Cesare P, McNaughton P
Department of Physiology, King's College London, Strand, United Kingdom.
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15435-9. doi: 10.1073/pnas.93.26.15435.
Pain differs from other sensations in many respects. Primary pain-sensitive neurons respond to a wide variety of noxious stimuli, in contrast to the relatively specific responses characteristic of other sensory systems, and the response is often observed to sensitize on repeated presentation of a painful stimulus, while adaptation is typically observed in other sensory systems. In most cases the cellular mechanisms of transduction and sensitization in response to painful stimuli are not understood. We report here that application of pulses of noxious heat to a subpopulation of isolated primary sensory neurons rapidly activates an inward current. The ion channel activated by heat discriminates poorly among alkali cations. Calcium ions both carry current and partially suppress the current carried by other ions. The current is markedly increased by bradykinin, a potent algogenic nonapeptide that is known to be released in vivo by tissue damage. Phosphatase inhibitors prolong the sensitization caused by bradykinin, and a similar sensitization is caused by activators of protein kinase C. We conclude that bradykinin sensitizes the response to heat by activating protein kinase C.
疼痛在许多方面与其他感觉不同。与其他感觉系统相对特异的反应特性不同，初级痛觉敏感神经元对多种有害刺激作出反应，并且经常观察到在重复呈现疼痛刺激时反应会敏感化，而在其他感觉系统中通常观察到适应现象。在大多数情况下，对疼痛刺激作出反应时的转导和敏感化的细胞机制尚不清楚。我们在此报告，对分离的初级感觉神经元亚群施加有害热脉冲会迅速激活内向电流。受热激活的离子通道对碱金属阳离子的区分能力很差。钙离子既携带电流又部分抑制其他离子携带的电流。缓激肽可使电流显著增加，缓激肽是一种有效的致痛九肽，已知在体内由组织损伤释放。磷酸酶抑制剂可延长缓激肽引起的敏感化，蛋白激酶C的激活剂也会引起类似的敏感化。我们得出结论，缓激肽通过激活蛋白激酶C使对热的反应敏感化。
