The Open Pain Journal

2010, 3 : 144-152
Published online 2010 November 24. DOI: 10.2174/1876386301003010144
Publisher ID: TOPAINJ-3-144

RESEARCH ARTICLE
Contribution of Primary Afferent Input to Trigeminal Astroglial Hyperactivity, Cytokine Induction and NMDA Receptor Phosphorylation

H. Wang , W. Guo , K. Yang , F. Wei , R. Dubner and K. Ren, *
Department of Neural and Pain Sciences, Dental School and Program in Neuroscience, University of Maryland, Baltimore, MD 21201, USA

* Address correspondence to this author at the 650 West Baltimore Street, Dental-8 South, Baltimore, MD 21201, USA; Tel: 410 706 3250; Fax: 410 706 0865; E-mail: kren@umaryland.edu

ABSTRACT

We tested the hypothesis that primary afferent inputs play a role in astroglial hyperactivity after tissue injury.We first injected complete Freund's adjuvant (CFA, 0.05 ml, 1:1 oil/saline) into the masseter muscle, which upregulated glial fibrillary acidic protein (GFAP), a marker of astrocytes, interleukin (IL)-1β, an inflammatory cytokine, and phosphorylation of serine896 of the NR1 subunit (P-NR1) of the NMDA receptor in the subnuclei interpolaris/caudalis (Vi/Vc) transition zone, an important structure for processing trigeminal nociceptive input. Local anesthetic block with lidocaine (2%) of the masseter muscle at 10 min prior to injection of CFA into the same site significantly reduced the CFA-induced increase in GFAP, IL-1β and P-NR1 (p<0.05, n=4/group). We then tested the effect of peripheral electrical stimulation (ES). The ES protocol was burst stimulation consisting of trains of 4 square pulses (10-100 Hz, 0.1-3 mA, 0.5 ms pulse width). Under pentobarbital anesthesia, an ES was delivered every 0.2 s for a total of 30 min. The Vi/Vc tissues were processed for immunohistochemistry or western blot analysis at 10-120 min after ES. Compared to naive and SHAM-treated rats, there was increased immunoreactivity against GFAP, IL-1β and P-NR1 in the Vi/Vc in rats receiving ES. Double staining showed that IL-1β was selectively localized in GFAP-positive astroglia, and P-NR1- immunoreactivity was localized to neurons. These findings indicate that primary afferent inputs are necessary and sufficient to induce astroglial hyperactivity and upregulation of IL-1β, as well as neuronal NMDA receptor phosphorylation.

Keywords:

Health Complaints, NEO-PI-R, Pain Sensitivity, Personality Traits, TMD.