title: The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain.
abstract: BACKGROUND
  Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats.
  
  
  METHODS
  Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model.
  
  
  RESULTS
  After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model.
  
  
  CONCLUSIONS
  Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration.
authors: Department of Biochemistry, Rush University Medical Center, Cohn Research BD 516, 1735 West Harrison Street, Chicago, IL 60612, USA.
authors: Jae-Sung
authors: JS
authors: Kim
authors: Jeffrey S
authors: JS
authors: Kroin
authors: Xin
authors: X
authors: Li
authors: Howard S
authors: HS
authors: An
authors: Asokumar
authors: A
authors: Buvanendran
authors: Dongyao
authors: D
authors: Yan
authors: Kenneth J
authors: KJ
authors: Tuman
authors: Andre J
authors: AJ
authors: van Wijnen
authors: Di
authors: D
authors: Chen
authors: Hee-Jeong
authors: HJ
authors: Im
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055959:Intervertebral Disc Degeneration / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D017116:Low Back Pain / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid