Effect of a peripheral NMDA receptor antagonist on glutamate-evoked masseter muscle pain and mechanical sensitization in women

AIMS: To test the hypothesis that local injection of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine would significantly attenuate glutamate-evoked masseter mechanical sensitization and muscle pain in healthy young women either taking oral contraceptives (W+OC) or not taking oral contraceptives (W-OC). METHODS: Experimental pain was evoked in 47 healthy female subjects (W+OC, n=25; W-OC, n=22) by 2 injections of glutamate (0.2 mL, 1 mol/L) into the masseter muscle. A first injection of glutamate alone was followed by a second injection, 35 minutes later, of glutamate combined with ketamine (0, 1, or 10 mmol/L). Evoked pain intensity was scored on a 10-cm electronic visual analog scale (VAS). Distribution of perceived pain was drawn on a lateral view of the face (pain drawing). Masseter muscle pressure pain thresholds (PPT) and pressure-pain tolerances (PPTOL) were determined bilaterally before and at regular time intervals after injections. Analyses of variance (ANOVA) were used to test the data. RESULTS: There were no main effects of ketamine on any of the VAS pain parameters or on the pain drawing (ANOVAs: P > .055). Furthermore, there were no differences in PPT, PPTOL, VAS peak pain, duration, overall VAS pain, or pain drawing when W-OC were compared with W+OC (ANOVAs: P > .087). Repeated injection of glutamate alone significantly decreased PPT and PPTOL (ANOVAs: P < .001); however, this effect was not significantly attenuated by ketamine. CONCLUSIONS: Peripherally administered ketamine had no effect on glutamate-evoked masseter muscle pain and sensitization in healthy young women, which contrasts with recent observations in healthy young men. Further studies will be needed to reveal the mechanisms that underlie this apparent sex-related difference in ketamine-mediated analgesia.