Glutamate-Induced Temporomandibular Joint Pain is Partially Mediated by NMDA Receptors

Objectives:

To determine if injection of glutamate into the healthy human temporomandibular joint (TMJ) evokes pain through peripheral NMDA receptors and if sex or sex-steroid hormones influences this pain.

Methods:

Fifty-one healthy individuals were included; 15 males (median age = 27 years) and 36 females (age = 26 years). Double-blind intraarticular injections of 0.2 mL glutamate (1.0 mol/L) or 0.2 mL glutamate + ketamine (10 mmol/L) were performed in a randomized order into the TMJ. Maximum resting TMJ pain intensity, pain duration and area under the pain curve were assessed on a continuous electronic visual analogue scale (0-10) before and during 25 min after each injection. Venous blood samples were obtained and analyzed for serum levels of estradiol, progesterone and testosterone.

Results:

Glutamate evoked a TMJ resting pain of a median duration of 8 min. The median maximum resting pain intensity was 4.6 and the median area under the curve was 59 AU. Females reported a significantly higher maximum pain intensity than males (p = 0.048). There was no significant influence of gender or sex-steroid hormone levels.

In the males, co-injection of the NMDA antagonist ketamine significantly reduced the area under the pain curve to 57% (p = 0.024) whereas in the females, co-injection with ketamine significantly reduced the maximum pain intensity, duration and area under the curve to 90%, 65% and 54%, respectively (p = 0.026, p = 0.010 and p < 0.001). The effect of ketamine was not significantly related to sex-steroid hormone levels in either gender.

Conclusions:

Glutamate evokes pain in the TMJ, partially via the peripheral NMDA receptor. The degree of NMDA receptor modulation of glutamate-induced pain seems to be larger in females although no sex hormone-related effect was found. Supported by National Institute of Dental and Craniofacial Research Grant 1 R01 DE15420-01.