Department of Neurosurgery, Rhode Island Hospital and Brown Alpert Medical School, RI 02903, USA.
Neurosci Lett. 2011 Jul 8;498(2):138-42. doi: 10.1016/j.neulet.2011.04.077. Epub 2011 May 6.
We hypothesized that microglia in the ventral posterolateral (VPL) nucleus of the thalamus are reactive following peripheral nerve injury, and that inhibition of microglia by minocycline injection in the VPL attenuates thermal hyperalgesia. Our results show increased expression of OX-42 co-localized with phosphorylated p38MAPK (P-p38) in the VPL seven days after chronic constriction injury (CCI) of the sciatic nerve. However, astrocytic GFAP expression in the VPL is unchanged 7 and 14 days after CCI. Microinjection of minocycline into the VPL contralateral to CCI reverses thermal hyperalgesia, whereas vehicle injection has no effect on paw withdrawal latency. Minocycline abrogates the increased expression of OX-42 in the VPL after CCI. Therefore, peripheral nerve injury favors a hyperactive microglial phenotype in the VPL, suggesting remote neuroimmune signaling from the damaged nerve to the brain, concomitant with neuropathic behavior that is reversed by local intervention in the VPL to inhibit microglia.
我们假设，背外侧腹后核（VPL）中的小胶质细胞在周围神经损伤后会发生反应，并且 VPL 中小胶质细胞的抑制作用（通过米诺环素注射）可以减轻热痛觉过敏。我们的结果显示，在坐骨神经慢性缩窄性损伤（CCI）后 7 天，VPL 中 OX-42 的表达增加，并与磷酸化 p38MAPK（P-p38）共定位。然而，CCI 后 7 天和 14 天，VPL 中的星形胶质细胞 GFAP 表达不变。CCI 对侧 VPL 内注射米诺环素可逆转热痛觉过敏，而载体注射对爪撤回潜伏期没有影响。米诺环素消除了 CCI 后 VPL 中 OX-42 的表达增加。因此，周围神经损伤有利于 VPL 中小胶质细胞的高活性表型，表明来自受损神经的远程神经免疫信号到大脑，同时伴有神经病理性行为，通过 VPL 中的局部干预抑制小胶质细胞可以逆转这种行为。
