Effect of Peripheral NMDA Receptor Antagonists on Masseter Muscle Pain

OBJECTIVES: NMDA receptor mechanisms within the brain are implicated in chronic pain conditions, however, peripheral NMDA receptors could also play a role. The aim of this placebo-controlled, double blind, cross-over study was to test the efficacy of peripherally applied ketamine, a NMDA receptor antagonist, on experimental jaw-muscle pain. METHODS: Fourteen healthy men (mean age ± SD: 27 ± 5 years) participated in four sessions separated by 1 week. During each session, an initial injection of a sterile solution of either glutamate (0.2 ml; 1.0 M; pH = 7.2) or buffered hypertonic saline (0.2 ml; 1.0 M; pH = 7.4) into the right masseter muscle was followed, 30 min later, by a second injection of the same solution alone (control) or in combination with ketamine (10 mM; Ketalar, Park Davis). Ketamine alone was injected into the left masseter to test its effect on masseter pressure pain thresholds (PPT). Subjects rated the pain evoked by glutamate or hypertonic saline injection on an electronic visual analogue scale (VAS). Mean relative VAS pain scores (injection 2 divided by injection 1) were calculated for each session. RESULTS: When compared with control sessions, co-injection of ketamine with glutamate significantly decreased the mean relative VAS pain score by 44% (Student-Newman-Keul: P < 0.05), whereas co-injection of ketamine with hypertonic saline did not significantly alter the pain score. Injection of ketamine alone into the left masseter produced no significant changes in masseter PPTs compared with baseline (Paired t-test: P < 0.05). CONCLUSION: These findings suggest that peripherally applied NMDA receptor antagonists specifically attenuate glutamate-evoked muscle pain and that glutamate-sensitive receptors could represent an important target for pharmacological management of chronic jaw-muscle pain. Supported by Danish National Research Foundation and Boston Children's Hospital Pain Research Endowment Fund.