Abstract
BackgroundThe trigeminal ganglion (TG) plays a central role in cranial pain. Administration of complete Freund’s adjuvant (CFA) into the temporomandibular joint (TMJ) elicits activation of TG. Kynurenic acid (KYNA) is an endogenous excitatory amino acid receptor blocker, which may have an anti-inflammatory effect. We hypothesize that KYNA may reduce CFA-induced activation within the TG.MethodsA local inflammation was induced by administration of CFA into the TMJ in rats. KYNA and kynurenic acid amide 2 (KYNAA2) were intraperitoneally administered. We investigated changes of mitogen-activated protein kinases (MAPKs as ERK1/2, p38 and SAPK/JNK), NF-κB, CaMKII and DREAM, in addition to calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in the TG, with immunohistochemistry and Western blot at 2 and 10 days post-CFA injection.ResultsWe showed CFA-induces increases in pERK1/2, pp38, CaMKII, NF-κB and DREAM immunohistochemistry after 2 and 10 days. KYNAA2 displayed stronger effects on MAPKs than KYNA. Increased expression of CaMKII, NF-κB and DREAM were found in the neurons. Western blot showed significantly increase in pERK expression at 10 days post-CFA, which decreased after 10 days of KYNA treatment. Two days post-CFA, a significantly increase in pp38 expression was found, which decreased after 2 days of KYNA and KYNAA2 treatment.ConclusionsThe CFA-induced inflammatory model for the TG activation provided a time-related expression of MAPK (pERK1/2, pp38) and NF-κB. It involves both the neuronal and glial activation, which points to possible neuron-glia interactions during this process. The administration of the endogenous NMDA-receptor antagonists, KYNA and its derivative KYNAA2, resulted in the inhibition of the induced signaling system of the TG, which further points the importance of the glutamate receptors in this mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s10194-015-0581-x) contains supplementary material, which is available to authorized users.
Highlights
The trigeminal ganglion (TG) plays a central role in cranial pain
High-intensity pERK1/2 immunoreactivity was observed in Satellite glial cell (SGC) at 2 days (Fig. 3b) and at 10 days post-complete Freund’s adjuvant (CFA) injection in the temporomandibular joint (TMJ) (Fig. 3c)
We found at day 2 and at day 10 post-CFA injection, an increased expression of pERK1/2 and pp38 in neurons or SGCs, while only neurons showed an increased Nuclear factor kappa B (NF-κB) and calmodulindependent protein kinase II (CaMKII) immunoreactivity
Summary
Administration of complete Freund’s adjuvant (CFA) into the temporomandibular joint (TMJ) elicits activation of TG. The trigeminal ganglion (TG) through the mandibular branch (V3) of the trigeminal nerve projects sensory innervation to the temporomandibular joint (TMJ) capsule. TG contains mainly two populations of cells: neurons of different size and satellite glial cells (SGCs). The neurons project both in central and peripheral direction with unmyelinated C-fibers and thinly myelinated. Numerous studies have used chemical stimulation of peripheral nerve branches with Complete Freund’s adjuvant (CFA) as an inflammatory model for investigating changes in the levels of various messenger and mediator molecules within the TG and in the CNS after experimentally induced TMJ inflammation [4,5,6].
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