选择性向电压通道以实现止痛:当前状态和未来方向
Emily A Gordon1, Sidharth Tyagi2,3,4, Sulayman D Dib-Hajj2,3,4
1Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Pain
|October 14, 2025
概括
电压通道 (Nav) 对于疼痛信号至关重要. 批准用于急性疼痛的Nav1.8阻断剂suzetrigine代表了一种针对这些与疼痛相关的道的新类止痛药.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 电压关闭的通道 (Nav) 对于可刺激细胞 (包括疼痛感应神经元 (nociceptors) 中的动作潜能产生至关重要.
- 特定的Nav亚型集中在痛感受体中,它们与疼痛疾病的遗传联系突出了它们作为止痛药物点的重要性.
- 开发特定亚型的Nav抑制剂一直很困难,但最近的进展提供了新的治疗途径.
研究的目的:
- 审查电压通道在疼痛中的作用,并讨论针对这些通道的新型治疗策略.
- 突出 Nav1.8 作为疼痛管理的目标的重要性.
- 探索超越小分子的新兴方法,用于选择性Nav异型向.
主要方法:
- 审查现有的文学关于Nav通道功能在 nociception.
- 对将Nav亚型与疼痛障碍联系起来的遗传数据的分析.
- 讨论导航向止痛药的临床前和临床发展.
主要成果:
- Nav1.8通道阻断剂suzetrigine已被批准用于急性疼痛的临床使用.
- 目前正在探索各种新的策略,包括阿马,寡核酸,RNA编辑,抗体和向蛋白质降解,用于选择性Nav异型向.
- 遗传证据强烈支持特定的Nav亚型在疼痛病理生理学中的作用.
结论:
- 苏泽特里金的批准标志着在Nav针对性疼痛管理方面迈出了重要的一步.
- 新兴的治疗方式显示出开发更有选择性和有效的止痛药的希望.
- 针对特定的Nav通道亚型为新型疼痛疗法提供了一个有希望的未来.
相关概念视频
Voltage-gated Ion Channels
10.3K
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
10.3K
Analgesia and Pain Management
1.5K
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
1.5K
Non-gated Ion Channels
8.0K
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
8.0K
Local Anesthetics: Differential Sensitivity of Nerve Fibers
1.4K
Local anesthetics (LAs) block the sodium channels of nerve trunks, sensory nerve endings, and neuromuscular junctions. Although LAs can block all kinds of nerves, the sensitivity of nerve fibers differs according to nerve types and structures. LAs are known to block myelinated fibers faster than unmyelinated ones. Also, they block pain or sensory neurons at low concentrations without affecting the motor neurons involved in muscle contractions. This helps relieve labor pain without affecting the...
1.4K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.8K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
3.8K
Local Anesthetics: Mechanism of Action
3.2K
Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
3.2K


