Pain 51 98.36 Very High Very High Very High
Perioperative pain 17 98.24 Very High Very High Very High
agonist 170 98.04 Very High Very High Very High
allodynia 34 94.48 High High
Cannabinoid 102 94.00 High High
Disease Link Frequency Relevance Heat
Cancer 51 99.64 Very High Very High Very High
Necrosis 51 99.40 Very High Very High Very High
Nervous System Injury 153 98.96 Very High Very High Very High
INFLAMMATION 391 98.82 Very High Very High Very High
Pain 85 98.36 Very High Very High Very High
Post Operative Pain 17 98.24 Very High Very High Very High
Hypersensitivity 85 98.08 Very High Very High Very High
Neuropathic Pain 119 96.80 Very High Very High Very High
Drug Induced Neurotoxicity 17 96.20 Very High Very High Very High
Neurological Disease 17 95.92 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The reduction of microglial TNF production by CBR2 activation may explain the antinociceptive effects of CBR2 agonists in rodent pain models.
Positive_regulation (activation) of CBR2 associated with pain, agonist and antinociceptive
1) Confidence 0.25 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.80 Pain Relevance 0.66
Multiple pathways are involved in the production of this pro-inflammatory cytokine, but our results show a time dependent effect of CBR2 activation on MKP induction (15 min incubation), ERK dephosphorylation (30 min incubation) and decreased TNF (60–120 min incubation), suggesting that p-ERK is instrumental in TNF expression in LPS-stimulated primary microglia.
Positive_regulation (activation) of CBR2 in microglia associated with inflammation and cytokine
2) Confidence 0.25 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.56 Pain Relevance 0.51
Accordingly, in vitro CBR2 activation reduces tumor necrosis factor-?
Positive_regulation (activation) of CBR2 associated with necrosis and cancer
3) Confidence 0.25 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 1.38 Pain Relevance 0.66
Nonetheless, the specific intracellular mechanism of action by which CBR2 activation alters the microglial phenotype has not been previously reported.
Positive_regulation (activation) of CBR2
4) Confidence 0.25 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 1.34 Pain Relevance 0.53
We confirmed that microglial CBR2 activation reduces TNF expression [11,16] and ERK dephosphorylation results in a significant reduction of TNF in primary microglia [21].
Positive_regulation (activation) of CBR2 in microglia
5) Confidence 0.25 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.40 Pain Relevance 0.32
Using a rat paw incision or a peripheral nerve injury model we have previously shown that in vivo spinal CBR2 activation reduces glial reactivity, measured as a reduction in the expression of CR3/CD11b or ionized calcium-binding adaptor molecule 1 (Iba-1) in microglia [12,13].
Positive_regulation (activation) of CBR2 in paw associated with nervous system injury and peripheral nerve injury
6) Confidence 0.18 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 1.09 Pain Relevance 0.79
To study the effects of CBR2 activation on cell migration in LPS-stimulated microglia we used the following groups: LPS + JWH015 (0.01–1 ?
Positive_regulation (activation) of CBR2 in microglia
7) Confidence 0.18 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0 Pain Relevance 0.13
CBR2 activation and p-ERK inhibition reduce microglial migration
Positive_regulation (activation) of CBR2
8) Confidence 0.18 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0 Pain Relevance 0.18
Therefore, we also hypothesized that microglial CBR2 activation reduces p-ERK by inducing MKP-1 and MKP-3.
Positive_regulation (activation) of CBR2
9) Confidence 0.17 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.63 Pain Relevance 0.23
Our results uncover a cellular microglial pathway triggered by CBR2 activation.
Positive_regulation (activation) of CBR2
10) Confidence 0.17 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2704199 Disease Relevance 0.39 Pain Relevance 0.22
Additionally, to probe that CBR2 activation reduces p-ERK by inducing MKP-1 and/or MKP-3, we challenged the effects of JWH015 (1 ?
Positive_regulation (activation) of CBR2
11) Confidence 0.17 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0 Pain Relevance 0.09
Herein, we study a specific signaling pathway in primary microglia to elucidate the molecular mechanisms of action of CBR2 activation.


Positive_regulation (activation) of CBR2 in microglia
12) Confidence 0.17 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.52 Pain Relevance 0.21
Second, CBR2 activation by endocannabinoids seems to promote chemotaxis via ERK phosphorylation in BV-2 cells [45,46].
Positive_regulation (activation) of CBR2 associated with endocannabinoid
13) Confidence 0.17 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.48 Pain Relevance 0.41
We have shown that selective CBR2 activation reduces spinal glial reactivity and behavioral hypersensitivity in animal models of pain (see references above).
Positive_regulation (activation) of CBR2 in spinal associated with pain and hypersensitivity
14) Confidence 0.17 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.66 Pain Relevance 0.55
We hypothesized that CBR2 activation reduces microglial p-ERK, and subsequently TNF production and cell migration.
Positive_regulation (activation) of CBR2
15) Confidence 0.17 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 1.08 Pain Relevance 0.35
Microglial CBR2 activation induces MKP-1/3 and reduces p-ERK and TNF
Positive_regulation (activation) of CBR2
16) Confidence 0.17 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.51 Pain Relevance 0.20
We propose that CBR2 activation induces these effects via MKP-3 induction.
Positive_regulation (activation) of CBR2
17) Confidence 0.17 Published 2009 Journal Mol Pain Section Body Doc Link PMC2704199 Disease Relevance 0.71 Pain Relevance 0.63

General Comments

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