Driessen B, Bültmann R, Jurna I, Baldauf J
University of California, Veterinary Medical Teaching Hospital, Davis 95616, USA.
Brain Res. 1998 Jun 15;796(1-2):284-90. doi: 10.1016/s0006-8993(98)00369-2.
To investigate the possible role of spinal purinoceptors in nociception, the potent P2-purinoceptor antagonist reactive red 2 was studied in rats under urethane anesthesia in which nociceptive activity was elicited by electrical stimulation of afferent C fibers in the sural nerve and recorded from single neurons in the ventrobasal complex of the thalamus. Intrathecal (i.t.) application of reactive red 2 (6-200 micrograms) caused a dose-dependent reduction of the evoked activity in thalamic neurons. The estimated ED50 was 30 micrograms, and the maximum depression of nociceptive activity amounted to about 70% of the control activity at a dose of 100 micrograms. Morphine, administered i.t. at a maximally effective dose (80 micrograms), inhibited the evoked nociceptive activity by only up to 55% of the control activity. An i.t. co-injection of reactive red 2 (100 micrograms) and morphine (80 micrograms) caused a maximum reduction of the evoked thalamic activity by up to 85% of the control activity, thus, exceeding significantly the effect elicited by either drug alone. Similarly, i.t. co-injection of almost equipotent dosages of reactive red 2 (30 micrograms) and morphine (30 micrograms) caused a maximum reduction of the evoked activity by up to 72% of the control activity, which again exceeded significantly the effect of either drug alone. The results suggest that in rats reactive red 2 exerts antinociception by blockade of P2-purinoceptors in the spinal cord and, hence, support the idea that ATP may play an important role in spinal transmission of nociceptive signals. An activation of the spinal opioid system does not seem to contribute to the effect of reactive red 2 but might act additive or even synergistically with its antinociceptive action.
为了研究脊髓嘌呤受体在伤害感受中的可能作用，在乌拉坦麻醉的大鼠中研究了强效P2嘌呤受体拮抗剂活性红2，其中通过电刺激腓肠神经中的传入C纤维引发伤害感受活性，并从丘脑腹侧基底复合体中的单个神经元进行记录。鞘内（i.t.）应用活性红2（6 - 200微克）导致丘脑神经元诱发活性呈剂量依赖性降低。估计的ED50为30微克，在100微克剂量时，伤害感受活性的最大抑制量达到对照活性的约70%。以最大有效剂量（80微克）鞘内注射吗啡，仅能将诱发的伤害感受活性抑制至对照活性的55%。鞘内共同注射活性红2（100微克）和吗啡（80微克）可使诱发的丘脑活性最大降低至对照活性的85%，因此，显著超过单独使用任何一种药物所产生的效果。同样，鞘内共同注射几乎等效剂量的活性红2（30微克）和吗啡（30微克）可使诱发活性最大降低至对照活性的72%，这再次显著超过单独使用任何一种药物的效果。结果表明，在大鼠中活性红2通过阻断脊髓中的P2嘌呤受体发挥抗伤害感受作用，因此，支持了ATP可能在伤害性信号的脊髓传递中起重要作用的观点。脊髓阿片系统的激活似乎对活性红2的作用没有贡献，但可能与其抗伤害感受作用相加甚至协同作用。
