A neural circuit from paratenial thalamic nucleus to anterior cingulate cortex for the regulation of opioid-induced hyperalgesia in male rats

Peng-Fei Zhu; Xuan Wang; Bin Nie; Mei-Hong Li; Yu-Ting Li; Bo Wu; Chen-Hong Li; Fang Luo

doi:10.1016/j.nbd.2024.106745

A neural circuit from paratenial thalamic nucleus to anterior cingulate cortex for the regulation of opioid-induced hyperalgesia in male rats

Neurobiol Dis. 2024 Nov 26:203:106745. doi: 10.1016/j.nbd.2024.106745. Online ahead of print.

Authors

Peng-Fei Zhu¹, Xuan Wang¹, Bin Nie¹, Mei-Hong Li¹, Yu-Ting Li², Bo Wu², Chen-Hong Li³, Fang Luo⁴

Affiliations

¹ Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
² The Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University, Wuhan, Hubei 430074, China.
³ The Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment, College of Biomedical Engineering, South-Central Minzu University, Wuhan, Hubei 430074, China. Electronic address: lichen@mail.scuec.edu.cn.
⁴ Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China. Electronic address: luofang0909@hotmail.com.

PMID: 39603279
DOI: 10.1016/j.nbd.2024.106745

Abstract

Prolonged use of opioids can lead to increased sensitivity to painful stimuli, a condition referred to as opioid-induced hyperalgesia (OIH). However, the mechanisms underlying this contradictory situation remain unclear. This study elucidates the pivotal role of the paratenial thalamic nucleus (PT)-anterior cingulate cortex (ACC) neuronal circuit in the development of OIH in male rats. Immunofluorescence and electrophysiology experiments demonstrated aberrant activation of PT glutamatergic neurons (PT^Glu) in rats with OIH. Optogenetic or chemogenetic activation of the PT^Glu-ACC circuit aggravates mechanical and thermal hyperalgesia. Conversely, the inhibition of neuronal circuits showed analgesic effects. Additionally, PT^Glu neurons project to both ACC pyramidal neurons and interneurons. Moreover, OIH affects the function of the ACC microcircuit, leading to decreased feedforward inhibition and an inhibitory/excitatory (I/E) imbalance in ACC pyramidal neurons. In conclusion, our findings highlighted the role of the PT^Glu-ACC neuronal circuit in the development of opioid-induced hyperalgesia, suggesting that this circuit is a promising therapeutic target for addressing the side effects of opioids.

Keywords: Fentanyl; Neural circuit; Opioid-induced hyperalgesia; Optogenetics; Patch-clamp recordings.