Stucky C L, Thayer S A, Seybold V S
Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis 55455, USA.
Neuroscience. 1996 Oct;74(4):1111-23. doi: 10.1016/0306-4522(96)00264-3.
Prostaglandins sensitize some nociceptors to noxious mechanical, thermal and chemical stimuli; however, not all nociceptors are sensitized by prostaglandins. We used cultures of dorsal root ganglion neurons from neonatal rats to determine whether prostaglandins differentially alter the responsiveness of populations of neurons to the chemical stimulus bradykinin. Groups of dorsal root ganglion neurons were defined by size of the cell soma and by the presence of immunoreactivity for substance P. An increase in the concentration of free intracellular Ca2+ was used as an indicator of responsiveness to bradykinin. Pretreatment (5 min) with prostaglandin E2 (100 nM) increased the proportion of intermediate-size neurons (somal areas of 240-320 microns2) that responded to 30 nM bradykinin by two-fold but did not alter the proportion of small-size neurons (somal areas of 160-239 microns2) that responded. Pretreatment with prostaglandin E2 had no effect on the maximum increase in free intracellular Ca2+ evoked by 30 nM bradykinin in either population of neurons, defined by size. Although pretreatment with PGE2 did not increase the proportion of intermediate-size neurons that responded to a lower concentration of bradykinin (3 nM), it did increase the concentration of free intracellular Ca2+ evoked by 3 nM bradykinin. Both results were consistent with a leftward shift in the stimulus-response relationship for bradykinin following pretreatment with PGE2. Small- and intermediate-size neurons that responded to bradykinin also differed in their expression of immunoreactivity for substance P. Furthermore, intermediate-size neurons that expressed immunoreactivity for substance P were more likely to respond to bradykinin after treatment with prostaglandin E2. These results support the hypothesis that prostaglandin E2 sensitizes some normally unresponsive primary afferent neurons to chemical stimuli. One population of neurons which becomes responsive to bradykinin after treatment with prostaglandin E2 can be defined based on cell size, and furthermore, these neurons are likely to express substance P. During inflammation, recruitment of primary afferent neurons that are immunoreactive for substance P would enhance the participation of substance P in central mechanisms that contribute to hyperalgesia.
前列腺素可使一些伤害感受器对有害的机械、热和化学刺激敏感化；然而，并非所有伤害感受器都会被前列腺素敏感化。我们利用新生大鼠背根神经节神经元培养物来确定前列腺素是否会差异性地改变神经元群体对化学刺激缓激肽的反应性。背根神经节神经元群体是根据细胞体大小和P物质免疫反应性的存在来定义的。细胞内游离Ca2+浓度的增加被用作对缓激肽反应性的指标。用前列腺素E2（100 nM）预处理（5分钟）可使对30 nM缓激肽有反应的中等大小神经元（细胞体面积为240 - 320平方微米）的比例增加两倍，但不会改变对缓激肽有反应的小尺寸神经元（细胞体面积为160 - 239平方微米）的比例。前列腺素E2预处理对30 nM缓激肽在按大小定义的任一神经元群体中诱发的细胞内游离Ca2+的最大增加量均无影响。虽然用PGE2预处理不会增加对较低浓度缓激肽（3 nM）有反应的中等大小神经元的比例，但它确实会增加3 nM缓激肽诱发的细胞内游离Ca2+的浓度。这两个结果都与用PGE2预处理后缓激肽的刺激 - 反应关系向左移动一致。对缓激肽有反应的小尺寸和中等大小神经元在P物质免疫反应性的表达上也有所不同。此外，表达P物质免疫反应性的中等大小神经元在用前列腺素E2处理后更有可能对缓激肽产生反应。这些结果支持了前列腺素E2使一些正常无反应的初级传入神经元对化学刺激敏感化的假说。在用前列腺素E2处理后对缓激肽有反应的一类神经元可以根据细胞大小来定义，而且，这些神经元可能表达P物质。在炎症过程中，招募对P物质有免疫反应性的初级传入神经元会增强P物质在导致痛觉过敏的中枢机制中的参与度。
