Nicholas Vaudreuil1, Tiffany Kadow2, Takashi Yurube3, Robert Hartman4, Kevin Ngo2, Qing Dong2, Pedro Pohl5, J Paulo Coelho6, James Kang7, Nam Vo2, Gwendolyn Sowa6. 1. Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 200 Lothrop St, EBST 1640, Pittsburgh, PA 15261, USA. Electronic address: vaudreuilnj@upmc.edu. 2. Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 200 Lothrop St, EBST 1640, Pittsburgh, PA 15261, USA. 3. Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. 4. Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center, 200 Lothrop St, EBST 1640, Pittsburgh, PA 15261, USA. 5. Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 200 Lothrop St, EBST 1640, Pittsburgh, PA 15261, USA; Discipline of Orthopaedic Surgery and Traumatology, Spine Surgery Group, ABC Medical School (FMABC), 321 Dr. Henrique Calderazzo ST - 5th Floor, 09190-615 Sao Paulo, Brazil. 6. Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 200 Lothrop St, EBST 1640, Pittsburgh, PA 15261, USA; Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center, 200 Lothrop St, EBST 1640, Pittsburgh, PA 15261, USA. 7. Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
Abstract
BACKGROUND CONTEXT: Non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used treatment for low back pain (LBP). Literature on NSAID use in articular cartilage has shown detrimental effects; however, minimal data exist to detail the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a major cause of LBP, we explored the effects of indomethacin, a commonly used NSAID, on disc matrix homeostasis in an animal model of IDD. PURPOSE: This study aimed to determine the effects of oral indomethacin administration on IDD in an in vivo rabbit model. This study hypothesized that indomethacin use would accelerate the progression of IDD based upon serial imaging and tissue outcomes. STUDY DESIGN/ SETTING: This was a laboratory-based, controlled, in vivo evaluation of the effects of oral indomethacin administration on rabbit intervertebral discs. METHODS: Six skeletally mature New Zealand white rabbits were divided into two groups: disc puncture alone to induce IDD (Puncture group) and disc puncture plus indomethacin (Punc+Ind group). The Punc+Ind group received daily administration of 6mg/kg oral indomethacin. Serial magnetic resonance imaging (MRI) was obtained at 0, 4, 8, and 12 weeks. The MRI index and the nucleus pulposus (NP) area were calculated. Discs were harvested at 12 weeks for determination of disc glycosaminoglycan (GAG) content, relative gene expression measured by real-time polymerase chain reaction, and histologic analyses. RESULTS: The MRI index and the NP area of punctured discs in the Punc+Ind group demonstrated no worsening of degeneration compared with the Puncture group. Histologic analysis was consistent with less severe disc degeneration in the Punc+Ind group. Minimal differences in gene expression of matrix genes were observed between Puncture and Punc+Ind groups. The GAG content was higher in animals receiving indomethacin in both annulus fibrosus and NP at adjacent uninjured discs. CONCLUSIONS: Oral indomethacin administration did not result in acceleration of IDD in an in vivo rabbit model. Future research is needed to ascertain long-term effects of indomethacin and other NSAIDs on disc matrix homeostasis.
BACKGROUND CONTEXT: Non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used treatment for low back pain (LBP). Literature on NSAID use in articular cartilage has shown detrimental effects; however, minimal data exist to detail the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a major cause of LBP, we explored the effects of indomethacin, a commonly used NSAID, on disc matrix homeostasis in an animal model of IDD. PURPOSE: This study aimed to determine the effects of oral indomethacin administration on IDD in an in vivo rabbit model. This study hypothesized that indomethacin use would accelerate the progression of IDD based upon serial imaging and tissue outcomes. STUDY DESIGN/ SETTING: This was a laboratory-based, controlled, in vivo evaluation of the effects of oral indomethacin administration on rabbit intervertebral discs. METHODS: Six skeletally mature New Zealand white rabbits were divided into two groups: disc puncture alone to induce IDD (Puncture group) and disc puncture plus indomethacin (Punc+Ind group). The Punc+Ind group received daily administration of 6mg/kg oral indomethacin. Serial magnetic resonance imaging (MRI) was obtained at 0, 4, 8, and 12 weeks. The MRI index and the nucleus pulposus (NP) area were calculated. Discs were harvested at 12 weeks for determination of disc glycosaminoglycan (GAG) content, relative gene expression measured by real-time polymerase chain reaction, and histologic analyses. RESULTS: The MRI index and the NP area of punctured discs in the Punc+Ind group demonstrated no worsening of degeneration compared with the Puncture group. Histologic analysis was consistent with less severe disc degeneration in the Punc+Ind group. Minimal differences in gene expression of matrix genes were observed between Puncture and Punc+Ind groups. The GAG content was higher in animals receiving indomethacin in both annulus fibrosus and NP at adjacent uninjured discs. CONCLUSIONS: Oral indomethacin administration did not result in acceleration of IDD in an in vivo rabbit model. Future research is needed to ascertain long-term effects of indomethacin and other NSAIDs on disc matrix homeostasis.
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