Yamamoto Sumii, Takahashi Yukari, Kato Fusao
Department of Anesthesiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Department of Neuroscience, The Jikei University School of Medicine, Minato, Tokyo 105-8461, Japan.
Neurobiol Pain. 2021 Nov 18;10:100078. doi: 10.1016/j.ynpai.2021.100078. eCollection 2021 Aug-Dec.
Pregabalin (PGB) is a synthetic amino acid compound most widely prescribed for chronic peripheral and central neuropathic pain. PGB is a ligand for the αδ 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.
普瑞巴林（PGB）是一种合成氨基酸化合物，是治疗慢性外周和中枢神经性疼痛最常用的药物。PGB是电压依赖性钙通道αδ亚基的配体，其结合可减少神经递质释放，从而抑制突触传递。杏仁核中央核（CeA）是慢性疼痛中伤害感受-情绪联系增强的关键部位。伤害性信息通过以下两条途径传递至CeA：1）起源于基底外侧杏仁核（BLA）的途径，该途径携带由丘脑皮质系统介导的伤害性信息；2）起源于脑桥外侧臂旁核外侧部（LPB）的途径，该途径形成脊髓-臂旁-杏仁核通路的最终路径，直接从脊髓背角浅层传递伤害性信息。我们使用全细胞膜片钳技术比较了PGB对右侧CeA神经元兴奋性突触后电流的影响，这些电流是在电刺激BLA和LPB通路时产生的。通过在左后爪足底注射福尔马林溶液诱导炎性疼痛。在注射福尔马林8小时后，PGB降低了BLA至CeA突触传递的兴奋性突触后电流（EPSCs）幅度，同时成对脉冲比率（PPR）显著增加，表明突触前终末的释放概率降低。此外，PGB的这些作用仅在炎性条件下可见。即使在福尔马林处理的小鼠中，PGB也不影响LPB至CeA通路的突触传递。这些结果表明，PGB不仅改善了慢性伤害性疼痛患者异常增强的伤害感受，还改善了各种与疼痛相关的认知和情感后果。
