Pain Reduction Effects of a Ketamine Metabolite Using Models of Pain in Mice
Abstract
Purpose: Nearly 2/3rd of U.S. veterans report experiencing pain in the past three months. Over 9% claim their pain to be severe, resulting in significant pain-related limitations to work capability and social life. There is a considerable need to identify novel pain therapeutics to address this pain problem and increase operational readiness. (2R,6R)-hydroxynorketamine (HNK) is a ketamine metabolite that has been shown to share some of ketamine's therapeutic potential for depression while lacking its adverse side effects. Since ketamine has demonstrated utility in treating pain without the respiratory depression effects caused by opioid medications, it was natural to question whether (2R,6R)-HNK also produced analgesic effects. Methods: (2R,6R)-HNK treatment was tested in different preclinical pain models using C57BL/J6 mice. Experiments characterizing the time course, comparison between sexes, and mechanism of action were conducted under the selected models and compared with reference analgesic drugs. The potential for (2R,6R)-HNK to reverse opioid tolerance and augment opioid analgesia was also investigated. Findings: (2R,6R)-HNK produced antinociception in healthy mice and reversed hypersensitivity in animals with induced pain conditions. The antinociceptive effects of (2R,6R)-HNK was dependent on AMPA receptor activity and was independent of opioid receptors. (2R,6R)-HNK increased opioid responses in a model of opioid tolerance, potentially enhancing opioid-based analgesia during a critical treatment period. These results provide evidence that encourages future support of clinical research examining (2R,6R)-HNK as a novel analgesic and its AMP A receptor-dependent mechanism of analgesia. Implications for Military Nursing: As integral members of the health care team, military nurses share responsibility for addressing the critical need to treat pain within our veteran population.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 22, 2023
- Accession Number
- AD1193791
Entities
People
- Jonathan G. Yost
Organizations
- Uniformed Services University of the Health Sciences