Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain

• DOI: 10.1523/jneurosci.0176-07.2007
• Publication Date: 2007-05-30T16:23:42Z
• Authors: Wei Guo; Hu Wang; Mineo Watanabe; Kohei Shimizu; Shiping Zou; Stacey C. LaGraize; Feng Wei; Ronald Dubner; Ke Ren
• Keywords: Proinflammatory cytokine

The emerging literature implicates a role for glia/cytokines in persistent pain. However, the mechanisms by which these non-neural elements contribute to CNS activity-dependent plasticity and pain are unclear. Using trigeminal model of inflammatory hyperalgesia, here we provide evidence that demonstrates mechanism glia interact with neurons, leading hyperalgesia. In response masseter inflammation, there was an upregulation glial fibrillary acidic proteins (GFAPs), marker astroglia, interleukin-1β (IL-1β), prototype proinflammatory cytokine, region nucleus specifically related processing deep orofacial input. activated astroglia exhibited hypertrophy increased level connexin 43, astroglial gap junction protein. upregulated IL-1β selectively localized astrocytes but not microglia neurons. Local anesthesia nerve prevented increase GFAP after substance P, neurotransmitter primary afferents, induced similar increases IL-1β, blocked nitric oxide synthase inhibitor N G -nitro- l -arginine methyl ester. Injection IL-1 receptor antagonist fluorocitrate, inhibitor, attenuated hyperalgesia NMDA phosphorylation inflammation. vitro application NR1 phosphorylation, antagonist, PKC (chelerythrine), IP 3 (2-aminoethoxydiphenylborate), inhibitors phospholipase C [1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1 H -pyrrole-2,5-dione] A 2 (arachidonyltrifluoromethyl ketone). These findings activation tissue injury, concomitant induction, coupling through signaling.