Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic PainReportar como inadecuado




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Postherpetic neuralgia PHN, the most common complication of herpes zoster HZ, plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate astrocytic specific inhibitor whereas minocycline microglial specific inhibitor had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide NO produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor NMDAR phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and -NO-Astrocyte-Cytokine-NMDAR-Neuron- pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN.



Autor: Gui-He Zhang , Miao-Miao Lv , Shuang Wang , Lei Chen , Nian-Song Qian , Yu Tang, Xu-Dong Zhang, Peng-Cheng Ren, Chang-Jun Gao , X

Fuente: http://plos.srce.hr/



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