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利多卡因与QX-572联合应用在小鼠中诱发不同的疼痛行为。

Co-application of lidocaine and QX-572 induces divergent pain behaviours in mice.

作者信息

Shao Cui-Jie, Gao Yong, Zhao Li, Jin Dan, Wang Dan, Wang De-Qiang

机构信息

Department of Pain, The Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong, China.

The People's Hospital of Binzhou, Binzhou, Shandong, China.

出版信息

J Pharm Pharmacol. 2015 Sep;67(9):1272-8. doi: 10.1111/jphp.12419. Epub 2015 Apr 23.

Abstract

OBJECTIVES

We investigated the analgesic effects of lidocaine (LDC) and lidocane derivative, QX-572, co-application on the evoked pain behaviour (complete Freund's Adjuvant (CFA)-induced) and spontaneous pain behaviour (formalin-induced) in mice.

METHODS

The experiments were performed using adult male Kunming mice. Formalin-induced acute pain model and CFA-induced chronic pain model was established by injecting formalin and CFA, respectively. Separate injections of LDC and QX-572, or co-injection of LDC and QX-572, were performed to observe the differences in neurobehavioural responses, paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT).

KEY FINDINGS

QX-572 injection alone did not influence PWL and MWT, but injection of LDC alone led to a substantial, but short-lived, elevation in PWL and MWT (45 min). Co-injection of LDC and QX-572, however, resulted in a significant increase in PWL and MWT (120 min) compared with the LDC group. Injection of LDC and QX-572 combination in the adjacent sciatic nerve also produced a long-lasting sensory-specific nerve block. Additionally, intraplantar co-injection of LDC and QX-572 combination inhibited spontaneous pain in formalin-treated mice, but did not detectably attenuated hyperalgesia and allodynia in CFA-treated mice.

CONCLUSIONS

Our results provide evidence that QX-572 induced sensory-selective blockade and co-injection of QX-572 and LDC enhance pain blockade, as evident from formalin-treated mice.

摘要

目的

我们研究了利多卡因(LDC)和利多卡因衍生物QX - 572联合应用对小鼠诱发疼痛行为(完全弗氏佐剂(CFA)诱导)和自发疼痛行为(福尔马林诱导)的镇痛作用。

方法

实验使用成年雄性昆明小鼠进行。分别通过注射福尔马林和CFA建立福尔马林诱导的急性疼痛模型和CFA诱导的慢性疼痛模型。分别注射LDC和QX - 572,或联合注射LDC和QX - 572,观察神经行为反应、爪退缩潜伏期(PWL)和机械性退缩阈值(MWT)的差异。

主要发现

单独注射QX - 572不影响PWL和MWT,但单独注射LDC导致PWL和MWT显著但短暂升高(45分钟)。然而,与LDC组相比,联合注射LDC和QX - 572导致PWL和MWT显著增加(120分钟)。在相邻坐骨神经注射LDC和QX - 572组合也产生了持久的感觉特异性神经阻滞。此外,足底联合注射LDC和QX - 572组合可抑制福尔马林处理小鼠的自发疼痛,但未检测到对CFA处理小鼠的痛觉过敏和异常性疼痛有明显减轻作用。

结论

我们的结果提供了证据,表明QX - 572诱导感觉选择性阻滞,并且从福尔马林处理的小鼠中可以明显看出,联合注射QX - 572和LDC可增强疼痛阻滞效果。

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