Kuraishi Y, Hirota N, Sato Y, Hanashima N, Takagi H, Satoh M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Neuroscience. 1989;30(1):241-50. doi: 10.1016/0306-4522(89)90369-2.
Characteristics of in situ substance P release from the lumbar dorsal horn were investigated in decerebrated rabbits. Noxious mechanical stimuli produced by pinching the skin of a hind leg ipsilateral to the perfusion site remarkably and significantly increased the release of immunoreactive substance P, which was identified as substance P itself, using separation with high-performance liquid chromatography and radioimmunoassay. The noxious pinch did not affect the release of immunoreactive substance P, when applied to the contralateral hind leg. Both the basal and pinch-evoked release of immunoreactive substance P were largest in the dorsolateral part of the dorsal horn. The pinch-evoked release of immunoreactive substance P was abolished when the dorsal horn was perfused with a Ca2+-free medium containing 7 mM Mg2+ or with a medium with 10 microM tetrodotoxin added. The evoked release of immunoreactive substance P was also abolished following pretreatment of a stimulated region with the local anesthetic dibucaine, a procedure which inhibited the pinch-evoked aversive behavior in freely-moving rabbits. Among a variety of natural stimuli applied to the hind leg, noxious pinch and a subcutaneous injection of formaldehyde solution significantly evoked the release of immunoreactive substance P from the dorsal horn. The most intense heat or scalding stimulation increased the immunoreactive substance P release in two out of five experiments. However, other natural stimuli such as ice-cold, warm, noxious heat and innocuous mechanical stimuli produced no apparent changes in the release of immunoreactive substance P. These results suggest that among the noxious stimuli, only mechanical and inflammatory but not thermal stimuli lead to a release of substance P from the primary afferent terminals in the dorsal horn. The present findings suggest that, at least in rabbits, substance P-containing primary afferents have high-threshold mechanoreceptors. Substance P may participate in the transmission of information related to noxious mechanical and inflammatory stimulation from the periphery to the dorsal horn.
在去大脑的兔中研究了腰髓背角原位P物质释放的特征。通过捏灌注部位同侧后肢皮肤产生的伤害性机械刺激显著且明显地增加了免疫反应性P物质的释放，使用高效液相色谱分离和放射免疫测定法确定其为P物质本身。当将伤害性捏压应用于对侧后肢时，其不影响免疫反应性P物质的释放。免疫反应性P物质的基础释放和捏压诱发释放均在背角的背外侧部分最大。当背角用含7 mM Mg2+的无钙培养基或添加了10 μM河豚毒素的培养基灌注时，捏压诱发的免疫反应性P物质释放被消除。在用局部麻醉药丁卡因预处理刺激区域后，诱发的免疫反应性P物质释放也被消除，该操作抑制了自由活动兔的捏压诱发的厌恶行为。在应用于后肢的各种自然刺激中，伤害性捏压和皮下注射甲醛溶液显著诱发了背角免疫反应性P物质的释放。在五个实验中的两个实验中，最强的热或烫伤刺激增加了免疫反应性P物质的释放。然而，其他自然刺激，如冰冷、温暖、伤害性热和无害机械刺激，在免疫反应性P物质的释放方面未产生明显变化。这些结果表明，在伤害性刺激中，只有机械性和炎症性刺激而非热刺激导致背角初级传入终末释放P物质。目前的研究结果表明，至少在兔中，含P物质的初级传入纤维具有高阈值机械感受器。P物质可能参与与伤害性机械和炎症刺激相关的信息从外周向背角的传递。
