IL-1beta in the trigeminal subnucleus caudalis contributes to extra-territorial allodynia/hyperalgesia following a trigeminal nerve injury.
IL-1beta in the trigeminal subnucleus caudalis contributes to extra-territorial allodynia/hyperalgesia following a trigeminal nerve injury.
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DOI：
10.1016/j.ejpain.2010.10.006
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发表时间：
2011
影响因子：
3.6
通讯作者：
Kouji Takahashi;Mineo Watanabe;Y. Suekawa;G. Ito;T. Inubushi;N. Hirose;K. Murasaki;S. Hiyama;T. Uchida;K. Tanne
中科院分区：
文献类型：
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作者：
Kouji Takahashi;Mineo Watanabe;Y. Suekawa;G. Ito;T. Inubushi;N. Hirose;K. Murasaki;S. Hiyama;T. Uchida;K. Tanne
据报道，由三叉神经的第二分支支配的须垫（WP）区域在颏神经（MN：三叉神经的第三分支）横断后显示异常性疼痛/痛觉过敏。然而，这种域外疼痛诱导的机制仍然不清楚。已知胶质细胞和细胞因子可促进有害输入的感知，从而提高了这些非神经元元素参与非损伤皮肤区域的异常性疼痛/痛觉过敏的诱导和扩散的可能性。MN横断后1天，在非损伤皮肤区域的同侧WP区域出现触觉异常性疼痛/痛觉过敏。触觉异常性疼痛/痛觉过敏持续超过56天。MN切断后，星形胶质细胞和小胶质细胞似乎处于活化状态，三叉神经尾侧亚核（Vc）中的星形胶质细胞中白细胞介素（IL）-1 β上调。通过IL-1受体拮抗剂IL-1 ra（i.t.，0.05、0.5和5 pg/大鼠）。在MN横断大鼠的WP区进行非伤害性机械刺激后，在Vc中观察到Fos样免疫反应（Fos-Li）神经元。IL-1 ra的给药也剂量依赖性地减少了Fos-Li神经元的数量。施用NMDA受体的非竞争性拮抗剂MK-801（i.t.，5μg/大鼠）逆转异常性疼痛/痛觉过敏。I型IL-1受体（IL-1 RI）定位于Fos-和磷酸化NR 1-免疫反应神经元。这些结果表明，Vc中的IL-1 β在MN横断后域外触觉异常性疼痛/痛觉过敏的发展中起重要作用。
It has been reported that the whisker pad (WP) area, which is innervated by the second branch of the trigeminal nerve, shows allodynia/hyperalgesia following transection of the mental nerve (MN: the third branch of the trigeminal nerve). However, the mechanisms of this extra‐territorial pain induction still remain unclear. Glia and cytokines are known to facilitate perception of noxious input, raising a possibility that these non‐neuronal elements are involved in the induction and spread of allodynia/hyperalgesia at non‐injured skin territory. One day after MN transection, tactile allodynia/hyperalgesia developed on the ipsilateral WP area, which is in the non‐injured skin territory. The tactile allodynia/hyperalgesia lasted for more than 56 days. In response to MN transection, astrocytes and microglia appeared to be in an activated state, and interleukin (IL)‐1beta was up‐regulated in astrocytes in the trigeminal subnucleus caudalis (Vc). Allodynia/hyperalgesia at WP area induced by MN transection was attenuated dose‐dependently by IL‐1 receptor antagonist IL‐1ra (i.t., 0.05, 0.5, and 5pg/rat). Fos‐like immunoreactive (Fos‐Li) neurons were observed in the Vc after non‐noxious mechanical stimulation of the WP area in the rats with MN transection. Administration of IL‐1ra also attenuated the number of Fos‐Li neurons dose‐dependently. Administration of a noncompetitive antagonist of NMDA receptors MK‐801 (i.t., 5μg/rat) reversed allodynia/hyperalgesia. IL‐1 receptor type I (IL‐1RI) was localized in Fos‐ and phospho NR1‐immunoreactive neurons. These results suggest that IL‐1beta in the Vc plays an important role in the development of extra‐territorial tactile allodynia/hyperalgesia after MN transection.