The sensitization of peripheral C-fibers to lysophosphatidic acid in bone cancer pain

Aims: Lysophosphatidic acid (LPA) is released from injured tissue and cancer cells and is involved in the induction of neuropathic pain. The present study explores whether LPA plays a role in the development of osteocarcinoma-induced pain. Main methods: The bone cancer model was established using the Walker 256 mammary gland carcinoma cell line, and cancer-related behavioral and physiological changes were observed using von Frey, X-ray and immunohistochemical methods. The role of LPA in the bone cancer model and related mechanisms were examined by using in vitro single fiber recording and western blot. Key findings: Rats exhibited severe hyperalgesia 2 weeks after the cancer cell implantation. Several changes were observed at this time point including: ipsilateral dorsal root ganglion (DRG) neurons were labeled by injured neurons marker ATF3; LPA(1) receptor expression in DRG neurons was increased; sural C-fibers were more sensitive to IPA stimuli, and this response could be blocked by LPA receptor and substance P receptor antagonists. Significance: These data indicate that LPA is involved in the induction of bone cancer pain through mechanisms of peripheral C-fibers sensitization. LPA and its downstream molecules possibly are promising therapeutic targets for treatment of cancer pain. (c) 2010 Elsevier Inc. All rights reserved.