Modulating the Pronociceptive Effect of Sleep Deprivation: A Possible Role for Cholinergic Neurons in the Medial Habenula
Xiang‑Sha Yin1,2,4 · Bai‑Rong Chen1,2 · Xi‑Chun Ye1,2 · Yun Wang1,2,31 Department of Neurobiology, School of Basic Medical Sciences and Neuroscience Research Institute, Peking University, Beijing 100083, China
2 Key Lab for Neuroscience, Ministry of Education of China and National Health Commission and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China
3 PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China
4 Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing 100730, China
Abstract
Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain, yet the precise neural mechanisms underlying this association remain elusive. In our study, we explored the contribution of cholinergic neurons within the medial habenula (MHb) to hyperalgesia induced by sleep deprivation in rats. Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results. Interestingly, we did not find a direct response of MHb cholinergic neurons to pain stimulation. Further investigation identified the interpeduncular nucleus (IPN) and the paraventricular nucleus of the thalamus (PVT) as key players in the pro-nociceptive effect of sleep deprivation. Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia. These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation, highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.
Keywords
Medial habenula; Cholinergic; Sleep deprivation; Pronociceptive efect; Hyperalgesia
