The effects of racemic ketamine on painful stimulation of skin and viscera in human subjects

Abstract

Evidence suggests that NMDA receptors may have a differential role in the modulation of visceral and somatic pain. Specifically, animal data indicate an analgesic role of NMDA-R antagonists in acute visceral but not acute somatic pain. In humans analgesic effects are documented in acute somatic pain, while the role of NMDA-R antagonists in acute visceral pain is still questionable. We, therefore, conducted a study in humans comparing the analgesic effects of ketamine in an experimental model of visceral and cutaneous pain. In a double-blind, randomized, cross-over study, 11 healthy volunteers (3M, 8F) participated in two experimental sessions in which they evaluated perceptions induced by balloon distention of the distal esophagus and contact heat on the upper chest during continuous computer-controlled i.v. infusion of either ketamine (60 and 120 ng/mL) or saline. Two stimulus intensities producing non-painful and painful sensation were used for each stimulus modality. Subjects reported maximum pain intensity and unpleasantness on visual analog scales (VAS). For noxious visceral stimulation, low dose ketamine produced significant attenuation of both pain intensity and unpleasantness. In contrast, for noxious cutaneous stimulation, ketamine reduced pain unpleasantness, but not perceived intensity. In addition, ketamine did not alter the perception of innocuous stimuli in either modality. Our results confirm the analgesic effects of low-dose ketamine, with minimal side effects, on acute visceral pain and indicate a similar but smaller effect on acute cutaneous pain. A decrease in the unpleasantness but not in the intensity of cutaneous pain may reflect the differential effect of NMDA-R antagonists for the two pain states observed in animal models.