Peripheral purinergic receptor modulation influences the trigeminal ganglia nitroxidergic system in an experimental murine model of inflammatory orofacial pain

Borsani, Elisa; Albertini, Roberta; Labanca, Mauro; Lonati, Claudio; Rezzani, Rita; Rodella, Luigi Fabrizio

doi:10.1002/jnr.22420

Cited by 16 publications

(18 citation statements)

References 57 publications

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“…To characterize PlGF expression, double immunofluorescenct stainings for PlGF (sc-27134; 1:50; Santa Cruz Biotechnology, Santa Cruz, CA, Taylor and Goldenberg, 2007) and NF-H (MAB5448/clone TA51; 1:500; Millipore, De Girolamo et al, 2000) for axons, Neu-N (MAB377/ clone A60; 1:250; Millipore, Borsani et al, 2010) for neuronal cell nuclei, S100 (ZO311; 1/200; DakoCytomation, Gould et al, 1986) for quiescent SCs, p75NGFr (AB1554; 1/200; Millipore, Runyan and Phelps, 2009) for proliferating SCs, von Willebrand factor (vWF; AB6994; 1/2000; Abcam, Yin et al, 2010) for endothelial cells, patched-1 (Ptc-1; sc-9016/H-267; 1/50; Santa Cruz Biotechnology, Chen et al, 2007) for fibroblasts, CD11b (MCA74; 1/250; Serotec, Springer et al, 1979) for macrophages, P0 (AB9352; 1/50; Millipore) for peripheral myelin, were performed. After drying, tissue sections were fixed in cold acetone for 10 min at 4°C.…”

Section: Immunofluorescent Stainingsmentioning

confidence: 99%

Involvement of placental growth factor in Wallerian degeneration

Chaballe

Sempels

et al. 2010

Glia

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Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively in successful and aborted axon regeneration. In the peripheral nervous system, Schwann cells (SCs) and macrophages, under the control of a network of cytokines and chemokines, represent the main cell types involved in this process. Within this network, the role of placental growth factor (PlGF) remains totally unknown. However, properties like monocyte activation/attraction, ability to increase expression of pro-inflammatory molecules, as well as neuroprotective effects, make it a candidate likely implicated in this process. Also, nothing is described about the expression and localization of this molecule in the peripheral nervous system. To address these original questions, we decided to study PlGF expression under physiological and degenerative conditions and to explore its role in WD, using a model of sciatic nerve transection in wild-type and Pgf(-/-) mice. Our data show dynamic changes of PlGF expression, from periaxonal in normal nerve to SCs 24h postinjury, in parallel with a p65/NF-κB recruitment on Pgf promoter. After injury, SC proliferation is reduced by 30% in absence of PlGF. Macrophage invasion is significantly delayed in Pgf(-/-) mice compared with wild-type mice, which results in worse functional recovery. MCP-1 and proMMP-9 exhibit a 3-fold reduction of their relative expressions in Pgf(-/-) injured nerves, as demonstrated by cytokine array. In conclusion, this work originally describes PlGF as a novel member of the cytokine network of WD.

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Section: Immunofluorescent Stainingsmentioning

confidence: 99%

Involvement of placental growth factor in Wallerian degeneration

Chaballe

Sempels

et al. 2010

Glia

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“…It was proposed that NO can contribute to the excitation of sensory neurons and to pain (Cairns et al, 2014;Steel et al, 1994;Wang, Tsai, Chen, Lin, & Lue, 2013), but the underlying mechanisms have not been clarified. Afferent firing or excitatory transmitters such as calcitonin gene-related peptide (CGRP; Li, Vause, & Durham, 2008) or ATP (Borsani et al, 2010) raise intracellular Ca 2+ ([Ca 2+ ] in ) in sensory neurons, which in turn induces NOS activation and NO production. Sensory neurons are enveloped by satellite glial cells (SGCs) with a gap of only 20 nm between these cells types (Hanani, 2005(Hanani, , 2015Pannese, 2018).…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide as a messenger between neurons and satellite glial cells in dorsal root ganglia

Belzer

Hanani

2019

Glia

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Abnormal neuronal activity in sensory ganglia contributes to chronic pain. There is evidence that signals can spread between cells in these ganglia, which may contribute to this activity. Satellite glial cells (SGCs) in sensory ganglia undergo activation following peripheral injury and participate in cellular communication via gap junctions and chemical signaling. Nitric oxide (NO) is released from neurons in dorsal root ganglia (DRG) and induces cyclic GMP (cGMP) production in SCGs, but its role in SGC activation and neuronal excitability has not been explored. It was previously reported that induction of intestinal inflammation with dinitrobenzoate sulfonate (DNBS) increased gap junctional communications among SGCs, which contributed to neuronal excitability and pain. Here we show that DNBS induced SGC activation in mouse DRG, as assayed by glial fibrillary acidic protein upregulation. DNBS also upregulated cGMP level in SGCs, consistent with NO production. In vitro studies on intact ganglia from DNBS‐treated mice showed that blocking NO synthesis inhibited both SGCs activation and cGMP upregulation, indicating an ongoing NO production. Application of NO donor in vitro induced SGC activation, augmented gap junctional communications, and raised neuronal excitability, as assessed by electrical recordings. The cGMP analog 8‐Br‐cGMP mimicked these actions, confirming the role of the NO‐cGMP pathway in intraganglionic communications. NO also augmented Ca2+ waves propagation in DRG cultures. It is proposed that NO synthesis in DRG neurons increases after peripheral inflammation and that NO induces SGC activation, which in turn contributes to neuronal hyperexcitability. Thus, NO plays a major role in neuron–SGC communication.

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“…However, the vast majority of reported applications of the formalin model is extra-trigeminal, with formalin injection to the hindpaw. Therefore, one of our main rationales was to adapt the formalin model to trigeminally-innervated areas [5; 22], using mice. In terms of which mouse line to subject to trigeminal formalin injections, we decided to use Trpv4 −/− mice, so that the role of TRPV4 in trigeminal irritant pain could be assessed, based on our previous findings that TRPV4 was critical for airborne irritation in upper airways [19] and a key contributor to temporomandibular joint pain induced by arthritogenic irritant [8].…”

Section: Introductionmentioning

confidence: 99%

TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor

Chen

Kanju

Fang

et al. 2014

Pain

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Detection of external irritants by head nociceptor neurons has deep evolutionary roots. Irritant-induced aversive behavior is a popular pain model in laboratory animals. It is used widely in the formalin-model, where formaldehyde is injected into the rodent paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model has elucidated many anti-pain compounds and pain-modulating signaling pathways. We have adopted this model to trigeminally-innervated territories in mice. Also, we have examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior, because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons, also because we have recently defined TRPV4’s role in response to air-borne irritants, and in a model for temporomandibular joint pain. We found TRPV4 to be important for trigeminal nocifensive behavior evoked by formalin whiskerpad injections. This conclusion is supported by studies with Trpv4−/− mice and TRPV4-specific antagonists. Our results imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4 can be activated directly by formalin to gate Ca++. Using TRPA1-blocker and Trpa1−/− mice, we found that both TRP channels co-contribute to the formalin trigeminal pain response. These results imply TRPV4 as an important signaling molecule in irritation-evoked trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel analgesics, possibly for specific targeting of trigeminal pain disorders, such as migraine, headaches, TMJ, facial and dental pain, and irritation of trigeminally-innervated surface epithelia.

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Peripheral purinergic receptor modulation influences the trigeminal ganglia nitroxidergic system in an experimental murine model of inflammatory orofacial pain

Cited by 16 publications

References 57 publications

Involvement of placental growth factor in Wallerian degeneration

Involvement of placental growth factor in Wallerian degeneration

Nitric oxide as a messenger between neurons and satellite glial cells in dorsal root ganglia

TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor

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