西普罗酚通过调节脊髓和海马中的 α2GABAARs、NR2B 和 P-CaMKIIα 水平缓解瑞芬太尼引起的痛觉过敏。

Ciprofol alleviates remifentanil-induced hyperalgesia by regulating α2GABAARs, NR2B, and P-CaMKIIα levels in the spinal cord and hippocampus.

机构信息

Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China.

Bengbu Medical University, Bengbu 233030, Anhui, China.

出版信息

J Pharm Pharmacol. 2024 Jun 1;76(6):736-745. doi: 10.1093/jpp/rgae027.

DOI:10.1093/jpp/rgae027

PMID:38530642

Abstract

OBJECTIVES

Several studies have shown that propofol administration during surgery effectively attenuates remifentanil-induced hyperalgesia (RIH). Ciprofol, a novel intravenous sedative agent analogous to propofol, has not yet been proven efficacious in alleviating RIH. The present study aimed to investigate the effect of ciprofol on RIH and the possible mechanisms involved.

METHODS

The RIH model was established by an infusion of remifentanil (1 μg·kg-1·min-1) 60 min in rats with incisional pain. Ciprofol (0.1, 0.25, and 0.4 mg·kg-1·min-1) was simultaneously infused to evaluate its effect on RIH. The antinociception of ciprofol was verified by measured paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). γ-aminobutyric acid type A receptor α2 subunit (α2GABAAR), N-methyl-d-aspartate receptor NR2B subunit (NR2B), calcium/calmodulin-dependent protein kinase II α (CaMKIIα), and phosphorylated CaMKIIα (P-CaMKIIα) in the spinal cord and hippocampus of rats were assessed by western blotting and immunohistochemistry.

KEY FINDINGS

The results showed that ciprofol dose-dependently increased PWMT and PWTL values in RIH rats. Moreover, ciprofol upregulated α2GABAAR and downregulated NR2B and P-CaMKIIα in the rat spinal cord and hippocampus.

CONCLUSIONS

Ciprofol alleviates RIH effectively, and the anti-hyperalgesic mechanisms may involve increasing α2GABAAR levels and decreasing NR2B and P-CaMKIIα levels in the spinal cord and hippocampus.

摘要

目的

多项研究表明，手术期间给予异丙酚可有效减轻瑞芬太尼引起的痛觉过敏（RIH）。西普罗尔，一种类似于异丙酚的新型静脉镇静剂，尚未被证明能有效缓解 RIH。本研究旨在探讨西普罗尔对 RIH 的影响及其可能涉及的机制。

方法

通过在切口疼痛大鼠中输注瑞芬太尼（1μg·kg-1·min-1）60 分钟建立 RIH 模型。同时输注西普罗尔（0.1、0.25 和 0.4mg·kg-1·min-1），以评估其对 RIH 的作用。通过测量 paw withdrawal mechanical threshold (PWMT) 和 paw withdrawal thermal latency (PWTL) 来验证西普罗尔的镇痛作用。通过 Western blot 和免疫组织化学评估大鼠脊髓和海马中的γ-氨基丁酸 A 型受体α2 亚基（α2GABAAR）、N-甲基-D-天冬氨酸受体 NR2B 亚基（NR2B）、钙/钙调蛋白依赖性蛋白激酶 IIα（CaMKIIα）和磷酸化 CaMKIIα（P-CaMKIIα）。