School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
Toxins (Basel). 2017 Nov 16;9(11):372. doi: 10.3390/toxins9110372.
Chronic pain is a complex and debilitating condition associated with a large personal and socioeconomic burden. Current pharmacological approaches to treating chronic pain such as opioids, antidepressants and anticonvulsants exhibit limited efficacy in many patients and are associated with dose-limiting side effects that hinder their clinical use. Therefore, improved strategies for the pharmacological treatment of pathological pain are urgently needed. G-protein coupled receptors (GPCRs) are ubiquitously expressed on the surface of cells and act to transduce extracellular signals and regulate physiological processes. In the context of pain, numerous and diverse families of GPCRs expressed in pain pathways regulate most aspects of physiological and pathological pain and are thus implicated as potential targets for therapy of chronic pain. In the search for novel compounds that produce analgesia via GPCR modulation, animal venoms offer an enormous and virtually untapped source of potent and selective peptide molecules. While many venom peptides target voltage-gated and ligand-gated ion channels to inhibit neuronal excitability and blunt synaptic transmission of pain signals, only a small proportion are known to interact with GPCRs. Of these, only a few have shown analgesic potential in vivo. Here we review the current state of knowledge regarding venom peptides that target GPCRs to produce analgesia, and their development as therapeutic compounds.
慢性疼痛是一种复杂且使人虚弱的病症，会给个人和社会经济带来沉重负担。目前治疗慢性疼痛的药理学方法，如阿片类药物、抗抑郁药和抗惊厥药，在许多患者中疗效有限，且存在剂量限制的副作用，这限制了它们的临床应用。因此，迫切需要改善病理性疼痛的药物治疗策略。G 蛋白偶联受体（GPCRs）广泛表达于细胞表面，作用是转导细胞外信号并调节生理过程。在疼痛方面，疼痛通路中表达的众多不同家族的 GPCR 调节着生理和病理性疼痛的大多数方面，因此被认为是治疗慢性疼痛的潜在靶点。在寻找通过 GPCR 调节产生镇痛作用的新型化合物的过程中，动物毒液提供了大量且几乎未开发的潜在有效和选择性肽分子来源。虽然许多毒液肽针对电压门控和配体门控离子通道，以抑制神经元兴奋性并减轻疼痛信号的突触传递，但已知只有一小部分与 GPCR 相互作用。其中，只有少数在体内显示出镇痛潜力。本文综述了目前关于靶向 GPCR 产生镇痛作用的毒液肽的知识状态，以及它们作为治疗化合物的开发情况。
