Effect Of Intrathecal Down-Regulation Of 5-HT_5A Receptors By Rna Interference In Rats With Chemotherapy-Evoked Hyperalegsia

Objective: To investigate the role of 5-HT5A receptors in rats with chemotherapy-evoked hyperalgesia by intrathecal injection 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 (P<0.01), and levels of 5-HT5AR mRNA were increased. But after intrathecal injection, expressions of 5-HT5AR 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 (P<0.05).Conclusions: 5-HT5AR is involved in the mechanism of chemotherapy-evoked hyperalgesia and may has antinociceptive effect.