INT50972

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Context Info
Confidence 0.51
First Reported 1995
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 39
Total Number 51
Disease Relevance 32.22
Pain Relevance 17.29

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

cell differentiation (Ntrk1) plasma membrane (Ntrk1) kinase activity (Ntrk1)
cytoplasm (Ntrk1)
Anatomy Link Frequency
sensory neurons 4
nociceptors 4
neurons 4
sensory nerve 4
nerve 3
Ntrk1 (Mus musculus)
Pain Link Frequency Relevance Heat
Trk A 8 100.00 Very High Very High Very High
Morphine 6 100.00 Very High Very High Very High
nociceptor 363 99.98 Very High Very High Very High
analgesia 9 99.90 Very High Very High Very High
Pain 423 99.86 Very High Very High Very High
Nerve growth factor 722 99.68 Very High Very High Very High
dorsal root ganglion 150 98.92 Very High Very High Very High
Cancer pain 276 98.76 Very High Very High Very High
Osteoarthritis 62 98.68 Very High Very High Very High
Dorsal horn 13 98.60 Very High Very High Very High
Disease Link Frequency Relevance Heat
Nociception 176 100.00 Very High Very High Very High
Repression 41 100.00 Very High Very High Very High
Pain 457 99.86 Very High Very High Very High
Death 286 99.76 Very High Very High Very High
Bone Fracture 12 99.76 Very High Very High Very High
Cancer 674 99.52 Very High Very High Very High
Disease 262 99.44 Very High Very High Very High
Neuroma 300 99.24 Very High Very High Very High
Ganglion Cysts 801 98.92 Very High Very High Very High
Frailty 80 98.68 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We conclude that femoral nerve blocks improve analgesia and decrease morphine use after TKR.
Negative_regulation (decrease) of TKR in femoral nerve associated with morphine and analgesia
1) Confidence 0.51 Published 1998 Journal Anesth. Analg. Section Abstract Doc Link 9661553 Disease Relevance 0.38 Pain Relevance 1.77
The number of TG neurons was strongly decreased in the knockout mice as compared to wildtype and heterozygous mice (82%, 39%, and 48% reduction for trkA, trkB and trkC, respectively).
Negative_regulation (reduction) of trkA in neurons associated with targeted disruption
2) Confidence 0.48 Published 2004 Journal Acta Histochem. Section Abstract Doc Link 15530548 Disease Relevance 0.47 Pain Relevance 0.29
The reduction in TrkA suggests a relative deficit in NGF signaling, as NGF positively regulates trkA gene expression. proNGF may increase apoptotic signaling via p75NTR, altering the balance between neuronal survival and death.
Negative_regulation (reduction) of TrkA in neuronal associated with nerve growth factor, apoptosis and death
3) Confidence 0.48 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604901 Disease Relevance 0.78 Pain Relevance 0.50
For many years, K252a was thought to be a weak TrkA inhibitor, but was subsequently shown to be a potent inhibitor of the MLKs.
Negative_regulation (inhibitor) of TrkA
4) Confidence 0.48 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604901 Disease Relevance 0.56 Pain Relevance 0.43
On the other hand, Runx1 is essential for the late repression of trkA and induction of Ret when TrkA+ and Ret+ neurons segregate (Figure 1b) [34].
Negative_regulation (repression) of trkA in neurons associated with repression
5) Confidence 0.46 Published 2008 Journal Neural Develop Section Body Doc Link PMC2531103 Disease Relevance 0.65 Pain Relevance 0.28
However, in a model of bone fracture pain, with Trk inhibition at 2 days post fracture, where nerve sprouting has not yet occurred, the full analgesic effect is achieved 6-8 hours following acute administration [23].
Negative_regulation (inhibition) of Trk in nerve associated with pain, bone fracture and analgesic
6) Confidence 0.44 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004846 Disease Relevance 0.41 Pain Relevance 1.01
Interestingly, the cancer and its associated stromal cells induced a remarkable sprouting and neuroma formation by sensory nerve fibers that innervate the tumor-bearing bone and this sprouting and neuroma formation was markedly attenuated by Trk inhibition.
Negative_regulation (inhibition) of Trk in sensory nerve associated with cancer and neuroma
7) Confidence 0.44 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004846 Disease Relevance 1.46 Pain Relevance 0.46
These results indicate that the population of corneal sensory neurones is markedly depleted in trkA (-/-) mutant mice.
Negative_regulation (depleted) of trkA
8) Confidence 0.43 Published 1998 Journal Eur. J. Neurosci. Section Abstract Doc Link 9753121 Disease Relevance 0.14 Pain Relevance 0.18
In accordance, we found cellular defects and revealed a loss of nociceptive (TrkA) and proprioceptive (TrkC) sensory neurons.
Negative_regulation (loss) of TrkA in sensory neurons associated with nociception
9) Confidence 0.39 Published 2006 Journal BMC Dev Biol Section Body Doc Link PMC1687209 Disease Relevance 0.79 Pain Relevance 0.08
However, in mutant mice in which NGF/TrkA signaling has been abolished by inactivation of the trkA gene, BSI-staining in the DRG and dorsal horn is completely eliminated.
Negative_regulation (inactivation) of trkA in dorsal horn associated with dorsal root ganglion and dorsal horn
10) Confidence 0.39 Published 1995 Journal J. Neurosci. Section Abstract Doc Link 7666178 Disease Relevance 0.75 Pain Relevance 0.43
These data indicate that the abrogation of Necdin results in a partial loss of sensory neurons expressing TrkA and TrkC receptors.
Spec (partial) Negative_regulation (loss) of TrkA in sensory neurons
11) Confidence 0.39 Published 2006 Journal BMC Dev Biol Section Body Doc Link PMC1687209 Disease Relevance 0.31 Pain Relevance 0
Again the loss of Trk A sensory neurons could explain this difference.
Negative_regulation (loss) of Trk in sensory neurons associated with trk a
12) Confidence 0.39 Published 2006 Journal BMC Dev Biol Section Body Doc Link PMC1687209 Disease Relevance 0.35 Pain Relevance 0.09
Indeed, a role of Necdin in neurite outgrowth depending on NGF might explain this discrepancy: a deficiency in axonal outgrowth would then lead to an alteration of neuronal differentiation and an additional loss of TrkA cell death, in later embryogenesis stages.
Negative_regulation (loss) of TrkA in neuronal associated with nociception and death
13) Confidence 0.39 Published 2006 Journal BMC Dev Biol Section Body Doc Link PMC1687209 Disease Relevance 0.67 Pain Relevance 0.03
With this in mind, we report a loss of 27% of TrkA expressing cells at E13.5 and a 40% loss of TrkA expressing cells at P0, a substantial reduction between E13.5 and P0.
Negative_regulation (loss) of TrkA associated with nociception
14) Confidence 0.39 Published 2006 Journal BMC Dev Biol Section Body Doc Link PMC1687209 Disease Relevance 0.65 Pain Relevance 0.03
The Trk inhibitor (ARRY-470; Array BioPharma, Boulder, CO) is a potent inhibitor of the tropomyosin kinase family of neurotrophin receptors, demonstrating nanomolar cellular inhibition of TrkA (6.5 nM), TrkB (8.1 nM), and TrkC (10.6 nM) and a high level of selectivity over a panel of kinases run at the ATP Km at 1.0 uM and non-kinase receptors [48](Additional file 1 Table S1 and S2).
Negative_regulation (inhibition) of TrkA
15) Confidence 0.38 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004846 Disease Relevance 0.22 Pain Relevance 0.08
In addition, immunohistochemistry of the protein gene product 9.5 (PGP 9.5) demonstrated that trkA deficiency caused a marked reduction of varicose endings in the epithelium of the palatal mucosa.
Negative_regulation (deficiency) of trkA in epithelium
16) Confidence 0.36 Published 2004 Journal Acta Histochem. Section Abstract Doc Link 15530548 Disease Relevance 0.68 Pain Relevance 0.29
Indeed, neurotrophins cause cell death in approximately 30% of cultured hippocampal neurons expressing p75, but which lack the cognate Trk receptor, potentially limiting the therapeutic utility of the neurotrophins themselves [50].


Negative_regulation (lack) of Trk in neurons associated with death
17) Confidence 0.35 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604901 Disease Relevance 0.97 Pain Relevance 0.04
These effects may be related to the known redox regulation of TrkA.
Negative_regulation (regulation) of TrkA
18) Confidence 0.35 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604901 Disease Relevance 0.32 Pain Relevance 0.27
More specific MLK inhibitors that lack the TrkA inhibitory activity can still enhance neurotrophin action.
Negative_regulation (lack) of TrkA
19) Confidence 0.35 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604901 Disease Relevance 0.47 Pain Relevance 0.43
However considering the cellular defects, we cannot immediately explain the sensory defects observed: from a loss of sensory TrkA cells, we would expect an increased pain threshold in Necdin deficient mice but we observe the opposite effect, (a higher sensitivity in the hot-plate test).
Negative_regulation (loss) of TrkA associated with nociception and pain threshold
20) Confidence 0.34 Published 2006 Journal BMC Dev Biol Section Body Doc Link PMC1687209 Disease Relevance 0.80 Pain Relevance 0.10

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