Effect of intrathecal down-regulation of 5-HT_(5A) receptors by RNA interference in rats with chemotherapy-evoked hyperalgesia

Objective:To investigate the role of 5-HT5A receptors in rats with chemo the rapy-evoked hyperalgesia by intra the calinjection of adenovirus-mediated small-interference RNA.Methods:Adult male SD rats were randomly divided into 2 groups:model group(n=10,intraperitoneal injection of vincristine)and control group(n=10,intraperitoneal injection of normal saline).The mechanical hyperalgesia were measured as the paw withdrawal thresholds(PWT)and the expression of 5-HT5AR mRNA in L4、5 spinal cord were determined by RT-PCR.Thirty rats with chemotherapy-evoked hyperalgesia were randomly divided into 3 groups after the formation of chemotherapy pain model:experimental group,negative control group and blank control group,which respectively were treated with intrathecal injection of Ad-5-HT5AR-siRNA,Ad-X-HK and normal saline.Expressions of 5-HT5AR mRNA and PWT after intrathecal injection were assessed respectively.Results:Compared with control group,PWT of rats in model group were significantly decreased(P0.01),and levels of 5-HT5AR mRNA were increased.But after intrathecal injection,expressions of 5-HT5AR mRNA were down-regulated in experimental group.Meanwhile,PWT of rats in experimental group were lower than those in negative control group and blank control group(P0.05).Conclusion:5-HT5AR is involved in the mechanism of chemotherapy-evoked hyperalgesia and may has antinociceptive effect.