Clonidine And Dexmedetomidine’s Effect On The Changes Of Expression Of Growth Associated Protein-43Mrna In Rat Dorsal Root Ganglion During The Development Of Neuropathic Pain

Objective To observe the effect of α2adrenergic receptor agonists clonidine （CL） and dexmedetomidine （Dex） on expression of growth associated protein-43（GAP-43） mRNA in dorsal root ganglions of rats with sciatic sciatic nerve chronic constriction injury. Meanwhile, to investigate the effect of a2adrenergic receptor agonists clonidine and dexmedetomidine on the GAP-43, which can provide a rationale for neuropathic pain prevention and treatment.Methods seventy-two male SD rats weighing180-250g were randomly divided into4groups:sham operation group （S group）, control group （C group）, clonidine group （CL group） and dexmedetomidine group （Dex group）. There were18rats in each group. In S group, the right sciatic nerves were exposed but not ligated, and in other groups four ligatures were placed around the right sciatic nerve. From the instant after operation,0.4mg/kg clonidine and50.0μg/kg dexmedetomidine were injected separately and intraperitoneally into CL group and Dex group daily, and respectively the same volume normal saline was injected into S group and CCI group. Mechanical and thermal pain threshold were measured by paw withdrawal latencies at1d before operation and the3rd,7th,14th d after operation. After that, the L4₆dorsal root ganglions to the chronic constriction injured sciatic nerves were harvested. Reverse transcription-polymerase chain reaction （RT-PCR） and agarose gel electrophoresis analysis were used to examine the expression of GAP-43mRNA.Results1. Mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL）:MWT and TWL of group C, CL and Dex markedly reduced at the3rd,7th,14th d after operation compared with those before operation and with group S （P<0.05）. MWT and TWL of group CL and Dex at the3rd7th,14th d after operation was significantly increased compared with those of group C （P<0.05）. MWT and TWL of group Dex at the3rd7th,14th d after operation was significantly higher than those of group CL（P<0.05）. Compared with3rd d, MWT and TWL of group C, CL and Dex markedly reduced at the7th d （P<0.05）. Compared with7rd d, MWT and TWL of group CL and Dex markedly increased at the14rd d （P<0.05）, but which of group C had no significance（P>0.05）.2. GAP-43mRNA expression in the dorsal root ganglions:GAP-43mRNA expression of group C, CL and Dex in the dorsal root ganglions was significantly increased at the3rd,7th,14th d after operation compared with those before operation and with group S （P<0.05）. GAP-43mRNA expression of group CL and Dex in the dorsal root ganglions at the3rd,7th,14th d after operation was evidently reduced compared with those of group C （P<0.05）. GAP-43mRNA expression of group Dex in the dorsal root ganglions at the3rd,7th,14th d after operation was lower than those of group CL（P<0.05）. Compared with3rd d, GAP-43mRNA expression of group C, CL and Dex in the dorsal root ganglions was significantly increased at the7th d after operation （P<0.05）. Compared with7th d, GAP-43mRNA expression of group CL and Dex in the dorsal root ganglions was significantly reduced at the14th d after operation （P<0.05）, but which of group C had no significance（P>0.05）.Conclusions1. Clonidine and dexmedetomidine injection can both relieve rat’s symptom of heat and mechanical hyperalgesia after sciatic nerve chronic constriction injury. Dexmedetomidine shows better analgesic effects on chronic neuropathic pain of rats than clonidine.2. Clonidine and dexmedetomidine can both reduce GAP-43mRNA expression in the dorsal root ganglions of rats after sciatic nerves chronic constriction injured. Dexmedetomidine shows better analgesic effects on chronic neuropathic pain of rats than clonidine.