title: Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.
abstract: Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Xi-Tuan
authors.initials: XT
authors.lastname: Ji
authors.forename: Nian-Song
authors.initials: NS
authors.lastname: Qian
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Jin-Mao
authors.initials: JM
authors.lastname: Li
authors.forename: Xin-Kui
authors.initials: XK
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhao
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
authors.forename: Dong
authors.initials: D
authors.lastname: Jia
authors.forename: Le
authors.initials: L
authors.lastname: Niu
mesh_terms: D015074:2-Aminoadipic Acid / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control; D007278:Injections, Spinal; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008911:Minocycline / Q000494:pharmacology; D009437:Neuralgia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D010147:Pain Measurement; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D014750:Vincristine
chemical_list: D053583:Interleukin-1beta; D016194:Receptors, N-Methyl-D-Aspartate; D015074:2-Aminoadipic Acid; D014750:Vincristine; D008911:Minocycline