Michot Benoit, Deumens Ronald, Hermans Emmanuel
Institute of Neuroscience, Université catholique de Louvain, Avenue Hippocrate B1.54.10, 1200 Brussels, Belgium.
Institute of Neuroscience, Université catholique de Louvain, Avenue Hippocrate B1.54.10, 1200 Brussels, Belgium.
Neurosci Lett. 2017 Jul 13;653:113-119. doi: 10.1016/j.neulet.2017.05.035. Epub 2017 May 19.
The differential pharmacological responsiveness of cephalic and extra-cephalic neuropathic pain has been proposed to relate to distinct mechanisms that may involve neuroinflammatory reactions mediated by glial cells. Astrocytes are particularly important for neuronal sensitization in neuropathic pain, in part through modulation of glutamatergic transmission. Because the metabotropic glutamate receptor 5 (mGluR5) is involved in the astrocytic regulation of the glutamatergic system, we investigated modifications of its expression in models of cephalic versus extra-cephalic neuropathic pain. Adult male rats underwent unilateral chronic constriction injury (CCI) of either the infraorbital nerve (ION) or the sciatic nerve (SN). Seven days later, mGluR5 and the astrocyte marker GFAP (glial fibrillary acidic protein) were overexpressed and appeared localized mainly in the superficial lamina of the trigeminal nucleus in CCI-ION and the spinal cord dorsal horn in CCI-SN rats. In addition, colocalization of GFAP and mGluR5 strongly suggested an increase of astrocytic mGluR5 expression in nerve-injured rats compared to sham animals. The present data show an upregulation of astrocytic mGluR5 in central structures in both CCI-ION and CCI-SN. This suggests that the pharmacological modulation of mGluR5 could be a new approach to reduce both cephalic and extra-cephalic neuropathic pain.
有人提出，头部和头部以外的神经性疼痛的不同药理反应性与可能涉及胶质细胞介导的神经炎症反应的不同机制有关。星形胶质细胞对神经性疼痛中的神经元致敏特别重要，部分原因是通过调节谷氨酸能传递。由于代谢型谷氨酸受体5（mGluR5）参与谷氨酸能系统的星形胶质细胞调节，我们研究了其在头部与头部以外神经性疼痛模型中的表达变化。成年雄性大鼠接受眶下神经（ION）或坐骨神经（SN）的单侧慢性压迫损伤（CCI）。7天后，mGluR5和星形胶质细胞标志物GFAP（胶质纤维酸性蛋白）在CCI-ION大鼠的三叉神经核浅层和CCI-SN大鼠的脊髓背角中过表达且主要定位于这些部位。此外，GFAP和mGluR5的共定位强烈表明，与假手术动物相比，神经损伤大鼠的星形胶质细胞mGluR5表达增加。目前的数据显示，在CCI-ION和CCI-SN中，中枢结构中的星形胶质细胞mGluR5均上调。这表明，对mGluR5进行药理调节可能是减轻头部和头部以外神经性疼痛的一种新方法。
