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Updated: May 25, 2026

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception
Ahmet Dogrul1, Melik Seyrek, Bulent Yalcin
1Department of Medical Pharmacology, Gulhane Military Academy of Medicine, Ankara, Turkey. dogrula@gata.edu.tr
Abstract:
Cannabinoids produce antinociceptive and antihyperalgesic effects mainly through activation of the inhibitory CB1 receptors. The demonstration that antinociceptive effects of systemic cannabinoids are significantly diminished following surgical dorsolateral funiculus lesion provides evidence that supraspinal sites and descending pain modulatory pathways play crucial roles in systemic cannabinoid analgesia. In this review, we will firstly provide a background, brief overview of descending modulatory pathways followed by descending pathways implicated in cannabinoid analgesia. We will then describe the recent evidence of the involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception. This review will provide evidences that systemically administered cannabinoids reinforce the descending serotonergic and noradrenergic pathways to produce acute antinociceptive effects via spinal 5-HT7, 5-HT2A and alpha-2 adrenoceptors activation.
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