Visceral pain originating from chronic inflammation of the pancreas is often intractable and difficult to manage clinically. However, the pathogenesis of the central nervous system underlying visceral pain is still poorly understood. The aim of the present study was to investigate the role of the midbrain ventrolateral periaqueductal gray (vlPAG) in a rat model of chronic visceral pain induced by pancreatitis. In the present study, we used a well-established rat model of chronic pancreatitis induced by tail vein injection of dibutyltin dichloride (DBTC). To assess the DBTC-induced visceral pain, we examined the abdominal withdrawal by von Frey filament test. We further studied the synaptic transmission in the vlPAG by whole-cell patch-clamp electrophysiological recordings. Rats receiving DBTC injection exhibited a significantly increased withdrawal frequency to mechanical stimulation of the abdomen compared to rats injected with vehicle. Interestingly, compared to rats injected with vehicle, we found that neurons dissected from DBTC-treated rats exhibited a significantly decreased synaptic strength, which was revealed by a diminishedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartic acid (AMPA/NMDA) ratio in the vlPAG. Moreover, our results further demonstrated that neurons obtained from DBTC-treated rats displayed a higher paired-pulse ratio, as well as less frequent and smaller amplitudes of miniature excitatory postsynaptic currents in the vlPAG compared to rats injected with vehicle. Furthermore, intra-vlPAG microinjection of AMPA alleviated DBTC-induced abdominal hypersensitivity. Taken together, our findings suggest that diminished glutamatergic synaptic strength via both presynaptic and postsynaptic mechanisms in the midbrain vlPAG is associated with DBTC-induced abdominal hypersensitivity. In addition, activation of AMPA receptors in the vlPAG alleviates DBTC-induced abdominal hypersensitivity.

中文翻译：

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导水管灰色中谷氨酸能突触强度的下降有助于维持实验性胰腺炎雄性大鼠的内脏痛。

由胰腺的慢性炎症引起的内脏疼痛通常是难治的，并且在临床上难以管理。然而，内脏疼痛的中枢神经系统的发病机制仍然知之甚少。本研究的目的是研究中脑腹侧导水管周围灰质（vlPAG）在胰腺炎引起的慢性内脏痛大鼠模型中的作用。在本研究中，我们使用由尾静脉注射二氯化二丁基锡（DBTC）诱发的慢性胰腺炎大鼠模型。为了评估DBTC引起的内脏疼痛，我们通过von Frey细丝试验检查了腹部退缩。我们通过全细胞膜片钳电生理记录进一步研究了vlPAG中的突触传递。与注射媒介物的大鼠相比，接受DBTC注射的大鼠表现出对腹部机械刺激的戒断频率显着增加。有趣的是，与注射媒介物的大鼠相比，我们发现从DBTC处理的大鼠中解剖出的神经元的突触强度显着降低，这是由α-氨基-3-羟基-5-羟基-5-甲基-4-异恶唑丙酸/ N-减少所揭示的。 vlPAG中的甲基-d-天冬氨酸（AMPA / NMDA）比。此外，我们的结果进一步证明，与用媒介物注射的大鼠相比，从DBTC处理的大鼠获得的神经元显示出更高的成对脉冲比率，以及在vlPAG中的微型兴奋性突触后突触电流的频率更低且幅度更小。此外，AMPA的vlPAG内显微注射减轻了DBTC引起的腹部超敏反应。两者合计，我们的发现表明中脑vlPAG中通过突触前和突触后机制减弱的谷氨酸能突触强度与DBTC引起的腹部超敏反应有关。此外，vlPAG中AMPA受体的激活减轻了DBTC引起的腹部超敏反应。