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Although spinal cord glial cells appear to play an important role in chronic pain development, the precise mechanisms involving descending facilitation pathways from the PAG following nerve injury are poorly understood. This study shows that cellular events that occur during glial activation in the VL\u2010PAG may promote descending facilitation from the PAG during neuropathic pain. Chronic constriction nerve injury (CCI) was induced by ligature construction of the sciatic nerve in male Sprague\u2010Dawley rats. Behavioral responses to noxious mechanical (paw withdrawal threshold; PWT) and thermal (paw withdrawal latency; PWL) stimuli were evaluated. After CCI, immunohistochemical and Western blot analysis of microglia and astrocytes in the VL\u2010PAG showed morphological and quantitative changes indicative of activation in microglia and astrocytes. Intra\u2010VL\u2010PAG injection of microglial or astrocytic inhibitors attenuated PWT and PWL at days 7 and 14, respectively, following CCI. We also evaluated the effects of intra\u2010VL\u2010PAG administration of the phosphorylated p38 mitogen\u2010activated protein kinase (p\u2010p38 MAPK) inhibitor SB 203580 at day 7 after CCI. This treatment abolished microglial activation and produced a significant time\u2010dependent attenuation of PWT and PWL. Western blot analysis showed localized expression of p\u2010p38 in the VL\u2010PAG after CCI. P\u2010p38 was expressed in labeled microglia of the VL\u2010PAG but was not present in astrocytes and neurons on day 7 after CCI. These results demonstrate that CCI\u2010induced neuropathic pain is associated with glial activation in the VL\u2010PAG, which likely participates in descending pain facilitation through the p38 MAPK signaling pathway. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23672","type":"journal-article","created":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T06:17:27Z","timestamp":1443680247000},"page":"50-61","source":"Crossref","is-referenced-by-count":77,"title":["Glial activation in the periaqueductal gray promotes descending facilitation of neuropathic pain through the p38 MAPK signaling pathway"],"prefix":"10.1002","volume":"94","author":[{"given":"Hua\u2010Dong","family":"Ni","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medical Center The First Affiliated Hospital of Jiaxing University Jiaxing People's Republic of 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