| Summary: | <p>Abstract</p> <p>Background</p> <p>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 LPA<sub>1 </sub>and TRPV1 in dorsal root ganglion (DRG) neurons contributes to the development of bone cancer pain.</p> <p>Results</p> <p>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 L<sub>4-6 </sub>segments. Immunohistochemistry staining revealed a high co-localization of LPA<sub>1 </sub>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 LPA<sub>1 </sub>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 LPA<sub>1 </sub>antagonist.</p> <p>Conclusion</p> <p>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.</p>
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