title: Sigma-1 Receptor Antagonist BD1047 Reduces Mechanical Allodynia in a Rat Model of Bone Cancer Pain through the Inhibition of Spinal NR1 Phosphorylation and Microglia Activation.
abstract: Previous studies have demonstrated that sigma-1 receptor plays important roles in the induction phase of rodent neuropathic pain; however, whether it is involved in bone cancer pain (BCP) and the underlying mechanisms remain elusive. The aim of this study was to examine the potential role of the spinal sigma-1 receptor in the development of bone cancer pain. Walker 256 mammary gland carcinoma cells were implanted into the intramedullary space of the right tibia of Sprague-Dawley rats to induce ongoing bone cancer-related pain behaviors; our findings indicated that, on days 7, 10, 14, and 21 after operation, the expression of sigma-1 receptor in the spinal cord was higher in BCP rats compared to the sham rats. Furthermore, intrathecal injection of 120 nmol of sigma-1 receptor antagonist BD1047 on days 5, 6, and 7 after operation attenuated mechanical allodynia as well as the associated induction of c-Fos and activation of microglial cells, NR1, and the subsequent Ca(2+)-dependent signals of BCP rats. These results suggest that sigma-1 receptor is involved in the development of bone cancer pain and that targeting sigma-1 receptor may be a new strategy for the treatment of bone cancer pain.
authors.affiliation: Department of Anesthesiology, Xuzhou Cancer Hospital, Affiliated Xuzhou Hospital, Jiangsu University, Xuzhou 221005, China ; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, China ; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou 221002, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Xuzhou Children's Hospital, Xuzhou 221006, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital, Xuzhou Medical College, Xuzhou 221006, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Oncology, Affiliated Hospital, Xuzhou Medical College, Xuzhou 221006, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Pain, Affiliated Hospital, Xuzhou Medical College, Xuzhou 221006, China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Xuzhou Maternity and Child Health Hospital, Xuzhou 221009, China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000503:physiopathology*; D004195:Disease Models, Animal; D005029:Ethylenediamines / Q000494:pharmacology* / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy*; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017480:Receptors, sigma / Q000032:analysis / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000378:metabolism*; D000097605:Sigma-1 Receptor
chemical_list: D005029:Ethylenediamines; D048049:Extracellular Signal-Regulated MAP Kinases; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C409466:NR1 NMDA receptor; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin