Zhang Fuxing, Vadakkan Kujumon I, Kim Susan S, Wu Long-Jun, Shang Yuze, Zhuo Min
Department of Physiology, Faculty of Medicine, University of Toronto, University of Toronto Centre for Study of Pain, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Mol Pain. 2008 Apr 18;4:15. doi: 10.1186/1744-8069-4-15.
Neuronal plasticity along the pathway for sensory transmission including the spinal cord and cortex plays an important role in chronic pain, including inflammatory and neuropathic pain. While recent studies indicate that microglia in the spinal cord are involved in neuropathic pain, a systematic study has not been performed in other regions of the central nervous system (CNS). In the present study, we used heterozygous Cx3cr1GFP/+mice to characterize the morphological phenotypes of microglia following common peroneal nerve (CPN) ligation. We found that microglia showed a uniform distribution throughout the CNS, and peripheral nerve injury selectively activated microglia in the spinal cord dorsal horn and related ventral horn. In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), primary and secondary somatosensory cortex (S1 and S2), insular cortex (IC), amygdala, hippocampus, periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Our results provide strong evidence that nerve injury primarily activates microglia in the spinal cord of adult mice, and pain-related cortical plasticity is likely mediated by neurons.
包括脊髓和皮层在内的感觉传导通路中的神经元可塑性在慢性疼痛(包括炎性疼痛和神经性疼痛)中起重要作用。虽然最近的研究表明脊髓中的小胶质细胞参与神经性疼痛,但尚未在中枢神经系统(CNS)的其他区域进行系统研究。在本研究中,我们使用杂合子Cx3cr1GFP/+小鼠来表征腓总神经(CPN)结扎后小胶质细胞的形态学表型。我们发现小胶质细胞在整个中枢神经系统中呈均匀分布,而周围神经损伤选择性地激活了脊髓背角和相关腹角中的小胶质细胞。相比之下,中枢神经系统的脊髓上区域,包括前扣带回皮质(ACC)、前额叶皮质(PFC)、初级和次级体感皮层(S1和S2)、岛叶皮质(IC)、杏仁核、海马体、导水管周围灰质(PAG)和延髓头端腹内侧(RVM)中的小胶质细胞未被激活。我们的结果提供了强有力的证据,即神经损伤主要激活成年小鼠脊髓中的小胶质细胞,并且与疼痛相关的皮质可塑性可能由神经元介导。