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

ABSTRACT

BACKGROUND: It has been demonstrated that the expression of tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha 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-alpha protein levels in the pre-EP (4.7 +/- 1.2 pg/200 microg; P < 0.001) and post-EP (6.4 +/- 1.8 pg/200 microg; P < 0.001) groups were 2-3 times lower than the control group (14.4 +/- 1.2 pg/200 microg). 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-alpha expression and apoptosis in DRG after spinal nerve ligation injury.