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The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain

Jae-Sung Kim1, Jeffrey S Kroin2, Xin Li1, Howard S An3, Asokumar Buvanendran2, Dongyao Yan1, Kenneth J Tuman2, Andre J van Wijnen4, Di Chen1 and Hee-Jeong Im1356*

Author Affiliations

1 Department of Biochemistry, Rush University Medical Center, Cohn Research BD 516, 1735 West Harrison Street, Chicago, IL 60612, USA

2 Departement of Anesthesiology, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA

3 Department of Orthopedic Surgery, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA

4 Department of Cell Biology, University of Massachusetts, 55 Lake Avenue, North Worcester, MA 01655-0106, USA

5 Department of Internal Medicine, Section of Rheumatology, Rush University Medical Center, 1735 West Harrison Street, Chicago, IL 60612, USA

6 Department of Bioengineering, University of Illinois at Chicago, 851 South Morgan Street, 218 SEO, Chicago, IL 60607-7052, USA

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Arthritis Research & Therapy 2011, 13:R165  doi:10.1186/ar3485

Published: 13 October 2011



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.


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.


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.


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.

lumbar disk degeneration; pain pathway; chronic back pain; animal model; drug test; pain intervention