Takeda Mamoru, Tanimoto Takeshi, Kadoi Jun, Nasu Masanori, Takahashi Masayuki, Kitagawa Junichi, Matsumoto Shigeji
Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, 102-8159 Tokyo, Japan.
Pain. 2007 May;129(1-2):155-66. doi: 10.1016/j.pain.2006.10.007. Epub 2006 Nov 28.
Peripheral nerve injury activates satellite cells to produce interleukin 1beta (IL-1beta) which mediates inflammation and hyperalgesia. This study investigated the hypothesis that activation of satellite glial cells modulates the excitability of trigeminal ganglion (TRG) neurons via IL-1beta following inflammation. Inflammation was induced by injection of complete Freund's adjuvant (CFA) into the whisker pad area. The threshold for escape from mechanical stimulation applied to the whisker pad in inflamed rats was significantly lower than that in control. Two days post-CFA injection, the mean percentage of TRG neurons encircled by glial fibrillary acidic protein (GFAP)-/IL-1beta-immunoreactive cells was significantly increased compared to controls. GFAP and IL-1beta immunoreactivities were coexpressed in the same cells. Fluorogold (FG) labeling identified the site of inflammation. The number of FG-labeled IL-receptor type I (IL-1RI) TRG neurons in inflamed rats was significantly greater than in controls. In FG-labeled small TRG neurons, the size of IL-1beta (1 nM) induced-depolarization in inflamed rats was larger than in controls. IL-1beta application significantly increased firing rates evoked by depolarizing pulses in the neurons of inflamed rats, compared to controls. The response to IL-1beta was abolished by treatment with the IL-1RI antagonist. These results suggest that activation of satellite glial cells modulates the excitability of small-diameter TRG neurons via IL-1beta following inflammation, and that the upregulation of IL-1RI in the soma may contribute to the mechanism underlying inflammatory hyperalgesia. Therefore IL-1beta blockers are potential therapeutic agents for prevention of trigeminal hyperalgesia.
周围神经损伤会激活卫星细胞产生白细胞介素1β（IL-1β），该物质介导炎症和痛觉过敏。本研究调查了以下假说：在炎症发生后，卫星神经胶质细胞的激活通过IL-1β调节三叉神经节（TRG）神经元的兴奋性。通过向触须垫区域注射完全弗氏佐剂（CFA）诱导炎症。与对照组相比，炎症大鼠对触须垫施加机械刺激时的逃避阈值显著降低。在注射CFA两天后，与对照组相比，被胶质纤维酸性蛋白（GFAP）/IL-1β免疫反应性细胞包围的TRG神经元的平均百分比显著增加。GFAP和IL-1β免疫反应性在同一细胞中共表达。荧光金（FG）标记确定了炎症部位。炎症大鼠中FG标记的I型IL受体（IL-1RI）TRG神经元的数量显著多于对照组。在FG标记的小型TRG神经元中，炎症大鼠中IL-1β（1 nM）诱导的去极化幅度大于对照组。与对照组相比，应用IL-1β显著增加了炎症大鼠神经元中去极化脉冲诱发的放电频率。用IL-1RI拮抗剂处理可消除对IL-1β的反应。这些结果表明，在炎症发生后，卫星神经胶质细胞的激活通过IL-1β调节小直径TRG神经元的兴奋性，并且躯体中IL-1RI的上调可能有助于炎症性痛觉过敏的潜在机制。因此，IL-1β阻滞剂是预防三叉神经痛觉过敏的潜在治疗药物。
