Open AccessIntrathecal injection of lentivirus‐mediated glial cell line‐derived neurotrophic factor RNA interference relieves bone cancer‐induced pain in rats
Author(s) -
Meng Fufen,
Xu Yang,
Dan Qiqin,
Wei La,
Deng Yingjie,
Liu Jia,
He Mu,
Liu Wei,
Xia Qingjie,
Zhou Fiona H.,
Wang Tinghua,
Wang Xiyan
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12609
Subject(s) - bone cancer , medicine , glial cell line derived neurotrophic factor , neurotrophic factors , cancer pain , cancer , hyperalgesia , osteolysis , spinal cord , nociception , surgery , receptor , psychiatry
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.