Abstract
BackgroundIt 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.ResultsBone 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.ConclusionLPA 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.
Highlights
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
Given expression of LPA1 and TRPV1 in the dorsal root ganglion (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
Bone cancer-induced increase in expression of TRPV1 and capsaicin-induced currents in rat DRGs To elucidate the role of TRPV1 in bone cancer pain, we examined TRPV1 levels in the DRG at the L4-6 spinal segments 14 days after cancer cell implantation
Summary
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. Lysophosphatidic acid (LPA) is a lipid metabolite released after tissue injury, which induces diverse cellular responses including proliferation, adhesion, migration, morphogenesis, differentiation and survival [3]. Increasing evidence shows that LPA is a key mediator in cancer development including cancer cell proliferation, survival and migration [4,5,6,7]. Several studies have demonstrated that LPA1 participates in the development of neuropathic pain through the Rho pathway [11,15,16]
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