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Effects of Ethyl Pyruvate on Allodynia, TNF-α Expression, and Apoptosis in the Dorsal Root Ganglion after Spinal Nerve Ligation Injury

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Background:It has been demonstrated that the expression of tumor necrosis factor-a (TNF-a) and apoptotic cell death in the dorsal root ganglion (DRG) following spinal nerve constriction injury play a role in the initiation and continuation of hyperalgesia and allodynia. The present study was designed to investigate the effects of ethyl pyruvate (EP) on mechanical and cold allodynia, TNF-a expression, and apoptosis in DRG after spinal nerve ligation injury. Methods:Rats were divided into 3 groups: control, pre-EP, and post-EP. EP (50 mg/kg) was intraperitoneally injected 30 minutes before (pre-EP) or after (post-EP) surgery. Behavioral tests to determine mechanical and cold allodynia were conducted before surgery and 4 and 7 days after surgery. Seven days after surgery, TNF-a protein levels in DRG were evaluated by enzyme-linked immunosorbent assay, and DRG apoptosis was determined by immunohistochemical detection of activated caspase-3. Results:Treatment with EP significantly reduced mechanical and cold allodynia following spinal nerve ligation injury. TNF-a protein levels in the pre-EP (4.7 ± 1.2 pg/200 mg; P < 0.001) and post-EP (6.4 ± 1.8 pg/200 mg; P < 0.001) groups were 2−3 times lower than the control group (14.4 ± 1.2 pg/200 mg). The percentages of neurons and satellite cells that co-localized with caspase-3 were also significantly lower in the pre-EP and post-EP groups than the control group. Conclusions:These results demonstrate that EP has a strong anti-allodynic effect that acts through the inhibition of TNF-a expression and apoptosis in DRG after spinal nerve ligation injury.

Abstract

Background:It has been demonstrated that the expression of tumor necrosis factor-a (TNF-a) and apoptotic cell death in the dorsal root ganglion (DRG) following spinal nerve constriction injury play a role in the initiation and continuation of hyperalgesia and allodynia. The present study was designed to investigate the effects of ethyl pyruvate (EP) on mechanical and cold allodynia, TNF-a expression, and apoptosis in DRG after spinal nerve ligation injury. Methods:Rats were divided into 3 groups: control, pre-EP, and post-EP. EP (50 mg/kg) was intraperitoneally injected 30 minutes before (pre-EP) or after (post-EP) surgery. Behavioral tests to determine mechanical and cold allodynia were conducted before surgery and 4 and 7 days after surgery. Seven days after surgery, TNF-a protein levels in DRG were evaluated by enzyme-linked immunosorbent assay, and DRG apoptosis was determined by immunohistochemical detection of activated caspase-3. Results:Treatment with EP significantly reduced mechanical and cold allodynia following spinal nerve ligation injury. TNF-a protein levels in the pre-EP (4.7 ± 1.2 pg/200 mg; P < 0.001) and post-EP (6.4 ± 1.8 pg/200 mg; P < 0.001) groups were 2−3 times lower than the control group (14.4 ± 1.2 pg/200 mg). The percentages of neurons and satellite cells that co-localized with caspase-3 were also significantly lower in the pre-EP and post-EP groups than the control group. Conclusions:These results demonstrate that EP has a strong anti-allodynic effect that acts through the inhibition of TNF-a expression and apoptosis in DRG after spinal nerve ligation injury.

참고문헌 (33)

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