Winkler T, Sharma H S, Stålberg E, Olsson Y, Nyberg F
Department of Clinical Neurophysiology, University Hospital, Uppsala, Sweden.
Neurosci Res. 1994 Nov;21(1):91-101. doi: 10.1016/0168-0102(94)90072-8.
The possibility that opioid peptides participate in alteration of spinal cord conduction following trauma to the cord was investigated in a rat model using a pharmacological approach. Spinal cord injury was produced in urethane anesthetized animals by a longitudinal incision into the right dorsal horn of T10-11 segments (2 mm deep and 5 mm long). Spinal cord evoked potentials (SCEP) were recorded epidurally from the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral tibial and sural nerves at the ankle. SCEP from both rostral and caudal segments consisted of a small positive peak followed by a high negative peak. Infliction of trauma in untreated rats resulted in an immediate depression of the rostral maximal negative peak (MNP) amplitude. This depression was long-lasting. Later, a significant increase in the latency of the rostral MNP amplitude occurred. Naloxone was administered in a high dosage (10 mg/kg, i.p.) to block mu-, delta- and kappa-opioid receptors 30 min before injury. This drug treatment inhibited the immediate post-injury decrease of the rostral MNP amplitude without any significant effect on latency changes. Measurement of water content in the traumatized spinal cord segment showed a significant reduction in the drug treated animals 5 h after trauma (71.46 +/- 0.54) as compared with untreated controls (74.65 +/- 0.76). However, 1 mg or 5 mg/kg dosages of the drug were not effective in reducing the SCEP changes or edema after injury. These results strongly suggest that blockade of kappa-opioid receptors with high doses of naloxone is important in reduction of trauma induced alteration of SCEP and edema formation in spinal cord injury.
采用药理学方法，在大鼠模型中研究了阿片肽在脊髓创伤后参与脊髓传导改变的可能性。在乌拉坦麻醉的动物中，通过在T10 - 11节段的右背角纵向切开（深2 mm，长5 mm）造成脊髓损伤。在踝关节处刺激同侧胫神经和腓肠神经后，从T9（头端）和T12（尾端）节段硬膜外记录脊髓诱发电位（SCEP）。头端和尾端节段的SCEP均由一个小的正峰和随后的一个高负峰组成。未处理大鼠遭受创伤后，头端最大负峰（MNP）振幅立即降低。这种降低是持久的。随后，头端MNP振幅的潜伏期显著增加。在损伤前30分钟给予高剂量（10 mg/kg，腹腔注射）纳洛酮以阻断μ、δ和κ阿片受体。这种药物治疗抑制了损伤后即刻头端MNP振幅的降低，而对潜伏期变化无任何显著影响。测量创伤脊髓节段的含水量显示，创伤后5小时，药物处理组动物（71.46 +/- 0.54）与未处理对照组（74.65 +/- 0.76）相比显著降低。然而，1 mg或5 mg/kg剂量的该药物在减轻损伤后的SCEP变化或水肿方面无效。这些结果强烈表明，高剂量纳洛酮阻断κ阿片受体对于减轻脊髓损伤中创伤诱导的SCEP改变和水肿形成很重要。
