P2X 受体在慢性疼痛状态下的伤害性信号传导。
Nociceptive signaling of P2X receptors in chronic pain states.
机构信息
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
出版信息
Purinergic Signal. 2021 Mar;17(1):41-47. doi: 10.1007/s11302-020-09743-w. Epub 2020 Oct 5.
Abstract
P2X3 monomeric receptors (P2X3Rs) and P2X2/3 heteromeric receptors (P2X2/3Rs) in primary sensory neurons and microglial P2X4 monomeric receptors (P2X4Rs) in the spinal dorsal horn (SDH) play important roles in neuropathic pain. In particular, P2X4R in the spinal microglia during peripheral nerve injury (PNI), experimental autoimmune neuritis, and herpes models are useful to explore the potential strategies for developing new drugs to treat neuropathic pain. Recently, novel P2X4 antagonists, NP-1815-PX and NC-2600, were developed, which demonstrated potent and specific inhibition against rodent and human P2X4Rs. The phase I study of NC-2600 has been completed, and no serious side effects were reported. The roles played by purinergic receptors in evoking neuropathic pain provide crucial insights into the pathogenesis of neuropathic pain.
摘要
P2X3 单体型受体 (P2X3Rs) 和 P2X2/3 异源型受体 (P2X2/3Rs) 在初级感觉神经元和脊髓背角 (SDH) 的小胶质细胞 P2X4 单体型受体 (P2X4Rs) 在神经性疼痛中发挥重要作用。特别是在周围神经损伤 (PNI)、实验性自身免疫性神经炎和疱疹模型中小胶质细胞中的 P2X4R，对于探索开发治疗神经性疼痛的新药的潜在策略非常有用。最近，开发了新型 P2X4 拮抗剂 NP-1815-PX 和 NC-2600，它们对啮齿动物和人类 P2X4R 表现出强大和特异的抑制作用。NC-2600 的 I 期研究已经完成，没有报告严重的副作用。嘌呤能受体在引发神经性疼痛中的作用为神经性疼痛的发病机制提供了重要的见解。
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