title: Changes in expression of mRNA for interleukin-8 and effects of interleukin-8 receptor inhibitor in the spinal dorsal horn in a rat model of lumbar disc herniation.
abstract: METHODS
  Autologous nucleus pulposus obtained from coccygeal intervertebral discs was grafted on the proximal of L5 dorsal root ganglion. Pain behavior, mRNA expression of Interleukin-8 (IL-8), and immunohistochemical changes were assessed.
  
  
  OBJECTIVE
  The purpose of this study is to investigate temporal changes of IL-8 expression in the spinal cord and dorsal root ganglion and the pain-related behaviors with time course and to elucidate whether repertaxin (IL-8 receptor inhibitor) attenuates pain-related behaviors in a rat model of lumbar disc herniation.
  
  
  BACKGROUND
  Inflammatory mediators like cytokines and chemokines have been implicated in radicular pain because of disc herniation. IL-8, known as CXCL8, is a chemokine, which has been reported to be associated with painful degenerative disc disorders and chronic inflammatory pain states.
  
  
  METHODS
  Lumbar disc herniated rat model was made by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the dorsal root ganglion. Rats were tested for mechanical allodynia and thermal hyperalgesia at 2 days before surgery, and on days 1, 5, 10, 20, 30, 40, 50, and 60 postoperatively. Experimental group was intrathecally injected with the IL-8 receptor inhibitor at L5 level on postoperative day 10. Mechanical allodynia of the plantar surface of both hindpaw was tested on 30 minutes, 1, 3 hours, 1, 3, 5, and 10 days after administration. For the staining of astrocytes and microglia, immunohistochemical study was done 20 days after surgery.
  
  
  RESULTS
  Mechanical allodynia in ipsilateral hindpaw developed 1 day after surgery and lasted until 60 days and thermal withdrawal latency decreased significantly on the ipsilateral side 10 days after surgery and gradually increased through day 60. The IL-8 receptor inhibitor attenuated the mechanical allodynia caused by nucleus pulposus when it was administered on postoperative day 10 and reduced microglial activation and phosphorylated form of mitogen-activated protein kinase (pERK) expression in the spinal dorsal horn.
  
  
  CONCLUSIONS
  IL-8 might be a potential therapeutic target in chronic radicular neuropathic pain because of disc herniation, CXCL8 inhibitor could be one of its promising therapeutic agents.
authors.affiliation: Institute of Medical Science, Yeungnam University, Seoul, Korea.
authors.forename: Su-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Park
authors.forename: Yun-Woo
authors.initials: YW
authors.lastname: Cho
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Jung
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Lee
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Jang
authors.forename: Hea-Woon
authors.initials: HW
authors.lastname: Park
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D007405:Intervertebral Disc Displacement / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D008159:Lumbar Vertebrae / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D054360:Chemokine CXCL1; D016209:Interleukin-8; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D013449:Sulfonamides; C490707:reparixin