Cardioprotection induced in a mouse model of neuropathic pain via anterior nucleus of paraventricular thalamus

Yi-Fen Cheng,Wei-Hsin Chen,Chien-Chang Chen,Bai-Chuang Shyu,Yen-Hui Chen,Hsi-Chien Shih,Ya-Ting Chang

doi:10.1038/s41467-017-00891-z

Abstract

Myocardial infarction is the leading cause of death worldwide. Restoration of blood flow rescues myocardium but also causes ischemia-reperfusion injury. Here, we show that in a mouse model of chronic neuropathic pain, ischemia-reperfusion injury following myocardial infarction is reduced, and this cardioprotection is induced via an anterior nucleus of paraventricular thalamus (PVA)-dependent parasympathetic pathway. Pharmacological inhibition of extracellular signal-regulated kinase activation in the PVA abolishes neuropathic pain-induced cardioprotection, whereas activation of PVA neurons pharmacologically, or optogenetic stimulation, is sufficient to induce cardioprotection. Furthermore, neuropathic injury and optogenetic stimulation of PVA neurons reduce the heart rate. These results suggest that the parasympathetic nerve is responsible for this unexpected cardioprotective effect of chronic neuropathic pain in mice.

Highlights

Ischemic heart disease or myocardial ischemia is the leading cause of death worldwide and often responsible for sudden death[1]
We showed that the extracellular signal-regulated kinase (ERK) activity and neuronal activity in the anterior nucleus of the paraventricular thalamus (PVA), a brain region located at the rostral portion of paraventricular thalamus (PVT), is required for the spared nerve injury (SNI)-induced cardioprotection
To ensure the difference in the infarct size is not caused by different myocardium injury, we measured the area at risk (AAR) and found there is no difference among these three groups

Summary

Introduction

Ischemic heart disease or myocardial ischemia is the leading cause of death worldwide and often responsible for sudden death[1]. A recent study demonstrated that acute (15 min), delayed (24 h), or chronic (9 days) RIPC elicited similar cardioprotective effects in mice[15]. This study suggests that cardioprotection could be achieved by both acute and delayed or chronic phase of conditioning It is unclear whether pre-existing chronic pain will have a similar cardioprotective effect. Several studies examine the relationship between chronic pain and cardiovascular diseases (CVD) risk focused on the elevated blood pressure or hypertension[20,21,22,23,24]. These studies show that there is a positive relationship between chronic pain and CVD risk It is unclear whether this is a relationship between chronic pain and ischemic heart diseases. Our results demonstrate that chronic pain induces cardioprotection via a central mechanism involving activation of PVA neurons

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