title: Effect of ZBD-2 on chronic pain, depressive-like behaviors, and recovery of motor function following spinal cord injury in mice.
abstract: In addition to debilitating sensory and motor deficits, patients with spinal cord injury (SCI) may experience chronic hyperpathic pain (SCI-pain). Recent studies have revealed that translocator protein (TSPO) is involved in repairing neural cells as well as reducing anxiety and depression. However, the role of TSPO in SCI-pain and pain-induced depression remains unknown. The present study aimed to determine the effects of a new TSPO ligand, ZBD-2, on SCI-pain and consequent pain-induced depressive-like behaviors in mice. Treatment with ZBD-2 at either dose significantly attenuated the symptoms of chronic SCI-pain and pain-induced depressive-like behaviors. ZBD-2 reversed SCI-induced elevation of serum corticosterone levels, an index of hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, administration of ZBD-2 inhibited decreases in the expression of synaptic plasticity-related signaling proteins, including brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding protein (CREB). Moreover, ZBD-2 administration reversed chronic, SCI-induced gliocyte activation at the lesion site. Therefore, ZBD-2 may improve chronic SCI-pain and pain-induced depressive-like behaviors via suppression of gliocyte activation and restoration of the synaptic plasticity-related signaling systems.
authors.affiliation: Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China.
authors.forename: Lin Tao
authors.initials: LT
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Liu-Kun
authors.initials: LK
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xu-Bo
authors.initials: XB
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China. Electronic address: 13813889089@139.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: yangqifmmu@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, 210002, China. Electronic address: jnzhao2002@163.com.
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Zhao
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D059350:Chronic Pain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D003863:Depression / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011688:Purinones / Q000494:pharmacology*; D011897:Random Allocation; D018079:Receptors, GABA / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology
chemical_list: D000081:Acetamides; C463819:Bzrp protein, mouse; D002491:Central Nervous System Agents; C000605004:N-benzyl-N-ethyl-2-(7,8-dihydro-7-benzyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide; D011688:Purinones; D018079:Receptors, GABA
keywords: Depression; Microglia; Pain; Spinal cord injury