NSAID use in intervertebral disc degeneration: what are the effects on matrix homeostasis in vivo?

Abstract

Background Context Non-steroidal anti-inflammatory (NSAID) agents are a widely utilized 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 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) were obtained at 0, 4, 8, and 12 weeks. MRI index and 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 histological analyses. Results MRI index and NP area of punctured discs in the Punc+Ind group demonstrated no worsening of degeneration compared to the Puncture group. Histological 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. GAG content was higher in animals receiving indomethacin in both annulus fibrosus (AF) 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.

Photopolymerizable biogel scaffold seeded with mesenchymal stem cells: safety and efficacy evaluation of novel treatment for intervertebral disc degeneration

“…Our small sample size precluded our ability to test all possible intervention groups (i.e., “MSCs + gel” without light or “MSCs + light” without gel) and required us to limit the focus of our investigations. Although the small sample size limited our ability to detect significant changes, it is consistent with the previously reported animal studies of this nature . A second limitation was the use of a severe and rapid disc degeneration model.…”

“…The third group ( n = 3) was randomly selected as the treatment group treated with both annular puncture and later injection into the NP of stabbed discs with the photopolymerizable biogel seeded with MSCs (“MSC + Gel”). The number of rabbits per group was determined by prior experience with this rabbit model …”

“…Rabbits in the Stab and MSC + Gel groups underwent a previously described and validated method of annular stab to induce IDD . This method of inducing disc injury has been shown to result in findings consistent with IDD including characteristic histologic and magnetic resonance imaging (MRI) changes . Prior to surgery, rabbits were brought to a veterinary operating room, sedated, endotracheally intubated, and placed under general anesthesia.…”

“…The number of rabbits per group was determined by prior experience with this rabbit model. [13][14][15][16][17] Annular Puncture Surgery Rabbits in the Stab and MSC þ Gel groups underwent a previously described and validated method of annular stab to induce IDD. 17 This method of inducing disc injury has been shown to result in findings consistent with IDD including characteristic histologic and magnetic resonance imaging (MRI) changes.…”

“…17 This method of inducing disc injury has been shown to result in findings consistent with IDD including characteristic histologic and magnetic resonance imaging (MRI) changes. 14,15 Prior to surgery, rabbits were brought to a veterinary operating room, sedated, endotracheally intubated, and placed under general anesthesia. The rabbits were placed in the lateral decubitus position and the spine was approached via an anterolateral retroperitoneal approach.…”