title: Interleukin-6 and interleukin-6 receptor expression, localization, and involvement in pain-sensing neuron activation in a mouse intervertebral disc injury model.
abstract: The pathological mechanism of intractable low back pain is unclear. However, intervertebral disc (IVD) degeneration is a primary cause of low back pain, and pain-related mediators, such as interleukin-6 (IL-6), have been correlated with discogenic pain. The objective of this study is to elucidate the mechanism of local IL-6 and IL-6 receptor (IL-6R) expression after IVD injury as well as determine the involvement of IL-6/IL-6 signaling in discogenic pain. To do this, quantitative and immunohistological analyses in a mouse model of IVD injury were performed. Firstly, we measured the local expression levels of IL-6 and IL-6R in IVDs by enzyme-linked immunosorbent assay (ELISA). Secondly, we immunohistochemically confirmed their localization in injured IVDs. Lastly, we evaluated the effects of intradiscal injection of an IL-6 inhibitor by evaluating pain-related protein, calcitonin gene-related peptide (CGRP), expression in dorsal root ganglia (DRG) neurons that innervate IVDs. Injured IVDs showed increased production of IL-6 and IL-6R. IL-6 and IL-6R expression in the injured IVD were predominantly localized in the annulus fibrosus and endplate, and intradiscal injection of the IL-6 inhibitor suppressed CGRP expression in the DRG neurons. These results show that IL-6 and IL-6R expression levels are responsive to IVD injury and that inhibition of IL-6/IL-6R signaling may be a promising analgesic treatment for degenerative disc diseases.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sainoh
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Sumihisa
authors.initials: S
authors.lastname: Orita
authors.affiliation: Department of Orthopaedic Surgery, Kitasato University, Kanagawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyagi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakuma
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yamauchi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Kubota
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oikawa
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inage
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shiga
authors.affiliation: Department of Orthopaedic Surgery, Kitasato University, Kanagawa, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.affiliation: Department of Orthopaedic Surgery, Eastern Chiba Medical Center, Chiba, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohtori
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D017116:Low Back Pain / Q000378:metabolism; D008159:Lumbar Vertebrae; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059225:Nociception; D011897:Random Allocation; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C577686:interleukin-6, mouse
keywords: discogenic pain; inflammatory cytokines; interleukin-6; interleukin-6 receptor; intervertebral disc