Interindividual differences in the analgesic response to ketamine in chronic orofacial pain

The analgesic effect of the N-methyl-D-aspartate (NMDA) receptor blocker ketamine in 17 patients (13 females and four males, age 32-88 years) who had suffered neuropathic orofacial pain for time periods ranging from 6 months to 28 years was examined. The patients were given an i.m. test-dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam. Four patients did not experience any analgesic effect of the i.m. test dose. The remaining 13 patients experienced an analgesic effect which lasted for less than 1 h (transient effect) in seven and for several hours (long-term effect) in six. One week later they were given 4 mg/kg ketamine to be taken orally in combination with a hypnotic drug for three consecutive nights. All patients who reported a long-term analgesic effect after i.m. ketamine also reported reduced pain intensity on days after taking ketamine at night. The findings of this open study are in accord with the results from a previous double-blind randomized investigation. In order to evaluate the role of age and pain duration for the analgesic effect of ketamine, we pooled the data from the two studies and performed a correlation analysis of 43 patients. We found a positive correlation between a long pain-history and lack of analgesic effect and also between a short pain-history and a long-term analgesic effect of low-dose ketamine. The apparent relationship between patient age and ketamine response was, however, not statistically significant. Further, patients with pain following a nerve lesion and patients without a known lesion of peripheral nerves were equally distributed between the three response groups. These results indicate that pain mechanisms are subject to alterations with time and that these alterations involve transition from NMDA to non-NMDA receptor mediated transmission in central pain pathways.