INT151120

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Context Info
Confidence 0.59
First Reported 2008
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 18
Total Number 21
Disease Relevance 21.09
Pain Relevance 14.46

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

signal transduction (Tlr4) plasma membrane (Tlr4) intracellular (Tlr4)
cytoplasm (Tlr4)
Anatomy Link Frequency
liver 1
muscle 1
adipose tissue 1
microglial cells 1
Tlr4 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Cancer pain 397 99.92 Very High Very High Very High
Neuropathic pain 173 99.92 Very High Very High Very High
Eae 222 99.84 Very High Very High Very High
intrathecal 140 99.84 Very High Very High Very High
allodynia 96 99.36 Very High Very High Very High
Stimulus evoked pain 17 98.96 Very High Very High Very High
cytokine 224 98.94 Very High Very High Very High
Inflammation 152 98.74 Very High Very High Very High
Analgesic 16 98.56 Very High Very High Very High
Pain 167 98.04 Very High Very High Very High
Disease Link Frequency Relevance Heat
Neuropathic Pain 349 99.92 Very High Very High Very High
Enteropathy 2 99.92 Very High Very High Very High
Injury 249 99.84 Very High Very High Very High
Bone Cancer 432 99.72 Very High Very High Very High
Insulin Resistance 60 99.58 Very High Very High Very High
Hypersensitivity 143 98.96 Very High Very High Very High
Toxicity 6 98.88 Very High Very High Very High
INFLAMMATION 194 98.74 Very High Very High Very High
Pain 284 98.28 Very High Very High Very High
Hyperalgesia 93 98.04 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
during the CCI to demonstrate there has the same effect as TLR4 inhibition on CCI-induced allodynia should be verified in future.
Negative_regulation (inhibition) of TLR4 associated with allodynia and eae
1) Confidence 0.59 Published 2010 Journal International Journal of Medical Sciences Section Body Doc Link PMC2920570 Disease Relevance 1.86 Pain Relevance 1.42
In addition, we have also demonstrated that suppression of TLR4 with intrathecal siRNA delivery could alleviate pain responses in a rat CCI model, suggesting that siRNA targeting TLR4 could be of practical value in clinical situation.



Negative_regulation (suppression) of TLR4 associated with pain, eae and intrathecal
2) Confidence 0.59 Published 2010 Journal International Journal of Medical Sciences Section Body Doc Link PMC2920570 Disease Relevance 1.56 Pain Relevance 1.26
In the present study, we demonstrated that atorvastatin improves survival in septic rats, decreases circulating inflammatory cytokines and improves insulin resistance, in parallel with a decrease in TLR4 signaling and an improvement in insulin signaling in liver, muscle and adipose tissue.
Negative_regulation (decrease) of TLR4 in liver associated with inflammation, obesity, insulin resistance and cytokine
3) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 1.35 Pain Relevance 0.30
However, systemic administration of a TLR4 inhibitor may result in non-specific toxicity as well as systemic side effects.
Negative_regulation (inhibitor) of TLR4 associated with toxicity
4) Confidence 0.43 Published 2010 Journal International Journal of Medical Sciences Section Body Doc Link PMC2920570 Disease Relevance 1.46 Pain Relevance 1.21
Methodology/Principal Findings: In this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI) model and explored the feasibility of treating neuropathic pain by inhibiting TLR4.
Negative_regulation (inhibiting) of TLR4 associated with eae, injury and neuropathic pain
5) Confidence 0.43 Published 2010 Journal International Journal of Medical Sciences Section Abstract Doc Link PMC2920570 Disease Relevance 1.41 Pain Relevance 1.10
The decrease in TLR4 also led to a significant decrease in proinflammatory cytokines, i.e., TNF-?
Negative_regulation (decrease) of TLR4 associated with cytokine
6) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.44 Pain Relevance 0.41
TLR4 siRNA439 treatment caused a significant decrease (58% ± 8 in IBCP group (Fig. 6A), 43% ± 7 in WBCP group (Fig. 6B) (n = 4)) in the TLR4 mRNA level compared with that in normal rats.
Negative_regulation (decrease) of TLR4 mRNA
7) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.65 Pain Relevance 0.57
Third, we tested whether TLR4 blockade by intrathecal injection of siRNA could reverse well-established bone cancer pain, and not simply prevent its initial development, because reversal is the more clinically relevant endpoint.
Negative_regulation (blockade) of TLR4 associated with cancer pain, bone cancer and intrathecal
8) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 1.23 Pain Relevance 0.71
To assure the effectiveness of the siRNA sequences for intrathecal injection, the ability of these siRNAs to knockdown TLR4 mRNA was determined in vitro.
Negative_regulation (knockdown) of TLR4 mRNA associated with intrathecal
9) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.27 Pain Relevance 0.39
g) reduced TLR4 mRNA by 83% (siRNA439), 61% (siRNA312), 55% (siRNA1495), and 53% (siRNA2062), respectively, compared with a vehicle-treated group, 24 h after transfection in a microglial cells line (HAPI).
Negative_regulation (reduced) of TLR4 mRNA in microglial cells
10) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.26 Pain Relevance 0.38
Blocking the TLR4 signaling pathway could potentiate analgesic effects in bone cancer pain.
Negative_regulation (Blocking) of TLR4 associated with cancer pain, analgesic and bone cancer
11) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 1.32 Pain Relevance 0.95
Identification of optimal siRNAs for knockdown of TLR4 in cell culture
Negative_regulation (knockdown) of TLR4
12) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.29 Pain Relevance 0.42
siRNA-mediated knockdown of TLR4 leads to decreased bone cancer pain-induced microglial activation and proinflammatory cytokine expression
Negative_regulation (knockdown) of TLR4 associated with cancer pain, bone cancer and cytokine
13) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2819998 Disease Relevance 0.40 Pain Relevance 0.54
We found that prolonged knockdown of TLR4 during the 3-day administration of TLR4 small interfering RNA (siRNA; 2 microg/rat/day, i.t.) could attenuate hyperalgesia developed by Walker 256 cells' inoculation and decrease the phosphorylation of p38 as well as the increase of IL-1beta and TNF-alpha expression.
Negative_regulation (knockdown) of TLR4 associated with hyperalgesia
14) Confidence 0.41 Published 2010 Journal Brain Res. Section Abstract Doc Link 20478276 Disease Relevance 1.21 Pain Relevance 1.13
Suppression of TLR4 attenuates neuropathic pain in CCI rats
Negative_regulation (Suppression) of TLR4 associated with eae and neuropathic pain
15) Confidence 0.38 Published 2010 Journal International Journal of Medical Sciences Section Body Doc Link PMC2920570 Disease Relevance 1.49 Pain Relevance 1.46
Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-?
Negative_regulation (suppression) of TLR4 associated with allodynia, thermal hyperalgesia, eae and intrathecal
16) Confidence 0.38 Published 2010 Journal International Journal of Medical Sciences Section Abstract Doc Link PMC2920570 Disease Relevance 1.39 Pain Relevance 1.10
Second, we do not know whether inhibition of TLR4 with blocking antibodies affect the IRAK-3 response.
Spec (whether) Negative_regulation (inhibition) of TLR4
17) Confidence 0.38 Published 2010 Journal Respir Res Section Body Doc Link PMC2841148 Disease Relevance 0.59 Pain Relevance 0.32
These findings suggest that LcS exhibits a prophylactic effect on indomethacin-induced enteropathy by suppressing the LPS/TLR4 signaling pathway and that this probiotic effect of LcS may be mediated by L-lactic acid.
Negative_regulation (suppressing) of TLR4 associated with enteropathy
18) Confidence 0.22 Published 2009 Journal Am. J. Physiol. Gastrointest. Liver Physiol. Section Abstract Doc Link 19589943 Disease Relevance 0.70 Pain Relevance 0.03
In the present study, we demonstrated that atorvastatin improves survival in septic rats, decreases circulating inflammatory cytokines and improves insulin resistance, in parallel with a decrease in TLR4 signaling and an improvement in insulin signaling in liver, muscle and adipose tissue.
Negative_regulation (decrease) of TLR4 in muscle associated with inflammation, obesity, insulin resistance and cytokine
19) Confidence 0.17 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 1.35 Pain Relevance 0.30
In the present study, we demonstrated that atorvastatin improves survival in septic rats, decreases circulating inflammatory cytokines and improves insulin resistance, in parallel with a decrease in TLR4 signaling and an improvement in insulin signaling in liver, muscle and adipose tissue.
Negative_regulation (decrease) of TLR4 in adipose tissue associated with inflammation, obesity, insulin resistance and cytokine
20) Confidence 0.17 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997789 Disease Relevance 1.35 Pain Relevance 0.30

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