The rat intervertebral disc degeneration pain model: Relationship among biological and structural alterations and pain

Jae Sung Kim, Jeffrey S. Kroin, Xin Li, Howard S. An, Asokumar Buvanendran, Dongyao Yan, Kenneth J. Tuman, Andre J van Wijnen, Di Chen, Hee Jeong Im

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Introduction: Degeneration of the interverterbral disc is an increasing cause of low back pain. To gain insight into relationships between biological processes, structural alterations, and behavioral pain, we created an animal model in rats. Methods: Disc degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar discs (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 measuring pain upon external pressure on injured lumbar discs using an algometer. Biochemical, histological assessments and radiographs of injured discs were performed. Therapeutic modulation of chronic pain using pharmaceutical drugs was investigated in this animal model. Results: After removal of NP, pressure hyperalgesia developed over the lower back. At 9 weeks post surgery there were damaged or degenerated discs with proteoglycan loss and narrowing of disc height. These biological and structural changes in discs 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 as well as the anti-inflammatory drugs celecoxib (50 mg/kg; selective inhibitor of cyclooxygenase-2 (COX-2)) and ketorolac (20 mg/kg; inhibitor of COX-1 and -2) did not exhibit significant anti-hyperalgesic effects, in our disc injury animal model. Conclusions: Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disc 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 back pain patients due to disc degeneration.

Original languageEnglish (US)
JournalArthritis Research & Therapy
DOIs
StateAccepted/In press - Oct 13 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Rheumatology
  • Medicine(all)

Cite this

Kim, J. S., Kroin, J. S., Li, X., An, H. S., Buvanendran, A., Yan, D., Tuman, K. J., van Wijnen, A. J., Chen, D., & Im, H. J. (Accepted/In press). The rat intervertebral disc degeneration pain model: Relationship among biological and structural alterations and pain. Arthritis Research & Therapy. https://doi.org/10.1186/ar3485