Glutamate Signaling, Associated With Satellite Glial Cells That Envelop Small Trigeminal Ganglion Neurons Is Highly Involved in the Neuropathic Pain

Abstract Recent studies implicate glutamate release from satellite glial cells (SGCs) surrounding the primary sensory neurons in the mechanisms of pathologic pain. However, little is known about the population of SGCs in the trigeminal ganglion that is involved in glutamate signaling associated with craniofacial neuropathic pain. To address this issue, we used quantitative analysis of electron microscopic immunogold labeling to investigate the changes in glutamate levels in trigeminal neurons and their enveloping SGCs in a rat model of craniofacial neuropathic pain, chronic constriction injury of inferior alveolar nerve (CCI-ION). The density of immunogold, a measure for glutamate concentration, in the neuronal cell bodies of all sizes, and in the SGCs surrounding them, was significantly higher in rats with CCI-ION than in sham-operated rats. This effect was more pronounced for the small neurons (2.2 times higher) and their SGCs (1.8 times higher) than for the medium and the large neurons and their SGCs, respectively. These findings suggest that each populations of SGCs and their surrounding trigeminal neurons of different type are involved in the glutamate signaling associated with neuropathic pain at a different level.

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Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain

Neuron Glia Biology ◽

10.1017/s1740925x07000427 ◽

2006 ◽

Vol 2 (4) ◽

pp. 247-257 ◽

Cited By ~ 81

Author(s):

Jean-Philippe Vit ◽

Luc Jasmin ◽

Aditi Bhargava ◽

Peter T. Ohara

Keyword(s):

Neuropathic Pain ◽

Glial Cells ◽

Trigeminal Ganglion ◽

Connexin 43 ◽

Purinergic Receptor ◽

Cell Activity ◽

Pain Behavior ◽

Spontaneous Pain ◽

Satellite Glial Cells ◽

Ganglion Neurons

AbstractSatellite glial cells (SGCs) tightly envelop the perikarya of primary sensory neurons in peripheral ganglion and are identified by their morphology and the presence of proteins not found in ganglion neurons. These SGC-unique proteins include the inwardly rectifying K+ channel Kir4.1, the connexin-43 (Cx43) subunit of gap junctions, the purinergic receptor P2Y4 and soluble guanylate cyclase. We also present evidence that the small-conductance Ca2+-activated K+ channel SK3 is present only in SGCs and that SGCs divide following nerve injury. All the above proteins are involved, either directly or indirectly, in potassium ion (K+) buffering and, thus, can influence the level of neuronal excitability, which, in turn, has been associated with neuropathic pain conditions. We used in vivo RNA interference to reduce the expression of Cx43 (present only in SGCs) in the rat trigeminal ganglion and show that this results in the development of spontaneous pain behavior. The pain behavior is present only when Cx43 is reduced and returns to normal when Cx43 concentrations are restored. This finding shows that perturbation of a single SGC-specific protein is sufficient to induce pain responses and demonstrates the importance of PNS glial cell activity in the pathophysiology of neuropathic pain.

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Nitric oxide-proton stimulation of trigeminal ganglion neurons increases mitogen-activated protein kinase and phosphatase expression in neurons and satellite glial cells

Neuroscience ◽

10.1016/j.neuroscience.2008.09.035 ◽

2008 ◽

Vol 157 (3) ◽

pp. 542-555 ◽

Cited By ~ 25

Author(s):

S.E. Freeman ◽

V.V. Patil ◽

P.L. Durham

Keyword(s):

Nitric Oxide ◽

Protein Kinase ◽

Glial Cells ◽

Trigeminal Ganglion ◽

Mitogen Activated Protein Kinase ◽

Satellite Glial Cells ◽

Mitogen Activated Protein ◽

Trigeminal Ganglion Neurons ◽

Ganglion Neurons ◽

Stimulation Of

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Glutamate release from satellite glial cells of the murine trigeminal ganglion

Neuroscience Letters ◽

10.1016/j.neulet.2014.06.047 ◽

2014 ◽

Vol 578 ◽

pp. 143-147 ◽

Cited By ~ 14

Author(s):

Lysann Wagner ◽

Rebekah A. Warwick ◽

Thomas Pannicke ◽

Andreas Reichenbach ◽

Antje Grosche ◽

...

Keyword(s):

Glial Cells ◽

Trigeminal Ganglion ◽

Glutamate Release ◽

Satellite Glial Cells

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Development of functional units within trigeminal ganglia correlates with increased expression of proteins involved in neuron–glia interactions

Neuron Glia Biology ◽

10.1017/s1740925x10000232 ◽

2010 ◽

Vol 6 (3) ◽

pp. 171-181 ◽

Cited By ~ 10

Author(s):

Paul L. Durham ◽

F.G. Garrett

Keyword(s):

Postnatal Development ◽

Glial Cells ◽

Trigeminal Ganglion ◽

Neuronal Excitability ◽

Neuronal Cell ◽

Neuronal Cell Body ◽

Steady Increase ◽

Trigeminal Ganglia ◽

Satellite Glial Cells ◽

Functional Units

Cell bodies of trigeminal nerves, which are located in the trigeminal ganglion, are completely surrounded by satellite glial cells and together form a functional unit that regulates neuronal excitability. The goals of this study were to investigate the cellular organization of the rat trigeminal ganglia during postnatal development and correlate those findings with expression of proteins implicated in neuron–glia interactions. During postnatal development there was an increase in the volume of the neuronal cell body, which correlated with a steady increase in the number of glial cells associated with an individual neuron from an average of 2.16 at birth to 7.35 on day 56 in young adults. Interestingly, while the levels of the inwardly rectifying K+ channel Kir4.1 were barely detectable during the first week, its expression in satellite glial cells increased by day 9 and correlated with initial formation of functional units. Similarly, expression of the vesicle docking protein SNAP-25 and neuropeptide calcitonin gene-related peptide was readily detected beginning on day 9 and remained elevated throughout postnatal development. Based on our findings, we propose that the expression of proteins involved in facilitating neuron–glia interactions temporally correlates with the formation of mature functional units during postnatal development of trigeminal ganglion.

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Differential expression of connexins in trigeminal ganglion neurons and satellite glial cells in response to chronic or acute joint inflammation

Neuron Glia Biology ◽

10.1017/s1740925x09990093 ◽

2008 ◽

Vol 4 (4) ◽

pp. 295-306 ◽

Cited By ~ 48

Author(s):

Filip G. Garrett ◽

Paul L. Durham

Keyword(s):

Glial Cells ◽

Trigeminal Ganglion ◽

Joint Inflammation ◽

Plaque Formation ◽

Cx43 Expression ◽

Satellite Glial Cells ◽

Inflammatory Stimuli ◽

Trigeminal Ganglion Neurons ◽

Ganglion Neurons ◽

Satellite Glia

Trigeminal nerve activation in response to inflammatory stimuli has been shown to increase neuron–glia communication via gap junctions in trigeminal ganglion. The goal of this study was to identify changes in the expression of gap junction proteins, connexins (Cxs), in trigeminal ganglia in response to acute or chronic joint inflammation. Although mRNA for Cxs 26, 36, 40 and 43 was detected under basal conditions, protein expression of only Cxs 26, 36 and 40 increased following capsaicin or complete Freund's adjuvant (CFA) injection into the temporomandibular joint (TMJ). While Cx26 plaque formation between neurons and satellite glia was transiently increased following capsaicin injections, Cx26 plaque formation between neurons and satellite glia was sustained in response to CFA. Interestingly, levels of Cx36 and Cx40 were only elevated in neurons following capsaicin or CFA injections, but the temporal response was similar to that observed for Cx26. In contrast, Cx43 expression was not increased in neurons or satellite glial cells in response to CFA or capsaicin. Thus, trigeminal ganglion neurons and satellite glia can differentially regulate Cx expression in response to the type and duration of inflammatory stimuli, which likely facilitates increased neuron–glia communication during acute and chronic inflammation and pain in the TMJ.

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Investigating the expression of metabotropic glutamate receptors in trigeminal ganglion neurons and satellite glial cells: implications for craniofacial pain

Journal of Receptors and Signal Transduction ◽

10.3109/10799893.2014.885049 ◽

2014 ◽

Vol 34 (4) ◽

pp. 261-269 ◽

Cited By ~ 15

Author(s):

Dennis Boye Larsen ◽

Gunda Ingemann Kristensen ◽

Vinodenee Panchalingam ◽

Jens Christian Laursen ◽

Jeppe Nørgaard Poulsen ◽

...

Keyword(s):

Glutamate Receptors ◽

Glial Cells ◽

Trigeminal Ganglion ◽

Metabotropic Glutamate Receptors ◽

Satellite Glial Cells ◽

Metabotropic Glutamate ◽

Craniofacial Pain ◽

Trigeminal Ganglion Neurons ◽

Ganglion Neurons

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Satellite glial cells in sensory ganglia express functional transient receptor potential ankyrin 1 that is sensitized in neuropathic and inflammatory pain

Molecular Pain ◽

10.1177/1744806920925425 ◽

2020 ◽

Vol 16 ◽

pp. 174480692092542 ◽

Cited By ~ 2

Author(s):

Seung Min Shin ◽

Brandon Itson-Zoske ◽

Yongsong Cai ◽

Chensheng Qiu ◽

Bin Pan ◽

...

Keyword(s):

Neuropathic Pain ◽

Nerve Injury ◽

Glial Cells ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Allyl Isothiocyanate ◽

Sensory Ganglia ◽

Satellite Glial Cells ◽

Intracellular Ca ◽

Transient Receptor

Transient receptor potential ankyrin 1 (TRPA1) is well documented as an important molecule in pain hypersensitivity following inflammation and nerve injury and in many other cellular biological processes. Here, we show that TRPA1 is expressed not only by sensory neurons of the dorsal root ganglia (DRG) but also in their adjacent satellite glial cells (SGCs), as well as nonmyelinating Schwann cells. TRPA1 immunoreactivity is also detected in various cutaneous structures of sensory neuronal terminals, including small and large caliber cutaneous sensory fibers and endings. The SGC-expressed TRPA1 is functional. Like DRG neurons, dissociated SGCs exhibit a robust response to the TRPA1-selective agonist allyl isothiocyanate (AITC) by an increase of intracellular Ca2+ concentration ([Ca2+]i). These responses are abolished by the TRPA1 antagonist HC030031 and are absent in SGCs and neurons from global TRPA1 null mice. SGCs and neurons harvested from DRG proximal to painful tissue inflammation induced by plantar injection of complete Freund’s adjuvant show greater AITC-evoked elevation of [Ca2+]i and slower recovery compared to sham controls. Similar TRPA1 sensitization occurs in both SGCs and neurons during neuropathic pain induced by spared nerve injury. Together, these results show that functional TRPA1 is expressed by sensory ganglia SGCs, and TRPA1 function in SGCs is enhanced after both peripheral inflammation and nerve injury, and suggest that TRPA1 in SGCs may contribute to inflammatory and neuropathic pain.

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