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外周神经病变的临床前模型与药物研究综述

Navigating Preclinical Models and Medications for Peripheral Neuropathy: A Review.

作者信息

Jali Abdulmajeed M, Banji David, Banji Otilia J F, Hurubi Khalid Y, Tawhari Faisal Y, Alameer Atheer A, Dohal Atyaf S, Zanqoti Raha A

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.

Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.

出版信息

Pharmaceuticals (Basel). 2024 Jul 31;17(8):1010. doi: 10.3390/ph17081010.

Abstract

Peripheral neuropathy (PN) is a multifaceted disorder characterised by peripheral nerve damage, manifesting in symptoms like pain, weakness, and autonomic dysfunction. This review assesses preclinical models in PN research, evaluating their relevance to human disease and their role in therapeutic development. The Streptozotocin (STZ)-induced diabetic rat model is widely used to simulate diabetic neuropathy but has limitations in faithfully replicating disease onset and progression. Cisplatin-induced PN models are suitable for studying chemotherapy-induced peripheral neuropathy (CIPN) and closely resemble human pathology. However, they may not fully replicate the spectrum of sensory and motor deficits. Paclitaxel-induced models also contribute to understanding CIPN mechanisms and testing neuroprotective agents. Surgical or trauma-induced models offer insights into nerve regeneration and repair strategies. Medications such as gabapentin, pregabalin, duloxetine, and fluoxetine have demonstrated promise in these models, enhancing our understanding of their therapeutic efficacy. Despite progress, developing models that accurately mirror human PN remains imperative due to its complex nature. Continuous refinement and innovative approaches are critical for effective drug discovery. This review underscores the strengths and limitations of current models and advocates for an integrated approach to address the complexities of PN better and optimise treatment outcomes.

摘要

周围神经病变(PN)是一种多方面的疾病,其特征为周围神经损伤,表现为疼痛、无力和自主神经功能障碍等症状。本综述评估了PN研究中的临床前模型,评估它们与人类疾病的相关性及其在治疗开发中的作用。链脲佐菌素(STZ)诱导的糖尿病大鼠模型被广泛用于模拟糖尿病神经病变,但在忠实地复制疾病的发生和进展方面存在局限性。顺铂诱导的PN模型适用于研究化疗诱导的周围神经病变(CIPN),且与人类病理学非常相似。然而,它们可能无法完全复制感觉和运动功能障碍的范围。紫杉醇诱导的模型也有助于理解CIPN机制和测试神经保护剂。手术或创伤诱导的模型为神经再生和修复策略提供了见解。加巴喷丁、普瑞巴林、度洛西汀和氟西汀等药物在这些模型中已显示出前景,增进了我们对其治疗效果的理解。尽管取得了进展,但由于PN的性质复杂,开发能够准确反映人类PN的模型仍然势在必行。持续改进和创新方法对于有效的药物发现至关重要。本综述强调了当前模型的优势和局限性,并主张采用综合方法来更好地应对PN的复杂性并优化治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fb1/11357099/691766907bbc/pharmaceuticals-17-01010-g001.jpg

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