Rueff A, Dray A
Sandoz Institute for Medical Research, London, U.K.
Neuroscience. 1993 May;54(2):527-35. doi: 10.1016/0306-4522(93)90272-h.
The sensitization of peripheral nociceptors by different prostaglandins was studied in an in vitro preparation of the neonatal spinal cord with functionally attached tail. Nociceptors in the rat tail were activated by chemical (bradykinin, capsaicin) and thermal (heated saline) stimuli and responses were recorded as a depolarization of a ventral root in the lumbar region of the spinal cord (L3-L5). Responses evoked by bradykinin, capsaicin or submaximal thermal stimulation were enhanced in the presence of prostaglandin E1, prostaglandin E2, prostaglandin F2 alpha, prostaglandin I2 and the stable prostaglandin I2 analogue cicaprost, but not by prostaglandin D2. Cyclic AMP and threshold concentrations of bradykinin also induced an enhancement of responses to chemical and thermal stimuli. Responses evoked by small concentrations of bradykinin on unsensitized preparations were reduced by indomethacin or aspirin, whereas responses to maximal concentrations of bradykinin were not affected. Immunocytochemical localization of protein gene product 9.5 and growth associated protein 43 indicated that the neuronal innervation of subepidermal skin layers was preserved in the tail following removal of the most superficial skin layers which was performed in order to facilitate drug access to peripheral nerve endings. These results indicate that different prostaglandins and cyclic AMP sensitize peripheral nerve endings to noxious stimulation without directly activating nociceptors. The stimulation of nociceptors by bradykinin was only partially mediated via arachidonic acid metabolites whereas bradykinin-induced sensitization was independent of cyclo-oxygenase activity.
在一种带有功能性连接尾巴的新生脊髓体外制备物中，研究了不同前列腺素对外周伤害感受器的致敏作用。通过化学刺激（缓激肽、辣椒素）和热刺激（热盐水）激活大鼠尾巴中的伤害感受器，并将反应记录为脊髓腰段（L3-L5）腹根的去极化。在前列腺素E1、前列腺素E2、前列腺素F2α、前列腺素I2和稳定的前列腺素I2类似物西卡前列素存在的情况下，缓激肽、辣椒素或次最大热刺激所诱发的反应增强，但前列腺素D2不会使其增强。环磷酸腺苷（cAMP）和阈浓度的缓激肽也会导致对化学和热刺激的反应增强。消炎痛或阿司匹林可降低未致敏制剂对低浓度缓激肽诱发的反应，而对高浓度缓激肽的反应则无影响。蛋白质基因产物9.5和生长相关蛋白43的免疫细胞化学定位表明，为便于药物进入外周神经末梢而去除最表层皮肤后，尾巴中表皮下皮肤层的神经支配得以保留。这些结果表明，不同的前列腺素和环磷酸腺苷使外周神经末梢对伤害性刺激敏感，而不直接激活伤害感受器。缓激肽对伤害感受器的刺激仅部分通过花生四烯酸代谢产物介导，而缓激肽诱导的致敏作用与环氧化酶活性无关。
