Activation of c-jun N-terminal kinase in spinal cord contributes to breast cancer induced bone pain in rats.
BACKGROUND
The most frequent pain in patients with metastatic breast and prostate cancer is bone pain, which can be severe and difficult to treat. The mechanisms underlying this pain remain unclear. Here we investigated the role of c-jun N-terminal kinase (JNK) pathway in the spinal cord in cancer-induced bone pain (CIBP).


RESULTS
In this study, we used an established rat CIBP model to investigate the possible role of JNK activation in the spinal cord. After intra-tibial inoculation with Walker 256 rat mammary gland carcinoma cells, the rats displayed mechanical allodynia on day 5, which lasted to day 16. The activation of JNK in neurons and astrocytes in the spinal cord was found on day 12 and day 16 after intra-tibial inoculation with carcinoma cells. A single intrathecal injection with JNK inhibitor SP600125 by lumbar puncture attenuated mechanical allodynia on day 12, and repeated intrathecal injection of SP600126 from day 10 to day 14 had a cumulative analgesic effect on CIBP.


CONCLUSIONS
Taken together, our results demonstrated for the first time that JNK activation in the spinal cord is required in the maintenance of CIBP. Inhibition of the spinal JNK pathway may provide a new therapy for CIBP management.
Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
Xiao-Wei
XW
Wang
Shan
S
Hu
Qi-Liang
QL
Mao-Ying
Qian
Q
Li
Chang-Jiang
CJ
Yang
Hui
H
Zhang
Wen-Li
WL
Mi
Gen-Cheng
GC
Wu
Yan-Qing
YQ
Wang
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage / Q000494:pharmacology; D002279:Carcinoma 256, Walker / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007278:Injections, Spinal; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000150:complications* / Q000473:pathology; D009368:Neoplasm Transplantation; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013977:Tibia / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D000700:Analgesics; D000873:Anthracenes; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases