Chen Yan-Ping, Chen Shao-Rui, Pan Hui-Lin
Department of Anesthesiology, H187, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
J Pharmacol Exp Ther. 2005 Aug;314(2):611-7. doi: 10.1124/jpet.105.085563. Epub 2005 Apr 21.
Cholinergic circuitry and muscarinic receptors within the spinal cord have been proposed to contribute to the analgesic effects of systemic morphine. In this study, we determined whether the descending pathways are involved in the inhibitory effect of systemic morphine on dorsal horn projection neurons mediated by activation of the spinal cholinergic system. Single-unit activity of dorsal horn projection neurons was recorded in anesthetized rats. The neuronal responses to mechanical stimuli applied to the receptive field were determined before and after intravenous injection of morphine. The inhibitory effect of intravenous morphine on dorsal horn neurons was also tested before and after topical spinal application of the muscarinic antagonist atropine in both intact and spinally transected rats. Intravenous injection of 2.5 mg/kg morphine significantly inhibited the evoked response of dorsal horn neurons in both intact and spinally transected rats. Spinal topical application of the mu opioid antagonist H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) completely blocked the effect of morphine on dorsal horn neurons. In addition, spinal application of 10 microM atropine significantly attenuated the effect of systemic morphine. In rats subjected to cervical spinal transection, atropine produced a similar attenuation of the inhibitory effect of systemic morphine on dorsal horn neurons. Data from this electrophysiological study suggest that systemic morphine inhibits ascending dorsal horn neurons through stimulation of spinal mu opioid receptors. Furthermore, activation of the local spinal cholinergic circuitry and muscarinic receptors is involved in the inhibitory effect of systemic morphine on dorsal horn projection neurons independent of descending pathways.
脊髓内的胆碱能神经回路和毒蕈碱受体被认为有助于全身吗啡的镇痛作用。在本研究中，我们确定下行通路是否参与全身吗啡对脊髓胆碱能系统激活介导的背角投射神经元的抑制作用。在麻醉大鼠中记录背角投射神经元的单单位活动。在静脉注射吗啡前后，测定神经元对施加于感受野的机械刺激的反应。在完整和脊髓横断的大鼠中，在脊髓局部应用毒蕈碱拮抗剂阿托品前后，也测试了静脉注射吗啡对背角神经元的抑制作用。静脉注射2.5mg/kg吗啡显著抑制了完整和脊髓横断大鼠背角神经元的诱发反应。脊髓局部应用μ阿片拮抗剂H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2)(CTAP)完全阻断了吗啡对背角神经元的作用。此外，脊髓应用10μM阿托品显著减弱了全身吗啡的作用。在颈段脊髓横断的大鼠中，阿托品对全身吗啡对背角神经元的抑制作用产生了类似的减弱作用。这项电生理研究的数据表明，全身吗啡通过刺激脊髓μ阿片受体抑制背角神经元的上行活动。此外，局部脊髓胆碱能神经回路和毒蕈碱受体的激活参与了全身吗啡对背角投射神经元的抑制作用，且与下行通路无关。
