Department of Pharmacology, College of Medicine, The University of Arizona, Tucson.
Department of Anesthesiology, College of Medicine, The University of Arizona, Tucson.
J Vis Exp. 2022 Oct 6(188). doi: 10.3791/64555.
Management of chronic pain remains challenging to this day, and current treatments are associated with adverse effects, including tolerance and addiction. Chronic neuropathic pain results from lesions or diseases in the somatosensory system. To investigate potential therapies with reduced side effects, animal pain models are the gold standard in preclinical studies. Therefore, well-characterized and well-described models are crucial for the development and validation of innovative therapies. Partial ligation of the sciatic nerve (pSNL) is a procedure that induces chronic neuropathic pain in mice, characterized by mechanical and thermal hypersensitivity, ongoing pain, and changes in limb temperature, making this model a great fit to study neuropathic pain preclinically. pSNL is an advantageous model to study neuropathic pain as it reproduces many symptoms observed in humans with neuropathic pain. Furthermore, the surgical procedure is relatively fast and straightforward to perform. Unilateral pSNL of one limb allows for comparison between the ipsilateral and contralateral paws, as well as evaluation of central sensitization. To induce chronic neuropathic hypersensitivity, a 9-0 non-absorbable nylon thread is used to ligate the dorsal third of the sciatic nerve. This article describes the surgical procedure and characterizes the development of chronic neuropathic pain through multiple commonly used behavioral tests. As a plethora of innovative therapies are now being investigated to treat chronic pain, this article provides crucial concepts for standardization and an accurate description of surgeries required to induce neuropathic pain.
慢性疼痛的管理至今仍是一项挑战,目前的治疗方法与不良反应相关,包括耐受性和成瘾性。慢性神经性疼痛是由躯体感觉系统的损伤或疾病引起的。为了研究潜在的副作用较小的治疗方法,动物疼痛模型是临床前研究的金标准。因此,具有良好特征和描述的模型对于创新疗法的开发和验证至关重要。坐骨神经部分结扎(pSNL)是一种在小鼠中诱导慢性神经性疼痛的程序,其特征是机械和热敏感性增加、持续性疼痛以及肢体温度变化,这使得该模型非常适合在临床前研究神经性疼痛。pSNL 是研究神经性疼痛的一个有利模型,因为它再现了许多患有神经性疼痛的人类所观察到的症状。此外,手术过程相对快速且简单。单肢单侧 pSNL 允许对同侧和对侧爪子进行比较,以及评估中枢敏化。为了诱导慢性神经性过敏,使用 9-0 非吸收尼龙线结扎坐骨神经的背侧三分之一。本文描述了手术过程,并通过多种常用的行为测试来描述慢性神经性疼痛的发展。由于现在有大量的创新疗法正在被研究用于治疗慢性疼痛,本文为标准化和准确描述诱导神经性疼痛所需的手术提供了关键概念。