title: Intervertebral disc degeneration-induced expression of pain-related molecules: glial cell-derived neurotropic factor as a key factor.
abstract: BACKGROUND
  Discogenic low back pain has been shown to develop into chronic intractable pain due to an unknown pathogenesis. To study the mechanism of discogenic pain, we analyzed the serial expression of pain-related molecules in the dorsal root ganglia (DRG) and thalamus using a newly developed rat model of disc degeneration.
  
  
  METHODS
  Ten microliters of complete Freund's adjuvant was injected into the L5-6 disc of male Sprague-Dawley rats for 10 minutes using a 26-gauge needle. Using a behavioral test, rats with significant pain were selected and subsequently serial gene expression of pain-related molecules in the DRG and the thalamus was analyzed by reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  The expression of tumor necrosis factor-α and interleukin-1β significantly increased at 4 and 8 weeks in the DRG of rats with pain. Furthermore, interleukin-6 was significantly increased at 4 weeks in the DRG; however, these cytokines did not show a significant change in the thalamus. Calcitonin gene-related peptide and substance P were significantly increased in DRG at 4 and 8 weeks and in the thalamus at 2 and 4 weeks. The level of nerve growth factor-β did not significantly increase in the DRG or thalamus, whereas glial cell line-derived neurotropic factor (GDNF) was significantly increased at 2 weeks and was sustained through 8 weeks in both the DRG and thalamus.
  
  
  CONCLUSIONS
  The disc degeneration rat model described herein led to significant pain of a chronic nature. The gradual and persistent increase of GDNF in both the thalamus and DRG suggests that GDNF might be a key factor in the development of intractable, chronic discogenic pain.
authors.affiliation: Clinical Genomic Institute, Korea University College of Health Science, Seoul, Republic of Korea.
authors.forename: Woon-Won
authors.initials: WW
authors.lastname: Jung
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Jong-Ryeul
authors.initials: JR
authors.lastname: Shon
authors.forename: Min
authors.initials: M
authors.lastname: Lee
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: Donggeun
authors.initials: D
authors.lastname: Sul
authors.forename: Heung Sik
authors.initials: HS
authors.lastname: Na
authors.forename: Joo Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung-Jo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007249:Inflammation / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D018377:Neurotransmitter Agents / Q000378:metabolism; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013788:Thalamus / Q000502:physiology
chemical_list: D016207:Cytokines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018377:Neurotransmitter Agents; D012313:RNA; D020932:Nerve Growth Factor