Satellite glial cells in dorsal root ganglia are activated in experimental autoimmune encephalomyelitis

Warwick, Rebekah A.; Ledgerwood, Craig; Brenner, Talma; Hanani, Menachem

doi:10.1016/j.neulet.2014.03.033

Cited by 20 publications

(12 citation statements)

References 23 publications

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“…Therefore, the possibility that hemichannels may participate in the release of gliotransmitters which enhance neuronal activity cannot be ruled out. Similar results have been observed in mouse models of experimental neuropathic autoimmune encephalomyelitis (Warwick et al, 2014 ), diabetes mellitus (Hanani et al, 2014 ), sepsis (Blum et al, 2017 ) and chemotherapy-induced peripheral neuropathy (Warwick and Hanani, 2013 ). In all these studies an increase in gap junctional communication between SGCs was observed, but the molecular mechanism behind this phenomenon remains unknown.…”

Section: Dorsal Root Ganglia (Drg)supporting

confidence: 75%

Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

Retamal

Riquelme

Stehberg

et al. 2017

Front. Mol. Neurosci.

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In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia). It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs). Recent evidence shows that connexin43 (Cx43) hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons. This communication may be exerted via the release of bioactive molecules from SGCs and their subsequent action on receptors located at the soma of sensory neurons. The glio-neuronal communication seems to be relevant for the establishment of chronic pain, hyperalgesia and pathologies associated with tissue inflammation. Based on the current literature, it is possible to propose that Cx43 hemichannels expressed in SGCs could be a novel pharmacological target for treating chronic pain, which need to be directly evaluated in future studies.

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Section: Dorsal Root Ganglia (Drg)supporting

confidence: 75%

Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

Retamal

Riquelme

Stehberg

et al. 2017

Front. Mol. Neurosci.

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“…The identity of these ATF3+ profiles remains to be determined. Some may correspond to satellite glial cells that surround DRG cell bodies and that are activated during EAE (Warwick et al, 2014). This pattern of ATF3+ labeling is somewhat reminiscent of the ATF3 expression seen in Schwann cells located at the distal stump of injured sciatic nerve axons (Hunt et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

“…Molecular changes have been reported in peripheral sensory ganglia in EAE (Begum et al, 2013; Warwick et al, 2014; Zhu et al, 2013). For example, in myelin basic protein-induced EAE, TNFα and fractalkine expression in the DRG correlates with motor symptom severity.…”

Section: Discussionmentioning

confidence: 98%

Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE

Frezel¹,

Sohet²,

Daneman³

et al. 2016

Experimental Neurology

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Experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis produced by immunization with myelin oligodendrocyte glycoprotein (MOG) and adjuvants, results from profound T-cell mediated CNS demyelination. EAE is characterized by progressive, ascending motor dysfunction and symptoms of ongoing pain and hypersensitivity, in some cases preceding or concomitant with the motor deficits. In this regard, the EAE model mimics major features of multiple sclerosis, where a central neuropathic pain state is common. Although the latter condition is presumed to arise from a CNS loss of inhibitory controls secondary to the demyelination, dysfunction of sensory neurons may also contribute. Based on our previous studies that demonstrated the utility of monitoring expression of activating transcription factor 3 (ATF3), a sensitive marker of injured sensory neurons, here we followed both ATF3 and CD4+ T cells invasion of sensory ganglia (as well as the CNS) at different stages of the EAE model. We found that ATF3 is induced in peripheral sensory ganglia and brainstem well before the appearance of motor deficits. Unexpectedly, the ATF3 induction always preceded T cell infiltration, typically in adjacent, but non-overlapping regions. Surprisingly, control administration of the pertussis toxin and/or Complete Freund's adjuvants, without MOG, induced ATF3 in sensory neurons. In contrast, T cell infiltration only occurred with MOG. Taken together, our results suggest that the clinical manifestations in the EAE result not only from central demyelination but also from neuronal stress and subsequent pathophysiology of sensory neurons.

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“…However, previous studies using EAE models to investigate the neuropathic pain mechanism in MS revealed the involvement of both neurological and immunological factors in the PNS, including satellite glia-cell activation 44 and elevated levels of tumor necrosis factor α 45 and brain-derived neurotrophic factor 46 , in DRG of EAE animals. Moreover, our EAEnp mouse model is supported by evidence of mild symptoms accompanied by hyperalgesia in the rat EAE model, which also does not contain PTX 13 47 .…”

Section: Discussionmentioning

confidence: 98%

Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis

Wang

Chung

Liao

et al. 2017

Sci Rep

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Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain. Elicited pain levels were as high in Asic1a−/−, Asic2−/− and Asic3−/− mice as wild-type mice even though only Asic1a−/− mice showed reduced EAE disease severity, which indicates that pain in EAE was independent of disease severity. We thus adopted an EAE model without pertussis toxin (EAEnp) to restrain activated immunity in the periphery and evaluate the PNS contribution to pain. Both EAE and EAEnp mice showed similar pain behaviors and peripheral neuropathy in nerve fibers and DRG neurons. Moreover, pregabalin significantly reduced neuropathic pain in both EAE and EAEnp mice. Our findings highlight the essential role of the PNS in neuropathic pain in EAE and pave the way for future development of analgesics without side effects in the CNS.

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Satellite glial cells in dorsal root ganglia are activated in experimental autoimmune encephalomyelitis

Cited by 20 publications

References 23 publications

Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE

Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis

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