title: Intrathecal injection of lentivirus-mediated glial cell line-derived neurotrophic factor RNA interference relieves bone cancer-induced pain in rats.
abstract: 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 RNAi (Lvs-siGDNF) significantly attenuated mechanical and thermal hyperalgesia, as shown by increases in paw withdrawal thresholds and tail-flick latencies, respectively. Furthermore, Lvs-siGDNF 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-siGDNF gene therapy appeared to be a beneficial method for the treatment of bone cancer pain. As the effect of Lvs-siGDNF 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.
authors.affiliation: Department of Anesthesia, Xinjiang Tumor Hospital, Urumqi, China.
authors.forename: Fu-Fen
authors.initials: FF
authors.lastname: Meng
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Qi-Qin
authors.initials: QQ
authors.lastname: Dan
authors.forename: La
authors.initials: L
authors.lastname: Wei
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Deng
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Mu
authors.initials: M
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Xia
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Zhou
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
authors.forename: Xi-Yan
authors.initials: XY
authors.lastname: Wang
mesh_terms: D000698:Analgesia / Q000379:methods*; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications* / Q000556:secondary*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D006930:Hyperalgesia / Q000628:therapy; D007278:Injections, Spinal; D016086:Lentivirus; D009020:Morphine / Q000627:therapeutic use; D009457:Neuroglia / Q000378:metabolism; D010146:Pain / Q000209:etiology*; D059408:Pain Management / Q000379:methods*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D034741:RNA, Small Interfering; D009020:Morphine
keywords: Bone cancer pain; GDNF; RNA interference; lentivirus; spinal cord