Effect of intrathecal injection of dexmedetomidine on protein kinase C expression of spinal dorsal horn neurons in a rat model of chronic neuralgia / 中国组织工程研究

ABSTRACT

BACKGROUND:Dexmedetomidine is an efficient, highly selective alpha-2 adrenergic receptor agonist, with sedative, analgesia and anti-anxiety effects, it has little impact on the respiration. OBJECTIVE:To observe the analgesic effect induced by intrathecal injection of dexmedetomidine in rat model of spared nerve injury. METHODS:A total of 60 male Sprague-Dawley rats were randomly divided into three groups (n=12)normal control group, dexmedetomidine group and saline group. Except for the normal control group, spared nerve injury model was established in the rats of dexmedetomidine group and saline group. Dexmedetomidine group was treated with intrathecal injection of dexmedetomidine 3μg/kg every day within 14 days after injury. Saline group was given equal volume of saline for 14 days. The thermal withdrawal latency and mechanical withdrawal threshold were measured respectively before injury, after injury, before injection, and 2, 7, 14 days after intrathecal injection. Four rats were sacrificed in each group at day 2, 7 and 14 after injection, and the lumbar segments (L 4-6 Hematoxylin-eosin staining was performed to detect the morphology of the spinal dorsal horn neurons and ) of the spinal cord were removed. Real-time RT-PCR and western blot analysis were used to determine the expression of protein kinase C mRNA and protein in the spinal dorsal horn neurons. immunohistochemistry staining was carried out to assess the expression level and distribution of protein kinase C. RESULTS AND CONCLUSION:The thermal withdrawal latency and mechanical withdrawal threshold in dexmedetomidine group and saline group were significantly decreased compared with normal control group before or after injection (P<0.05). However, both the thermal withdrawal latency and mechanical withdrawal threshold in dexmedetomidine group after intrathecal injection were significantly higher than those in saline group (P<0.05). The protein kinase C expression in spinal dorsal horn neurons was significantly decreased in dexmedetomidine group compared with saline, and reached to the most lowest levels as normal control group on 14 days after injection. Moreover, the apoptosis of spinal dorsal horn neurons in dexmedetomidine group was lighter than that in saline group, and was similar to the morphology of neurons in normal control group on 14 days after injection. Intrathecal injection of dexmedetomidine could attenuate the hyperalgesia induced by spared nerve injury, which might be associated with the inhibition of protein kinase C expression in spinal dorsal horn.