Effect Of Dexmedetomidine On The Expression Of P38Mitogen-activated Protein Kinase And Brain-derived Neurotrophic Factor MRNA In Spinal Cord Of Rat With Neuropathic Pain

Objective:To investigate the analgesic effects of dexmedetomidine on p38mitogen-activated protein kinase （p38MAPK） and brain-derived neurotrophic factor （BDNF） mRNA expression in the spinal cord of rat with sciatic nerve chronic constriction injury （CCI） induced neuropathic pain, and explore the potential mechanism of dexmedetomidine on the neuropathic pain, which provides a theoretical basis and method for the treatment of neuropathic pain.Methods:Seventy-two male SD rats weighing180-220g were randomly divided into3groups （n=24each）:sham operation group （group S）, chronic constriction injury group （group C）, dexmedetomidine group （group D）. In group S the right sciatic nerves was exposed but not ligated, in group C and group S four ligatures were placed around the right sciatic nerve. From the instant after operation50ug/kg of dexmedetomidine was injected separately and intraperitoneally into group D daily, and respectively the same volume normal saline was injected into group S and group C. Mechanical and thermal pain threshold was measured by paw withdrawal latencies at Id before operation and the1,3,7,14d after operation. After the measurement of pain threshold at1,3,7,14d after operation, the L4₆segments of the spinal cord were removed for determination of the expression of p38MAPK and BDNF mRNA by reverse transcription-polymerase chain reaction （RT-PCR）.Results:Mechanical and thermal pain threshold was markedly reduced at1,3,7,14d after operation, and p38MAPK and BDNF mRNA expression was significantly up-regulated in group C as compared with group S （P<0.05）; Compared with group C the mechanical and thermal pain threshold was significantly increased at the3,7,14d after operation, and p38MAPK and BDNF mRNA expression was markedly down-regulated in group D （P<0.05）; In group C and group D the mechanical and thermal pain threshold was significantly reduced at1,3,7,14d after operation compared with before operation, and to a minimum at the7d after operation （P<0.05）; Compared with l d after operation, the p38MAPK and BDNF mRNA in group C and group D was significantly increased at the3,7,14d after operation, and to the highest at the7d after operation （P<0.05）; The correlation analysis on p38MAPK mRNA and BDNF mRNA revealed the Pearson correlation coefficient was0.901, suggesting a strong positive correlation between p38MAPK mRNA and BDNF mRNA （P<.05）.Conclusion:Dexmedetomidine showed an obvious analgesic effects on CCI of rats, which was possibly mediated via the decrease of p38MAPK, and down-regulation of BDNF expression in the spinal cord.