INT205203

Context Info Confidence 0.39 First Reported 2006 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 6 Total Number 15 Disease Relevance 11.83 Pain Relevance 8.08

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

Anatomy Link Frequency neurons 6 Schwann cells 4 cerebral cortex 1 dorsal root ganglion 1 TSCs 1 Lpar1 (Rattus norvegicus)

Pain Link Frequency Relevance Heat dorsal root ganglion 477 99.84 Cancer pain 180 99.20 Neuropathic pain 90 98.40 cerebral cortex 6 98.32 Kinase C 333 95.84 nociceptor 54 94.52 antagonist 54 90.32 qutenza 216 89.08 Peripheral nervous system 12 87.60 Pain 81 87.00

Disease Link Frequency Relevance Heat Ganglion Cysts 486 99.84 Bone Cancer 387 99.52 Cancer Pain 27 99.20 Neuropathic Pain 144 98.40 Cancer 297 95.56 Nervous System Injury 51 89.76 Stress 21 87.88 Pain 99 87.00 Targeted Disruption 9 83.60 Demyelinating Disease 18 81.36

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The findings that co-localization of TRPV1 and LPA1 receptor EDG-2 and bone cancer induced an increase in LPA1 receptor expression in DRG [40] provide further support for these phenomena.

Gene_expression (expression) of LPA1 receptor associated with dorsal root ganglion and bone cancer

1) Confidence 0.39 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 1.97 Pain Relevance 1.41

As shown in Figure 2 a large population of DRG neurons expressed TRPV1 (red) and EDG-2 (green).

Gene_expression (expressed) of EDG-2 in neurons associated with dorsal root ganglion

2) Confidence 0.39 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 0.88 Pain Relevance 0.53

Among the six subtypes, LPA1 receptor is the main subtype expressed in dorsal root ganglion (DRG) [11].

Gene_expression (expressed) of LPA1 receptor in dorsal root ganglion associated with ganglion cysts and dorsal root ganglion

3) Confidence 0.39 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 1.21 Pain Relevance 0.51

TRPV1 and EDG-2 were widely co-expressed in DRG neurons (orange).

Gene_expression (expressed) of EDG-2 in neurons associated with dorsal root ganglion

4) Confidence 0.39 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 0.87 Pain Relevance 0.53

Among the six LPA receptors, LPA1, LPA2, LPA3, LPA4, LPA5 and LPA6, LPA1 receptor is the main subtype expressed in the DRG neurons [11].

Gene_expression (expressed) of LPA1 receptor in neurons associated with dorsal root ganglion

5) Confidence 0.39 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 0.78 Pain Relevance 0.87

Among the six LPA receptors, LPA1, LPA2, LPA3, LPA4, LPA5 and LPA6, LPA1 receptor is the main subtype expressed in the DRG neurons [11].

Gene_expression (expressed) of LPA1 in neurons associated with dorsal root ganglion

6) Confidence 0.34 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 0.80 Pain Relevance 0.88

Given expression of LPA1 and TRPV1 in the DRG neurons, the present study focused on whether LPA1 is involved in bone cancer pain via cross-talking with TRPV1 and the possible signal pathways in the peripheral mechanism underlying bone cancer pain.

Gene_expression (expression) of LPA1 in neurons associated with dorsal root ganglion, cancer pain and bone cancer

7) Confidence 0.30 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 1.51 Pain Relevance 1.30

Inhibition of the LPA1 receptor or synthesis of LPA may be a novel therapy for cancer pain.

Gene_expression (synthesis) of LPA1 receptor associated with cancer pain

8) Confidence 0.30 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 1.21 Pain Relevance 0.71

Amongst six subtypes LPA1-6, LPA1 receptors is the main subtype expressed in DRG neurons and activated under the neuropathic pain state [11,15,44].

Gene_expression (expressed) of LPA1 in neurons associated with dorsal root ganglion and neuropathic pain

9) Confidence 0.30 Published 2010 Journal Mol Pain Section Body Doc Link PMC3004845 Disease Relevance 1.97 Pain Relevance 1.17

Weiner and Chun studied the expression of LPL receptors in Schwann cells (SC) in vivo and in vitro using total RNA by Northern blot analysis, and reported that LPA1 was expressed at high level by SCs in vivo and in vitro, whereas S1P1 was only expressed in SCs in vivo.

Gene_expression (expressed) of LPA1 in Schwann cells

10) Confidence 0.24 Published 2006 Journal Acta Histochemica et Cytochemica Section Body Doc Link PMC1828080 Disease Relevance 0.19 Pain Relevance 0

Especially, Weiner and Chun demonstrated that LPA1 was expressed by postnatal SCs, and that LPA promotes SC survival via LPA1 activation and a pathway including Gi, PI3K (phosphoinositide-3-kinase) and Akt [23].

Gene_expression (expressed) of LPA1 in SCs

11) Confidence 0.24 Published 2006 Journal Acta Histochemica et Cytochemica Section Body Doc Link PMC1828080 Disease Relevance 0.16 Pain Relevance 0.09

The first lysophosphatidic acid (LPA) receptor gene identified was the “ventricular zone gene-1 (vzg-1/LPA1)”, which was abundantly expressed in the ventricular zone of the embryonic cerebral cortex [3].

Gene_expression (expressed) of LPA1 in cerebral cortex associated with cerebral cortex

12) Confidence 0.24 Published 2006 Journal Acta Histochemica et Cytochemica Section Body Doc Link PMC1828080 Disease Relevance 0.14 Pain Relevance 0.08

Other types of LPL receptor genes, including LPA1, S1P2, S1P3, and S1P4, were expressed in both types of Schwann cells.

Gene_expression (expressed) of LPA1 in Schwann cells

13) Confidence 0.24 Published 2006 Journal Acta Histochemica et Cytochemica Section Body Doc Link PMC1828080 Disease Relevance 0 Pain Relevance 0

By using our previously reported method of selectively and efficiently collecting TSCs, we have analyzed the difference in expression patterns of lysophospholipid (LPL) receptor genes (LPA1, LPA2, LPA3, S1P1, S1P2, S1P3, S1P4, and S1P5) between TSCs and myelinating Schwann cells (MSCs).

Spec (analyzed) Gene_expression (expression) of LPA1 in TSCs

14) Confidence 0.19 Published 2006 Journal Acta Histochemica et Cytochemica Section Abstract Doc Link PMC1828080 Disease Relevance 0.09 Pain Relevance 0

Other types of LPL receptor genes, including LPA1, S1P2, S1P3, S1P4, were expressed in both types of Schwann cells.

Gene_expression (expressed) of LPA1 in Schwann cells

15) Confidence 0.19 Published 2006 Journal Acta Histochemica et Cytochemica Section Abstract Doc Link PMC1828080 Disease Relevance 0.07 Pain Relevance 0

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