Jurna Ilmar
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, D-6650 Homburg/SaarF.R.G.
Pain. 1988 Dec;35(3):349-354. doi: 10.1016/0304-3959(88)90144-3.
The opiate antagonist naloxone has been reported to cause pain relief. Therefore, the effect was determined of naloxone, injected intravenously, on the activity in single neurones of the dorsomedial part of the ventral nucleus (VDM) in the thalamus of rats under urethane anaesthesia elicited by electrical stimulation of nociceptive afferents in the sural nerve. Naloxone inhibited evoked nociceptive activity in a dose-dependent manner. High doses (5 mg/kg and 1 mg/kg) either increased or reduced the activity, inhibition prevailing at the lower dose. At lower doses (0.5 mg/kg, 0.2 mg/kg and 0.1 mg/kg), naloxone caused only inhibition, the ED50 being 0.36 mg/kg. The (+)-isomer of naloxone (0.2 mg/kg and 2 mg/kg) was ineffective, indicating that the effects of naloxone, which is the (-)-isomer, are stereospecific. The opposing effects exerted by naloxone at high and low doses may be due to the processing of nociceptive messages delivered to the thalamus by multiple endogenous opioid systems with differing susceptibility to naloxone. The results present evidence that naloxone at low doses may cause relief in particular conditions of pain.
据报道，阿片类拮抗剂纳洛酮可缓解疼痛。因此，本研究测定了静脉注射纳洛酮对在乌拉坦麻醉下的大鼠丘脑腹侧核背内侧部分（VDM）单个神经元活动的影响，该活动由电刺激腓肠神经中的伤害性传入纤维诱发。纳洛酮以剂量依赖性方式抑制诱发的伤害性活动。高剂量（5mg/kg和1mg/kg）可增加或降低活动，较低剂量时抑制作用占主导。在较低剂量（0.5mg/kg、0.2mg/kg和0.1mg/kg）时，纳洛酮仅引起抑制作用，ED50为0.36mg/kg。纳洛酮的（+）-异构体（0.2mg/kg和2mg/kg）无效，表明作为（-）-异构体的纳洛酮的作用具有立体特异性。纳洛酮在高剂量和低剂量时产生的相反作用可能是由于多个对纳洛酮敏感性不同的内源性阿片系统传递到丘脑的伤害性信息的处理方式不同。结果表明，低剂量的纳洛酮在特定疼痛情况下可能会缓解疼痛。
