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The midbrain ventrolateral periaqueductal gray (VL-PAG) is a key component that mediates pain modulation. 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-PAG 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-Dawley 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-PAG showed morphological and quantitative changes indicative of activation in microglia and astrocytes. Intra-VL-PAG 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-VL-PAG administration of the phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) inhibitor SB 203580 at day 7 after CCI. This treatment abolished microglial activation and produced a significant time-dependent attenuation of PWT and PWL. Western blot analysis showed localized expression of p-p38 in the VL-PAG after CCI. P-p38 was expressed in labeled microglia of the VL-PAG but was not present in astrocytes and neurons on day 7 after CCI. These results demonstrate that CCI-induced neuropathic pain is associated with glial activation in the VL-PAG, which likely participates in descending pain facilitation through the p38 MAPK signaling pathway.
Pubmed ID: 26423029 RIS Download
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on July 18,2023. Software package to capture, process, measure, analyze and share images and data.
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets The initial immunization was performed with a preparation of full length human recombinant GFAP expressed in bacteria and highly purified
View all literature mentionsThis monoclonal targets p38 MAPK, phospho (Thr180 / Tyr182)
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis monoclonal targets NeuN clone A60 Alexa Fluor 488 conjugated
View all literature mentionsSoftware package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.
View all literature mentionsThis polyclonal targets Mouse GFAP
View all literature mentionsThis polyclonal targets Fluorescein isothiocyanate-conjugated IgG fraction of polyclonal donkey antiserum to goat IgG heavy and light chains
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