Inhibition of toll-like receptor 4 alleviates hyperalgesia induced by acute dural inflammation in experimental migraine.
Mol Pain
; 14: 1744806918754612, 2018.
Article
em En
| MEDLINE
| ID: mdl-29310498
ABSTRACT
Objective Although nociceptive sensitisation is an important pathophysiological process in migraine and migraine chronification, its underlying mechanisms remain unclear. Toll-like receptor 4 (TLR4), a pattern-recognition molecule, has a critical role in both neuropathic pain and morphine tolerance. The present study examined whether elements of the TLR4 pathway contribute to hyperalgesia induced by dural inflammation in rats. Methods A rat model of migraine was established by infusing a dural inflammatory soup. A group pretreated with TAK-242 was used to inhibit the activation of TLR4. The protein levels of TLR4 and its downstream molecules in the trigeminal pathway were examined by Western blot and immunofluorescence. The expression of activated microglia and astrocytes was also analysed. Levels of interleukin-1 beta, tumour necrosis factor-alpha, and brain-derived neurotrophic factor were measured by enzyme-linked immunosorbent assay. Results Acute inflammatory soup infusion induced time-dependent facial mechanical hyperalgesia, which was blocked by TAK-242 pretreatment. The inflammatory soup stimulus increased the production of TLR4 downstream molecules and interleukin-1 beta. Higher levels of microglia activation and brain-derived neurotrophic factor release were observed following the administration of the inflammatory soup but were alleviated by TAK-242. Conclusions These data suggest that the TLR4 signalling pathway promotes hyperalgesia induced by acute inflammatory soup delivery by stimulating the production of proinflammatory cytokines and activating microglia.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Dura-Máter
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Receptor 4 Toll-Like
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Hiperalgesia
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Inflamação
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Transtornos de Enxaqueca
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Pain
Assunto da revista:
BIOLOGIA MOLECULAR
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NEUROLOGIA
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PSICOFISIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China