Abstract
Myocardial infarction is the leading cause of death worldwide. Restored blood flow quickly rescues myocardium but also causes ischemia-reperfusion (IR) injury. Chronic pain affects up to 25% of population worldwide. Whether there is any correlation between IR injury and chronic pain is unknown. Here we show that chronic neuropathic pain reduces IR injury via an anterior nucleus of paraventricular thalamus (PVA)-dependent parasympathetic pathway in mice. Intra-PVA infusion of U0126, a MEK inhibitor, prevents the activation of ERK and abolishes spared nerve injury (SNI)-induced cardioprotection. We also demonstrate that activation of PVA neurons by phorbol 12, 13-dibutyrate (PDBu) or optogenetic stimulation is sufficient to induce cardioprotection. The PVA-dependent cardioprotection is abolished by hexamethethonum and glycopyrrolate but not propranolol. Furthermore, SNI surgery and optogenetic stimulation of PVA neurons reduce the heart rate. These results suggest that the parasympathetic nerve mediates this cardioprotection. Thus, we reveal a novel mechanism linking chronic neuropathic pain and cardioprotection via a PVA-dependent parasympathetic pathway.
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