INT100115

Context Info Confidence 0.76 First Reported 2002 Last Reported 2008 Negated 1 Speculated 3 Reported most in Body Documents 34 Total Number 51 Disease Relevance 39.15 Pain Relevance 15.69

plasma membrane (Slc12a2)

Anatomy Link Frequency spinal cord 7 neurons 6 kidney 3 nephron 2 proximal 2 Slc12a2 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Inflammatory mediators 598 99.88 Hippocampus 44 99.88 Spinal cord 368 99.68 spinal dorsal horn 18 99.68 qutenza 50 99.60 Dorsal horn neuron 19 99.60 Hyperalgesia 337 99.48 GABAergic 184 99.48 IPN 5 99.12 Neuropathic pain 243 98.56

Disease Link Frequency Relevance Heat Epilepsy 101 99.86 Chronic Renal Failure 1984 99.84 INFLAMMATION 884 99.68 Hyperalgesia 673 99.48 Targeted Disruption 45 99.48 Spinal Cord Injury 864 99.40 Malformations Of Cortical Development 4 99.36 Inflammatory Pain 7 99.12 Neuropathic Pain 411 98.56 Pain 105 98.56

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We also used a monoclonal antibody to the NKCC1 form of the Na-K-2Cl cotransporter to show that NKCC1 is expressed in optic nerves as shown in Western blotting and is colocalized in GFAP immunopositive astrocytes.

Gene_expression (expressed) of NKCC1 in optic nerves

1) Confidence 0.76 Published 2002 Journal Glia Section Abstract Doc Link 11754210 Disease Relevance 0.18 Pain Relevance 0.31

Cation chloride cotransporters, K(+)-Cl(-) cotransporter 2 (KCC2) and Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) are reported to be expressed in the neurons in the spinal cord and regulate intracellular Cl(-) concentration.

Gene_expression (expressed) of NKCC1 in spinal cord associated with spinal cord

2) Confidence 0.75 Published 2006 Journal Neurosci. Res. Section Abstract Doc Link 17007947 Disease Relevance 0.44 Pain Relevance 0.46

While the expression of NKCC1 in DRG neurons is well documented (e.g. [13] and references therein), there are conflicting results about the expression of KCC2.

Gene_expression (expression) of NKCC1 in neurons

3) Confidence 0.73 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.64 Pain Relevance 0.32

For DRG neurons, the expression of NKCC1 is well documented [13,22], while the expression of KCC2 is controversial [23,24].

Gene_expression (expression) of NKCC1 in neurons

4) Confidence 0.73 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.45 Pain Relevance 0.45

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.

Gene_expression (expression) of NKCC1

5) Confidence 0.73 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.15 Pain Relevance 0.08

0.001) above control, while the total expression level of NKCC1 showed no response (Fig. 3).

Gene_expression (expression) of NKCC1

6) Confidence 0.73 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.33 Pain Relevance 0.17

We investigated the expression of potassium-chloride co-transporter 2 (KCC2) and sodium-potassium-chloride co-transporter 1 (NKCC1) in the rat spinal cord after peripheral inflammation induced by complete Freund's adjuvant (CFA) injection.

Spec (investigated) Gene_expression (expression) of NKCC1 in spinal cord associated with inflammation and spinal cord

7) Confidence 0.69 Published 2008 Journal Neuroscience Section Abstract Doc Link 18262726 Disease Relevance 0.86 Pain Relevance 0.76

Our results suggest that the expression of KCC2, but not that of NKCC1, was significantly reduced in CFA-injected rats.

Gene_expression (expression) of NKCC1

8) Confidence 0.69 Published 2008 Journal Neuroscience Section Abstract Doc Link 18262726 Disease Relevance 0.94 Pain Relevance 0.85

Expression of NKCC1 and KCC2 following SCI

Gene_expression (Expression) of NKCC1 associated with spinal cord injury

9) Confidence 0.65 Published 2008 Journal Mol Pain Section Body Doc Link PMC2561007 Disease Relevance 1.13 Pain Relevance 0.42

A low level of NKCC1 protein was expressed in the spinal cord tissue at baseline (Figure 2A). ?

Gene_expression (expressed) of NKCC1 in spinal cord associated with spinal cord

10) Confidence 0.65 Published 2008 Journal Mol Pain Section Body Doc Link PMC2561007 Disease Relevance 1.08 Pain Relevance 0.37

These results imply that altered NKCC1 and KCC2 expression may lead to GABAergic derangement and contribute to the induction and maintenance of the chronic neuropathic pain following SCI.

Gene_expression (expression) of NKCC1 associated with spinal cord injury, gabaergic and neuropathic pain

11) Confidence 0.65 Published 2008 Journal Mol Pain Section Body Doc Link PMC2561007 Disease Relevance 1.16 Pain Relevance 1.00

This data indicate a significant increase in the expression of NKCC1 and, conversely, a decrease in KCC2 expression at the epicenter on day 14 post-SCI (prior to the chronic phase of post-SCI neuropathic hyperalgesia).

Gene_expression (expression) of NKCC1 associated with hyperalgesia, spinal cord injury and neuropathic pain

12) Confidence 0.65 Published 2008 Journal Mol Pain Section Body Doc Link PMC2561007 Disease Relevance 1.34 Pain Relevance 0.35

Both NKCC1 and KCC2 are expressed in spinal cords and function to regulate intracellular Cl- concentration.

Gene_expression (expressed) of NKCC1 in spinal cords

13) Confidence 0.65 Published 2008 Journal Mol Pain Section Body Doc Link PMC2561007 Disease Relevance 1.36 Pain Relevance 1.21

The effect of the mediators is consistent with increased Cl- accumulation, as NKCC1 expression is enhanced, while KCC2 expression is attenuated.

Gene_expression (expression) of NKCC1

14) Confidence 0.63 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.24 Pain Relevance 0.12

These data demonstrate that NKCC1 and KCC2 expression levels remain unchanged over 2 hr of treatment with inflammatory mediators.

Gene_expression (expression) of NKCC1 associated with inflammatory mediators

15) Confidence 0.63 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.16 Pain Relevance 0.08

The antisera directed against NKCC1 (C-14 antibody) and p-NKCC1 showed a virtually perfect match in the DRG sections (Fig. 4A) indicating that both non-phosphorylated and phosphorylated forms of NKCC1 are present in most neurons.

Gene_expression (antibody) of NKCC1 in neurons

16) Confidence 0.63 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.28 Pain Relevance 0.14

We, therefore, investigated expression changes of KCC2 and NKCC1 in the spinal dorsal horn of the rat after the intraplantar injection of formalin as an acute nociceptive stimulus.

Spec (investigated) Gene_expression (expression) of NKCC1 in spinal associated with nociception and spinal dorsal horn

17) Confidence 0.58 Published 2006 Journal Neurosci. Res. Section Abstract Doc Link 17007947 Disease Relevance 0.65 Pain Relevance 0.70

NKCC1 is very weakly expressed in adult dorsal horn neurons [29,30] but is the dominant cation-chloride co-transporter in primary afferents [31], and thus NKCC1 leads to GABA exerting a depolarizing, albeit inhibitory, action on sensory terminals.

Gene_expression (expressed) of NKCC1 in neurons associated with gaba and dorsal horn neuron

18) Confidence 0.58 Published 2007 Journal Mol Pain Section Body Doc Link PMC2093929 Disease Relevance 0.13 Pain Relevance 0.41

Our objective was to monitor changes of the intracellular Cl- concentration as well as changes in expression of NKCC1 and KCC2 in the presence of inflammatory mediators.

Gene_expression (expression) of NKCC1 associated with inflammatory mediators

19) Confidence 0.56 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.55 Pain Relevance 0.42

We find that inflammatory mediators cause an increase of Cl- levels in DRG neurons which correlates with enhanced NKCC1 expression and decreased KCC2 expression.

Gene_expression (expression) of NKCC1 in neurons associated with inflammatory mediators

20) Confidence 0.56 Published 2008 Journal Mol Pain Section Body Doc Link PMC2526990 Disease Relevance 0.56 Pain Relevance 0.46

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