The prefrontal ventrolateral orbital cortex (VLO) is involved in antinociception. It has been found that dopamine receptors, adrenoceptors, serotonin receptors and μ-opioid receptors are involved in this effect through direct/indirect activation of the VLO output neurons. However, the effect of CB1 receptors on the VLO modulation of pain has not been studied. In this study, we investigated whether activation of CB1 receptors in the VLO modulates nociception. A common peroneal nerve (CPN) ligation model was used to induce neuropathic pain in male mice. On day 13 after CPN ligation, spontaneous firing of the VLO pyramidal neurons was recorded and CB1 receptor level in the VLO was detected. Mechanical allodynia was measured after HU210 was microinjected into the VLO. Relative contribution of CB1 receptors on GABAergic neurons and glutamatergic neurons was determined by CB1 receptor knockdown using a viral strategy. Our data indicated that on day 13 after nerve injury, spontaneous firing of the VLO pyramidal neurons reduced significantly but was enhanced by intraperitoneal injection of HU210 (20 μg/kg), a potent CB1 receptor agonist. Expression of CB1 receptor in the VLO was up-regulated. Microinjection of HU210 into the VLO attenuated allodynia, and this effect was blocked by pre-microinjection of specific CB1 receptor antagonist AM281. Deletion of CB1 receptors on GABAergic neurons in the VLO can completely block HU210-induced analgesia. Thus, it can be concluded that activation of CB1 receptors on GABAergic interneurons in the VLO may be involved in analgesia effect of cannabinoids.

前额腹外侧眶皮质（VLO）参与抗伤害感受。已经发现，通过直接/间接激活VLO输出神经元，多巴胺受体，肾上腺素受体，5-羟色胺受体和μ阿片样物质受体参与了该作用。但是，尚未研究CB1受体对VLO调节疼痛的作用。在这项研究中，我们调查了VLO中CB1受体的激活是否调节伤害感受。腓总神经（CPN）结扎模型用于诱发雄性小鼠的神经性疼痛。CPN结扎后第13天，记录了VLO锥体神经元的自发放电，并检测到VLO中的CB1受体水平。将HU210微量注入VLO后测量机械性异常性疼痛。CB1受体对GABA能神经元和谷氨酸能神经元的相对贡献通过病毒策略通过CB1受体敲低来确定。我们的数据表明，在神经损伤后的第13天，VLO锥体神经元的自发放电显着降低，但腹膜内注射强效CB1受体激动剂HU210（20μg/ kg）会增强。VLO中CB1受体的表达上调。将HU210显微注射到VLO中可减轻异常性疼痛，并且通过预先显微注射特异性CB1受体拮抗剂AM281可以阻止这种作用。VLO中GABA能神经元上CB1受体的缺失可以完全阻断HU210引起的镇痛作用。因此，可以得出结论，VLO中GABA能神经元上的CB1受体的激活可能与大麻素的镇痛作用有关。