Texas A&M University School of Dentistry, Dallas, TX 75246, United States.
Dept Ophthalmology and of Molecular Microbiology and Genetics, University of Pittsburg, 203 Lothrop, St. Pittsburgh, PA 15213, United States.
Neuroscience. 2022 Aug 1;496:16-26. doi: 10.1016/j.neuroscience.2022.06.003. Epub 2022 Jun 6.
Varicella zoster virus (VZV) is responsible for chronic pain. VZV injection has similarities to herpes zoster (HZ) "shingles" pain in humans. In this study orofacial pain was induced by injecting male rats with the human VZV. The amygdala and parabrachial have been implicated to control affective/motivational orofacial pain. Recently our lab reported neurexin 3α (Nrxn3α) is expressed in the central amygdala and parabrachial. GABAergic neurons descend from the central amygdala to the lateral parabrachial region and Nrxn3α is important for presynaptic (γ-Aminobutyric acid) GABA release. Thus, we hypothesized that lateral parabrachial neuronal activity and orofacial pain are controlled by Nrxn3α within the central amygdala. To test the hypothesis Nrxn3α expression was knocked down (i.e., using short hairpin RNA or shRNA) in the central amygdala and GABA release and neuronal activity were quantitated in the parabrachial concomitant with measurement of the VZV induced pain response. Results revealed that attenuating Nrxn3 expression within the amygdala reduces GABA release in the parabrachial and increases neuronal activity within the lateral parabrachial region. Attenuating Nrxn3 expression also increases VZV associated orofacial pain. Activating GABAergic neurons within the central amygdala with opsins increase GABA release in the parabrachial and reduced the pain response after Nrxn3 shRNA treatment. These results are consistent with the idea that Nrxn3 within the central amygdala controls VZV associated pain by regulating GABA release in the lateral parabrachial that then controls the activity of ascending pain neurons.
水痘带状疱疹病毒（VZV）是导致慢性疼痛的原因。VZV 注射与人疱疹病毒（HZ）“带状疱疹”疼痛有相似之处。在这项研究中，通过向雄性大鼠注射人类 VZV 来诱发口腔疼痛。杏仁核和臂旁核被认为控制情感/动机性口腔疼痛。最近，我们实验室报告说神经连接蛋白 3α（Nrxn3α）在中央杏仁核和臂旁核表达。来自中央杏仁核的 GABA 能神经元下降到外侧臂旁区域，并且 Nrxn3α对于突触前（γ-氨基丁酸）GABA 释放很重要。因此，我们假设外侧臂旁神经元活性和口腔疼痛受到中央杏仁核内 Nrxn3α的控制。为了验证这一假设，我们在中央杏仁核中敲低了 Nrxn3α的表达（即使用短发夹 RNA 或 shRNA），同时在测量 VZV 诱导的疼痛反应的同时定量测量了臂旁核中的 GABA 释放和神经元活性。结果表明，在杏仁核内减弱 Nrxn3 表达会减少臂旁核中的 GABA 释放，并增加外侧臂旁区域的神经元活性。减弱 Nrxn3 表达也会增加与 VZV 相关的口腔疼痛。用光遗传学激活中央杏仁核中的 GABA 能神经元会增加臂旁核中的 GABA 释放，并减少 Nrxn3 shRNA 处理后的疼痛反应。这些结果与这样一种观点一致，即中央杏仁核内的 Nrxn3 通过调节外侧臂旁的 GABA 释放来控制与 VZV 相关的疼痛，从而控制上行疼痛神经元的活性。
