Kelly S, Chapman V
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
J Neurophysiol. 2001 Dec;86(6):3061-4. doi: 10.1152/jn.2001.86.6.3061.
Cannabinoid1 (CB1) receptors are located at CNS sites, including the spinal cord, involved in somatosensory processing. Analgesia is one of the tetrad of behaviors associated with cannabinoid agonists. Here, effects of a potent cannabinoid CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) on evoked responses of dorsal horn neurons in anesthetized rats were investigated. Extracellular recordings of convergent dorsal horn neurons were made in halothane anesthetized Sprague-Dawley rats (n = 16). Effects of spinal application of ACEA on electrically evoked responses of dorsal horn neurons were studied. Mean maximal effects of 0.5, 5, 50, and 500 ng/50 microl ACEA on the C-fiber-mediated postdischarge response were 79 +/- 6, 62 +/- 10, and 54 +/- 7% (P < 0.01), 45 +/- 6% (P < 0.01), of control, respectively. ACEA (500 ng/50 microl) also reduced the C-fiber-evoked nonpotentiated responses of neurons (59 +/- 9% of control, P < 0.05) and Adelta-fiber-evoked responses of neurons (68 +/- 10% of control, P < 0.01). Minor effects of ACEA on Abeta-fiber-evoked responses were observed. Spinal pre-administration of the selective CB1 receptor antagonist SR141716A (0.01 microg/50 microl) significantly reduced effects of ACEA (500 ng/50 microl) on postdischarge responses of dorsal horn neurons. This study demonstrates that spinal CB1 receptors modulate the transmission of C- and Adelta-fiber-evoked responses in anesthetized rats; this may reflect pre- and/or postsynaptic effects of cannabinoids on nociceptive transmission. CB1 receptors inhibit synaptic release of glutamate in rat dorsolateral striatum, a similar mechanism of action may underlie the effects of ACEA on noxious evoked responses of spinal neurons reported here.
大麻素1（CB1）受体位于中枢神经系统部位，包括参与躯体感觉处理的脊髓。镇痛是与大麻素激动剂相关的四种行为之一。在此，研究了一种强效大麻素CB1受体激动剂花生四烯酰-2-氯乙酰胺（ACEA）对麻醉大鼠背角神经元诱发反应的影响。在氟烷麻醉的Sprague-Dawley大鼠（n = 16）中对汇聚的背角神经元进行细胞外记录。研究了脊髓应用ACEA对背角神经元电诱发反应的影响。0.5、5、50和500 ng/50微升ACEA对C纤维介导的放电后反应的平均最大效应分别为对照的79±6%、62±10%和54±7%（P < 0.01）、45±6%（P < 0.01）。ACEA（500 ng/50微升）也降低了神经元的C纤维诱发的非增强反应（为对照的59±9%，P < 0.05）和Aδ纤维诱发的神经元反应（为对照的68±10%，P < 0.01）。观察到ACEA对Aβ纤维诱发反应的影响较小。脊髓预先给予选择性CB1受体拮抗剂SR141716A（0.01微克/50微升）显著降低了ACEA（500 ng/50微升）对背角神经元放电后反应的影响。本研究表明，脊髓CB1受体调节麻醉大鼠中C纤维和Aδ纤维诱发反应的传递；这可能反映了大麻素对伤害性传递的突触前和/或突触后作用。CB1受体抑制大鼠背外侧纹状体中谷氨酸的突触释放，这里报道的ACEA对脊髓神经元有害诱发反应的作用可能有类似的作用机制。
