Kessler W, Kirchhoff C, Reeh P W, Handwerker H O
Institut für Physiologie und Biokybernetik, Universität Erlangen-Nürnberg, Federal Republic of Germany.
Exp Brain Res. 1992;91(3):467-76. doi: 10.1007/BF00227842.
A broad mixture of inflammatory mediators ("inflammatory soup") was used to investigate the responsiveness of primary afferents from rat hairy skin in an in vitro skin-saphenous nerve preparation. In addition, a conditioning effect of the tachykinin substance P on chemosensitivity of nociceptors was examined. Inflammatory soup (IS) was made up in synthetic interstitial fluid from bradykinin, serotonin, histamin and prostaglandin E2 (all 10(-5) M). In addition, the potassium and the hydrogen ion concentration (7 mM, pH 7.0) and the temperature (39.5 degrees C) were elevated. The latter agents, in a control solution, did not excite nociceptors (n = 5). IS was repeatedly superfused over the receptive fields for 5 min at 10 min intervals; substance P (SP 10(-6) and 10(-5) M) was applied during the last 5 min of the interval and during the subsequent IS stimulation. IS excited more than 80% of the mechano-heat sensitive ("polymodal") afferents with slowly conducting nerve fibres (n = 72), but none of the low-threshold mechanoreceptive slow and fast conducting units (n = 17). Slow conducting afferents with high mechanical threshold (n = 35) were weakly, and less frequently (< 20%), driven by IS. A majority, but not all, of the responsive units showed tachyphylaxis upon repeated IS application. None, however, lost its responsiveness completely. Conditioning heat stimulation (32-46.5 degrees C in 20 s) did not enhance the subsequent IS response, which may indicate that sensitizing substances normally released by a noxious heat stimulus were already contained in IS. No sensitization to mechanical (von Frey) or heat stimulation could be established in the period after the IS response had subsided and after the washout was completed, respectively. A short-lived sensitization may have been overlooked under these temporal restrictions. Conditioning SP in 10(-5) M but not in 10(-6) M concentration significantly increased the IS response of polymodal C fibres, by 58% on average (n = 14). SP did not excite the units. Comparing with previous data, we conclude that there is a significant synergism between inflammatory mediators, acting to induce more intense and more sustained discharge via many nociceptors than single mediators alone could achieve. Conditioning substance P can further enhance this algogenic action. Mechanisms of interaction and relative contributions of single substances remain to be elucidated.
使用多种炎症介质的混合物（“炎症介质汤”），在体外皮肤 - 隐神经制备中研究大鼠有毛皮肤初级传入神经的反应性。此外，还研究了速激肽P物质对伤害感受器化学敏感性的调节作用。炎症介质汤（IS）由缓激肽、5 - 羟色胺、组胺和前列腺素E2（均为10⁻⁵ M）在合成组织液中配制而成。此外，钾离子和氢离子浓度（7 mM，pH 7.0）以及温度（39.5℃）都有所升高。在对照溶液中，后几种试剂不会兴奋伤害感受器（n = 5）。IS以10分钟的间隔在感受野上反复灌流5分钟；在间隔的最后5分钟以及随后的IS刺激期间施加P物质（SP 10⁻⁶和10⁻⁵ M）。IS兴奋了超过80%的具有缓慢传导神经纤维的机械热敏感（“多模式”）传入神经（n = 72），但未兴奋任何低阈值机械感受性的慢传导和快传导单位（n = 17）。具有高机械阈值的慢传导传入神经（n = 35）受到IS的驱动较弱且频率较低（<20%）。大多数（但不是全部）反应单位在反复应用IS后出现快速耐受。然而，没有一个完全失去其反应性。预处理热刺激（20秒内32 - 46.5℃）并未增强随后的IS反应，这可能表明有害热刺激通常释放的致敏物质已包含在IS中。在IS反应消退后以及冲洗完成后的时间段内，分别无法建立对机械（von Frey）或热刺激敏感化。在这些时间限制下，短暂的敏感化可能被忽略了。10⁻⁵ M浓度而非10⁻⁶ M浓度的预处理SP显著增加了多模式C纤维的IS反应，平均增加了58%（n = 14）。SP未兴奋这些单位。与先前的数据相比，我们得出结论，炎症介质之间存在显著的协同作用，通过许多伤害感受器诱导比单一介质单独作用更强烈、更持久的放电。预处理P物质可进一步增强这种致痛作用。单一物质的相互作用机制和相对贡献仍有待阐明。
