Involvement of spinal PKA/CREB signaling pathway in the development of bone cancer pain.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 3
Abstract
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. Conclusion: 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.
Authors and Affiliations
Li-Hua Hang, Jian-Ping Yang, Dong-Hua Shao, Zheng Chen, Hong Wang
Keywords
Related Articles
- EP ID EP125725
- DOI -
- Views 84
- Downloads 0
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB): a new potential therapeutic target in atherosclerosis?
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a crucial transcription factor that participates in a number of physiological and pathological conditions, including immune response, apoptosis, c...
Treatment of inflammatory bowel disease (IBD).
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which includes Crohn's disease (CD) and ulcerative colitis (UC). These diseases have become important health problems. Med...
Exendin-4 reduces glycemia by increasing liver glucokinase activity: an insulin independent effect.
Exendin-4 is a stable peptide agonist of GLP-1 receptor that exhibits insulinotropic actions. Some in vivo studies indicated insulin-independent glucoregulatory actions of exendin-4. That finding prompted us to evaluate...
Synergistic protective effect of picroside II and NGF on PC12 cells against oxidative stress induced by H(2)O(2).
Epidemiological studies suggest that nerve growth factor (NGF) is associated with a reduced risk of acute or chronic neuropathies. We studied the synergistic protective effect of picroside II and NGF against the oxidativ...
Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats.
Background: Crocin and safranal are the active substances of saffron and have many biological properties. In the present study, we compared the effects of crocin, safranal and diclofenac on local inflammation and its ind...