Nihon University School of Dentistry at Matsudo, Department of Removable Prosthodontics, 2-870-1, Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan.
Neuroscience. 2012 Aug 30;218:359-66. doi: 10.1016/j.neuroscience.2012.05.016. Epub 2012 May 17.
Our previous studies have demonstrated that application of inflammatory irritant mustard oil (MO) to the tooth pulp induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0-1.2%), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (analysis of variance (ANOVA), p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states.
我们之前的研究表明，将炎性刺激剂芥子油（MO）应用于牙髓会导致大鼠髓质背角（MDH）中髓质谷氨酸释放和中枢敏化，以及大鼠颅面肌肉中的伤害感受运动反应。最近有证据表明，影响谷氨酸能神经传递的抗惊厥药物，如普瑞巴林，在几种疼痛状态下是有效的。本研究旨在探讨普瑞巴林是否能减轻髓质中谷氨酸的释放，以及 MO 应用于牙髓所引起的这些伤害感受效应，表现为咬肌和舌肌的肌电图（EMG）活动增加。雄性成年大鼠用异氟烷（1.0-1.2%）麻醉，通过双侧插入咬肌和前二腹肌的针电极和颏舌肌记录咀嚼肌和舌肌的 EMG 活动，并通过活体微透析评估髓质中谷氨酸的释放。在 MO 或对照（矿物油）应用于牙髓前 30 分钟，给予普瑞巴林或对照（等渗盐水）。矿物油应用于上颌第一磨牙牙髓不会改变基线 EMG 活动和谷氨酸释放。然而，MO 应用于牙髓会显著增加下颌和舌肌的髓质谷氨酸释放和 EMG 活动几分钟。相比之下，普瑞巴林预处理，而不是对照物，在 MO 应用于牙髓后，显著且剂量依赖性地减轻了这些肌肉中的髓质谷氨酸释放和 EMG 活动（方差分析（ANOVA），p<0.05）。这些结果表明，普瑞巴林可能减轻这种急性炎症性牙髓疼痛模型中的髓质谷氨酸释放和相关的伤害感受运动反应，并且可能对治疗口腔炎症性疼痛状态有用。
