INT166119

Context Info Confidence 0.51 First Reported 2008 Last Reported 2010 Negated 1 Speculated 1 Reported most in Body Documents 17 Total Number 19 Disease Relevance 13.86 Pain Relevance 8.70

signal transduction (Lpar1) plasma membrane (Lpar1) cytoplasm (Lpar1) signal transducer activity (Lpar1)

Anatomy Link Frequency nerve 12 plasma 2 OVCAR-3 2 Lpar1 (Mus musculus)

Pain Link Frequency Relevance Heat Spinal cord 370 100.00 Neuropathic pain 243 100.00 intrathecal 55 99.84 Sciatic nerve 98 99.44 antagonist 39 99.38 Brush evoked pain 48 98.22 dorsal root ganglion 121 98.20 spinal dorsal horn 47 96.04 Hyperalgesia 36 95.48 allodynia 82 94.84

Disease Link Frequency Relevance Heat Neuropathic Pain 374 100.00 Cancer 54 99.84 Ovarian Cancer 68 99.78 Ganglion Cysts 196 99.68 Nervous System Injury 214 99.56 Urological Neuroanatomy 45 99.48 Injury 36 99.40 Hypercalcemia 2 99.04 Metastasis 20 98.80 Targeted Disruption 36 96.12

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These findings suggest that the marked reduction of neuropathic pain in atx+/- mice can be attributed to a reduction in LPA production following nerve injury.

Negative_regulation (reduction) of Gene_expression (production) of LPA in nerve associated with nervous system injury and neuropathic pain

1) Confidence 0.51 Published 2008 Journal Mol Pain Section Body Doc Link PMC2277392 Disease Relevance 1.17 Pain Relevance 0.74

In addition, LPA-induced LPA production in the presence of rATX was significantly decreased in Lpar3-/- mice, but not in Lpar1-/- or Lpar2-/- mice (Fig. 4c).

Negative_regulation (decreased) of Gene_expression (production) of LPA

2) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0.39 Pain Relevance 0.54

The LPA synthesis induced by LPC in both the SC and DR was reduced to the basal level by 1 day and remained at this level for the succeeding days, possibly because of degradation and diffusion.

Spec (possibly) Negative_regulation (reduced) of Gene_expression (synthesis) of LPA associated with spinal cord

3) Confidence 0.51 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0.17 Pain Relevance 0.17

In a study with 30 ovarian cancer patients, LPA1 expression was decreased, whereas LPA2 and LPA3 were increased (Murph et al., 2008) in the tumour tissue. siRNA-mediated knock-down of LPA2 and LPA3 in SKOV and OVCAR-3 ovarian cancer cell lines reduced aggressiveness and increased survival after xenografting (Yu et al., 2008).

Negative_regulation (decreased) of Gene_expression (expression) of LPA1 in OVCAR-3 associated with targeted disruption, cancer, aggression and ovarian cancer

4) Confidence 0.38 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 1.54 Pain Relevance 0.12

Therefore, targeted inhibition of LPA biosynthesis as well as LPA1 receptor would be a valuable way to prevent nerve injury-induced neuropathic pain.

Negative_regulation (inhibition) of Gene_expression (biosynthesis) of LPA in nerve associated with nervous system injury and neuropathic pain

5) Confidence 0.38 Published 2008 Journal Mol Pain Section Body Doc Link PMC2277392 Disease Relevance 1.35 Pain Relevance 0.74

Therefore, targeted inhibition of ATX-mediated LPA biosynthesis as well as LPA1 receptor and its downstream pathways may represent a novel way to prevent nerve injury-induced neuropathic pain.

Negative_regulation (inhibition) of Gene_expression (biosynthesis) of LPA in nerve associated with nervous system injury and neuropathic pain

6) Confidence 0.38 Published 2008 Journal Mol Pain Section Abstract Doc Link PMC2277392 Disease Relevance 1.20 Pain Relevance 0.71

LPA-induced LPA production was also entirely absent in Lpar3-/- mice (Fig. 3c and 3d).

Negative_regulation (absent) of Neg (absent) Gene_expression (production) of LPA

7) Confidence 0.37 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0 Pain Relevance 0.31

The lack of LPA production in the DRG, SPN or SCN may be simply related to the topological distance from the injection site of LPC.

Negative_regulation (lack) of Gene_expression (production) of LPA associated with ganglion cysts, urological neuroanatomy and sciatic nerve

8) Confidence 0.37 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0.20 Pain Relevance 0.10

LPC-induced LPA production in the SC and DR was attenuated in atx+/- mice at 1 h after LPC treatment, compared with WT mice (Fig. 2a).

Negative_regulation (attenuated) of Gene_expression (production) of LPA associated with spinal cord

9) Confidence 0.37 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0.18 Pain Relevance 0.33

LPC-induced LPA production was markedly diminished in ATX heterozygotes, and was abolished in mice that were deficient in LPA3, but not LPA1 or LPA2 receptors.

Negative_regulation (diminished) of Gene_expression (production) of LPA

10) Confidence 0.37 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2780384 Disease Relevance 0.40 Pain Relevance 0.58

LPC-induced LPA production was markedly diminished in ATX heterozygotes, and was abolished in mice that were deficient in LPA3, but not LPA1 or LPA2 receptors.

Negative_regulation (abolished) of Gene_expression (production) of LPA

11) Confidence 0.37 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2780384 Disease Relevance 0.40 Pain Relevance 0.58

Experiments to evaluate LPA and LPC production following nerve injury and clarify the relationship of ATX to LPA production are the next important issues to be addressed.

Negative_regulation (evaluate) of Gene_expression (production) of LPA in nerve associated with nervous system injury

12) Confidence 0.37 Published 2008 Journal Mol Pain Section Body Doc Link PMC2277392 Disease Relevance 1.40 Pain Relevance 0.96

I.t. injection of LPA (1 nmol) caused a time-dependent increase in LPA levels in the SC and DR that lasted until 3 h post-treatment, followed by a slight decline in LPA levels at 5 h.

Negative_regulation (decline) of Gene_expression (levels) of LPA associated with spinal cord

13) Confidence 0.37 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0.23 Pain Relevance 0.14

In addition, LPA-induced LPA production in the presence of rATX was significantly decreased in Lpar3-/- mice, but not in Lpar1-/- or Lpar2-/- mice (Fig. 4c).

Negative_regulation (decreased) of Gene_expression (production) of LPA-induced

14) Confidence 0.37 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0.39 Pain Relevance 0.54

A plasma enzyme called autotaxin (ATX) is responsible for the most of LPA production in our bodies.

Negative_regulation (most) of Gene_expression (production) of LPA in plasma

15) Confidence 0.36 Published 2010 Journal Biochimie Section Abstract Doc Link 20417246 Disease Relevance 0.34 Pain Relevance 0.13

Silencing expression or utilizing pharmacological inhibition of LPA1 in cancer cells reduces bone metastasis progression.

Negative_regulation (inhibition) of Gene_expression (expression) of LPA1 associated with cancer and metastasis

16) Confidence 0.28 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 1.14 Pain Relevance 0.04

The LPA production was significantly attenuated in ATX heterozygous mutant mice, whereas the concentration and activity of ATX in cerebrospinal fluid were not affected by nerve injury.

Negative_regulation (attenuated) of Gene_expression (production) of LPA in nerve associated with nervous system injury

17) Confidence 0.16 Published 2010 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 20123931 Disease Relevance 1.10 Pain Relevance 0.47

Both de novo LPA production and neuropathic pain-like behaviors were substantially abolished by intrathecal injection of arachidonyl trifluoromethyl ketone, a mixed inhibitor of cPLA2 and iPLA2, or bromoenol lactone, an iPLA2 inhibitor, at 1 h after injury.

Negative_regulation (abolished) of Gene_expression (production) of LPA associated with injury, neuropathic pain and intrathecal

18) Confidence 0.16 Published 2010 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 20123931 Disease Relevance 1.20 Pain Relevance 0.62

To determine the role of lysophospholipid-derived lipid mediators such as PAF and LPA in nerve injury-induced tactile allodynia, we administered PAFR and LPA receptor (LPAR) antagonists to nerve-injured rats because inhibitors of PAF and LPA biosynthetic enzymes are not available.

Negative_regulation (inhibitors) of Gene_expression (biosynthetic) of LPA in nerve associated with brush evoked pain, nervous system injury and antagonist

19) Confidence 0.02 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2862737 Disease Relevance 1.06 Pain Relevance 0.89

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