Miyamoto Keisuke, Kume Kazuhiko, Ohsawa Masahiro
Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
J Pharmacol Sci. 2017 Jul;134(3):158-165. doi: 10.1016/j.jphs.2017.05.010. Epub 2017 Jun 21.
Plastic changes that increase nociceptive transmission are observed in several brain regions under conditions of chronic pain. Synaptic plasticity in the anterior cingulate cortex (ACC) is particularly associated with neuropathic pain. Glial cells are considered candidates for the modulation of neural plastic changes in the central nervous system. In this study, we aimed to investigate the role of ACC glial cells in the development of neuropathic pain. First, we examined the expression of glial cells in the ACC of nerve-ligated mice. The expression of astrocytes and microglia was increased in the ACC of nerve-ligated mice, which was reversed by intracerebroventricular (i.c.v) treatment with the microglia inhibitor minocycline. Then, we examined the effect of minocycline on mechanical allodynia in nerve-ligated mice. I.c.v. and intra-ACC treatment with minocycline partially inhibited mechanical allodynia in the nerve-ligated mice. The expression of phosphorylated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit at Ser831, but not at Ser845, was increased in the ACC of the nerve-ligated mice compared to sham-operated mice, which was attenuated by minocycline administration. These results suggest that the activation of microglia in the ACC is involved in the development of hyperalgesia in mice with neuropathic pain.
在慢性疼痛状态下，多个脑区会出现增强伤害性感受传递的可塑性变化。前扣带回皮质（ACC）的突触可塑性与神经性疼痛尤为相关。神经胶质细胞被认为是中枢神经系统中调节神经可塑性变化的候选因素。在本研究中，我们旨在探究ACC神经胶质细胞在神经性疼痛发展中的作用。首先，我们检测了神经结扎小鼠ACC中神经胶质细胞的表达。神经结扎小鼠的ACC中星形胶质细胞和小胶质细胞的表达增加，而通过脑室内（i.c.v）给予小胶质细胞抑制剂米诺环素可使其逆转。然后，我们检测了米诺环素对神经结扎小鼠机械性异常性疼痛的影响。脑室内和ACC内给予米诺环素可部分抑制神经结扎小鼠的机械性异常性疼痛。与假手术小鼠相比，神经结扎小鼠的ACC中磷酸化α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体GluR1亚基在Ser831位点而非Ser845位点的表达增加，而米诺环素给药可使其减弱。这些结果表明，ACC中小胶质细胞的激活参与了神经性疼痛小鼠痛觉过敏的发展。
