Expression of Vesicular Glutamate Transporters VGLUT1 and VGLUT2 in the Rat Dental Pulp and Trigeminal Ganglion following Inflammation

Abstract

BackgroundThere is increasing evidence that peripheral glutamate signaling mechanism is involved in the nociceptive transmission during pathological conditions. However, little is known about the glutamate signaling mechanism and related specific type of vesicular glutamate transporter (VGLUT) in the dental pulp following inflammation. To address this issue, we investigated expression and protein levels of VGLUT1 and VGLUT2 in the dental pulp and trigeminal ganglion (TG) following complete Freund’s adjuvant (CFA) application to the rat dental pulp by light microscopic immunohistochemistry and Western blot analysis.ResultsThe density of VGLUT2− immunopositive (+) axons in the dental pulp and the number of VGLUT2+ soma in the TG increased significantly in the CFA-treated group, compared to control group. The protein levels of VGLUT2 in the dental pulp and TG were also significantly higher in the CFA-treated group than control group by Western blot analysis. The density of VGLUT1+ axons in the dental pulp and soma in the TG remained unchanged in the CFA-treated group.ConclusionsThese findings suggest that glutamate signaling that is mediated by VGLUT2 in the pulpal axons may be enhanced in the inflamed dental pulp, which may contribute to pulpal axon sensitization leading to hyperalgesia following inflammation.

Expression of vesicular glutamate transporters in transient receptor potential melastatin 8 (TRPM8)-positive dental afferents in the mouse

“…The proportion of VGLUT2+ neurons in the mouse TG in the present study (37%) was lower than previously reported: from only a few neurons or almost all neurons in rat DRG (Oliveira et al, 2003; Landry et al, 2004), 65–69% in mouse DRG (Brumovsky et al, 2007; Malet et al, 2013), 15% or 85% in rat TG (Li et al, 2003; Yang et al, 2014). This variability may be due to differences in sensitivity of the antibodies used, choice of threshold levels for VGLUT2-immunoreactivity, species, or DRG vs. TG.…”

“…Recent reports, including studies using VGLUT2-deficient mice, suggest that VGLUT2-dependant glutamate release from primary sensory afferents plays an important role in normal acute nociception and pathologic pain (Moechars et al, 2006; Leo et al, 2009; Liu et al, 2010; Scherrer et al, 2010; Lagerstrom et al, 2011; Rogoz et al, 2012). Specifically, VGLUT2 increases in the trigeminal ganglion (TG) neurons following Complete Freund’s Adjuvant (CFA)-induced pulpal inflammation, suggesting that VGLUT2-dependant glutamate signaling may mediate pulpal inflammatory pain (Yang et al, 2014). However, little is known about the alteration in expression of TRPM8 and the associated VGLUTs in TG neurons following dental pulp inflammation.…”

Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall

“…Glutamate is the major excitatory neurotransmitter in the vertebrate central nervous system (Fremeau et al, 2004, Wojcik et al, 2004) and is used by primary sensory neurons in TG (Yang et al, 2014) and DRG (Brumovsky et al, 2007, Miller et al, 2011) of the peripheral nervous system. In primary sensory neurons in DRG, neurotransmitter glutamate production utilizing the glutamate-glutamine cycle is important for sensory function (Miller et al, 1993, Miller et al, 2002, Miller et al, 2012).…”

“…Among them, VGLUT1 and VGLUT2 have been more intensively studied due to the availability of reliable specific antibodies. Both VGLUT1 & 2 are present in somatic and visceral DRG sensory neurons (Hwang et al, 2004, Brumovsky et al, 2007, Miller et al, 2011, Yang et al, 2014), in enteric neurons (Brumovsky et al, 2011), and in vagal afferent neurons innervating the gastrointestinal tract and heart (Lawrence and Jarrott, 1994, Lawrence, 1995, Berthoud et al, 1997, Corbett et al, 2005, Raab and Neuhuber, 2007). In the current study, the discovery of many neurons expressing GLS, VGLUT1, and VGLUT2 provides novel information regarding the presence of glutamatergic neurons in rat cardiac intrinsic ganglia.…”

“…This is unique for the ICG plexus compared to other peripheral neurons such as DRG sensory neurons (Oliveira et al, 2003, Brumovsky et al, 2007, Brumovsky et al, 2011). In DRG, neurons with large area profiles express VGLUT1 and are mechano-sensitive (proprioceptive), while many small to medium sized neurons express VGLUT2 and are nociceptive (Landry et al, 2004, Brumovsky et al, 2007, Lagerstrom et al, 2011, Yang et al, 2014). VGLUT2 is expressed more broadly in DRG neurons including small, medium and large neurons, while VGLUT1 is observed in discrete subpopulations of mostly large and medium visceral and non-visceral neurons (Malet and Brumovsky, 2015).…”