Szallasi A, Farkas-Szallasi T, Tucker J B, Lundberg J M, Hökfelt T, Krause J E
Department of Pharmacology, Karolinska Institute, S-171 77, Stockholm,
Brain Res. 1999 Jan 9;815(2):177-84. doi: 10.1016/s0006-8993(98)01168-8.
Capsaicin depletes the sensory neuropeptide substance P (SP) in the rat due to a combination of neuron loss and decreased synthesis in the surviving cells. Resiniferatoxin (RTX) mimics most, but not all, capsaicin actions. In the present study, the effects of RTX (300 microg/kg, s.c.) were examined on mRNA levels for SP and its receptor in the adult rat. The percentage of dorsal root ganglia (DRG) neuronal profiles showing an in situ hybridization signal for preprotachykinin mRNAs encoding SP was not altered following RTX treatment (up to 8 weeks), though the signal became perceptibly weaker. In accord, 2 weeks after RTX administration a 60% decrease was observed in the steady-state levels of SP-encoding mRNAs using Northern blot analysis, leaving the ratio of beta- and gamma-preprotachykinin mRNAs unchanged. No change was, however, observed in mRNA levels encoding tachykinins NK-1 receptors in the dorsal horn, the spinal targets for SP. The present findings suggest that RTX does not kill SP-positive DRG neurons, though it suppresses the synthesis of SP. Since RTX treatment does not alter NK-1 receptor expression, this reduced SP synthesis is likely to play a central role in the analgesic actions of RTX.
辣椒素可使大鼠体内的感觉神经肽P物质（SP）减少，这是神经元丢失和存活细胞中合成减少共同作用的结果。树脂毒素（RTX）模拟了大部分但并非全部辣椒素的作用。在本研究中，检测了RTX（300微克/千克，皮下注射）对成年大鼠中SP及其受体mRNA水平的影响。尽管原位杂交信号明显变弱，但经RTX处理（长达8周）后，显示编码SP的前速激肽原mRNA原位杂交信号的背根神经节（DRG）神经元轮廓的百分比未发生改变。与此一致的是，在给予RTX两周后，使用Northern印迹分析观察到编码SP的mRNA稳态水平下降了60%，而β-和γ-前速激肽原mRNA的比例保持不变。然而，在脊髓背角（SP的脊髓靶点）中，编码速激肽NK-1受体的mRNA水平未观察到变化。目前的研究结果表明，RTX不会杀死SP阳性的DRG神经元，尽管它会抑制SP的合成。由于RTX处理不会改变NK-1受体的表达，这种SP合成的减少可能在RTX的镇痛作用中起核心作用。
