Khangura Ravneet Kaur, Sharma Jasmine, Bali Anjana, Singh Nirmal, Jaggi Amteshwar Singh
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
Akal College of Pharmacy and Technical Education, Mastuana Sahib 148002, Sangrur, India.
Korean J Physiol Pharmacol. 2019 Jan;23(1):1-20. doi: 10.4196/kjpp.2019.23.1.1. Epub 2018 Dec 26.
Neuropathic pain is a complex chronic pain state caused by the dysfunction of somatosensory nervous system, and it affects the millions of people worldwide. At present, there are very few medical treatments available for neuropathic pain management and the intolerable side effects of medications may further worsen the symptoms. Despite the presence of profound knowledge that delineates the pathophysiology and mechanisms leading to neuropathic pain, the unmet clinical needs demand more research in this field that would ultimately assist to ameliorate the pain conditions. Efforts are being made globally to explore and understand the basic molecular mechanisms responsible for somatosensory dysfunction in preclinical pain models. The present review highlights some of the novel molecular targets like D-amino acid oxidase, endoplasmic reticulum stress receptors, sigma receptors, hyperpolarization-activated cyclic nucleotide-gated cation channels, histone deacetylase, Wnt/β-catenin and Wnt/Ryk, ephrins and Eph receptor tyrosine kinase, Cdh-1 and mitochondrial ATPase that are implicated in the induction of neuropathic pain. Studies conducted on the different animal models and observed results have been summarized with an aim to facilitate the efforts made in the drug discovery. The diligent analysis and exploitation of these targets may help in the identification of some promising therapies that can better manage neuropathic pain and improve the health of patients.
神经病理性疼痛是一种由躯体感觉神经系统功能障碍引起的复杂慢性疼痛状态,全球数百万人受其影响。目前,用于管理神经病理性疼痛的医学治疗方法非常少,而且药物难以忍受的副作用可能会使症状进一步恶化。尽管人们对导致神经病理性疼痛的病理生理学和机制已有深入了解,但未满足的临床需求要求在该领域开展更多研究,这最终将有助于改善疼痛状况。全球正在努力探索和了解临床前疼痛模型中导致躯体感觉功能障碍的基本分子机制。本综述重点介绍了一些新的分子靶点,如D-氨基酸氧化酶、内质网应激受体、σ受体、超极化激活的环核苷酸门控阳离子通道、组蛋白脱乙酰酶、Wnt/β-连环蛋白和Wnt/Ryk、 Ephrin和Eph受体酪氨酸激酶、Cdh-1和线粒体ATP酶,它们与神经病理性疼痛的诱导有关。对不同动物模型进行的研究及观察结果进行了总结,旨在推动药物研发工作。对这些靶点的深入分析和利用可能有助于确定一些有前景的疗法,从而更好地管理神经病理性疼痛并改善患者健康。