The objective of this study was to explore the role of cyclic
adenosine monophosphate-
protein kinase A (cAMP-PKA) signaling in the development of
bone cancer pain in rats. Female Sprague-Dawley rats (N=48) were divided randomly into four groups:
sham (n=8),
tumor cell implantation (TCI) (n=16), TCI+saline (n=8), and TCI+PKA inhibitor (n=16).
Bone cancer-induced
pain behaviors -
thermal hyperalgesia and
mechanical allodynia - were tested at postoperative days -3, -1, 1, 3, 5, 7, 10, and 14. A
PKA inhibitor,
Rp-cAMPS (1 mmol/l/20 μl), was injected intrathecally on postoperative days 3, 4, and 5 (early phase) or 7, 8, and 9 postoperative days (late phase). The expression of PKA
mRNA in dorsal root ganglia (DRG) was detected by reverse transcription-PCR. The concentration of cAMP and activity of PKA in DRG and spinal cord were measured by
enzyme-linked
immunosorbent assay. TCI treatment induced significant
pain behaviors, manifested as
thermal hyperalgesia and
mechanical allodynia. Spinal administration of the
PKA inhibitor Rp-cAMPS during the early phase and late phase significantly delayed or reversed, respectively, TCI-induced
thermal hyperalgesia and
mechanical allodynia. TCI treatment also led to obvious
tumor growth and bone destruction. The level of PKA
mRNA in the DRG, as well as the concentration of cAMP and the activity of PKA, in both the DRG and spinal cord were significantly increased after TCI treatment (P<0.01). We conclude that the inhibition of the cAMP-PKA signaling pathway may reduce
bone cancer pain.