title: Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain.
abstract: Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line-derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Zhuofeng
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, The Maternal and Child Health Hospital of Hunan Province, Changsha, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Wangyuan
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Qulian
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhong
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Zongbin
authors.identifier: http://orcid.org/0000-0002-0447-8648
authors.initials: Z
authors.lastname: Song
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism*; D000072716:Cancer Pain / Q000378:metabolism*; D002279:Carcinoma 256, Walker / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor
keywords: GDNF; bone cancer pain; hyperalgesia; hyperexcitability; spinal cord