Correlation of Ketamine and Classic Psychedelics with Pain-Related Neural Connectivity: A Scoping Review of Clinical Experiments on a Potential Therapeutic Target Concerning Ketamine and Classical Psychedelics Administration for Pain Relief

Purpose: Ketamine and classic psychedelics have recently gained increased scientific interest regarding their role in pain management, while there is evidence that pain induces neural connectivity changes. We performed a scoping review to investigate the correlation of ketamine and classic psychedelics with pain-related neural connectivity, aiming to find potential therapeutic targets for these medications administration for pain relief. Methods: We searched PubMed and Scopus databases for articles with the purpose to explore the correlation between ketamine and classic psychedelics administration with pain-related neural connectivity. From each included article we extracted the following data: authors, medication under investigation, number of participants, pain-related brain regions whose connectivity was involved, and correlation of the medication with this connectivity. Results: Six articles were included. Four of them concerned ketamine, one concerned lysergic acid diethylamide (LSD), and one was about psilocybin. The three medications notably altered connectivity between brain regions related to cognitive and emotional aspects of pain. Ketamine mainly correlated with connectivity involving large-scale neural networks (default mode and salience network). Baseline connectivity, especially regarding medial prefrontal cortex-precuneus and default mode network-antinociceptive pathways, may predict ketamine treatment response. Conclusions: There is a remarkable correlation of ketamine and classic psychedelics (LSD and psilocybin) with pain-related neural connectivity. Further research will shed more light on the promising role of neural connectivity as a therapeutic target concerning ketamine and classic psychedelics for pain management.