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Endogenous μ-opioid - neuropeptide Y Y1 receptor synergy silences chronic postoperative pain

Nelson, T. S.; Santos, D. F. S.; Prasoon, P.; Gralinski, M.; Allen, H. N.; Taylor, B. K.

2022-07-05 neuroscience
10.1101/2022.07.05.498802 bioRxiv
Show abstract

Tissue injury creates a delicate balance between latent pain sensitization (LS) and compensatory endogenous analgesia. Inhibitory G protein-coupled receptor (GPCR) interactions that oppose LS, including -opioid receptor (MOR) and neuropeptide Y Y1 receptor (Y1R) activity, persist in the spinal cord dorsal horn (DH) for months, even after the resolution of normal pain thresholds. Here, we demonstrate that following recovery from surgical incision, a potent endogenous analgesic synergy between MOR and Y1R activity persists within DH interneurons to reduce the intensity and duration of latent postoperative hyperalgesia and ongoing pain. Failure of such endogenous GPCR signaling to maintain LS in remission may underlie the transition from acute to chronic pain states.

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