INT14587

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Context Info
Confidence 0.20
First Reported 1990
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 44
Total Number 44
Disease Relevance 20.37
Pain Relevance 16.72

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
neurons 16
nociceptors 2
visceral 1
horn 1
pore 1
Cl (Mus musculus)
Pain Link Frequency Relevance Heat
gABA 504 100.00 Very High Very High Very High
Inflammatory mediators 1472 99.80 Very High Very High Very High
Pain 70 99.70 Very High Very High Very High
alcohol 1 99.68 Very High Very High Very High
Inflammation 590 99.56 Very High Very High Very High
local anesthetic 2 99.38 Very High Very High Very High
Hyperalgesia 398 99.12 Very High Very High Very High
Neuropathic pain 54 99.12 Very High Very High Very High
imagery 163 99.10 Very High Very High Very High
nociceptor 384 99.08 Very High Very High Very High
Disease Link Frequency Relevance Heat
Peripheral Arterial Disease 133 99.92 Very High Very High Very High
Nociception 391 99.74 Very High Very High Very High
Pain 70 99.70 Very High Very High Very High
INFLAMMATION 2126 99.60 Very High Very High Very High
Disease 71 99.56 Very High Very High Very High
Neurological Disease 33 99.38 Very High Very High Very High
Hyperalgesia 426 99.20 Very High Very High Very High
Neuropathic Pain 190 99.12 Very High Very High Very High
Injury 34 98.64 Very High Very High Very High
Targeted Disruption 48 98.62 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Furthermore, increasing the bulk membrane fluidity with the local anesthetics benzyl alcohol and n-alkanols increased the Cl- transport rates up to 10-fold.
Positive_regulation (increased) of Cl associated with alcohol and local anesthetic
1) Confidence 0.20 Published 1990 Journal Biochemistry Section Abstract Doc Link 1698453 Disease Relevance 0 Pain Relevance 0.15
These findings suggest a role for a reduced endosomal Cl- accumulation in Dent's disease and, by extension, point to the importance of Cl- concentration for organelle physiology [26].
Positive_regulation (accumulation) of Cl associated with disease
2) Confidence 0.14 Published 2010 Journal Orphanet J Rare Dis Section Body Doc Link PMC2964617 Disease Relevance 0.79 Pain Relevance 0.04
This finding provides strong evidence that dBest1 is indeed the channel pore and is the volume-sensitive Cl?
Positive_regulation (sensitive) of Cl in pore
3) Confidence 0.08 Published 2008 Journal The Journal of General Physiology Section Body Doc Link PMC2571971 Disease Relevance 0.05 Pain Relevance 0
The present study of the AE3 knockout mouse provides further evidence that AE3 plays an essential role in catalyzing Cl?
Positive_regulation (catalyzing) of Cl associated with targeted disruption
4) Confidence 0.07 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1950688 Disease Relevance 0.17 Pain Relevance 0.10
Thus, the DRG neurons in our assay recapitulate the disinhibition process of dorsal-horn neurons by increasing Cl- uptake and by attenuating Cl- extrusion.


Positive_regulation (increasing) of Cl in horn
5) Confidence 0.06 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.53 Pain Relevance 0.40
A number of similar observations have led to the concept that various forms of neurological disorders are associated with increased Cl- accumulation and with the resulting failure of GABAergic or glycinergic inhibition [8].
Positive_regulation (accumulation) of Cl associated with neurological disease and gabaergic
6) Confidence 0.06 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.73 Pain Relevance 0.37
Moreover, nociceptive lamina-I dorsal-horn neurons in a model of neuropathic pain display a depolarized ECl due to increased Cl- accumulation [31] and the consequent occurrence of excitatory Cl- currents.
Positive_regulation (accumulation) of Cl in neurons associated with nociception and neuropathic pain
7) Confidence 0.06 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.74 Pain Relevance 0.37
They clearly demonstrate an increase of Cl- accumulation in reponse to inflammatory mediators, but they do not give information about which level of [Cl-]i is reached during the experiments.
Positive_regulation (accumulation) of Cl associated with inflammatory mediators
8) Confidence 0.06 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.46 Pain Relevance 0.23
This observation suggests that the enhanced Cl- accumulation is not the consequence of transcriptional upregulation of NKCC1 or the downregulation of KCC2 transcription.
Positive_regulation (accumulation) of Cl
9) Confidence 0.06 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.40 Pain Relevance 0.20
Cl- accumulation increases already after 2 hr (Fig. 2B) when the co-transporters are still at control level.
Positive_regulation (accumulation) of Cl
10) Confidence 0.06 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.19 Pain Relevance 0.10
Cl at the doses of 25, 50, 100 & 200 mg/kg and Os at the doses of 25, 75 & 150 mg/kg were screened in the murine model of isoproterenol induced myocardial necrosis and the optimum dose exhibiting maximum cardioprotective effect was evaluated.
Positive_regulation (screened) of Cl associated with necrosis
11) Confidence 0.04 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1397864 Disease Relevance 0.28 Pain Relevance 0.06
The effect of the mediators is consistent with increased Cl- accumulation, as NKCC1 expression is enhanced, while KCC2 expression is attenuated.


Positive_regulation (increased) of Cl
12) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.25 Pain Relevance 0.12
The spinal afferents of nociceptors express GABAA receptors which mediate PAD by conducting Cl- efflux.
Positive_regulation (conducting) of Cl in nociceptors associated with nociceptor and peripheral arterial disease
13) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.46 Pain Relevance 0.65
To test whether NKCC1 phosphorylation may contribute to the early rise of Cl- levels (< 3 hr), we stained 9 DRG sections from 3 animals with an antibody raised specifically against the phosphorylated form of NKCC1 (p-NKCC1).
Positive_regulation (rise) of Cl
14) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.22 Pain Relevance 0.11
While the precise role of peripheral GABA in the generation or modulation of nociceptive signals remains to be explored, these findings point to a bimodal function of GABA-induced Cl- currents in the periphery.
Positive_regulation (induced) of Cl associated with nociception and gaba
15) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.49 Pain Relevance 0.99
Moreover, the GABAergic interneurons could mediate lateral sensitization between adjacent nociceptors, or between nociceptors and low-threshold mechanoreceptors which also increase their [Cl-]i, giving rise to secondary hyperalgesia or allodynia, respectively.
Positive_regulation (increase) of Cl in nociceptors associated with hyperalgesia, allodynia, nociceptor and gabaergic
16) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.68 Pain Relevance 1.25
While the changes in NKCC1 and KCC2 expression are consistent with increased Cl- accumulation, the time course of the expression changes lags behind the rise in [Cl-]i.
Positive_regulation (increased) of Cl
17) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.15 Pain Relevance 0.07
In which way could a general increase of [Cl-]i in DRG neurons contribute to inflammatory hyperalgesia?
Positive_regulation (increase) of Cl in neurons associated with hyperalgesia and inflammation
18) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.47 Pain Relevance 0.57
In contrast, Cl- extrusion in neurons is mediated by the K+-Cl- cotransporter KCC2 (SLC12A5).
Positive_regulation (mediated) of Cl in neurons
19) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.53 Pain Relevance 0.50
In this context, an upregulation of peripheral [Cl-]i during inflammation is expected to potentiate excitatory GABAergic potentials and to amplify the algogenic effect of peripheral GABA.
Positive_regulation (upregulation) of Cl associated with gaba, algogenic, inflammation and gabaergic
20) Confidence 0.04 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.73 Pain Relevance 1.01

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