Neuron-glia interaction is a key mechanism underlying persistent orofacial pain

Iwata, Koichi; Katagiri, Ayano; Shinoda, Masamichi

doi:10.2334/josnusd.16-0858

Cited by 28 publications

(28 citation statements)

References 26 publications

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“…Without the availability of specific and sensitive antibody against HK-1, we cannot further confirm it experimentally. The concomitant upregulation of HK-1 in trigeminal sensory neurons and SGCs is of particular importance, since an increasing amount of evidence points to the importance of neuron-glia crosstalk in chronic pain conditions, including orofacial pain [2,6,[95][96][97][98]. Other neuropeptides released from peptidergic sensory neurons have already been suggested to have a prominent role in glial cell activation during sensitization.…”

Section: Discussionmentioning

confidence: 99%

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Aczél

Kecskés

Kun

et al. 2020

IJMS

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A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from the central terminals of primary afferents sensitize the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization in chronic orofacial pain and migraine. In the present study, we investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) encoded by the Tac4 gene in the trigeminal system. HK-1 had been shown to participate in inflammation and hyperalgesia in various models, but its role has not been investigated in orofacial pain or headache. In the complete Freund’s adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that Tac4 expression increased in the TG in response to inflammation. Duration-dependent Tac4 upregulation was associated with the extent of the facial allodynia. Tac4 was detected in both TG neurons and satellite glial cells (SGC) by the ultrasensitive RNAscope in situ hybridization. We also compared gene expression changes of selected neuronal and glial sensitization and neuroinflammation markers between wild-type and Tac4-deficient (Tac4-/-) mice. Expression of the SGC/astrocyte marker in the TG and TNC was significantly lower in intact and saline/CFA-treated Tac4-/- mice. The procedural stress-related increase of the SGC/astrocyte marker was also strongly attenuated in Tac4-/- mice. Analysis of TG samples with a mouse neuroinflammation panel of 770 genes revealed that regulation of microglia and cytotoxic cell-related genes were significantly different in saline-treated Tac4-/- mice compared to their wild-types. It is concluded that HK-1 may participate in neuron-glia interactions both under physiological and inflammatory conditions and mediate pain in the trigeminal system.

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Section: Discussionmentioning

confidence: 99%

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Aczél

Kecskés

Kun

et al. 2020

IJMS

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“…The infiltration and activation of M1 and M2 macrophages may develop in not only the injured and inflamed region of the peripheral nerve but also the sensory ganglion [40]. Furthermore, TG neuronal excitability is regulated by certain chemical mediators, which are induced following orofacial pathogenesis by the functional transcellular communication between macrophages and TG neurons [49]. Long-lasting TG neuronal hyperexcitability further potentiates functional transcellular communication and initiates the enhancement of TG neuronal hyperexcitability, which leads to plastic changes in nociceptive neuronal excitability in the central nervous system (CNS).…”

Section: Neuron and Non-neuronal Cell Communication In Tgmentioning

confidence: 99%

Pathophysiological mechanisms of persistent orofacial pain

et al. 2020

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Nociceptive stimuli to the orofacial region are typically received by the peripheral terminal of trigeminal ganglion (TG) neurons, and noxious orofacial information is subsequently conveyed to the trigeminal spinal subnucleus caudalis and the upper cervical spinal cord (C1-C2). This information is further transmitted to the cortical somatosensory regions and limbic system via the thalamus, which then leads to the perception of pain. It is a well-established fact that the presence of abnormal pain in the orofacial region is etiologically associated with neuroplastic changes that may occur at any point in the pain transmission pathway from the peripheral to the central nervous system (CNS). Recently, several studies have reported that functional plastic changes in a large number of cells, including TG neurons, glial cells (satellite cells, microglia, and astrocytes), and immune cells (macrophages and neutrophils), contribute to the sensitization and disinhibition of neurons in the peripheral and CNS, which results in orofacial pain hypersensitivity.

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“…Convincing evidence supports the involvement of microglia in neuropathic and persistent orofacial pain [21]. In an experimental model of inferior alveolar and mental nerve injuries, microglial activation was observed for 14 continuous days, with evidence of delayed astrocytic activation [29].…”

Section: Neuroinflammatory Profile After Pulp Exposurementioning

confidence: 80%

“…There is increasing evidence that strongly supports the involvement of microglial and astrocytes activation in orofacial pain [21]. To evaluate whether EA at 2 Hz, affects the activation of microglia and astrocytes, we investigated the levels of Iba-1 and GFAP proteins in the Vc.…”

Section: Ea At Verum (Local and Distal) Acupoints Inhibits Microglialmentioning

confidence: 99%

Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model—A Basic Research

Romero

Lee

Fuh

et al. 2020

IJMS

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Irreversible pulpitis is an extremely painful condition and its consequence in the central nervous system (CNS) remains unclear. A mouse model of dental pulp injury (DPI) resembles the irreversible pulpitis profile in humans. This study sought to determine whether pain induced by DPI activates microglia and astrocytes in the trigeminal subnucleus caudalis (Vc), as well as increases levels of proinflammatory cytokines, and whether electroacupuncture (EA) can be a potential analgesic and neuroprotective therapy following DPI. Pain behavior was measured via head-withdrawal threshold (HWT) and burrowing behavior at days 1, 3, 7, 14 and 21 after DPI. A marked decrease in HWT and burrowing activity was observed from day 1 to 14 after DPI and no changes were seen on day 21. Microglial and astrocytes activation; along with high cytokine (TNFα, IL-1β, and IL-6) levels, were observed in the Vc at 21 days after DPI. These effects were attenuated by verum (local and distal) EA, as well as oral ibuprofen administration. The results suggest that DPI-induced pain and glial activations in the Vc and EA exert analgesic efficacy at both local and distal acupoints. Furthermore, verum (local and distal) EA might be associated with the modulations of microglial and astrocytes activation.

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Neuron-glia interaction is a key mechanism underlying persistent orofacial pain

Cited by 28 publications

References 26 publications

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Pathophysiological mechanisms of persistent orofacial pain

Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model—A Basic Research

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