Ketamine and Pain Relief

Dr. Shannon Granger                   

August 21, 2012

Estimation of the Contribution of Norketamine to Ketamine-induced Acute Pain Relief and Neurocognitive Impairment in Healthy Volunteers

Summary:          

                Ketamine is an NMDA receptor antagonist that is metabolized in the liver to an active metabolite, norketamine. The goal of this study was to assess norketamine’s role in analgesia and cognitive effects as no study to date has been performed elucidating these points. 

                12 healthy male volunteers aged 18-37 were selected and given rifampicin or placebo pretreatment to assess the effects of ketamine versus norketamine. Previous to the study, researchers showed that pretreatment with the antibiotic rifampicin caused a 10% reduction in ketamine and a 50% reduction of norketamine, thus the effect of norketamine could be deduced. It was hypothesized that norketamine contributed 20% to the ketamine induced effects such as analgesia. Subjects underwent three days of testing at three week intervals, one day 6 subjects took rifampicin and 6 took the placebo pill and received on normal saline infusion, on day 2 all 12 took the rifampicin and received an infusion of ketamine, on the third occasion all patients took the placebo pill and all received treatment with ketamine. Patients underwent a heat tolerance test in which heat pain was induced and pain was scored by the visual analogue scoring system, drug high was scored form 0-10 meaning maximal effect, and cognition was measured using a neurocognitive battery test.

                A descriptive analysis showed that ketamine produced greater analgesia, psychotropic effects and impaired cognition than did placebo. Additionally, norketamine had a negative contribution to pain intensity and appreciation when testing patients for heat sensitivity (meaning that norketamine had an opposing effect on ketamine). When norketamine levels were low, such as after rifampicin administration the VAS response was reduced and no hyperalgesia was observed. Norketamine also showed fewer effects on cognitive abilities in this study. Further studies are needed to confirm this study’s findings; however this study suggests that norketamine produces opposing effects to ketamine.