title: The Red Nucleus Interleukin-6 Participates in the Maintenance of Neuropathic Pain Induced by Spared Nerve Injury.
abstract: Previous studies have demonstrated that the red nucleus (RN) is involved in the regulation of neuropathic pain and plays both facilitated and inhibitory roles through different cytokines. Here, we aim to investigate the expression changes and roles of interleukin-6 (IL-6), a pleiotropic cytokine, as well as its receptor (IL-6R) in the RN of rats with neuropathic pain induced by spared nerve injury (SNI). Immunohistochemistry indicated that IL-6 and IL-6R were weakly expressed in the RN of normal rats, and were mainly co-localized with neurons and oligodendrocytes. Following SNI, the expression levels of IL-6 and IL-6R in the RN did not show obvious changes at 1 week and 2 weeks postinjury. However, both of them were significantly increased in the RN contralateral (but not ipsilateral) to the nerve ligation side at 3 weeks postinjury, and co-localized not only with neurons and oligodendrocytes, but also with numerous astrocytes. Injection of different doses of anti-IL-6 antibody (100, 250, 500 ng) into the RN contralateral to the nerve ligation side at 3 weeks postinjury dose-dependently increased the paw withdrawal threshold (PWT) of rats and alleviated SNI-induced mechanical allodynia. Conversely, injection of different doses of recombinant rat IL-6 (5.0, 10, 20 ng) into the unilateral RN of normal rats dose-dependently decreased the PWT of contralateral (but not ipsilateral) hind paw and evoked significant mechanical allodynia, which was similar to SNI-induced neuropathic allodynia. These results further support the conclusion that the RN is involved in the modulation of neuropathic pain, and suggest that IL-6 and IL-6R in the RN play a facilitated role in the later maintenance of SNI-induced neuropathic pain.
authors.affiliation: Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, 710061, Shaanxi, China.
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Ding
authors.affiliation: Department of Ophthalmology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China.
authors.forename: Yu-Shun
authors.initials: YS
authors.lastname: Xue
authors.affiliation: Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, 710061, Shaanxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, 710061, Shaanxi, China.
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Guo
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zeng
authors.affiliation: Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China. jywang@mail.xjtu.edu.cn.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, 710061, Shaanxi, China. jywang@mail.xjtu.edu.cn.
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000378:metabolism; D015850:Interleukin-6 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D009417:Nerve Tissue / Q000293:injuries*; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D009414:Nerve Growth Factors
keywords: Interleukin-6; Interleukin-6 receptor; Neuropathic pain; Red nucleus; Spared nerve injury