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Bone cancer pain is a common symptom in cancer patients with bone metastases and the underlying mechanisms are largely unknown. The aim of this study is to explore the endogenous analgesic mechanisms to develop new therapeutic strategies for bone‐cancer induced pain ( BCIP ) as a result of metastases.  MRMT ‐1 tumor cells were injected into bilateral tibia of rats and X‐rays showed that the area suffered from bone destruction, accompanied by an increase in osteoclast numbers. In addition, rats with bone cancer showed apparent mechanical and thermal hyperalgesia at day 28 after intratibial  MRMT ‐1 inoculation. However, intrathecal injection of morphine or lentivirus‐mediated glial cell line‐derived neurotrophic factor  RNA i (Lvs‐si GDNF ) significantly attenuated mechanical and thermal hyperalgesia, as shown by increases in paw withdrawal thresholds and tail‐flick latencies, respectively. Furthermore, Lvs‐si GDNF  interference not only substantially downregulated  GDNF  protein levels, but also reduced substance P immunoreactivity and downregulated the ratio of  pERK / ERK , where its activation is crucial for pain signaling, in the spinal dorsal horn of this model of bone‐cancer induced pain. In this study, Lvs‐si GDNF  gene therapy appeared to be a beneficial method for the treatment of bone cancer pain. As the effect of Lvs‐si GDNF  to relieve pain was similar to morphine, but it is not a narcotic, the use of  GDNF RNA  interference may be considered as a new therapeutic strategy for the treatment of bone cancer pain in the future.

Intrathecal injection of lentivirus‐mediated glial cell line‐derived neurotrophic factor RNA interference relieves bone cancer‐induced pain in rats