Dray A
Sandoz Institute for Medical Research, London.
Br J Anaesth. 1995 Aug;75(2):125-31. doi: 10.1093/bja/75.2.125.
While sensory fibres normally respond to a range of physical and chemical stimuli their activity and metabolism are profoundly altered by a variety of mediators generated by tissue injury and inflammation. These include substances produced by damaged tissue, substances of vascular origin as well as substances released by afferent fibres themselves, sympathetic fibres and various immune cells. The effects of inflammatory mediators, to activate or sensitize afferent fibres, are produced by changing membrane ion channels which are coupled directly via receptors or more commonly are regulated through receptor-coupled second messenger cascades. These latter processes also have the potential to alter gene transcription and thereby induce long-term alterations in the biochemistry of sensory neurones. This can have far-reaching consequences as the expression of novel proteins for ion channels (Na channels) and receptors (capsaicin, NPY) as well as the induction of novel enzymes (i-NOS) can profoundly affect the properties of nociceptors and their ability to transmit pain signals. However, such changes may be targeted successfully for the development of new analgesic and anti-inflammatory agents.
虽然感觉纤维通常对一系列物理和化学刺激作出反应，但其活动和代谢会因组织损伤和炎症产生的多种介质而发生深刻改变。这些介质包括受损组织产生的物质、血管源性物质以及传入纤维自身、交感神经纤维和各种免疫细胞释放的物质。炎症介质激活或致敏传入纤维的作用，是通过改变膜离子通道产生的，这些离子通道直接通过受体偶联，或者更常见的是通过受体偶联的第二信使级联反应进行调节。后一种过程也有可能改变基因转录，从而诱导感觉神经元生物化学的长期改变。这可能会产生深远的影响，因为离子通道（钠通道）和受体（辣椒素、神经肽Y）新蛋白的表达以及新酶（诱导型一氧化氮合酶）的诱导，会深刻影响伤害感受器的特性及其传递疼痛信号的能力。然而，这种变化可能会成功地成为开发新型镇痛和抗炎药物的靶点。
