Department of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China.
Department of Pharmacology, School of Pharmacy, and Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China; The 154th Central Hospital of PLA, Xinyang 464000, China.
Brain Res. 2019 Jun 1;1712:55-62. doi: 10.1016/j.brainres.2019.02.001. Epub 2019 Feb 4.
Patients with irritable bowel syndrome suffer from chronic visceral pain, and in some of them, this is accompanied by anxiety comorbidity. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the cytoplasmic polyadenylation of mRNAs and facilitates their translation. Our previous studies have shown that CPEB1 knockdown in the amygdala exerts anxiolytic but not analgesic effects in a mouse model of inflammatory pain. However, the roles of CPEB1 in the anterior cingulate cortex (ACC) in visceral pain modulation remain unclear. In this study, a visceral pain mouse model was established by injecting zymosan into the colon of mice. Zymosan injection significantly induced visceral pain- and anxiety-like behaviors in mice and increased the levels of GluA1, phosphorylated GluA1 at S845 and S831, and CPEB1 in the ACC. CPEB1 knockdown in the ACC by AAV-CPEB1-shRNA reduced zymosan-induced pain- and anxiety-like behaviors in mice. This observation was closely correlated with reduced AMPA receptor, synaptophysin, and PSD95 levels. These data suggest that CPEB1 in the ACC is a potential therapeutic target for visceral pain and anxiety comorbidity.
肠易激综合征患者患有慢性内脏疼痛，在其中一些患者中，这种疼痛伴有焦虑共病。细胞质多聚腺苷酸化元件结合蛋白 1（CPEB1）介导 mRNA 的细胞质多聚腺苷酸化，并促进其翻译。我们之前的研究表明，在炎症性疼痛的小鼠模型中，杏仁核中的 CPEB1 敲低具有抗焦虑作用，但没有镇痛作用。然而，CPEB1 在内脏疼痛调节中的前扣带皮层（ACC）中的作用尚不清楚。在这项研究中，通过向小鼠结肠注射酵母聚糖来建立内脏疼痛小鼠模型。酵母聚糖注射显著诱导小鼠内脏疼痛和焦虑样行为，并增加 ACC 中的 GluA1、磷酸化 GluA1 的 S845 和 S831 以及 CPEB1 的水平。通过 AAV-CPEB1-shRNA 在 ACC 中敲低 CPEB1 可降低酵母聚糖诱导的小鼠疼痛和焦虑样行为。这一观察结果与 AMPA 受体、突触小体蛋白和 PSD95 水平降低密切相关。这些数据表明，ACC 中的 CPEB1 是内脏疼痛和焦虑共病的潜在治疗靶点。
