Inhibition of toll-like receptor 4 alleviates hyperalgesia induced by acute           dural inflammation in experimental migraine

Min, Su; Ye, Ran; He, Zizi; Zhang, Mingjie; Hu, Guangda; Tang, Wenjing; Zhao, Delong; Yu, Shengyuan

doi:10.1177/1744806918754612

Cited by 45 publications

(48 citation statements)

References 27 publications

(34 reference statements)

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“…Inflammatory mechanism can be involved in pathogenesis of migraine patients, showed by our study due to the increased CRP in both study groups compared with control group. Other studies also demonstrated the contribution of inflammatory mechanism in migraine pathophysiology, neurogenic inflammation being one of the most important mechanism involved in this disease [19,20]. Smoking was also an important contributing factor to migraine pathophysiology as our result demonstrated, being demonstrated as an factor which enhance oxidative stress [21].…”

Section: Discussionsupporting

confidence: 78%

Evaluation of oxidative stress in migraine patients with visual aura - the experience of an Rehabilitation Hospital

Bulboacă¹,

Cluj-Napoca²,

Dogaru³

et al. 2018

Balneo

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Background: Although there are previous studies regarding the migraine pathophysiology, the clinical entity of migraine with aura can have an different pathophysiological mechanism compared with migraine without aura. One of the most important mechanism in migraine is represented by increasing of oxidative stress. The aim of this study was to study the levels of two oxidative stress molecules: nitric oxide (NO) and malondialdehyde (MDA) in migraine with visual aura compared with migraine without aura. Material and Method: a Control group (healthy volunteers) of 37 patients and 58 patient with migraine divided in Group 1 (migraine with visual aura) and Group 2 (migraine without aura) were taken in the study. All the patient were assessed regarding the age, body mass index, blood pressure, basal glycaemia, smoking/non-smoking status, C reactive protein and fibrinogen. Visual aura was assessed regarding transitive negative visual symptoms or positive visual symptoms. Oxidative status was assessed by measurements of the plasma levels of NO and MDA. Results; C reactive protein was significantly increased in both group 1 and 2 compared with control group, but with no statistical difference between group 1 and 2. Oxidative stress (NO and MDA) was significantly increased in both group 1 and 2 compared with control group. There was also found a statistical difference regarding NO and MDA levels between group 1 and 2. Conclusions; patients with visual aura have more intense oxidative stress that can contribute to cortical spreading depression mechanism involved in migraine pathophysiology. This difference between oxidative status in migraine with aura compared with migraine without aura can influence different clinical presentation of these patients. consequently, this difference can be a guide for further individualized therapies for migraine patients.

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Section: Discussionsupporting

confidence: 78%

Evaluation of oxidative stress in migraine patients with visual aura - the experience of an Rehabilitation Hospital

Bulboacă¹,

Cluj-Napoca²,

Dogaru³

et al. 2018

Balneo

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“…Toll-like receptor 4 (TLR4) plays a crucial role in the innate immunity, and is expressed in microglia [19,20] . A previous study reported that TLR4 had a critical role in experimental migraine [21] . Intriguingly, Miyoshi and co-workers found that nerve injury induced the expression of IL-18 in spinal microglia through TLR4/p38MAPK pathway [11] .…”

Section: Discussionmentioning

confidence: 96%

“…Glial cells were activated in the status of experimental migraine, and subsequently released various proinflammatory cytokines like IL-1β and TNF-α, causing hyperpathia or allodynia [2,21] .…”

Section: Discussionmentioning

confidence: 99%

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Involvement of Interleukin-18-Mediated Microglia/Astrocyte Interaction in Experimental Models of Migraine

Gong

Lin

et al. 2020

Preprint

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Background: The exact molecular mechanisms of migraine were not fully understood. Emerging evidence indicated that inflammation had a significant role in pathophysiological mechanisms of migraine. The present study aimed to investigate the involvement of Interleukin-18-Mediated Microglia/Astrocyte Interaction in the development of hyperpathia or allodynia induced by migraine. Methods: Experimental rat model of migraine was established by repetitive inflammatory soup (IS) dural infusions. The expression of Interleukin-18 (IL-18) and IL-18 receptor (IL-18R) was examined by quantitative real-time polymerase chain reaction or Western blot. The expression of activated microglia and astrocytes was examined by Western blot or immunofluorescence. The expression of nuclear factor-kappa B (NF-κB) was examined by Western blot. TAK-242 and anti-IL-18 antibody were used to inhibit the activation of toll-like receptor 4 (TLR4) and IL-18 pathway, respectively. Results: IS dural infusions elicited microglial activation and astrocytic activation. Meanwhile, IS dural infusions induced the upregulation of IL-18 and IL-18R in microglia and astrocytes, respectively. Blocking the IL-18 signaling pathway attenuated nociceptive behavior. Meanwhile, blocking IL-18 signaling also suppressed astrocytic activation, as well as activation of NF-κB. And IL-18 dural infusions induced nociceptive behavior and glia activation. Conclusions: IL-18, a product of microglial toll-like receptor 4 (TLR4) activation, acted on IL-18R expressed in astrocyte, and subsequently stimulated activation of NF-κB, leading to the astrocytic activation. Together, the present results suggest that IL-18-mediated microglia/astrocyte interactions in the medullary dorsal horn may participate in the development of hyperpathia or allodynia induced by migraine.

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“…A previous study revealed the TLR4-NF-κB signaling pathway an important role in the progress of hyperalgesia following IS dural infusions [21] . In this work, IS dural infusions induced an increase of NF-κB phosphorylation in the medullary dorsal horn (Fig.…”

Section: Microglia-derived Il-18 Mediated Astrocytic Activation Via Amentioning

confidence: 98%

Involvement of Interleukin-18-Mediated Microglia/Astrocyte Interaction in Experimental Models of Migraine

Gong

Lin

Lu³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The exact molecular mechanisms of migraine were not fully understood. Emerging evidence indicated that inflammation had a significant role in pathophysiological mechanisms of migraine. The present study aimed to investigate the role of Interleukin-18-Mediated Microglia/Astrocyte Interaction in the development of hyperpathia or allodynia induced by migraine. Methods Experimental rat model of migraine was established by repetitive inflammatory soup (IS) dural infusions. The expression of Interleukin-18 (IL-18) and IL-18 receptor (IL-18R) was examined by quantitative real-time polymerase chain reaction or Western blot. The expression of activated microglia and astrocytes was examined by Western blot or immunofluorescence. The expression of nuclear factor-kappa B (NF-κB) was examined by Western blot. TAK-242 and anti-IL-18 antibody were used to inhibit the activation of toll-like receptor 4 (TLR4) and IL-18 pathway, respectively. Results IS dural infusions elicited microglial activation and astrocytic activation. Meanwhile, IS dural infusions induced the upregulation of IL-18 and IL-18R in microglia and astrocytes, respectively. Blocking the IL-18 signaling pathway attenuated nociceptive behavior. Meanwhile, blocking IL-18 signaling also suppressed astrocytic activation, as well as activation of NF-κB. And IL-18 dural infusions induced nociceptive behavior and glia activation. Conclusions IL-18, a product of microglial toll-like receptor 4 (TLR4) activation, acted on IL-18R expressed in astrocyte, and subsequently stimulated activation of NF-κB, leading to the astrocytic activation. Together, the present results suggest that IL-18-mediated microglia/astrocyte interactions in the medullary dorsal horn may participate in the development of hyperpathia or allodynia induced by migraine.

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Inhibition of toll-like receptor 4 alleviates hyperalgesia induced by acute dural inflammation in experimental migraine

Cited by 45 publications

References 27 publications

Evaluation of oxidative stress in migraine patients with visual aura - the experience of an Rehabilitation Hospital

Evaluation of oxidative stress in migraine patients with visual aura - the experience of an Rehabilitation Hospital

Involvement of Interleukin-18-Mediated Microglia/Astrocyte Interaction in Experimental Models of Migraine

Involvement of Interleukin-18-Mediated Microglia/Astrocyte Interaction in Experimental Models of Migraine

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