An observational study on the effect of S(+)-ketamine on chronic pain versus experimental acute pain in Complex Regional Pain Syndrome type 1 patients

Abstract

Aims The aim of the study was to explore the analgesic effect of the N-methyl- d-aspartate receptor (NMDAR) antagonist ketamine in acute experimental versus chronic spontaneous pain in Complex Regional Pain Syndrome type 1 (CRPS-1) patients. Methods Ten patients suffering from chronic CRPS-1 and with a Visual Analogue pain Score (VAS) of >5 were recruited. Seven intravenous 5-min low-dose S(+)-ketamine infusions with increasing doses at 20-min intervals were applied. Spontaneous pain ratings and VAS responses to experimental heat stimuli were obtained during infusion and for 3-h following infusion. Results CRPS pain: Ketamine produced potent analgesia with a significant VAS reduction from 6.2 ± 0.2 to 0.4 ± 0.3 cm at the end of infusion. Analgesia persisted beyond the infusion period ( VAS = 2.8 ± 1.0 cm at 5-h), when measured plasma ketamine concentrations were low (<100 ng/ml). Experimental pain: Ketamine had a dose-dependent antinociceptive effect on experimental pain that ended immediately upon the termination of infusion. Discussion The data indicate that while ketamine’s effect on acute experimental pain is driven by pharmacokinetics, its effect on CRPS pain persisted beyond the infusion period when drug concentrations were below the analgesia threshold for acute pain. This indicates a disease modulatory role for ketamine in CRPS-1 pain, possibly via desensitization of NMDAR in the spinal cord or restoration of inhibitory sensory control in the brain.