QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 30, 2007, 27(22):6006-6018; doi:10.1523/JNEUROSCI.0176-07.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (34) Citing Articles via Google Scholar Google Scholar Articles by Guo, W. Articles by Ren, K. Search for Related Content PubMed PubMed Citation Articles by Guo, W. Articles by Ren, K. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Pain

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain

Wei Guo, ^* Hu Wang, ^* Mineo Watanabe, ^* Kohei Shimizu, Shiping Zou, Stacey C. LaGraize, Feng Wei, Ronald Dubner, and Ke Ren

Department of Biomedical Sciences, Program in Neuroscience, Dental School, University of Maryland, Baltimore, Maryland 21201

Correspondence should be addressed to Dr. Ke Ren, Department of Biomedical Sciences, 650 West Baltimore Street, Dental-7 South, Baltimore, MD 21201-1586. Email: kren{at}umaryland.edu

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 a trigeminal model of inflammatory hyperalgesia, here we provide evidence that demonstrates a mechanism by which glia interact with neurons, leading to activity-dependent plasticity and hyperalgesia. In response to masseter inflammation, there was an upregulation of glial fibrillary acidic proteins (GFAPs), a marker of astroglia, and interleukin-1ß (IL-1ß), a prototype proinflammatory cytokine, in the region of the trigeminal nucleus specifically related to the processing of deep orofacial input. The activated astroglia exhibited hypertrophy and an increased level of connexin 43, an astroglial gap junction protein. The upregulated IL-1ß was selectively localized to astrocytes but not to microglia and neurons. Local anesthesia of the masseter nerve prevented the increase in GFAP and IL-1ß after inflammation, and substance P, a prototype neurotransmitter of primary afferents, induced similar increases in GFAP and IL-1ß, which was blocked by a nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester. Injection of IL-1 receptor antagonist and fluorocitrate, a glial inhibitor, attenuated hyperalgesia and NMDA receptor phosphorylation after inflammation. In vitro application of IL-1ß induced NR1 phosphorylation, which was blocked by an IL-1 receptor antagonist, a PKC inhibitor (chelerythrine), an IP₃ receptor inhibitor (2-aminoethoxydiphenylborate), and inhibitors of phospholipase C [1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione] and phospholipase A₂ (arachidonyltrifluoromethyl ketone). These findings provide evidence of astroglial activation by tissue injury, concomitant IL-1ß induction, and the coupling of NMDA receptor phosphorylation through IL-1 receptor signaling.

Key words: GFAP; IL-1ß; NMDA receptor; gap junction; inflammation; rat

---

Received Jan. 16, 2007; revised April 30, 2007; accepted April 30, 2007.

Correspondence should be addressed to Dr. Ke Ren, Department of Biomedical Sciences, 650 West Baltimore Street, Dental-7 South, Baltimore, MD 21201-1586. Email: kren{at}umaryland.edu

This article has been cited by other articles:

				C. I. Svensson and E. Brodin Spinal Astrocytes in Pain Processing: Non-Neuronal Cells as Therapeutic Targets Mol. Interv., February 1, 2010; 10(1): 25 - 38. [Abstract] [Full Text] [PDF]

				A. Okada-Ogawa, I. Suzuki, B. J. Sessle, C.-Y. Chiang, M. W. Salter, J. O. Dostrovsky, Y. Tsuboi, M. Kondo, J. Kitagawa, A. Kobayashi, et al. Astroglia in Medullary Dorsal Horn (Trigeminal Spinal Subnucleus Caudalis) Are Involved in Trigeminal Neuropathic Pain Mechanisms J. Neurosci., September 9, 2009; 29(36): 11161 - 11171. [Abstract] [Full Text] [PDF]

				A. K. Clark, P. K. Yip, and M. Malcangio The Liberation of Fractalkine in the Dorsal Horn Requires Microglial Cathepsin S J. Neurosci., May 27, 2009; 29(21): 6945 - 6954. [Abstract] [Full Text] [PDF]

				Q. Xu, S. M. Garraway, A. R. Weyerbacher, S. J. Shin, and C. E. Inturrisi Activation of the Neuronal Extracellular Signal-Regulated Kinase 2 in the Spinal Cord Dorsal Horn Is Required for Complete Freund's Adjuvant-Induced Pain Hypersensitivity J. Neurosci., December 24, 2008; 28(52): 14087 - 14096. [Abstract] [Full Text] [PDF]

				F. Wei, W. Guo, S. Zou, K. Ren, and R. Dubner Supraspinal Glial-Neuronal Interactions Contribute to Descending Pain Facilitation J. Neurosci., October 15, 2008; 28(42): 10482 - 10495. [Abstract] [Full Text] [PDF]

				Y. Kawasaki, L. Zhang, J.-K. Cheng, and R.-R. Ji Cytokine Mechanisms of Central Sensitization: Distinct and Overlapping Role of Interleukin-1{beta}, Interleukin-6, and Tumor Necrosis Factor-{alpha} in Regulating Synaptic and Neuronal Activity in the Superficial Spinal Cord J. Neurosci., May 14, 2008; 28(20): 5189 - 5194. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help