Dexmedetomidine attenuates haemorrhage-induced thalamic pain by inhibiting the TLR4/NF-\u03baB/ERK1/2 pathway in mice

Tianfeng Huang,Yong Li,Liang Zong,Zehua Wang,Wenqing Hu,Dapeng Yu,Yingying Xu,Fan Yang,Ju Gao

doi:10.1007/s10787-021-00877-w

Tianfeng Huang, Yong Li + Show 7 more

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https://doi.org/10.1007/s10787-021-00877-w

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Abstract

BackgroundThalamic pain, a neuropathic pain syndrome, frequently occurs after stroke. This research aimed to investigate the effect of dexmedetomidine (DEX) on thalamic pain.MethodsThe cellular localization of the TLR4 protein was determined by immunostaining. The expression of Iba1, GFAP and protein associated with the TLR4/NF-κB/ERK1/2 pathway was measured by Western blotting. Continuous pain hypersensitivity was evaluated by behavioural tests. The results were analysed by one-way ANOVA, two-way ANOVA and Tukey’s post hoc test.ResultsThe results demonstrated that DEX obviously alleviated thalamic pain induced by haemorrhage on the ipsilateral side and delayed the development of pain hypersensitivity. Furthermore, the expression levels of Iba1, GFAP and proteins associated with the TLR4/NF-κB/ERK1/2 signalling pathway were greatly increased in mice with thalamic pain, but these effects were reversed by DEX.ConclusionOur findings suggest that DEX alleviates the inflammatory response during thalamic pain through the TLR4/NF-κB/ERK1/2 signalling pathway and might be a potential therapeutic agent for thalamic pain.

Highlights

Stroke, which has very high disability and mortality rates, is one of the most important diseases endangering human life and health worldwide
To evaluate pain hypersensitivity in the context of haemorrhage-induced thalamic pain, we measure the paw withdrawal frequencies of mice micro-injected with Collagenase IV (Coll IV) into the ventral posterior medial (VPM) and ventral posterior lateral (VPL)
The expression level of Toll-like receptor 4 (TLR4) was persistently increased by 1.8, 1.9, 2.0- and 2.3-fold on days 1, 3, 7 and 14 after unilateral Coll IV microinjection, respectively, in the ipsilateral thalamus compared with the contralateral thalamus (Fig. 1e, f)

Summary

Introduction

Stroke, which has very high disability and mortality rates, is one of the most important diseases endangering human life and health worldwide. Central post-stroke pain (CPSP), a chronic neuropathic pain syndrome, is Tianfeng Huang and Yong Li contributed to this work. A neuropathic pain syndrome, frequently occurs after stroke. The expression of Iba, GFAP and protein associated with the TLR4/NF-κB/ERK1/2 pathway was measured by Western blotting. Results The results demonstrated that DEX obviously alleviated thalamic pain induced by haemorrhage on the ipsilateral side and delayed the development of pain hypersensitivity. The expression levels of Iba, GFAP and proteins associated with the TLR4/NF-κB/ERK1/2 signalling pathway were greatly increased in mice with thalamic pain, but these effects were reversed by DEX. Conclusion Our findings suggest that DEX alleviates the inflammatory response during thalamic pain through the TLR4/ NF-κB/ERK1/2 signalling pathway and might be a potential therapeutic agent for thalamic pain

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