Peiser-Oliver Julian M, Evans Sally, Adams David J, Christie Macdonald J, Vandenberg Robert J, Mohammadi Sarasa A
School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia.
Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, NSW, Australia.
Front Pharmacol. 2022 May 25;13:860903. doi: 10.3389/fphar.2022.860903. eCollection 2022.
Animal models of human pain conditions allow for detailed interrogation of known and hypothesized mechanisms of pain physiology in awake, behaving organisms. The importance of the glycinergic system for pain modulation is well known; however, manipulation of this system to treat and alleviate pain has not yet reached the sophistication required for the clinic. Here, we review the current literature on what animal behavioral studies have allowed us to elucidate about glycinergic pain modulation, and the progress toward clinical treatments so far. First, we outline the animal pain models that have been used, such as nerve injury models for neuropathic pain, chemogenic pain models for acute and inflammatory pain, and other models that mimic painful human pathologies such as diabetic neuropathy. We then discuss the genetic approaches to animal models that have identified the crucial glycinergic machinery involved in neuropathic and inflammatory pain. Specifically, two glycine receptor (GlyR) subtypes, GlyRα1(β) and GlyRα3(β), and the two glycine transporters (GlyT), GlyT1 and GlyT2. Finally, we review the different pharmacological approaches to manipulating the glycinergic system for pain management in animal models, such as partial . full agonism, reversibility, and multi-target approaches. We discuss the benefits and pitfalls of using animal models in drug development broadly, as well as the progress of glycinergic treatments from preclinical to clinical trials.
人类疼痛状况的动物模型有助于在清醒、有行为能力的生物体中详细探究已知和假设的疼痛生理机制。甘氨酸能系统对疼痛调节的重要性已广为人知；然而，对该系统进行操作以治疗和减轻疼痛尚未达到临床所需的成熟程度。在此，我们回顾当前文献，内容涉及动物行为研究使我们对甘氨酸能疼痛调节的了解，以及迄今为止在临床治疗方面取得的进展。首先，我们概述已使用的动物疼痛模型，例如用于神经性疼痛的神经损伤模型、用于急性和炎性疼痛的化学源性疼痛模型，以及其他模拟人类疼痛病理状况（如糖尿病性神经病变）的模型。然后，我们讨论针对动物模型的基因方法，这些方法已确定了参与神经性和炎性疼痛的关键甘氨酸能机制。具体而言，两种甘氨酸受体（GlyR）亚型，即GlyRα1(β)和GlyRα3(β)，以及两种甘氨酸转运体（GlyT），即GlyT1和GlyT2。最后，我们回顾在动物模型中为疼痛管理而操纵甘氨酸能系统的不同药理学方法，例如部分、完全激动作用、可逆性和多靶点方法。我们广泛讨论在药物开发中使用动物模型的益处和缺陷，以及从临床前试验到临床试验的甘氨酸能治疗进展。
