解码疼痛:用于机械洞察和药物发现的下一代体外系统
Dara Khosrowshahi1,2, Liesbet Lagae1,2, Johanna Bolander2,3,4
1Department of Physics and Astronomy, KU Leuven, Leuven, Belgium.
概括
使用人类诱导的多能干细胞 (iPSCs) 开发先进的体外疼痛模型为了解慢性疼痛机制和制造有效止痛药提供了一个有希望的途径.
科学领域:
- 神经科学是一个神经科学.
- 生物技术是生物技术.
- 药理学 药理学是指药理学的学科.
背景情况:
- 慢性疼痛影响20%的人口,由于对疼痛病理生理学的理解不足,疼痛缓解效果有限.
- 目前的体内模型在研究人类疼痛机制方面存在局限性,阻碍了药物开发.
- 在生理学上相关的体外模型对于研究人类细胞和推进翻译研究至关重要.
研究的目的:
- 审查神经系统中疼痛和细胞交叉通话的分子机制.
- 评估当前的体内疼痛模型及其局限性.
- 探索使用人类诱导的多能干细胞 (iPSCs) 进行疼痛研究的体外建模策略.
主要方法:
- 对分子疼痛机制和细胞信号的审查.
- 对现有的体内疼痛模型进行分析.
- 探索使用iPSC衍生的人类感应器的体外模型.
- 在体外模型验证技术的评估 (电生理学,测试).
- 检查模仿体内微环境的共同培养模型.
主要成果:
- 人类iPSC可以在体外研究中分化为功能性 nociceptors.
- 先进的体外模型,包括共同培养,更好地复制人类疼痛生理学.
- 电生理学表征和特定测试验证这些体外系统.
- 这些模型有助于研究 nociceptor与非神经元细胞相互作用.
结论:
- 使用iPSC的体外模型对于理解人类疼痛机制至关重要.
- 这些模型改善了新型止痛药的查和开发,并减少了副作用.
- 需要进一步开发以提高体外疼痛模型的可预测性和相关性.
相关概念视频
Analgesia and Pain Management
791
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...
791
Drug Discovery: Overview
8.7K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
8.7K
Nociception
29.4K
Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
29.4K
Pain
631
Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
631
Non-gated Ion Channels
7.1K
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....
7.1K


