A brain-to-small intestine circuit mediates morphine-induced constipation in male mice.

ABSTRACT: Opioid-induced constipation is one of the most common and persistent side effect of opioid analgesics, yet the underlying neural mechanism(s) remain unclear. Here we show morphine-induced constipation is mediated by a neural circuit from glutamatergic neurons in the paraventricular nucleus of hypothalamus (PVN^Glu) to acetylcholinergic neurons in the dorsal motor nucleus of the vagus (DMV^Ach), and subsequently to the small intestine in mice. Microendoscopic calcium imaging revealed morphine inhibits the PVN^Glu→DMV^Ach→small intestine circuit, and this is accompanied by decreased small intestinal motility. Chemogenetic activation of this circuit, as well as pharmacological inhibition or knockdown of the μ-opioid receptor (MOR) in PVN^Glu n

SUBMITTER: Ma J 

PROVIDER: S-EPMC12847740 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature