title: The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection.
abstract: Our previous works have shown that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in neuropathic pain produced by lumber 5 ventral root transection (L5-VRT). In the present work we evaluate the role of interleukin-6 (IL-6), another key inflammatory cytokine, in the L5-VRT model. We found that IL-6 was up-regulated in the ipsilateral L4 and L5 dorsal root ganglian (DRG) neurons and in bilateral lumbar spinal cord following L5-VRT. Double immunofluorescence stainings revealed that in DRGs the increased immunoreactivity (IR) of IL-6 was almost restricted in neuronal cells, while in the spinal dorsal horn IL-6-IR up-regulated in both glial cells (astrocyte and microglia) and neurons. Intrathecal administration of IL-6 neutralizing antibody significantly delayed the induction of mechanical allodynia in bilateral hindpaws after L5-VRT. Furthermore, inhibition of TNF-α synthesis by intraperitoneal thalidomide prevented both mechanical allodynia and the up-regulation of IL-6 in DRGs following L5-VRT. These data suggested that the increased IL-6 in afferent neurons and spinal cord contribute to the development of neuropathic pain following motor fiber injury, and that TNF-α is responsible for the up-regulation of IL-6.
authors.affiliation: Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, PR China.
authors.forename: Xu-Hong
authors.initials: XH
authors.lastname: Wei
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Na
authors.forename: Guang-Jie
authors.initials: GJ
authors.lastname: Liao
authors.forename: Qiu-Ying
authors.initials: QY
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Cui
authors.forename: Feng-Ying
authors.initials: FY
authors.lastname: Chen
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zang
authors.forename: Xian-Guo
authors.initials: XG
authors.lastname: Liu
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D007839:Functional Laterality; D006930:Hyperalgesia / Q000209:etiology; D015850:Interleukin-6 / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000209:etiology* / Q000473:pathology*; D017288:Pain Threshold / Q000502:physiology; D011128:Polyradiculopathy / Q000150:complications* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000378:metabolism* / Q000473:pathology; D013127:Spinal Nerves / Q000293:injuries; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D039481:CD11b Antigen; D015850:Interleukin-6; D037102:Lectins; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha