Role of neuron-glial cross talk in the trigeminal ganglia to hyperalgesia

本研究的目的是调查是否在三叉神经节的神经元-胶质细胞的串扰有助于外周炎症过程中的伤害性三叉神经节神经元的神经元兴奋性的调制。将完全弗氏佐剂（CFA）注射到大鼠面部皮肤中以产生炎症。对机械刺激的逃避阈值，炎症大鼠明显低于对照组。注射CFA后2d，胶质细胞酸性蛋白（GFAP）/IL-1β免疫反应阳性的TRG神经元在同一细胞中共表达。荧光金标记确定了炎症部位。FG标记的IL-1受体I型（IL-1 RI）小TRG神经元数目在炎症大鼠明显多于对照组。在FG标记的小TRG神经元中，炎症大鼠IL-1β诱导的去极化范围大于对照组。在戊巴比妥钠麻醉的大鼠，记录了对电刺激须垫的α-伤害性TRG神经元反应。炎性大鼠Aσ-TRG神经元自发放电的数目和放电频率均显著高于对照组。局部电离子导入白细胞介素Ⅰ型受体拮抗剂（IL-1 ra）可使炎症大鼠Aσ-TRG神经元自发放电频率呈电流依赖性降低。机械阈值的伤害性TRG神经元在炎症大鼠显着低于对照组大鼠，但没有显着差异对照组和炎症大鼠离子电渗应用IL-1 ra后。这些结果表明，炎症通过三叉神经节内的IL-1β旁分泌作用调节支配面部皮肤的伤害性Aσ-TRG神经元的兴奋性。这种IL-1β的释放在确定三叉神经炎性痛觉过敏中可能是重要的。

The aim of the present study was to investigate whether neuron-glial cross talk in the trigeminal ganglia contribute to modulation of neuronal excitability of nociceptive trigeminal ganglion neurons during peripheral inflammation. Complete freund's adjuvant (CFA) was injected into rat facial skin to produce inflammation. The threshold for escape from mechanical stimulation applied to the whisker pad in inflamed rats was significantly lower than that in control. Two days after CFA injection, the mean percentage of TRG neurons encircled by glial fibrillary acidic protein (GFAP)/IL-1βimmunoreactivities were coexpressed in the same cells. Fluorogold labeling identified the site of inflammation. The number of FG-labeled IL-1 receptor type I (IL-1RI) small TRG neurons in inflamed rats was significantly greater than thai in control. In the FG labeled small TRG neurons, the size of IL-1β induced-depolarization in inflamed rats was larger than in control. Aσ-nociceptive TRG neurons responding to electrical stimulation of the whisker pad was recorded in pentobarbital-anesthetized rats. The number of Aσ-TRG neurons with spontaneous firings and their firing rate in inflamed rats were significantly larger than in control rats. The firing rates of the Aσ-TRG neuronal spontaneous activity were current-dependently decreased by local iontophoretic application of an interleukin I receptor type I antagonist (IL-1ra) in inflamed rats. The mechanical threshold of nociceptive-TRG neurons in inflamed rats was significantly lower than that in control rats, but was not significantly different between control rats and inflamed rats after iontophoretic application of an IL-1ra. These results suggest that under inflammation modulates the excitability of nociceptive Aσ-TRG neurons innervating the facial skin via IL-1β paracrine action within trigeminal ganglia. Such an IL-1β release could be important in determining trigeminal inflammatory hyperalgesia.