• Int J Clin Exp Patho · Jan 2012

    Down-regulation of GAP-43 by inhibition of caspases-3 in a rat model of neuropathic pain.

    • Feixiang Wu, Xuerong Miao, Jiaying Chen, Yuming Sun, Zhiqiang Liu, Yong Tao, and Weifeng Yu.
    • Department of Anesthesiology, Eastern Hepatobiliary Hospital, the Second Military Medical University No. 225 Changhai Road, Shanghai 200433, China.
    • Int J Clin Exp Patho. 2012 Jan 1;5(9):948-55.

    BackgroundNeuropathic pain remains a prevalent and persistent clinical problem due to incomplete understanding of its pathogenesis.ObjectiveThe present study aimed to investigate the role of caspase-3 in the neuropathic pain in rats with chronic constriction injury (CCI).MethodsSD rats were randomly assigned four groups (n=18 per group): sham group, normal saline group (NS group), Z-DEVD-FMK group (DEVD group) and RNA interference group (siRNA group). Z-DEVD-FMK (1 U/30 μl), siRNA targeting caspase-3 (10 μg/30 μl) and NS of equal volume were intrathecally administered once daily for 5 days starting 1 day before surgery in the DEVD, siRNA and NS group, respectively. Thermal hyperalgesia was assessed at one day before and 1, 2, 4, 5, 6, 7 and 10 days after surgery. The mRNA and protein expressions of caspase-3 were measured by real time PCR and immunofluorescence assay. Apoptosis was detected by TUNEL staining. GAP-43 expression was measured by immunofluorescence and western blot assays.ResultsThe right paw withdrawal latency (PWL) was decreased after CCI (P<0.05). TUNEL-positive neurons and the mRNA and protein expressions of caspase-3 in the spinal cord were increased significantly. After Z-DEVD-FMK or siRNA treatment, TUNEL-positive neurons were decreased, PWLs increased (P<0.05) and the mRNA and protein expressions of caspase-3 decreased. The expression of GAP-43, a sprouting related protein, was decreased in the DEVD and siRNA group as compared to NS group (P<0.05). Up-regulation of GAP-43 following CCI was decreased following caspase-3 inhibition. Following sciatic nerve ligation, the gene expression, translation and transcription are significantly changed in the neurons which finally results in neuron apoptosis. The neuron apoptosis induce the up-regulation of GAP-43 expression leading to hyperalgesia.ConclusionCaspase-3 mediated neuron apoptosis is probably responsible for the neuropathic pain in CCI rats. Inhibition of caspase-3 may serve as a treatment of neuropathic pain.

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