Background

Bone cancer pain (BCP) severely compromises the life quality of patients with advanced cancer or bone metastases.

Objective

This study investigates the analgesic effect of sodium aescinate (SA) on BCP, and the underlying mechanisms within the spinal cord (SC) and dorsal root ganglion (DRG). Walker 256 cells were intratibially inoculated into rats to establish a BCP model. 10, 20, and 40 g/L of SA was intrathecally injected, respectively, and then, hyperalgesia and allodynia were evaluated by measuring the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The effect of SA on neuroinflammation was observed by detecting the production of the pro-inflammatory cytokines based on RT-qPCR and ELISA. The NF-κB and p38 MAPK/c-Fos signaling was detected by WB analysis. Furthermore, RT-qPCR and WB analyses of Iba-1and CD206 were performed to assess microglial activation.

Result

The development of hyperalgesia and allodynia, and an increase of pro-inflammatory cytokines production, as well as microglial activation, were observed in the BCP rats. SA (40 g/L) not only relieved the pain-related behaviors induced by BCP but also suppressed the release of pro-inflammatory cytokines and the activation of microglia in the SC and DRG. SA could also inhibit p38 MAPK/c-Fos signaling in both the SC and DRG, which might contribute to the suppression of microglial activation.

Conclusion

Our findings suggest that SA plays a promising analgesic role in the BCP rats by suppressing inflammation and microglial activation, and these effects may be associated with the suppression of p38 MAPK/c-Fos signaling.