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

Tyler S Nelson; Diogo F S Santos; Pranav Prasoon; Margaret Gralinski; Heather N Allen; Bradley K Taylor

doi:10.1093/pnasnexus/pgad261

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

PNAS Nexus. 2023 Aug 14;2(8):pgad261. doi: 10.1093/pnasnexus/pgad261. eCollection 2023 Aug.

Authors

Tyler S Nelson^{1

2}, Diogo F S Santos¹, Pranav Prasoon¹, Margaret Gralinski¹, Heather N Allen¹, Bradley K Taylor¹

Affiliations

¹ Department 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.
² Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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) or 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 hypersensitivity and ongoing pain. Failure of such endogenous GPCR signaling to maintain LS in remission may underlie the transition from acute to chronic pain states.

Keywords: G-protein-coupled receptor; chronic postsurgical pain; endogenous analgesia; latent sensitization; neuropeptide Y Y1 receptor; spinal cord dorsal horn; synergy; μ-opioid receptor.

Abstract

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