title: Complete Freund's adjuvant-induced intervertebral discitis as an animal model for discogenic low back pain.
abstract: BACKGROUND
  Although numerous animal models for low back pain associated with intervertebral disk (IVD) degeneration have been proposed, insufficient data have been provided to make any conclusions regarding pain. Our aim in this study was to determine the reliability of complete Freund's adjuvant (CFA) injection into the rat spine as an animal model representing human discogenic pain.
  
  
  METHODS
  We studied IVD degenerative changes with pain development after a 10-microL CFA injection into the L5-6 IVD of adult rats using behavioral, histologic, and biochemical studies. Serial histologic changes were analyzed to detect degenerative changes. Expression of calcitonin gene-related peptide (CGRP), prostaglandin E (PGE), and inducible nitric oxide synthase (iNOS) were determined using immunohistochemistry or real-time polymerase chain reaction as support data for pain development. In addition, CGRP immunoreactivity (ir) at the IVD was considered indirect evidence of neural ingrowth into the IVD.
  
  
  RESULTS
  There was a significant increase of the hindpaw withdrawal response in the CFA group until 7 wk postoperatively (P < 0.05). Histologic analyses revealed progressive degenerative changes of the disks without any damage in adjacent structures, including nerve roots. In the CGRP-ir staining study, the bilateral dorsal horns and IVD had positive ir after intradiscal CFA injection. CGRP mRNA expression was increased in the dorsal root ganglion (DRG) at 2 and 4 wk, whereas PGE and iNOS mRNAs were markedly increased at 2 wk. The increment of CGRP expression was higher in allodynic rats compared with nonallodynic rats.
  
  
  CONCLUSIONS
  Intradiscal CFA injection led to chronic disk degeneration with allodynia, which was suggested by pain behavior and expression of pain-related mediators. The increment of CGRP, PGE, and iNOS also suggest pain-related signal processing between the IVD and the neural pathway in this animal model. This animal model may be useful for future research related to the pathophysiology and development of novel treatment for spine-related pain.
authors.affiliation: Department of Biomedical Science, Korea University Graduate School, Seoul, Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Lee
authors.forename: Byung-Jo
authors.initials: BJ
authors.lastname: Kim
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Lim
authors.forename: Seung Keun
authors.initials: SK
authors.lastname: Back
authors.forename: Ju-Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Yu
authors.forename: Sung-Ha
authors.initials: SH
authors.lastname: Hong
authors.forename: Joo Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: Woon-Won
authors.initials: WW
authors.lastname: Jung
authors.forename: Donggeun
authors.initials: D
authors.lastname: Sul
authors.forename: Heung Sik
authors.initials: HS
authors.lastname: Na
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D015299:Discitis / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007278:Injections, Spinal; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017116:Low Back Pain / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold; D016133:Polymerase Chain Reaction; D011458:Prostaglandins E / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D015398:Signal Transduction; D013997:Time Factors; D016474:Weight-Bearing
chemical_list: D011458:Prostaglandins E; D012333:RNA, Messenger; D005620:Freund's Adjuvant; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015740:Calcitonin Gene-Related Peptide