Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Science, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan.
Eur J Pain. 2011 May;15(5):467.e1-14. doi: 10.1016/j.ejpain.2010.10.006. Epub 2010 Nov 18.
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 5 pg/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., 5 μg/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.
据报道，第二支三叉神经分支支配的须垫（WP）区域在切断下颌神经（MN：三叉神经的第三支）后会出现痛觉过敏/痛觉异常。然而，这种异位疼痛诱导的机制仍不清楚。已知神经胶质细胞和细胞因子有助于感知有害输入，这增加了这些非神经元成分参与未受伤皮肤区域痛觉过敏/痛觉异常的诱导和传播的可能性。在 MN 切断后的第 1 天，同侧 WP 区域出现触觉痛觉过敏/痛觉异常，这是在未受伤的皮肤区域。触觉痛觉过敏/痛觉异常持续超过 56 天。对 MN 切断的反应，星形胶质细胞和小胶质细胞似乎处于激活状态，白细胞介素（IL）-1β在三叉神经尾核（Vc）中的星形胶质细胞中上调。MN 切断引起的 WP 区域的痛觉过敏/痛觉异常被 IL-1 受体拮抗剂 IL-1ra（i.t.，0.05、0.5 和 5 pg/rat）剂量依赖性地减弱。在 MN 切断的大鼠中，WP 区域的非伤害性机械刺激后，Vc 中观察到 Fos 样免疫反应（Fos-Li）神经元。IL-1ra 的给药也剂量依赖性地减轻了 Fos-Li 神经元的数量。NMDA 受体非竞争性拮抗剂 MK-801（i.t.，5 μg/rat）的给药逆转了痛觉过敏/痛觉异常。IL-1 受体 I 型（IL-1RI）定位于 Fos 和磷酸化 NR1-免疫反应性神经元。这些结果表明，Vc 中的 IL-1β 在 MN 切断后异位触觉痛觉过敏/痛觉异常的发展中起重要作用。
