Lidocaine suppresses the increased extracellular signal-regulated kinase/cyclic AMP response element-binding protein pathway and pro-inflammatory cytokines in a neuropathic pain model of rats

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Background and objectiveRats which have undergone spinal nerve ligation (SNL) display increases in the expression of extracellular signal-regulated kinase (ERK 1/2) and cyclic AMP response element-binding (CREB) protein. The present study was designed to determine whether lidocaine has a beneficial effect on the treatment of neuropathic pain by analysing related proteins.MethodsTwenty-four male Sprague–Dawley rats were randomly allocated to three groups (eight per group): sham-operated (control) group, a neuropathic pain and normal saline group (NP+NS), a neuropathic pain and lidocaine group (NP+Lido, 2 mg kg−1 h−1). Anaesthetised rats received left L5 and L6 SNL. The mechanical withdrawal threshold test was performed 7 days after SNL and for 7 days with the pump implanted (saline or lidocaine). At post-implanted pump day 7, their brains and spinal cords were harvested. ERK 1/2, CREB proteins and mRNA amounts of pro-inflammatory cytokines (tumour necrosis factor α, intercellular adhesion molecule 1, monocyte chemo-attractive protein 1 and macrophage inflammatory protein 2) were assessed by immunoblotting or reverse transcriptase-PCR on samples collected from the three groups.ResultsLidocaine increased the mechanical withdrawal threshold of a neuropathic rats. In only spinal tissues, ERK 1/2 and CREB proteins in the NP+Lido group was significantly reduced to 39%, and 48% in comparison with the NP+NS group. The NP+Lido group showed a significant reduction in mRNA amounts of pro-inflammatory cytokines compared with the NP+NS group (P < 0.05).ConclusionThese results suggest that lidocaine therapy may be effective in treating neuropathic pain after spinal nerve injury, and that these effects may occur via suppression of ERK 1/2 and CREB signalling proteins and anti-inflammatory effects.

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