Background: Cancer-induced bone pain (CIBP) is a common chronic pain
characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA
(TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which
has been reported to have an antinociceptive effect on neuropathic and inflammatory
pain through downregulation of the late proinflammatory cytokine high-mobility group
protein B1 (HMGB1).
Objective: To assess the antinociceptive effect of TSN IIA on CIBP.
Study Design: A randomized, double-blind, controlled animal trial was performed.
Setting: University lab in China.
Methods: A rat CIBP model was established by injecting Walker 256 mammary gland
carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g.,
flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold,
were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior
and the expression levels of spinal HMGB1, interleukin (IL)-1β, tumor necrosis factor
(TNF)-α, and IL-6 were determined. The effect of TSN IIA on the electrically evoked
response of spinal wide-dynamic range (WDR) neurons was performed in vivo.
Results: TSN IIA dose-dependently inhibited cancer-induced ongoing pain and
breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory
factors (IL-1β, TNF-α, and IL-6) were increased in the rat model, but they were
suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly
inhibited the neuronal responses of WDR neurons in spinal deep layers.
Limitations: Further studies are warranted to ascertain how TSN IIA attenuates
cancer-induced ongoing pain.
Conclusions: Our results indicate that TSN IIA attenuates cancer-induced ongoing
pain and breakthrough pain, possibly via suppression of central sensitization in CIBP
rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and
effective therapy for relieving CIBP.
Key words: Cancer-induced bone pain, high-mobility group protein B1, Tanshinone
IIA, ongoing pain, breakthrough pain