The Department of Neurology, The 88th Hospital of PLA, Tai'an, PR China; Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, PR China.
The Department of Nephrology, The 88th Hospital of PLA, Tai'an, PR China.
J Pain. 2019 Aug;20(8):917-931. doi: 10.1016/j.jpain.2018.11.014. Epub 2019 Feb 8.
There is substantial evidence supporting the notion that the primary somatosensory (S1) cortex is an important structure involved in the perceptional component of pain. However, investigations have mainly focused on other pain-related formations, and few reports have been provided to investigate the synaptic plasticity in the S1 cortex in response to persistent pain. In the present study, we report that bee venom (BV) injection triggered an imbalance between excitatory and inhibitory synaptic transmission in the S1 cortex in rats. Using a multi-electrode array recording, we found that BV-induced persistent inflammatory pain led to temporal and spatial enhancement of synaptic plasticity. Moreover, slice patch clamp recordings on identified pyramidal neurons demonstrated that BV injection increased presynaptic and postsynaptic transmission in excitatory synapses and decreased postsynaptic transmission in inhibitory synapses in the layer II/III neurons within the S1 cortex. In immunohistochemistry and Western blot sections, the distribution and expression of total AMPA receptor subunits and gamma-amino butyric acid-A (GABA) were unaffected, although the membrane fractions of GluR2 and GABA were decreased, and their cytosolic fractions were increased in contrast. The change of GluR1 was opposite to that of GluR2, and GluR3 did not change significantly. Our studies, therefore, provide direct evidence for both presynaptic and postsynaptic changes in synapses within the S1 cortex in persistent nociception, which are probably related to the membrane trafficking of GluR1, GluR2, and GABA. Perspective: Increased synaptic plasticity was detected in S1 after peripheral nociception, with enhanced excitatory and decreased inhibitory synaptic transmissions. Increased GluR1, and decreased GABAα1 and GluR2 membrane trafficking were detected. Therefore, the disrupted excitatory/inhibitory balance in transmissions is involved in nociception processing, and S1 can be a potential antinociceptive site.
有大量证据支持这样一种观点，即主要躯体感觉（S1）皮层是参与疼痛感知成分的重要结构。然而，研究主要集中在其他与疼痛相关的结构上，很少有报道调查 S1 皮层对持续性疼痛的突触可塑性。在本研究中，我们报告说，蜂毒（BV）注射在大鼠 S1 皮层中引发了兴奋性和抑制性突触传递之间的不平衡。使用多电极阵列记录，我们发现 BV 诱导的持续性炎症性疼痛导致了突触可塑性的时间和空间增强。此外，在 S1 皮层的 II/III 层神经元上进行的切片膜片钳记录表明，BV 注射增加了兴奋性突触中的突触前和突触后传递，并减少了抑制性突触中的突触后传递。在免疫组织化学和 Western blot 切片中，尽管 GluR2 和 GABA 的膜部分减少，细胞浆部分增加，但总 AMPA 受体亚基和γ-氨基丁酸-A（GABA）的分布和表达不受影响。GluR1 的变化与 GluR2 的变化相反，GluR3 没有明显变化。因此，我们的研究提供了直接证据，证明在持续性伤害感受中 S1 皮层内的突触发生了前突触和后突触变化，这可能与 GluR1、GluR2 和 GABA 的膜转运有关。展望：在外周伤害感受后，S1 中检测到突触的可塑性增加，兴奋性突触传递增强，抑制性突触传递减弱。检测到 GluR1 增加，GABAα1 和 GluR2 膜转运减少。因此，传递中的兴奋性/抑制性平衡的破坏参与了伤害感受处理，S1 可以是一个潜在的抗伤害感受部位。
