Opioids are often rst-line analgesics in pain therapy. However, prolonged use of opioids causes paradoxical pain, termed "opioid-induced hyperalgesia (OIH)". The infralimbic medial prefrontal cortex (IL-mPFC) has been suggested to be critical in in ammatory and neuropathic pain processing through its dynamic output from Layer V pyramidal neurons. Whether OIH condition induces excitability changes of these output neurons and what mechanisms underlie these changes remains elusive. Here, with combination of patch-clamp recording, immunohistochemistry, as well as optogenetics, we revealed that IL-mPFC Layer V pyramidal neurons exhibited hyperexcitability together with higher input resistance. In line with this, optogenetic and chemogenetic activation of these neurons aggravate behavioral hyperalgesia in male OIH rats. Inhibition of these neurons alleviates hyperalgesia in male OIH rats but exerts an opposite effect in male control rats. Electrophysiological analysis of hyperpolarization-activated cation current (Ih) demonstrated that decreased Ih is a prerequisite for the hyperexcitability of IL-mPFC output neurons. This decreased Ih was accompanied by a decrease in HCN1, but not HCN2, immunolabeling, in these neurons. In contrast, the application of HCN channel blocker increased the hyperalgesia threshold of male OIH rats. Consequently, we identi ed an HCN-channel-dependent hyperexcitability of IL-mPFC output neurons, which governs the development and maintenance of OIH in male rats.
Pericardial effusion complicating RFCA is not rare in patients with tachyarrhythmias, and it tends to develop into cardiac tamponade. Emergency pericardiocentesis and drainage are the most effective therapy. Female sex and atrial fibrillation may be independent risk factors of pericardial effusion after RFCA in patients with tachyarrhythmias.
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