Tanshinone IIA Exerts an Antinociceptive Effect in Rats with Cancer-induced Bone Pain.
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).



To assess the antinociceptive effect of TSN IIA on CIBP.



A randomized, double-blind, controlled animal trial was performed.



University lab in China.



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)-1beta, tumor necrosis factor (TNF)-alpha, 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.



TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1beta, TNF-alpha, 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.



Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain.



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.



Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain, breakthrough pain.
Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510280, China; Department of Anesthesiology, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia, 010017, China.
Wei
W
Hao
Lei
L
Chen
Department of Anesthesiology, the First Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia , 010000, China.
Li-Fang
LF
Wu
Department of Anesthesiology, the First Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia , 010000, China.
Fan
F
Yang
Department of C area of General Surgery, the First Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010000, China.
Jian-Xiang
JX
Niu
Alan D
AD
Kaye
Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510280, China.
Shi-Yuan
SY
Xu
D045784:Abietanes / Q000627:therapeutic use*; D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000150:complications*; D002681:China; D004311:Double-Blind Method; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D045784:Abietanes; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; C021751:tanshinone