目的:探讨腹腔注射右美托咪啶(dexmedetomidine,DEX)对糖尿病神经病理性疼痛(diabetic neuropathic pain,DNP)大鼠的镇痛作用以及对脊髓背角P2X3受体表达的影响.方法:建立DNP大鼠模型,检测大鼠机械痛阈;给予腹腔注射DEX(12.5、25、50 μg/kg.d)后,观察DEX对DNP大鼠的镇痛作用;免疫组化法检测大鼠L4~6脊髓背角P2X3受体表达变化.结果:糖尿病大鼠建模成功后28 d,糖尿病大鼠与正常大鼠比较机械痛阈值明显下降;从建模后35 d开始,DNP大鼠连续7d给予腹腔注射DEX后其机械痛阈值显著升高,脊髓背角P2X3受体表达显著下调;机械痛阈值升高幅度以及脊髓背角P2X3受体表达下调幅度与DEX剂量相关.结论:腹腔注射DEX通过下调DNP大鼠脊髓背角P2X3受体表达,对DNP大鼠产生镇痛作用.
Objective: To investigate the analgesic role of dexmedetomidine (DEX) on neuropathic pain in streptozotocin-induced diabetic rats and the alterations of spinal dorsal horn (SDH) P2X3 receptor expression. Methods: Male Sprague-Dawley (SD) rats were used in this study. Diabetes was induced by peritoneal injection with streptozotocin(STZ, 80 mg/kg) and the pain threshold was characterized by the mechanical withdrawal threshold testing. DEX ( 12.5, 25, 50 μg/kg.d ) was administered on 35 d post STZ injection for 7 consecutive days; The expressions of P2X3 receptor in L4-6 SDH were detected by immunohistochemisty assay. Results: The diabetic neuropathic pain (DNP) rats showed a significant decrease on MWT values accompanied with P2X3 receptor expressions increased in L4-6 SDH on 28d after STZ, i.p; The DNP rats were administered with DEX intraperitoneally for 7 consecutive days dose-dependently increased the MWT values and down-regulated P2X3 receptor expression in L4-6 SDH. Conclusions: These results imply that DEX exerts an analgesic effect in DNP rats via down-regulation of L4-6 SDH P2X3 receptor expression.