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Endogenous μ-opioid-Neuropeptide Y Y1 receptor synergy silences chronic postoperative pain in mice

Tyler S Nelson1,2, Diogo F S Santos1, Pranav Prasoon1

  • 1Department of Anesthesiology and Perioperative Medicine, Center for Neuroscience, Pittsburgh Center for Pain Research, Pittsburgh Project to end Opioid Misuse, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.

PNAS Nexus
|August 31, 2023
PubMed

Insights

Following surgical incision, a synergistic interaction between μ-opioid receptor (MOR) and neuropeptide Y Y1 receptor (Y1R) activity in the spinal cord dorsal horn reduces postoperative pain hypersensitivity. This endogenous analgesia may prevent the transition from acute to chronic pain.

Area of Science:

  • Neuroscience
  • Pain Research
  • Molecular Biology

Background:

  • Tissue injury disrupts the balance between pain sensitization and endogenous analgesia.
  • Inhibitory G-protein-coupled receptor (GPCR) pathways, such as μ-opioid receptor (MOR) and neuropeptide Y Y1 receptor (Y1R) activity, normally oppose pain sensitization.
  • These analgesic pathways persist in the spinal cord dorsal horn (DH) long after initial pain resolution.

Purpose of the Study:

  • To investigate the role of endogenous analgesic synergy between MOR and Y1R in managing latent postoperative pain hypersensitivity.
  • To determine if the failure of these pathways contributes to the development of chronic pain.

Main Methods:

  • The study focused on the spinal cord dorsal horn (DH) in a model of surgical incision.
  • Investigated the persistent activity of MOR and Y1R signaling in interneurons post-recovery.
  • Assessed the impact of this signaling on latent hypersensitivity and ongoing pain.

Main Results:

  • A potent endogenous analgesic synergy between MOR and Y1R activity was identified in DH interneurons after surgical recovery.
  • This synergy was shown to significantly reduce the intensity and duration of latent postoperative hypersensitivity.
  • Evidence suggests this pathway plays a crucial role in maintaining pain remission.

Conclusions:

  • Persistent endogenous analgesic synergy between MOR and Y1R in the DH is critical for resolving postoperative pain hypersensitivity.
  • Dysfunction in this GPCR signaling may be a key factor in the transition from acute to chronic pain states.
  • Targeting these pathways could offer new strategies for preventing chronic pain development.
Keywords:
G-protein-coupled receptorchronic postsurgical painendogenous analgesialatent sensitizationneuropeptide Y Y1 receptorspinal cord dorsal hornsynergyμ-opioid receptor

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