Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary.
Sci Rep. 2020 Jul 16;10(1):11715. doi: 10.1038/s41598-020-68638-3.
Although convincing experimental evidence indicates that Na/K/Cl cotransporter 1 (NKCC1) is involved in spinal nociceptive information processing and in the generation of hyperalgesia and allodynia in chronic pain states, the cellular distribution of NKCC1 in the superficial spinal dorsal horn is still poorly understood. Because this important piece of knowledge is missing, the effect of NKCC1 on pain processing is still open to conflicting interpretations. In this study, to provide the missing experimental data, we investigated the cellular distribution of NKCC1 in the superficial spinal dorsal horn by immunohistochemical methods. We demonstrated for the first time that almost all spinal axon terminals of peptidergic nociceptive primary afferents express NKCC1. In contrast, virtually all spinal axon terminals of nonpeptidergic nociceptive primary afferents were negative for NKCC1. Data on the colocalization of NKCC1 with axonal and glial markers indicated that it is almost exclusively expressed by axon terminals and glial cells in laminae I-IIo. In lamina IIi, however, we observed a strong immunostaining for NKCC1 also in the dendrites and cell bodies of PV-containing inhibitory neurons and a weak staining in PKCγ-containing excitatory neurons. Our results facilitate further thinking about the role of NKCC1 in spinal pain processing.
虽然令人信服的实验证据表明，钠离子/钾离子/氯离子共转运蛋白 1（NKCC1）参与了脊髓伤害性信息处理，并在慢性疼痛状态下产生了痛觉过敏和感觉异常，但 NKCC1 在脊髓浅层背角中的细胞分布仍知之甚少。由于缺少这一重要信息，NKCC1 对疼痛处理的影响仍然存在相互矛盾的解释。在这项研究中，为了提供缺失的实验数据，我们通过免疫组织化学方法研究了 NKCC1 在脊髓浅层背角中的细胞分布。我们首次证明，几乎所有肽能伤害性初级传入神经的脊髓轴突末梢都表达 NKCC1。相比之下，几乎所有非肽能伤害性初级传入神经的脊髓轴突末梢都没有 NKCC1 的表达。关于 NKCC1 与轴突和神经胶质标记物的共定位数据表明，它几乎只由 I-IIo 层中的轴突末梢和神经胶质细胞表达。然而，在 IIi 层，我们观察到 NKCC1 在含有 PV 的抑制性神经元的树突和胞体中也有强烈的免疫染色，而在含有 PKCγ的兴奋性神经元中则有较弱的染色。我们的研究结果有助于进一步思考 NKCC1 在脊髓疼痛处理中的作用。
