Cairns Brian E, Dong Xudong, Mann Mandeep K, Svensson Peter, Sessle Barry J, Arendt-Nielsen Lars, McErlane Keith M
Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada.
Pain. 2007 Nov;132(1-2):33-41. doi: 10.1016/j.pain.2007.01.023. Epub 2007 Mar 1.
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 50mg/kg) was measured with a glutamate-selective biosensor. The pre-injection baseline interstitial concentration of glutamate in the rat masseter muscle was 24+/-11 microM. Peak interstitial concentration after injection of 50mg/kg MSG was 63+/-18 microM and remained elevated above baseline for approximately 18 min. In vivo single unit recording experiments were undertaken to assess the effect of MSG (50mg/kg) on masseter afferent fibers. Injection of MSG evoked a brief discharge in one afferent fiber, and significantly decreased ( approximately 25%) the average afferent mechanical threshold (n=10) during the first 5 min after injection of MSG. Intravenous injection of ketamine (1mg/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.
有证据表明，在某些肌肉骨骼疼痛病症中，组织中谷氨酸浓度升高可能导致疼痛和敏感。在本研究中，将食品添加剂谷氨酸钠（MSG）静脉注射到大鼠体内，以确定其是否能显著提高咬肌间质中谷氨酸的浓度，以及给予MSG是否能通过N-甲基-D-天冬氨酸（NMDA）受体激活来兴奋和/或致敏传导缓慢的咬肌传入纤维。用谷氨酸选择性生物传感器测量全身注射等渗磷酸盐缓冲盐水（对照）或MSG（10和50mg/kg）后谷氨酸的间质浓度。大鼠咬肌中谷氨酸注射前的基线间质浓度为24±11μM。注射50mg/kg MSG后的间质浓度峰值为63±18μM，并在高于基线水平保持升高约18分钟。进行体内单单位记录实验以评估MSG（50mg/kg）对咬肌传入纤维的影响。注射MSG在一条传入纤维中引起短暂放电，并在注射MSG后的前5分钟内显著降低（约25%）平均传入机械阈值（n = 10）。在注射MSG前5分钟静脉注射氯胺酮（1mg/kg）可防止MSG引起的咬肌传入纤维机械阈值降低。目前的结果表明，咬肌中间质谷氨酸水平升高2至3倍足以通过NMDA受体激活来兴奋并诱导传入机械致敏。这些发现表明，间质谷氨酸浓度的适度升高可能会改变人类肌肉骨骼疼痛的敏感性。
