OPRM1/MRGPRX1 heterodimers drive opioid-induced itch through a peripheral mechanism - PubMed
5 hours ago
- #peripheral sensory neurons
- #OPRM1-MRGPRX1 heterodimers
- #opioid-induced itch
- Opioid-induced itch is a common side effect of opioid analgesics with poorly understood mechanisms, involving both central and peripheral pathways.
- OPRM1 forms heterodimers with MRGPRX1 in sensory neurons, switching signaling from Gαi/o-mediated cAMP inhibition to Gαq/11-driven calcium mobilization upon opioid activation.
- This heterodimerization triggers robust calcium responses and scratching behavior in mice, which can be reduced by OPRM1 or MRGPRX1 antagonists.
- In an atopic dermatitis mouse model, increased OPRM1 expression and β-endorphin levels in DRG neurons correlate with heightened itch and calcium responses.
- OPRD1 associates with MRGPRX2 but does not induce mast cell degranulation, indicating minimal contribution to peripheral itch signaling.
- Targeting OPRM1/MRGPRX1 heterodimers may offer new therapeutic strategies to alleviate opioid-induced itch without affecting analgesia.