NMDA antagonist effects on TMJ pain induced by hypertonic saline

Objectives:

To investigate if temporomandibular joint (TMJ) pain induced by intra-articular injection of hypertonic saline is attenuated by the N-Methyl-D-Asparate (NMDA) receptor antagonist ketamine in healthy subjects, and if so, if this is related to sex hormone levels.

Methods:

Fifteen healthy men (median age = 25 y) and 34 healthy women (median age = 26 y) participated in this randomized and double-blind cross-over study. A blood sample was drawn to analyze estradiol, progesterone, and testosterone levels. 0.2 mL of hypertonic saline (1 mol/L) or hypertonic saline + ketamine (10 mmol/L) was injected intra-articularly into the TMJ. The maximum pain intensity (0-10), area under the curve (auc, AU), and pain duration (min) were assessed continuously on an electronic visual analogue scale during 25 min. The other solution was then injected in the same manner. Statistical analyses used a significance level of p < 0.05. Results: Hypertonic saline induced pain of similar intensity, duration and auc in both sexes (Mann-Whitney; p > 0.224), with a median intensity of 7.0, duration of 6.2 min, and auc of 59 AU. Hypertonic saline + ketamine reduced the maximum pain intensity by 5%, pain duration by 16%, and auc by 20% (Wilcoxon; p = 0.380, p = 0.052 and p = 0.025, respectively), without sex differences (Mann-Whitney; p > 0.573). There were no significant correlations between pain variables or changes in pain variables and the sex hormone levels (Spearman; p > 0.071).

Conclusion:

Ketamine produces a modest attenuation of hypertonic saline-induced TMJ pain parameters in healthy subjects that is not affected by the level of sex hormones. Supported by NIDCR grant 1 R01 DE15420.