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


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.


RESULTS
Rats exhibited severe hyperalgesia 2weeks 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 LPA stimuli, and this response could be blocked by LPA receptor and substance P receptor antagonists.


CONCLUSIONS
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.
Zhao
Jun
J
Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Pan
Hai-Li
HL
Li
Ting-Ting
TT
Zhang
Yu-Qiu
YQ
Wei
Jen-Yu
JY
Zhao
Zhi-Qi
ZQ
D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D008246:Lysophospholipids / Q000378:metabolism*; D009368:Neoplasm Transplantation; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013497:Sural Nerve / Q000378:metabolism
D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid