Activation of CB1 receptors on GABAergic interneurons in the ventrolateral orbital cortex induces analgesia. (25th September 2020)

• Record Type: Journal Article
• Authors: Wu, Yuwei; Fu, Dongqin; Gu, Qiaofen; Li, Yongfeng; Qian, Zhaoqiang; Han, Jing; Liu, Zhiqiang; Ren, Wei; Liu, Yihui
• Is Part Of: Neuroscience letters. Volume 736(2020)
• Publication Date: 2020-09-25
• Subjects: Cannabinoids -- Common peroneal nerve -- CB1 receptor -- Ventrolateral orbital cortex -- Neuropathic pain; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.135286
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: HU210 activates the VLO in nerve injured mice. Nerve injury up-regulates CB1 receptors in the VLO. Microinjection of HU210 in the VLO produces analgesia. CB1 receptors on GABAergic neurons are necessary for HU210-evoked analgesia. Abstract: 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.