Reduced GABAA receptor α6 expression in the trigeminal ganglion enhanced myofascial nociceptive response.
Reduced GABAA receptor α6 expression in the trigeminal ganglion enhanced myofascial nociceptive response.
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DOI：
10.1016/j.neuroscience.2013.04.003
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发表时间：
2013-08-15
期刊：
影响因子：
3.3
通讯作者：
Bellinger LL
中科院分区：
文献类型：
--
作者：
Kramer PR;Bellinger LL
GABAA 受体的激活导致神经元活动的抑制。这种多亚基受体的一个亚基称为 α 6 (Gabrα6)，会导致炎症性颞下颌关节 (TMJ) 伤害感受，但 TMJ 疾病通常包括肌筋膜疼痛。为了解决 Gabrα6 在肌筋膜疼痛中的作用，我们假设 Gabrα6 在类似于炎症性 TMJ 关节炎的肌筋膜伤害性反应中具有抑制作用。为了检验这一假设，通过在雄性大鼠咬肌前表面部分的肌腱附着处两侧放置结扎线来诱导肌筋膜伤害性反应。结扎线放置四天后，通过向三叉神经节（TG）输注与 Gabrα6 基因（Gabra6 siRNA）或未知基因（对照 siRNA）具有同源性的小干扰 RNA（siRNA），可降低 Gabrα6 表达。 siRNA输注后，测量伤害性行为反应，即用冯弗雷细丝按压结扎线上方区域后的进食行为和头部缩回。通过定量磷酸化细胞外信号调节激酶 (p-ERK) 的量来测量 TG、三叉神经尾核和上颈区 (Vc-C1) 的神经元活动。测定了 TG 和 Vc-C1 中的总 Gabrα6 和 GABAA 受体含量。 Gabrα6 siRNA 输注可降低 Gabrα6 和 GABAA 受体的表达，并显着增加两种伤害性测定中的伤害性反应。 Gabra6 siRNA 输注还显着增加了结扎大鼠的 TG p-ERK 表达。从这些结果我们得出结论，由 Gabrα6 亚基组成的 GABAA 受体抑制三叉神经通路中的 TG 伤害性感觉传入，并在肌筋膜伤害性的调节中发挥重要作用。
Activation of the GABAA receptor results in inhibition of neuronal activity. One subunit of this multi-subunit receptor termed alpha 6 (Gabrα6) contributed to inflammatory temporomandibular joint (TMJ) nociception but TMJ disorders often include myofascial pain. To address Gabrα6 role in myofascial pain we hypothesized that Gabrα6 has an inhibitory role in myofascial nociceptive responses similar to inflammatory TMJ arthritis. To test this hypothesis a, myofascial nociceptive response was induced by placing a ligature bilaterally on the tendon attachment of the anterior superficial part of a male rat's masseter muscle. Four days after ligature placement Gabrα6 expression was reduced by infusing the trigeminal ganglia (TG) with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabra6 siRNA) or no known gene (control siRNA). After siRNA infusion nociceptive behavioral responses were measured, i.e., feeding behavior and head withdrawal after pressing upon the region above the ligature with von Frey filaments. Neuronal activity in the TG and trigeminal nucleus caudalis and upper cervical region (Vc–C1) was measured by quantitating the amount of phosphorylated extracellular signalregulated kinase (p-ERK). Total Gabrα6 and GABAA receptor contents in the TG and Vc–C1 were determined. Gabrα6 siRNA infusion reduced Gabrα6 and GABAA receptor expression and significantly increased the nociceptive response in both nociceptive assays. Gabra6 siRNA infusion also significantly increased TG p-ERK expression of the ligated rats. From these results we conclude GABAA receptors consisting of the Gabrα6 subunit inhibit TG nociceptive sensory afferents in the trigeminal pathway and have an important role in the regulation of myofascial nociception.
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影响因子：
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