Skip to main content
Article
Constitutive mu-Opioid Receptor Activity Leads to Long-Term Endogenous Analgesia and Dependence
Science (2013)
  • Renee R. Donahue, University of Kentucky
  • Gregory Corder, University of Kentucky
  • Suzanne Doolen, University of Kentucky
  • Michele K Winter, University of Kansas Medical Center
  • Brandon L Jutras, University of Kentucky
  • Y He, University of Illinois at Chicago
  • X Hu, University of Illinois at Chicago
  • Joseph S Wieskopf, McGill University
  • Jeffrey S Mogil, McGill University
  • Daniel R Storm, University of Washington - Seattle Campus
  • Z J Wang, University of Illinois at Chicago
  • Kenneth E McCarson, University of Kansas Medical Center
  • Bradley K Taylor, University of Kentucky
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 m-opioid receptor (MOR) constitutive activity (MORCA) 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, MORCA initiates both analgesic signaling and a compensatory opponent process that generates endogenous opioid dependence. Tonic MORCA suppression of withdrawal hyperalgesia may prevent the transition from acute to chronic pain.

Keywords
  • mu opioid receptor,
  • constitutive activity,
  • latent sensitization,
  • CFA,
  • post-surgical pain,
  • cAMP,
  • NB001,
  • AC1,
  • NMDA,
  • GTPgS binding,
  • 6B Naltrexol,
  • Naloxone,
  • Lidocaine,
  • CTOP,
  • forskolin,
  • MK-801,
  • naltrexone
Publication Date
2013
Citation Information
Renee R. Donahue, Gregory Corder, Suzanne Doolen, Michele K Winter, et al.. "Constitutive mu-Opioid Receptor Activity Leads to Long-Term Endogenous Analgesia and Dependence" Science Vol. 340 (2013)
Available at: http://works.bepress.com/renee_donahue/9/