Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386887307> ?p ?o ?g. }
- W4386887307 abstract "Chronic pain is a tremendous burden for afflicted individuals and society. Although opioids effectively relieve pain, significant adverse outcomes limit their utility and efficacy. To investigate alternate pain control mechanisms, we explored cholinergic signaling in the ventrolateral periaqueductal gray (vlPAG), a critical nexus for descending pain modulation. Biosensor assays revealed that pain states decreased acetylcholine release in vlPAG. Activation of cholinergic projections from the pedunculopontine tegmentum to vlPAG relieved pain, even in opioid-tolerant conditions, through ⍺7 nicotinic acetylcholine receptors (nAChRs). Activating ⍺7 nAChRs with agonists or stimulating endogenous acetylcholine inhibited vlPAG neuronal activity through Ca2+ and peroxisome proliferator-activated receptor α (PPAR⍺)-dependent signaling. In vivo 2-photon imaging revealed that chronic pain induces aberrant excitability of vlPAG neuronal ensembles and that ⍺7 nAChR-mediated inhibition of these cells relieves pain, even after opioid tolerance. Finally, pain relief through these cholinergic mechanisms was not associated with tolerance, reward, or withdrawal symptoms, highlighting its potential clinical relevance." @default.
- W4386887307 created "2023-09-21" @default.
- W4386887307 creator A5006625609 @default.
- W4386887307 creator A5051525208 @default.
- W4386887307 creator A5092908045 @default.
- W4386887307 date "2023-09-01" @default.
- W4386887307 modified "2023-09-28" @default.
- W4386887307 title "A cholinergic circuit that relieves pain despite opioid tolerance" @default.
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