Pain reduction effects of a ketamine metabolite using models of pain in mice

Treating persistent pain conditions with opioid medications is not only ineffective for long-term treatment but is also a preventable factor behind the current opioid crisis, which kills thousands of people each year. One way to address the opioid crisis is to identify better treatments to reduce pain. The purpose of this study is to determine the potential of a specific metabolite of ketamine named (2R,6R)-hydroxynorketamine (HNK) to be an effective alternative to opioids in reducing pain or opioid adjunct to make opioid pain treatment safer and more effective. The specific aims for this study are 1) to determine the pain reduction effects of (2R,6R)-HNK in healthy mice and mice with induced neuropathic and inflammatory pain, and 2) to examine the interaction between (2R,6R)-HNK and opioid-induced pain reduction in mice. To investigate these aims, C57BL/J6 mice will be tested utilizing various pain measurement tests after receiving (2R,6R)-HNK and compared to mice receiving saline as a placebo. Three pain conditions will be induced in groups of the mice to best answer the research question. These conditions include inflammatory pain, nerve pain, and tolerance to opioid medications. At the conclusion of this study, the results will clearly show whether (2R,6R)-HNK can reduce pain in healthy mice, in mice with inflammatory pain, and mice with nerve pain. The results will also show whether (2R,6R)-HNK can be utilized to enhance the pain reduction effects of opioids and reduce the tolerance observed after repeated opioid dosing.