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Published in: Molecular Pain 1/2010

Open Access 01-12-2010 | Research

Involvement of lysophosphatidic acid in bone cancer pain by potentiation of TRPV1 via PKCϵ pathway in dorsal root ganglion neurons

Authors: Hai-Li Pan, Yu-Qiu Zhang, Zhi-Qi Zhao

Published in: Molecular Pain | Issue 1/2010

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Abstract

Background

It has been demonstrated that lysophosphatidic acid (LPA) released from injury tissue and transient receptor potential vanilloid 1 (TRPV1) receptor are implicated in the induction of chronic pain. In the present study we examined whether an interaction between LPA receptor LPA1 and TRPV1 in dorsal root ganglion (DRG) neurons contributes to the development of bone cancer pain.

Results

Bone cancer was established by injection of mammary gland carcinoma cells into the rat tibia. Following the development of bone cancer pain, the TRPV1 expression and capsaicin-evoked currents were up-regulated in rat DRG neurons at L4-6 segments. Immunohistochemistry staining revealed a high co-localization of LPA1 with TRPV1 in DRG neurons. In isolated DRG neurons, whole-cell patch recording showed that capsaicin-induced currents were potentiated by LPA in a dose-dependent manner. The potentiation was blocked by either LPA1 antagonist, protein kinase C (PKC) inhibitor or PKCϵ inhibitor, but not by protein kinase A (PKA) inhibitor or Rho inhibitor. In the behavioral tests, both mechanical allodynia and thermal hyperalgesia in bone cancer rats were attenuated by LPA1 antagonist.

Conclusion

LPA potentiates TRPV1 current via a PKCϵ-dependent pathway in DRG neurons of rats with bone cancer, which may be a novel peripheral mechanism underlying the induction of bone cancer pain.
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Metadata
Title
Involvement of lysophosphatidic acid in bone cancer pain by potentiation of TRPV1 via PKCϵ pathway in dorsal root ganglion neurons
Authors
Hai-Li Pan
Yu-Qiu Zhang
Zhi-Qi Zhao
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2010
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-6-85

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