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

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 μ-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.

Mouse models of non-dystrophic and dystrophic myotonia exhibit nociplastic pain-like behaviors

“…Testing was performed as previously described( Nelson et al , 2022 , 2023 ; Gomez et al , 2023 a ). Mice were habituated to plexiglass chambers (80 × 80 × 110 mm) on a raised wire mesh platform for 60 minutes immediately prior to behavioral testing.…”

“…Testing was performed as previously described ( Nelson et al , 2022 , 2023 ; Gomez et al , 2023 a ). Immediately following dynamic brush testing, sensitivity to non-noxious cold testing was performed on mice in the same plexiglass chambers on a raised wire mesh platform.…”