The Role of GABA-ergic Neurons in the Trigeminal Root Ganglion

Objectives: This study was aimed at elucidating changes in the expression of gamma-aminobutyric acid (GABA)-ergic neurons of the trigeminal root ganglion (TRG) in rats which showed hyperalgesia and/or allodynia by artificially-induced chronic inflammation in their temporomandibular joint (TMJ) and facial skin. Although GABA is a main inhibitory neurotransmitter in the central nervous system (CNS), little is known about the role of GABA in the peripheral nervous system (PNS), including TRG.
Methods: Firstly, rats (200-250g, male) were injected Complete Freund’s Adjuvant (CFA) to induce inflammatory pain model, and Fluoro-Gold (FG) to label neuronal projection, to the TRG into the TMJ and facial skin. Then, 5-7days after the injection, the mechanical threshold for escape behavior was assessed with calibrated von Frey filaments to confirm the appearance of hyperalgesia and/or allodynia in the CFA injected animals.
TRG was dissociated to examine immunohistochemical expression of the 67 kDa form of glutamic acid decarboxylase (GAD67), a GABA precursor. According to some reports GAD expression in the CNS changes after inflammation, but it has not been elucidated as to how inflammation affects their expression and relationship with hyperalgesia or allodynia.
Results: We compared GAD67 expression of TRG neurons in rats with and without TMJ and facial skin inflammations (EXP and CONT groups, respectively). In the FG labeled TRG neurons, the proportion of GAD67 immunoreactive cells of EXP group was 16.0% (216/1353), which was about twice as much as that seen in CONT group (8.6%, 95/1102). In addition, by using extracellular recording, it was found that microiontophoretically applied baclofen inhibited TRG neurons excitation in pentobarbital-anesthetized rat.
Conclusions: Taken together, our results suggest that hyperalgesia and/or allodynia due to orofacial chronic inflammation may be related at least in part to the up-regulation of GAD67-positive GABA-ergic neurons in the TRG.