There is evidence that elevated tissue concentrations of glutamate may contribute to pain and sensitivity in certain musculoskeletal pain conditions. In the present study, the food additive monosodium glutamate (MSG) was injected intravenously into rats to determine whether it could significantly elevate interstitial concentrations of glutamate in the masseter muscle and whether MSG administration could excite and/or sensitize slowly conducting masseter afferent fibers through N-methyl-d-aspartate (NMDA) receptor activation. The interstitial concentration of glutamate after systemic injection of isotonic phosphate-buffered saline (control) or MSG (10 and 50 mg/kg) was measured with a glutamate-selective biosensor. The pre-injection baseline interstitial concentration of glutamate in the rat masseter muscle was 24 ± 11 μM. Peak interstitial concentration after injection of 50 mg/kg MSG was 63 ± 18 μM and remained elevated above baseline for ∼18 min. In vivo single unit recording experiments were undertaken to assess the effect of MSG (50 mg/kg) on masseter afferent fibers. Injection of MSG evoked a brief discharge in one afferent fiber, and significantly decreased (∼25%) the average afferent mechanical threshold (n = 10) during the first 5 min after injection of MSG. Intravenous injection of ketamine (1 mg/kg), 5 min prior to MSG, prevented the MSG-induced decreases in the mechanical threshold of masseter afferent fibers. The present results indicate that a 2- to 3-fold elevation in interstitial glutamate levels in the masseter muscle is sufficient to excite and induce afferent mechanical sensitization through NMDA receptor activation. These findings suggest that modest elevations of interstitial glutamate concentration could alter musculoskeletal pain sensitivity in humans.
aFaculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3
bDepartment of Clinical Oral Physiology, Dental School, Århus University, DK-8000 Århus C, Denmark
cFaculty of Dentistry, The University of Toronto, Toronto, Ont., Canada M5G 1G6
dLaboratory for Experimental Pain Research, Center for Sensory-Motor Interaction, Aalborg University, DK-9220 Aalborg, Denmark
*Corresponding author. Tel.: +1 604 822 7715; fax: +1 604 822 3035.
Submitted October 4, 2006; received in revised form January 9, 2007; accepted January 25, 2007.