Format

Send to

Choose Destination
Science. 2013 Sep 20;341(6152):1394-9. doi: 10.1126/science.1239403.

Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence.

Author information

1
Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.

Erratum in

  • Science. 2013 Nov 8;342(6159):693.

Abstract

Opioid receptor antagonists increase hyperalgesia in humans and animals, which indicates that endogenous activation of opioid receptors provides relief from acute pain; however, the mechanisms of long-term opioid inhibition of pathological pain have remained elusive. We found that tissue injury produced μ-opioid receptor (MOR) constitutive activity (MOR(CA)) that repressed spinal nociceptive signaling for months. Pharmacological blockade during the posthyperalgesia state with MOR inverse agonists reinstated central pain sensitization and precipitated hallmarks of opioid withdrawal (including adenosine 3',5'-monophosphate overshoot and hyperalgesia) that required N-methyl-D-aspartate receptor activation of adenylyl cyclase type 1. Thus, MOR(CA) initiates both analgesic signaling and a compensatory opponent process that generates endogenous opioid dependence. Tonic MOR(CA) suppression of withdrawal hyperalgesia may prevent the transition from acute to chronic pain.

Comment in

PMID:
24052307
PMCID:
PMC4440417
DOI:
10.1126/science.1239403
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center