Investigation of the Effect of Diabetes on Radiculopathy Induced by Nucleus Pulposus Application to the DRG in a Spontaneously Diabetic Rat Model.

<bold>Study Design: </bold>A controlled, interventional animal study.<bold>Objective: </bold>The aim of this study was to evaluate the effect of diabetes mellitus (DM) on radiculopathy due to lumbar disc herniation (LDH), by investigating pain-related behavior and the expression of tumor necrosis factor-alpha (TNF-α) and growth-associated protein 43 (GAP43) in type 2 diabetic rats following application of nucleus pulposus (NP) to the dorsal root ganglion (DRG).<bold>Summary Of Background Data: </bold>Previous clinical studies suggested negative effects of DM on radiculopathy due to LDH, and that inflammation and nerve regeneration could interact with DM and radiculopathy.<bold>Methods: </bold>We applied autologous NP to the left L5 DRG of adult male Wistar rats and Goto-Kakizaki rats. Behavioral testing measured the mechanical withdrawal threshold of rats. We immunohistochemically evaluated the localization of ionized calcium-binding adapter molecule-1 (Iba-1), receptor of advanced glycation end products (RAGE), and TNF-α in DRGs. TNF-α and GAP43 expression levels in DRG were determined by quantitative real-time PCR and western blotting.<bold>Results: </bold>The mechanical withdrawal threshold significantly declined in the non-DM NP group compared with the non-DM sham group for 28 days, whereas the decline in threshold extended to 35 days in the DM NP group compared with the DM sham group. RAGE and TNF-α expression in DRGs was colocalized in Iba-1 positive cells. The non-DM NP rats had higher TNF-α protein expression levels versus the non-DM sham rats on day 7, and the DM NP group had higher levels versus the DM sham group on days 7 and 14. The non-DM NP group had higher GAP43 mRNA expression than the non-DM sham group for 28 days, while the DM NP group had a higher level than the DM sham group for 35 days.<bold>Conclusion: </bold>DM prolongs the pain-related behavior caused by NP. The prolonged inflammation and nerve regeneration could elucidate the pathogenesis of continuous pain of radiculopathy initiated by LDH.<bold>Level Of Evidence: </bold>N /A. [ABSTRACT FROM AUTHOR]