Input-dependent synaptic suppression by pregabalin in the central amygdala in male mice with inflammatory pain.
Input-dependent synaptic suppression by pregabalin in the central amygdala in male mice with inflammatory pain.
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DOI：
10.1016/j.ynpai.2021.100078
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Kato F
中科院分区：
文献类型：
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作者：
Yamamoto S;Takahashi Y;Kato F
普瑞巴林减弱了中央杏仁核的突触传递。这种作用仅在潜伏性炎症性疼痛模型中观察到。只有中央杏仁核的基底外侧通路受到影响。臂旁核的增强传入对普瑞巴林不敏感。普瑞巴林(PGB)是一种合成氨基酸化合物，最广泛用于治疗慢性周围和中枢神经病理性疼痛。PGb是电压依赖性钙通道α2δ1亚单位的配基，它的结合减少了神经递质的释放，从而抑制了突触传递。杏仁中央核(CEA)是慢性疼痛中痛觉-情绪联系增强的核心部位。伤害性信息通过以下两条通路传递到CEA：1)杏仁基底外侧核(BLA)通路，由丘脑皮质系统传递伤害性信息；2)桥臂旁外侧核(LPB)外侧通路，构成脊椎-臂旁核-杏仁体通路的最终通路，直接从脊髓背角浅层传递伤害性信息。我们用全细胞膜片钳技术比较了银杏叶提取物对电刺激BLA和LPB通路时右侧CEA神经元兴奋性突触后电流的影响。足底左侧足底注射福尔马林溶液诱发炎性疼痛。在福尔马林后8小时，PGB降低了BLA到CEA突触传递的EPSCs幅度，同时伴随着PPR的显著增加，表明突触前终末的释放概率降低。此外，PGB的这些作用只在炎症条件下才能看到。PGB不影响LPB到CEA途径的突触传递，即使在福尔马林处理的小鼠中也是如此。这些结果表明，PGB不仅可以改善慢性肿瘤性疼痛患者异常增强的伤害性感受，还可以改善与疼痛相关的各种认知和情感后果。
Pregabalin attenuated the synaptic transmission in the central amygdala. This effect was only observed in the latent inflammatory pain model. Only the basolateral to central amygdala pathway was affected. The potentiated inputs from the parabrachial nucleus were pregabalin-insensitive. Pregabalin (PGB) is a synthetic amino acid compound most widely prescribed for chronic peripheral and central neuropathic pain. PGB is a ligand for the α2δ1 subunit of voltage-dependent calcium channels, and its binding reduces neurotransmitter release and thus inhibits synaptic transmission. The central nucleus of the amygdala (CeA) is a kernel site for the enhanced nociception-emotion link in chronic pain. The nociceptive information is conveyed to the CeA via the following two pathways: 1) the pathway arising from the basolateral amygdala (BLA), which carries nociceptive information mediated by the thalamocortical system, and 2) that arising from the external part of the pontine lateral parabrachial nucleus (LPB), that forms the final route of the spino-parabrachio-amygdaloid pathway that conveys nociceptive information directly from the superficial layer of the spinal dorsal horn. We compared the effects of PGB on the excitatory postsynaptic currents of neurons in the right CeA in response to electrical stimulation of BLA and LPB pathways using the whole-cell patch-clamp technique. Inflammatory pain was induced by intraplantar injection of formalin solution at the left hind paw. At eight hours post-formalin, PGB reduced EPSCs amplitude of the BLA-to-CeA synaptic transmission, accompanied by a significant increase in the PPR, suggesting a decreased release probability from the presynaptic terminals. In addition, these effects of PGB were only seen in inflammatory conditions. PGB did not affect the synaptic transmission at the LPB-to-CeA pathway, even in formalin-treated mice. These results suggest PGB improves not simply the aberrantly enhanced nociception but also various pain-associated cognitive and affective consequences in patients with chronic nociplastic pain.