Dickenson A, Hughes C, Rueff A, Dray A
Sandoz Institute for Medical Research, 5 Gower Place, LondonU.K. Department of Pharmacology, University College, LondonU.K.
Pain. 1990 Dec;43(3):353-362. doi: 10.1016/0304-3959(90)90032-9.
We have studied the effect of NE 19550 (olvanil, N-(4-hydroxy-3-methoxyphenyl) methyl-9Z-octadecenamide), a capsaicin analogue with approximately equipotent antinociceptive activity in vivo compared with capsaicin, on nociceptive responses recorded from spinal dorsal horn neurones in vivo and from a spinal ventral root in vitro. In adult rats anaesthetized with halothane, antinociceptive doses of olvanil (20-40 mumol/kg, s.c.) reduced C-fibre responses evoked in wide dynamic range, lumbar dorsal horn neurones, by peripheral transcutaneous electrical stimulation. Intradermal injection of olvanil, localized to a discrete region of the peripheral receptive field, did not activate C-fibres nor change C-fibre evoked activation of dorsal horn neurones. Spinal intrathecal administration of olvanil attenuated C-fibre evoked responses and, at the highest concentration, significantly reduced A beta-fibre evoked activity. In the neonatal rat spinal cord/tail preparation maintained in vitro, superfusion of the cord with olvanil (500 nM-5 microM) did not evoke a depolarization but responses to peripheral noxious stimulation were attenuated. In a similar in vitro preparation of the neonatal rat spinal cord, the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was measured in spinal cord superfusates. Capsaicin (2-10 microM) evoked a large release of CGRP-LI but olvanil (2-10 microM) produced only a small or undetectable release. Following the administration of each substance, however, the release of CGRP-LI evoked by a depolarizing potassium stimulus was significantly attenuated. These data indicate that C-fibre input to the dorsal horn was attenuated by acute systemic doses of olvanil that were antinociceptive in behavioural tests. This effect was unlikely to be due to impairment of C-fibre function by a peripheral locus of action but was more consistent with an action in the spinal cord in which the reduced release of a neurotransmitter substance from afferent nerve terminals may play a prominent role.
我们研究了NE 19550（奥伐尼尔，N-（4-羟基-3-甲氧基苯基）甲基-9Z-十八碳烯酰胺）的作用，它是一种辣椒素类似物，在体内与辣椒素相比具有大致相当的抗伤害感受活性，我们研究了其对在体脊髓背角神经元以及离体脊髓腹根记录的伤害性反应的影响。在用氟烷麻醉的成年大鼠中，抗伤害感受剂量的奥伐尼尔（20 - 40 μmol/kg，皮下注射）可减少外周经皮电刺激在宽动态范围腰段背角神经元中诱发的C纤维反应。将奥伐尼尔皮内注射到外周感受野的一个离散区域，既不会激活C纤维，也不会改变C纤维诱发的背角神经元激活。脊髓鞘内注射奥伐尼尔可减弱C纤维诱发的反应，并且在最高浓度时，显著降低Aβ纤维诱发的活动。在体外维持的新生大鼠脊髓/尾部标本中，用奥伐尼尔（500 nM - 5 μM）灌注脊髓不会引起去极化，但对外周伤害性刺激的反应会减弱。在新生大鼠脊髓的类似体外标本中，测量了脊髓灌流液中降钙素基因相关肽样免疫反应性（CGRP-LI）的释放。辣椒素（2 - 10 μM）可诱发大量CGRP-LI释放，但奥伐尼尔（2 - 10 μM）仅产生少量或无法检测到的释放。然而，在给予每种物质后，去极化钾刺激诱发的CGRP-LI释放均显著减弱。这些数据表明，在行为测试中具有抗伤害感受作用的急性全身剂量的奥伐尼尔可减弱传入背角的C纤维输入。这种作用不太可能是由于外周作用部位对C纤维功能的损害，而更符合在脊髓中的作用，即传入神经末梢神经递质物质释放减少可能起主要作用。
