Tumor Necrosis Factor-alpha and Apoptosis Following Spinal Nerve Ligation Injury in Rats
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Background:Spinal nerve ligation (SNL) injury in rats produces a pain syndrome that includes mechanical and thermal allodynia. Previous studies have indicated that proinflammatory cytokines such as tumor necrosis factor-a (TNF-a) play an important role in peripheral mediation of neuropathic pain, and that altered dorsal root ganglion (DRG) function and degree of DRG neuronal apoptosis are associated with spinal nerve injury. The present study was conducted to evaluate the expression of TNF-a and the extent of apoptosis in the dorsal root ganglion after SNL in rats. Methods:Sprague-Dawley rats were subjected to SNL of the left L5 and L6 spinal nerves distal to the DRG and proximal to the formation of the sciatic nerve. At postoperative day 8, TNF-a protein levels in the L5−6 DRG were compared between SNL and naive groups using ELISA. In addition, we compared the percentage of neurons injured in the DRG using immunostaining for apoptosis and localization of activated caspase-3. Results:SNL injury produced significant mechanical and cold allodynia throughout the 7-day experimental period. TNF-a protein levels were increased in the DRG in rats that had undergone SNL (12.7 ± 3.2 pg/100 mg, P ＜ 0.001) when compared with naïve rats (4.1 ± 1.4 pg/100 mg). The percentage of neurons or satellite cells co-localized with activated caspase-3 were also significantly higher in rats with SNL than in naïve rats (P ＜ 0.001, P ＜ 0.05, respectively). Conclusions:SNL injury produces mechanical and cold allodynia, as well as TNF-α elevation and apoptosis in the DRG. (Korean J Pain 2011; 24: 185-190)
Abstract
Background:Spinal nerve ligation (SNL) injury in rats produces a pain syndrome that includes mechanical and thermal allodynia. Previous studies have indicated that proinflammatory cytokines such as tumor necrosis factor-a (TNF-a) play an important role in peripheral mediation of neuropathic pain, and that altered dorsal root ganglion (DRG) function and degree of DRG neuronal apoptosis are associated with spinal nerve injury. The present study was conducted to evaluate the expression of TNF-a and the extent of apoptosis in the dorsal root ganglion after SNL in rats. Methods:Sprague-Dawley rats were subjected to SNL of the left L5 and L6 spinal nerves distal to the DRG and proximal to the formation of the sciatic nerve. At postoperative day 8, TNF-a protein levels in the L5−6 DRG were compared between SNL and naive groups using ELISA. In addition, we compared the percentage of neurons injured in the DRG using immunostaining for apoptosis and localization of activated caspase-3. Results:SNL injury produced significant mechanical and cold allodynia throughout the 7-day experimental period. TNF-a protein levels were increased in the DRG in rats that had undergone SNL (12.7 ± 3.2 pg/100 mg, P ＜ 0.001) when compared with naïve rats (4.1 ± 1.4 pg/100 mg). The percentage of neurons or satellite cells co-localized with activated caspase-3 were also significantly higher in rats with SNL than in naïve rats (P ＜ 0.001, P ＜ 0.05, respectively). Conclusions:SNL injury produces mechanical and cold allodynia, as well as TNF-α elevation and apoptosis in the DRG. (Korean J Pain 2011; 24: 185-190)
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