Kuroi Toshiya, Shimizu Toshihiko, Shibata Mamoru, Toriumi Haruki, Funakubo Megumi, Iwashita Tatsuo, Sato Hitoshi, Koizumi Kenzo, Suzuki Norihiro
Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.
Neuroreport. 2012 Jun 20;23(9):560-5. doi: 10.1097/WNR.0b013e3283546242.
TRPV1 is a nonselective cation channel in nociceptors. TRPV1 stimulation has been shown to lead to the activation of microglia and astrocytes in the dorsal horn of the spinal cord. However, information on the effect of TRPV1 stimulation on glial activation in the trigeminal nucleus caudalis (TNC) is lacking. Here, we stimulated TRPV1 in the trigeminal afferents by a repetitive injection of 10 mmol/l capsaicin into the whisker pad for 2 days (d2 group), 4 days (d4 group), or 6 days (d6 group). As a control (c group), the vehicle was injected for 2 days. Anti-Iba1 and anti-glial fibrillary acidic protein antibodies were used to immunostain microglia and astrocytes in the TNC, respectively. The ratio of the cross-sectional area immunoreactive for Iba1 to the entire area of the TNC was increased in the d2 group compared with the c group on the injected side. Microglia were recruited to the superficial layers of the TNC. The numbers of microglia were reduced in the d4 group and the d6 group compared with the d2 group. The ratio of the cross-sectional area immunoreactive for glial fibrillary acidic protein to the entire TNC showed a significant increase in d2 group and the d4 group compared with the c group on the injected side. Behavioral analysis indicated that mechanical allodynia began to develop after 2 days of capsaicin treatment and persisted for at least 6 days after the onset of the repetitive capsaicin injection. These data indicate that TRPV1 stimulation activates the microglia and astrocytes in temporally distinct ways and that the development of mechanical allodynia is independent of such glial activation.
瞬时感受器电位香草酸受体1（TRPV1）是伤害感受器中的一种非选择性阳离子通道。研究表明，TRPV1刺激可导致脊髓背角小胶质细胞和星形胶质细胞活化。然而，关于TRPV1刺激对三叉神经尾侧核（TNC）中胶质细胞活化的影响尚缺乏相关信息。在此，我们通过向须垫重复注射10 mmol/l辣椒素2天（d2组）、4天（d4组）或6天（d6组）来刺激三叉神经传入纤维中的TRPV1。作为对照（c组），注射赋形剂2天。分别使用抗离子钙接头蛋白1（Iba1）和抗胶质纤维酸性蛋白抗体对TNC中的小胶质细胞和星形胶质细胞进行免疫染色。与注射侧的c组相比，d2组中Iba1免疫反应性横截面积与TNC总面积的比值增加。小胶质细胞被募集到TNC的表层。与d2组相比，d4组和d6组中的小胶质细胞数量减少。与注射侧的c组相比，d2组和d4组中胶质纤维酸性蛋白免疫反应性横截面积与整个TNC的比值显著增加。行为分析表明，辣椒素治疗2天后开始出现机械性异常性疼痛，且在重复注射辣椒素开始后至少持续6天。这些数据表明，TRPV1刺激以时间上不同的方式激活小胶质细胞和星形胶质细胞，并且机械性异常性疼痛的发展与这种胶质细胞活化无关。
