Mu opioid receptors gate the locus coeruleus pain generator

• DOI: 10.1101/2023.10.20.562785
• Publication Date: 2023-10-24T02:35:19Z
• Authors: Makenzie R. Norris; Chao-Cheng Kuo; Samantha S. Dunn; Jenny R. Kim; Léa J. Becker; Gustavo Borges; Loc V. Thang; Kyle E. Parker; Jordan G. McCall
• Keywords: Locus coeruleus; Endogenous opioid

Abstract The locus coeruleus (LC) plays a paradoxical role in chronic pain. Although largely known as potent source of endogenous analgesia, increasing evidence suggests injury can transform the LC into pain generator. We sought to clarify this system Here, we show optogenetic inhibition activity is acutely antinociceptive. Following long-term spared nerve injury, same analgesic – further supporting its generator function. To identify inhibitory substrates that may naturally serve function, turned mu opioid receptors (LC-MOR). These provide powerful and exogenous activation LC-MOR therefore hypothesized LC-MOR-mediated critical how modulates Using cell type-selective conditional knockout rescue receptor signaling, these bidirectionally regulate thermal mechanical hyperalgesia providing functional gate on