Paus Ralf, Schmelz Martin, Bíró Tamás, Steinhoff Martin
Department of Dermatology and Allergy, University of Lübeck, Lubeck, Germany.
J Clin Invest. 2006 May;116(5):1174-86. doi: 10.1172/JCI28553.
This Review highlights selected frontiers in pruritus research and focuses on recently attained insights into the neurophysiological, neuroimmunological, and neuroendocrine mechanisms underlying skin-derived itch (pruritogenic pruritus), which may affect future antipruritic strategies. Special attention is paid to newly identified itch-specific neuronal pathways in the spinothalamic tract that are distinct from pain pathways and to CNS regions that process peripheral pruritogenic stimuli. In addition, the relation between itch and pain is discussed, with emphasis on how the intimate contacts between these closely related yet distinct sensory phenomena may be exploited therapeutically. Furthermore, newly identified or unduly neglected intracutaneous itch mediators (e.g., endovanilloids, proteases, cannabinoids, opioids, neurotrophins, and cytokines) and relevant receptors (e.g., vanilloid receptor channels and proteinase-activated, cannabinoid, opioid, cytokine, and new histamine receptors) are discussed. In summarizing promising new avenues for managing itch more effectively, we advocate therapeutic approaches that strive for the combination of peripherally active antiinflammatory agents with drugs that counteract chronic central itch sensitization.
本综述重点介绍了瘙痒研究的选定前沿领域，并聚焦于近期对皮肤源性瘙痒（致痒性瘙痒）潜在的神经生理、神经免疫和神经内分泌机制所取得的见解，这些见解可能会影响未来的止痒策略。特别关注了脊髓丘脑束中新发现的与疼痛通路不同的瘙痒特异性神经元通路，以及处理外周致痒性刺激的中枢神经系统区域。此外，还讨论了瘙痒与疼痛之间的关系，重点在于如何从治疗角度利用这两种密切相关但又不同的感觉现象之间的紧密联系。此外，还讨论了新发现的或未得到充分重视的皮内瘙痒介质（如内源性香草素、蛋白酶、大麻素、阿片类物质、神经营养因子和细胞因子）以及相关受体（如香草素受体通道和蛋白酶激活、大麻素、阿片类、细胞因子和新的组胺受体）。在总结更有效管理瘙痒的有前景的新途径时，我们提倡采用将外周活性抗炎药物与对抗慢性中枢性瘙痒致敏的药物相结合的治疗方法。
