TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice

Zhao, Lin-Xia; Jiang, Ming; Bai, Xue-Qiang; Cao, De‐Li; Wu, Xiaobo; Zhang, Jing; Guo, Jiwei; Chen, Tongtong; Wang, Juan; Wu, Hao; Gao, Yong‐Jing; Zhang, Zhijun

doi:10.1007/s12264-020-00621-4

Cited by 17 publications

(13 citation statements)

References 68 publications

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“…After TN, the deletion of TLR4 did not reduce the expression of MyD88, a downstream molecule of TLRs [ 49 ]. A recent study on TN showed that TLR8 activate ERK and p38, and further increase the expression of pro-inflammatory cytokines in the trigeminal ganglion neurons [ 50 ]. In our study, MyD88, which is an adaptor for all TLRs (except TLR3).…”

Section: Discussionmentioning

confidence: 99%

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

et al. 2021

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Objectives In this study, we investigated the possible analgesic effects of Botulinum toxin type A (BoNT/A) on trigeminal neuralgia (TN). A modified TN mouse model was established by chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) in mice, and the possible roles of microglia toll-like receptor 2 (TLR2) and neuroinflammation was investigated. Methods Male C57BL/6 mice were divided into 3 groups, including sham group, vehicle-treated TN group and BoNT/A-treated TN group. Bilateral mechanical pain hypersensitivity, anxiety-like and depressive-like behaviors were evaluated by using von Frey test, open field, elevated plus-maze testing, and forced swimming test in mice, respectively. The mRNA or protein expression levels of toll-like receptors (TLRs), glia activation markers and proinflammatory factors in the trigeminal nucleus caudalis (TNC) were tested by RT-qPCR, immunofluorescence and Western blotting. We also tested the pain behaviors of TN in Tlr2−/− mice. Results We found that unilateral subcutaneous injection of BoNT/A into the whisker pad on the ipsilateral side of dIoN-CCI mice significantly attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors induced by dIoN-CCI surgery in mice. The dIoN-CCI surgery significantly up-regulated the expression of TLR2, MyD88, CD11b (a microglia marker), IL-1β, TNF-α and IL-6 in the ipsilateral TNC in mice, and BoNT/A injection significantly inhibited the expression of these factors. Immunostaining results confirmed that BoNT/A injection significantly inhibited the microglia activation in the ipsilateral TNC in dIoN-CCI mice. TLR2 deficiency also alleviated bilateral mechanical pain hypersensitivity and the up-regulation of MyD88 expression in the TNC of dIoN-CCI mice. Conclusion These results indicate that unilateral injection of BoNT/A attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors in dIoN-CCI mice, and the analgesic effects of BoNT/A may be associated with the inhibition of TLR2-mediated neuroinflammation in the TNC.

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Section: Discussionmentioning

confidence: 99%

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

et al. 2021

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“…TLRs and Ca 2+ signaling interact with and regulate each other. TLRs (including TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9) have been demonstrated to participate in cytokine production, activation of immunocytes, inflammation, and antiviral innate responses by regulating Ca 2+ signaling ( Tauseef et al, 2012 ; De Dios et al, 2020 ; Zhao et al, 2020 ). In particular, TLR4, which recognizes bacterial lipopolysaccharides (LPSs), is widely reported to alter cytoplasmic Ca 2+ levels and activates Ca 2+ signaling by regulating various Ca 2+ channels.…”

Section: Ca 2+ Signaling In Innate Immune and Anti...mentioning

confidence: 99%

Calcium Ions Signaling: Targets for Attack and Utilization by Viruses

Sun²,

Yang³

et al. 2022

Front. Microbiol.

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Calcium, as a second intracellular messenger, participate in various physiological and biochemical processes, including cell growth and proliferation, energy metabolism, information transfer, cell death, and immune response. Ca2+ channels or pumps in plasma and organelle membranes and Ca2+-related proteins maintain Ca2+ homeostasis by regulating Ca2+ inflow, outflow and buffering to avoid any adverse effects caused by Ca2+ overload or depletion. Thus, Ca2+ signaling also provides a target for virus invasion, replication, proliferation and release. After hijacking the host cell, viruses exploit Ca2+ signaling to regulate apoptosis and resist host immunity to establish persistent infection. In this review, we discuss cellular Ca2+ signaling and channels, interaction of calcium-associated proteins with viruses, and host cell fate, as well as the role of Ca2+ in cell death and antiviral response during viral infection.

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“…For the study of TN, a variety of animal models (Table 1) [3,[40][41][42][43][44][45][46][47][48][49][50][51][52][53] have been developed. All of these animal models contributed to the discovery of vital information about the TN pathway or TN therapeutic management.…”

Section: Different Animal Models For Trigeminal Neuralgia Studymentioning

confidence: 99%

Recent update on trigeminal neuralgia

Islam

Park

2022

J Korean Ster Func Neurosurg

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Trigeminal neuralgia (TN), a long-term disorder affecting the trigeminal nerve, is a form of debilitating neuropathic pain. Although the underlying pathogenesis of TN is debatable, loss of myelin along the trigeminal nerve due to direct compression from a blood vessel or secondary to other conditions such as multiple sclerosis or stroke is thought to be the principal cause. Paroxysmal sporadic pain, with unilateral onset, is the main phenomenon of TN. TN is typically diagnosed clinically. Medications, surgery, and complementary techniques are among the current therapy options for altering the neural circuits associated with TN. Nevertheless, anti-epileptic and tricyclic antidepressant medications are recognized as first-line treatments, and surgical treatment may be required for patients who have not obtained a therapeutic effect with at least three medications, have experienced intolerable side effects, or have symptoms that are not resolving. Stimulation of brain regions is an emerging off-label technique that has the potential to offer pain relief from TN, but sufficient data and more extensive studies on both animals and humans are yet to be published. More specifically, convenient diagnostic techniques and affordable treatment modalities for TN have become crucial needs in order to reduce the psychological and socio-economical losses caused by TN.

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TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice

Cited by 17 publications

References 68 publications

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

Calcium Ions Signaling: Targets for Attack and Utilization by Viruses

Recent update on trigeminal neuralgia

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