Involvement of spinal PKA/CREB signaling pathway in the development of bone cancer pain.
BACKGROUND
It has been shown that spinal PKA/CREB signaling pathway is involved in neuropathic and inflammatory pain, but its effects on bone cancer pain have not previously been investigated. The aim of this study was to examine the potential role of the spinal PKA/CREB signaling pathway in the development of bone cancer pain.


METHODS
A bone cancer pain model was made by inoculation of Walker 256 cells into the intramedullary space of rat tibia. Western blot analysis examined the expression of PKAca (PKA catalytic subunit) and phospho-CREB (p-CREB) protein levels. The authors further investigated effects of intrathecal treatment with H-89 (a PKA inhibitor, 8 nmol) or forskolin (a PKA agonist, 10 nmol) on nociceptive behavior and the expression of PKAca and p-CREB.


RESULTS
On days 6, 9, and 15 after inoculation, the expression of PKAca and p-CREB protein levels were higher in the bone cancer pain rats compared to the sham rats. On day 9, intrathecal administration of H-89 significantly attenuated bone cancer-induced mechanical allodynia as well as upregulation of PKAca and p-CREB protein levels. These effects were completely abolished by intrathecal pretreatment with the PKA agonist forskolin.


CONCLUSIONS
The results suggest that the spinal PKA/CREB signaling pathway may participate in the development of bone cancer pain. The findings of this study may provide an evidence for developing novel analgesics to block bone cancer pain.
Department of Anesthesiology, the Affiliated People's Hospital of Jiangsu University, Zhenjiang Jiangsu 212002, PR China. zjhanglihua@yahoo.com
Li-Hua
LH
Hang
Jian-Ping
JP
Yang
Dong-Hua
DH
Shao
Zheng
Z
Chen
Hong
H
Wang
D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D010146:Pain / Q000209:etiology* / Q000235:genetics*; D010147:Pain Measurement / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D017362:Cyclic AMP Response Element-Binding Protein; D007546:Isoquinolines; D013449:Sulfonamides; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide