Tashiro A, Bereiter D A, Thompson R, Nishida Y
Department of Physiology, National Defense Medical College, Namiki 3-2, Tokorozawa City, Saitama 359-8513, Japan.
Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-214, 515 Delaware Street SE, Minneapolis, MN 55455, USA.
Neuroscience. 2014 Feb 14;259:53-62. doi: 10.1016/j.neuroscience.2013.11.053. Epub 2013 Dec 4.
Sensory input from the temporomandibular joint (TMJ) to neurons in superficial laminae at the spinomedullary (Vc/C1-2) region is strongly influenced by estrogen status. This study determined if GABAergic mechanisms play a role in estrogen modulation of TMJ nociceptive processing in ovariectomized female rats treated with high- (HE) or low-dose (LE) estradiol (E2) for 2days. Superficial laminae neurons were activated by ATP (1mM) injections into the joint space. The selective GABAA receptor antagonist, bicuculline methiodide (BMI, 5 or 50μM, 30μl), applied at the site of recording greatly enhanced the magnitude and duration of ATP-evoked responses in LE rats, but not in units from HE rats. The convergent cutaneous receptive field (RF) area of TMJ neurons was enlarged after BMI in LE but not HE rats, while resting discharge rates were increased after BMI independent of estrogen status. By contrast, the selective GABAA receptor agonist, muscimol (50μM, 30μl), significantly reduced the magnitude and duration of ATP-evoked activity, resting discharge rate, and cutaneous RF area of TMJ neurons in LE and HE rats, whereas lower doses (5μM) affected only units from LE rats. Protein levels of GABAA receptor β3 isoform at the Vc/C1-2 region were similar for HE and LE rats. These results suggest that GABAergic mechanisms contribute significantly to background discharge rates and TMJ-evoked input to superficial laminae neurons at the Vc/C1-2 region. Estrogen status may gate the magnitude of GABAergic influence on TMJ neurons at the earliest stages of nociceptive processing at the spinomedullary region.
来自颞下颌关节（TMJ）至脊髓延髓（Vc/C1-2）区域浅层神经元的感觉输入受雌激素状态的强烈影响。本研究确定了γ-氨基丁酸（GABA）能机制是否在经高剂量（HE）或低剂量（LE）雌二醇（E2）处理2天的去卵巢雌性大鼠TMJ伤害性感受处理的雌激素调节中发挥作用。通过向关节间隙注射三磷酸腺苷（ATP，1mM）激活浅层神经元。在记录部位应用选择性GABAA受体拮抗剂甲碘化荷包牡丹碱（BMI，5或50μM，30μl）可显著增强LE大鼠中ATP诱发反应的幅度和持续时间，但对HE大鼠的神经元无此作用。在LE大鼠而非HE大鼠中，BMI应用后TMJ神经元的汇聚性皮肤感受野（RF）面积增大，而静息放电率在BMI应用后增加，且与雌激素状态无关。相比之下，选择性GABAA受体激动剂蝇蕈醇（50μM，30μl）可显著降低LE和HE大鼠中TMJ神经元的ATP诱发活动幅度和持续时间、静息放电率以及皮肤RF面积，而较低剂量（5μM）仅影响LE大鼠的神经元。HE和LE大鼠在Vc/C1-2区域的GABAA受体β3亚型蛋白水平相似。这些结果表明，GABA能机制对Vc/C1-2区域浅层神经元的背景放电率和TMJ诱发输入有显著贡献。雌激素状态可能在脊髓延髓区域伤害性感受处理的最早阶段调节GABA能对TMJ神经元的影响程度。
