INT127008

Context Info Confidence 0.70 First Reported 2005 Last Reported 2007 Negated 0 Speculated 0 Reported most in Body Documents 2 Total Number 6 Disease Relevance 4.73 Pain Relevance 7.61

transport (Slc12a2) plasma membrane (Slc12a2) transmembrane transport (Slc12a2)

Anatomy Link Frequency plasma 1 spinal 1 spinal cord 1 Slc12a2 (Mus musculus)

Pain Link Frequency Relevance Heat qutenza 165 99.70 allodynia 400 99.32 Pain 74 98.76 GABAergic 30 98.66 c fibre 15 98.48 Spinal cord 14 98.44 Dopamine 170 98.24 Dorsal horn 35 98.16 intrathecal 150 98.04 agonist 70 97.44

Disease Link Frequency Relevance Heat Neuropathic Pain 405 99.32 Pain 45 98.76 Hyperalgesia 91 95.00 Targeted Disruption 15 94.20 Ganglion Cysts 35 90.00 INFLAMMATION 75 86.40 Peripheral Arterial Disease 20 82.80 Nociception 16 76.36 Dyspepsia 10 53.32 Injury 5 45.60

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Using subcellular fractionation of proteins and cross-linking of membrane proteins we have observed that intracolonic capsaicin induced a 50% increase in NKCC1 in the plasma membrane of lumbosacral spinal cord 90 and 180 min after instillation, in parallel with a similar decrease in the cytosolic fraction.

Positive_regulation (increase) of NKCC1 in spinal cord associated with qutenza and spinal cord

1) Confidence 0.70 Published 2005 Journal Neuroscience Section Abstract Doc Link 15893647 Disease Relevance 0.38 Pain Relevance 0.98

-fiber input that is GABAergic in nature [13], 2) stroking allodynia following capsaicin injection into the hindpaw is absent in NKCC1 knockout mice [8], 3) spinal application of the NKCC1 blocker BUM inhibits intraplantar capsaicin-evoked, secondary mechanical allodynia in rats [10] and 4) a painful visceral stimulus increases dorsal horn NKCC1 phosphorylation and membrane trafficking [11], both of which are mechanisms known to increase NKCC1 activity and intracellular Cl- concentrations [1,26].

Positive_regulation (increase) of NKCC1 in spinal associated with targeted disruption, pain, qutenza, allodynia, gabaergic and dorsal horn

2) Confidence 0.46 Published 2007 Journal Mol Pain Section Body Doc Link PMC1929059 Disease Relevance 0.87 Pain Relevance 1.21

We and others have proposed that GABAergic mechanisms may explain allodynia in inflamed conditions such that NKCC1 activity increases leading to a large depolarization in C-fibers, causing spiking, in response to A?

Positive_regulation (increases) of NKCC1 associated with c fibre, allodynia and gabaergic

3) Confidence 0.43 Published 2007 Journal Mol Pain Section Body Doc Link PMC1929059 Disease Relevance 0.90 Pain Relevance 1.32

Moreover, they suggest that endogenous TRPV1 agonists, released in the CNS in painful conditions, might stimulate TRPV1 receptors on primary afferents that, in turn, play a role in increasing NKCC1 activity leading to allodynia.

Positive_regulation (increasing) of NKCC1 associated with pain, allodynia and agonist

4) Confidence 0.43 Published 2007 Journal Mol Pain Section Abstract Doc Link PMC1929059 Disease Relevance 0.80 Pain Relevance 1.38

leading to an increase in NKCC1 activity causing touch evoked pain.

Positive_regulation (increase) of NKCC1 associated with pain

5) Confidence 0.43 Published 2007 Journal Mol Pain Section Body Doc Link PMC1929059 Disease Relevance 1.03 Pain Relevance 1.47

Finally, intracolonic capsaicin injection stimulates a rapid and transient increase in spinal phosphorylated NKCC1 and a long lasting increase in trafficking of NKCC1 protein to the plasma membrane [11].

Positive_regulation (increase) of NKCC1 in plasma associated with qutenza

6) Confidence 0.43 Published 2007 Journal Mol Pain Section Body Doc Link PMC1929059 Disease Relevance 0.74 Pain Relevance 1.25

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